Nowadays, the discovery and development of α-glucosidase inhibitors from natural products or their derivatives represents an attractive approach. Here we reported studies on a series of novel N-acyl-2-aminothiazoles fused (+)-nootkatone and evaluation for their α-glucosidase inhibitory activities. Most of (+)-nootkatone derivatives exhibited more potent α-glucosidase inhibitory ability than the positive drug acarbose. In particular, compounds II7 and II14 showed the most promising α-glucosidase inhibitory ability with IC50 values of 13.2 and 13.8 µM. II7 and II14 also exhibited relatively low cytotoxicities towards normal LO2 cells. Kinetic study indicated that compounds II7 and II14 inhibited the α-glucosidase in a noncompetitive manner, and molecular docking results were in line with the noncompetitive characteristics that II7 and II14 did not bind to the known active sites (Asp214, Glu276 and Asp349). Based on our findings, these (+)-nootkatone derivatives could be used as antidiabetic candidates.Increased anxiety sensitivity (AS), or the fear of anxiety-related cognitive, social, and physical symptoms which are misinterpreted as having harmful implications, has shown a relationship with substance use disorders. People with substance use disorders also experience addiction-related problems across domains of life functioning. However, few studies have evaluated the relationship between elevated AS and addiction-related problems across specific life areas. We evaluated, first, whether AS predicted addiction-related problems in a sample of treatment-refractory outpatients with opioid use disorders and, second, whether sex moderated the relationship between AS and addiction-related problems in this sample. Participants with treatment-refractory opioid use disorders (n = 92, 53.3% male) completed baseline assessments of AS (the Anxiety Sensitivity Index) and addiction-related problems (the Addiction Severity Index). Baseline AS total score was a significant independent predictor of both baseline Addiction Severity Index medical status (β = 0.29, t = 2.84, p = .006) and psychiatric status (β = 0.30, t = 2.99, p = .004) composite scores but was not associated with social, employment or legal difficulties. These findings were maintained when controlling for drug use severity, though baseline AS total score became a significant predictor of baseline legal difficulties (β = -0.23, t = -2.25, p = .027). There was no moderating role of sex on the relationship between baseline AS and addiction-related problems. Our findings suggest that, regardless of sex, elevated AS predicts increased addiction-related medical and psychiatric problems, and decreased legal problems when accounting for drug use severity, in outpatients with opioid use disorders.

Despite intense neuroscience research on the neurobiological underpinnings of Gambling Disorder (GD) and gambling-related decision-making, effective treatments targeting these dysfunctions are still lacking. Non Invasive Brain Stimulation (NIBS) techniques, such as transcranial Direct Current Stimulation (tDCS) and Transcranial Magnetic Stimulation (TMS), selectively modulate activity of brain circuits and have the potential to reverse alterations sustaining GD symptoms. Therefore, the aim of this systematic review was to determine the impact of different NIBS interventions on gambling-related decision processes.

We conducted a comprehensive and translational search in three online databases (MEDLINE via PubMed, Scopus, Web of Science), in accordance with the PRISMA guidelines. We included studies applying neuromodulation (TMS, tDCS) techniques in GD patients or assessing gambling-related decision-making in healthy subjects. In addition, we explored the potential impact of NIBS in drug-induced GD (e.g., Pinvestigate connectivity changes and laterality issues (unilateral versus bilateral; left versus right) of NIBS application in GD.

Gender bias in measures of cannabis problems may differentially affect how men and women endorse items. This gender invariance might mask, exaggerate, or otherwise obscure true distinctions in experiences of cannabis consequences.

The Cannabis-Associated Problems Questionnaire (CAPQ), a measure of interpersonal deficits, occupational impairment, psychological issues, and physical side effects related to cannabis use, contained items with gender-based differential item functioning (DIF) in previous work-a finding we aim to replicate and extend (Lavender, Looby, & Earleywine, 2008).

In a sample of 4053 cannabis users, gender differences were apparent in global scores on the CAPQ. A DIF analysis revealed two gender-biased items, including one identified previously. Removal of these items did not significantly alter the scale’s relation to cannabis use. Gender differences on the CAPQ persisted after removal of the two problematic items, indicating true gender differences still exist in men and women’s experiences of cannabis-related consequences. Gender appeared to significantly contribute to scores on the full CAPQ and the short-form of the CAPQ with biased item removed, even after controlling for indices of cannabis use.

These findings suggest that the CAPQ evidences less gender bias than previously thought, perhaps due to diminishing gender-based stereotypes. Future work might opt to use the short form of the CAPQ to minimize gender-based DIF. In addition, potential biases in measures of substance use problems deserve more attention.

These findings suggest that the CAPQ evidences less gender bias than previously thought, perhaps due to diminishing gender-based stereotypes. Future work might opt to use the short form of the CAPQ to minimize gender-based DIF. In addition, potential biases in measures of substance use problems deserve more attention.This study aimed to genotype the polymorphism (c.654G > A) in the exon 3 of the insulin-like growth factor 1 receptor gene (IGF1R) and to analyze its association with growth, body size, slaughter and meat quality traits in Colored Polish Merino sheep. In total, 67 traits were analyzed. The IGF1R polymorphism was genotyped using the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method. The MIXED procedure of the SAS software was used to assess the genotypic effects of the polymorphism (c.654G > A) on production traits of interest. The IGF1R c.654G > A genotypes were found to have a significant effect on the average daily gain between the 56th and 78th day of life, cold carcass, leg part, leg cut, fore shank, and kidney weights, as well as eye of loin depth, intramuscular fat content, and water-holding capacity of meat. The results suggest that the studied polymorphism may provide useful information for marker-assisted selection for increased meat performance in Colored Polish Merino sheep.The in vitro 3D model established from murine pluripotential stem cells (i.e., embryoid bodies (EBs)) is a dynamic model for endothelial differentiation. The aim of the present study was to investigate whether digital image analysis (DIA) can be applied on histological sections of EBs in order to quantify endothelial differentiation over time. The EBs were established in suspension cultures for 21 days in three independent replicate experiments. At day 4, 6, 9, 14, 18, and 21, the EBs were fixed in formaldehyde, embedded in paraffin and immunohistochemically (IHC) stained for CD31. The IHC-stained slides were digitally scanned and analysed using the Visiopharm® Quantitative Digital Pathology software Oncotopix™. The EBs developed CD31+ vascular-like structures during their differentiation. The quantitative DIA of the EBs showed that the log10 values of the relative CD31+ areas increased from -0.574 ± 0.470 (mean ± SD) at day 4 to 0.093 ± 0.688 (mean ± SD) at day 21 (p less then 0.001). The approach presented in this study is a fast, quantitative and reproducible alternative method for an otherwise time-consuming and observer-dependent histological investigation. The future perspectives for such a system would be implementation of a modified version of the method on different 3D cultures and IHC markers.Impaired brain development has been observed in newborns with congenital heart disease (CHD). We performed graph theoretical analyses and network-based statistics (NBS) to assess global brain network topology and identify subnetworks of altered connectivity in infants with CHD prior to cardiac surgery. Fifty-eight infants with critical/serious CHD prior to surgery and 116 matched healthy controls as part of the developing Human Connectome Project (dHCP) underwent MRI on a 3T system and high angular resolution diffusion MRI (HARDI) was obtained. Multi-tissue constrained spherical deconvolution, anatomically constrained probabilistic tractography (ACT) and spherical-deconvolution informed filtering of tractograms (SIFT2) was used to construct weighted structural networks. Network topology was assessed and NBS was used to identify structural connectivity differences between CHD and control groups. Structural networks were partitioned into core and peripheral nodes, and edges classed as core, peripheral, or feeder. NBS identified one subnetwork with reduced structural connectivity in CHD infants involving basal ganglia, amygdala, hippocampus, cerebellum, vermis, and temporal and parieto-occipital lobe, primarily affecting core nodes and edges. However, we did not find significantly different global network characteristics in CHD neonates. This locally affected sub-network with reduced connectivity could explain, at least in part, the neurodevelopmental impairments associated with CHD.

Multiple system atrophy (MSA) is an atypical parkinsonian syndrome and often difficult to discriminate clinically from progressive supranuclear palsy (PSP) and Parkinson’s disease (PD) in early stages. Although a characteristic metabolic brain network has been reported for MSA, it is unknown whether this network can provide a clinically useful biomarker in different centers. This study was aimed to identify and cross-validate MSA-related brain network and assess its ability for differential diagnosis and clinical correlations in Chinese and American patient cohorts.

We included

F-FDG PET scans retrospectively from 128 clinically diagnosed parkinsonian patients (34 MSA, 34 PSP and 60 PD) and 40 normal subjects in China and in the USA. Using PET images from 20 moderate-stage MSA patients of parkinsonian subtype and 20 normal subjects in both centers, we reproduced MSA-related pattern (MSAPRP) of spatial covariance and estimated its reliability. MSAPRP scores were evaluated in assessing differential diagnoluating disease discrimination and clinical correlates. This study supports differential diagnosis of MSA regardless of different patient populations, PET scanners and imaging protocols.

We have demonstrated reproducible metabolic topographies associated with MSA at both network and regional levels in two independent patient cohorts. Moreover, MSAPRP scores are sensitive for evaluating disease discrimination and clinical correlates. This study supports differential diagnosis of MSA regardless of different patient populations, PET scanners and imaging protocols.

Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation and a prevalent cause of surgically amenable epilepsy. While cellular and molecular biology data suggest that FCD lesional characteristics lie along a spectrum, this notion remains to be verified in vivo. We tested the hypothesis that machine learning applied to MRI captures FCD lesional variability at a mesoscopic scale.

We studied 46 patients with histologically verified FCD Type II and 35 age- and sex-matched healthy controls. We applied consensus clustering, an unsupervised learning technique that identifies stable clusters based on bootstrap-aggregation, to 3T multicontrast MRI (T1-weighted MRI and FLAIR) features of FCD normalized with respect to distributions in controls.

Lesions were parcellated into four classes with distinct structural profiles variably expressed within and across patients Class-1 with isolated white matter (WM) damage; Class-2 combining grey matter (GM) and WM alterations; Class-3 with alized treatments.

Machine learning applied to widely available MRI contrasts uncovers FCD Type II variability at a mesoscopic scale and identifies tissue classes with distinct structural dimensions, functional and histopathological profiles. Integrating in vivo staging of FCD traits with automated lesion detection is likely to inform the development of novel personalized treatments.The dorsolateral prefrontal cortex (DLPFC), a key structure in the executive system, has consistently emerged as a crucial element in the pathophysiology of obsessive-compulsive disorder (OCD). However, the neural primacy of the DLPFC remains elusive in this disorder. We investigated the causal interaction (measured by effective connectivity) between the DLPFC and the remaining brain areas using bivariate Granger causality analysis of resting-state fMRI collected from 88 medication-free OCD patients and 88 matched healthy controls. Additionally, we conducted seed-based functional connectivity (FC) analyses to identify network-level neural functional alterations using the bilateral DLPFC as seeds. OCD patients demonstrated reduced FC between the right DLPFC and right orbitofrontal cortex (OFC), and activity in the right OFC had an inhibitory effect on the right DLPFC. Additionally, we observed alterations in both feedforward and reciprocal influences between the inferior temporal gyrus (ITG) and the DLPFC in patients. Furthermore, activity in the cerebellum had an excitatory influence on the right DLPFC in OCD patients. These findings may help to elucidate the psychopathology of OCD by detailing the directional connectivity between the DLPFC and the rest of the brain, ultimately helping to identify regions that could serve as treatment targets in OCD.Anthracycline antineoplastic drugs (doxorubicin, epirubicin, daunorubicin) are „hazardous drugs for handling” by healthcare professionals. To monitor their occupational exposure, a highly sensitive ESI-UHPLC-MS/MS method for the assay of anthracyclines in urine was developed. The urine extraction consisted of SPE extraction method. A good linearity (r > 0.996), precision (CV less then 14.4%), and accuracy (bias less then 13.6%) were achieved for the three drugs. The lower limit of quantification (LOQ) was 10 ng/L. This LOQ value is equal to the LOQ of published methods except for epirubicin, for which the LOQ value is better by a factor of 10 (best published LOQ value 100 ng/L). Applying this method in routine, more than 77 healthcare professionals occupationally exposed to anthracyclines were monitored and 77 urines were analyzed. Two healthcare professionals (2.6%) were found to be contaminated to doxorubicin and/or epirubicin. The measured concentrations ranged from 17.7 to 218 ng/L. Such an efficient analytical tool, combining both high specificity and sensitivity is essential for reliable highlight of contamination during biological monitoring of healthcare professionals widely exposed to these drugs. This anthracycline antineoplastic drugs exposure monitoring allows healthcare professionals for assessing effectiveness individual and collective protective measures and for ensuring traceability of occupational exposure to these drugs.Information on water requirement of small mammals is sparse and the assessment of daily water consumption is an important aspect of the veterinary practice in exotic pet nutrition. Water and feed daily intake are interlaced, that way the water to feed ratio is a meaningful indication. However, various factors such as ambient temperature or the uptake of substances to be eliminated via the kidney (i.e. calcium) must be taken into account when estimation of water consumption is carried out. Moreover, behavioural abnormalities could affect water consumption, like in the case of water uptake as a substitute action. Adequate water supply for small mammals is indispensable for health reasons (prophylaxis of urolithiasis) and consequences relevant to animal welfare. For this purpose, data from different trials enrolling no. 5 Flemish Belgian (FB) and no. 5 New Zealand White (NZW) rabbits, no. 10 dwarf rabbits, no. 7 guinea pigs and no. 7 chinchilla, were obtained to assess water intake according to feed rationing. Water balance following feed rationing was seen to differ across the species of small mammals considered in these trials. The comparative approach pointed to species-dependent water intake behaviour. Due to the species-related high variation in water uptake, it is not possible to give general recommendations for water supply of small mammals. In addition, water uptake is also influenced by the water content of the food, absolute dry matter uptake and food composition. Nevertheless, an additional supply of drinking water is recommended for all species, since unsatisfactory water supply reduces dry matter intake and may lead to energy undersupply.The adsorption of methanol, ethanol and propan-1-ol at the solution-air and solid-solution interfaces, their aggregation in the aqueous media as well as wetting properties regarding their applications as additives or co-surfactants in the surfactants aqueous solution were discussed based on the literature data. Mutual influence of alcohols and surfactants on the solution-air and solid-solution interface tension was considered. For this purpose there were used different methods allowing to describe or predict changes of water surface tension as a function of alcohols concentration. These, in turn, as a function of alcohol and/or surfactant concentration were also analyzed by means of the methods applied for prediction of surface tension of aqueous solution of the classical surfactants mixture. The same considerations related to the behaviour of alcohol and surfactant at the solid-solution and solution-air interfaces were made. To explain the behaviour of alcohols and surfactants mixture at the solution-air and solid-solution interfaces the components and parameters of water, alcohols, surfactants and solids surface tension as well as the Gibbs free energy changes during the adsorption process were taken into account. It was proved that wettability of some solids can be predicted based on alcohol and surfactants adsorption as well as surface tension components and parameters. As follows the mutual influence of alcohol and surfactant on their adsorption at the solution-air and solid-solution interfaces as well as on the wetting properties at the alcohol concentration from zero to its critical aggregation concentration (CAC) is different from that at its concentration higher than CAC.Photocatalysis has attracted wide attention in eliminating volatile organic compounds (VOCs). This paper pays attention to the relationship between structure and performance of photocatalysts based on the fact that catalytic reactions arise on the surface of catalysts and the interface structure of photocatalysts plays key role in transfer efficiency of charges carriers. This review summarizes various surface/interface designs including unsaturated coordination such as oxygen vacancies, surface halogenations, and heterojunctions, homojunctions, facets, etc., as well as the application in photocatalytic degradation of VOCs. This paper reviews the influence of surface and interface properties of materials on VOCs molecules, effective strategies to promote the decomposition of VOCs from the perspectives of VOCs activation, reaction barrier etc., and presents various methods of photocatalyst design appropriately. The degradation path of highly toxic benzene VOCs are also summarized. In addition, the possible problems and suggestions for photocatalytic degradation of VOCs are proposed.This review is focused on new electrophoretic deposition (EPD) mechanisms for deposition biomacromolecules, such as biopolymers, proteins and enzymes. Among the rich literature sources of EPD of biopolymers, proteins and enzymes for biomedical applications we selected papers describing new fundamental deposition mechanisms. Such deposition mechanisms are of critical importance for further development of EPD method and its emerging biomedical applications. Our goal is to emphasize innovative ideas which have enriched colloid and interface science of EPD during recent years. We describe various mechanisms of cathodic and anodic EPD of charged biopolymers. Special attention is focused on in-situ chemical modification of biopolymers and crosslinking techniques. Recent innovations in the development of natural and biocompatible charged surfactants and film forming agents are outlined. Among the important advances in this area are the applications of bile acids and salts for EPD of neutral polymers. Such innovations allowed for the successful EPD of various electrically neutral functional polymers for biomedical applications. Particularly important are biosurfactant-polymer interactions, which facilitate dissolution, dispersion, charging, electrophoretic transport and deposit formation. Recent advances in EPD mechanisms addressed the problem of EPD of proteins and enzymes related to their charge reversal at the electrode surface. Conceptually new methods are described, which are based on the use of biopolymer complexes with metal ions, proteins, enzymes and other biomolecules. This review describes new developments in co-deposition of biomacromolecules and future trends in the development of new EPD mechanisms and strategies for biomedical applications.Although eutrophic urban rivers receiving loads of wastewater represent an important anthropogenic source of N2O, little is known as to how temperature and other environmental factors affect temporal variations in N2O emissions from wastewater treatment plants (WWTPs) and downstream rivers. Two-year monitoring at a WWTP and five river sites was complemented with available water quality data, laboratory incubations, and stable isotopes in N2O and NO3- to explore how wastewater effluents interact with seasonal changes in environmental conditions to affect downstream metabolic processes and N2O emissions from the lower Han River traversing the megacity Seoul. Water quality data from four WWTPs revealed significant inverse relationships between water temperature and the concentrations or fluxes of total N (TN) in effluents. Increased TN fluxes at low temperatures concurred with N2O surges in WWTP effluents and downstream rivers, counteracting the long-term decline in TN fluxes resulting from enhanced wastewater treatments. Incubation experiments with river water and sediment, in isolation or combined, implied the hypoxic winter sediment as a large source of N2O, whereas the anoxic summer sediment produced a smaller amount of N2O only when it was added with oxic water. For both WWTP effluents and downstream rivers, bulk isotope ratios and intramolecular distribution of 15N in N2O distinctly differed between summer and winter, indicating incomplete denitrification in the hypoxic sediment at low temperatures as a primary downstream source adding to WWTP-derived N2O. Winter surges in wastewater TN and sediment N2O release highlight temperature variability as an underappreciated control over anthropogenic N2O emissions from increasingly urbanized river systems worldwide.

Rhabdomyosarcoma (RMS) is the malignant tumor of skeletal muscles that origin from rhabdomyoblast. RMS is the most common soft tissue tumor in children, but this is a sporadic condition in adults and only 1% of any solid malignancies of an adult. The most prevalent subtype of RMS in an adult is a pleomorphic type.

We reported a case of a 57 years old woman with swelling on the left chest with pain for three years. Physical examination revealed swelling on the left chest with solid consistency and immobile. The thorax CT-scan with IV contrast suspicious soft tissue tumor on the anteromedial of the left chest wall that stuck to the left lung.

Histopathological examination confirmed the pleomorphic subtype of rhabdomyosarcoma. The interdisciplinary idea was reported to be superior to a single therapeutic modality. The patient underwent an incisional biopsy.

This is a case of pleomorphic rhabdomyosarcoma diagnosed base on histopathology from an incisional biopsy, and IHC performed wide excision gave satisfactory results.

This is a case of pleomorphic rhabdomyosarcoma diagnosed base on histopathology from an incisional biopsy, and IHC performed wide excision gave satisfactory results.

Lymphangioma is an abnormal proliferation of lymphatic vessels. Isolated splenic lymphangioma (SL) is rare; in the last 30 years only 22 cases were reported in the literature. Diagnosis is difficult by the absence of typical symptoms and signs. SL is often asymptomatic and occasionally detected through radiological exams or, after the onset of a life-threatening complication, at surgery or pathological examination. Surgery represents the treatment of choice.

A 22-year-old Caucasian male was admitted to the Emergency Department after a car accident, complaining of sudden onset, severe, left upper quadrant abdominal pain. Abdominal examination revealed mild abdominal distention and a severe abdominal pain on superficial and deep palpation of left upper abdominal quadrant with obvious muscle guarding and rebound tenderness. Abdominal computed tomography scan showed splenic rupture with hemoperitoneum. Laboratory tests reported severe anemia. The patient received blood transfusions and was taken emergently to the operating room for exploratory laparotomy, evacuation of hemoperitoneum and splenectomy. The postoperative course was uneventful, the patient was discharged on the 7th post-operative day. Diagnosis of microcystic SL was made at pathological examination.

Post-traumatic splenic rupture may be favored by the presence of a unknown and asymptomatic isolated SL. Although different types of treatment of SL are reported in the literature, splenectomy represents the treatment of choice to avoid complications.

Isolated SL is difficult to diagnose and suspect because of lack of pathognomonic symptoms and specific diagnostic signs. It can be diagnosed after the onset of a life-threatening complication. Splenectomy is the preferable definitive treatment.

Isolated SL is difficult to diagnose and suspect because of lack of pathognomonic symptoms and specific diagnostic signs. It can be diagnosed after the onset of a life-threatening complication. Splenectomy is the preferable definitive treatment.The ovaries, the main female reproductive organs, directly mediate ovulation and reproductive hormone secretion. These complex physiological processes are regulated by multiple genes and pathways. However, there is a lack of research on goat ovaries, and the molecular mechanisms underlying the signaling pathways remain unclear. In this study, Illumina HiSeq 4000 sequencing was used to sequence the transcriptomes of goat ovaries. The expression patterns of differentially expressed mRNAs in goat ovaries at both the follicular and luteal phases were determined by bioinformatics analysis. A total of 1,122, 014, 112 clean reads were obtained, and 3770 differentially expressed mRNAs were identified for further analysis. There were 1727 and 2043 upregulated mRNAs in the luteal phase and follicular phase, respectively. According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, some mRNAs that were highly expressed in ovaries during the luteal phase, such as HSD17B7, 3BHSD, and SRD5A2, may be related to the synthesis of progesterone. In addition, some mRNAs that were highly expressed in ovaries during the follicular phase, such as RPL12, RPS13 and RPL10, are related to the growth and maturation of oocytes. Taken together, the findings of this study provide genome-wide mRNA expression profiles for goat ovaries at the follicular and luteal phases and identify mRNAs associated with goat hormone secretion and follicular development. In addition, this study provides a theoretical basis for further investigation of goat reproductive regulation.

The present study was carried out to unfold the clinical significance of apoptosis stimulating protein of p53 (ASPP) 1 and ASPP2 expression in oral cancer (OC).

Tissue specimens (malignant and their corresponding adjacent normal) from 40 pathologically confirmed OC patients treated at the Institute were included in the study. ASPP1 and ASPP2 expression were examined using semi-quantitative RT-PCR.

The results indicated lower ASPP1 expression in OC tissues as compared to adjacent normal tissues (p = 0.085). Stratified analysis as per tumor site revealed significant down-regulation of ASPP1 in tongue cancer tissues (p = 0.005). Receiver operating characteristic curve depicted significant discriminatory efficacy in distinguishing tongue cancer tissues and adjacent normal tissues (p = 0.019). Moreover, ASPP1 expression was remarkably declined in stage II, III and IV OC tumors than stage I OC tumors (p = 0.007, 0.092 and 0.013, respectively). A similar trend was observed in buccal mucosa tumors on further an down-regulation of ASPP1 and ASPP2 may serve as potential diagnostic and prognostic indicators in OC.

Melanoma is an aggressive form of skin cancer for which there are no effective drugs for prolonged treatment. The existing kinase inhibitor antiglycolytic drugs (B-Raf serine/threonine kinase or BRAF inhibitors) are effective for a short time followed by a rapid onset of drug resistance.

Here, we show that a mitochondria-targeted analog of magnolol, Mito-magnolol (Mito-MGN), inhibits oxidative phosphorylation (OXPHOS) and proliferation of melanoma cells more potently than untargeted magnolol. Mito-MGN also inhibited tumor growth in murine melanoma xenografts. Mito-MGN decreased mitochondrial membrane potential and modulated energetic and mitophagy signaling proteins.

Results indicate that Mito-MGN is significantly more potent than the FDA-approved OXPHOS inhibitor in inhibiting proliferation of melanoma cells.

These findings have implications in the treatment of melanomas with enhanced OXPHOS status due to metabolic reprogramming or drug resistance.

These findings have implications in the treatment of melanomas with enhanced OXPHOS status due to metabolic reprogramming or drug resistance.In the fields of biocomputing and biomolecular, DNA molecules are applicable to be regarded as data of logical computing platform that uses elaborate logic gates to perform a variety of tasks. Graphene oxide (GO) is a type of novel nanomaterial, which brings new research focus to materials science and biosensors due to its special selectivity and excellent quenching ability. G-quadruplex as a unique DNA structure stimulates the intelligent application of DNA assembly on the strength of its exceptional binding activity. In this paper, we report a universal logic device assisted with GO and G-quadruplex under an enzyme-free condition. Integrated with the quenching ability of GO to the TAMRA (fluorophore, Carboxytetramethylrhodamine) and the enhancement of fluorescence intensity produced by the peculiar binding of G-quadruplex to the NMM (N-methylmesoporphyrin IX), a series of basic binary logic gates (AND. OR. INHIBIT. XOR) have been designed and verified through biological experiments. Given the modularity and programmability of this strategy, two advanced logic gates (half adder and half subtractor) were realized on the basis of the same work platform. The fluorescence signals generated from different input combinations possessed satisfactory results, which provided proof of feasibility. We believe that the proposed universal logical platform that operates at the nanoscale is expected to be utilized for future applications in molecular computing as well as disease diagnosis.Lipid digestion is critical for infant development, and yet, the interconnection between lipid digestion and the microbiota is largely understudied. This review focuses on digestion of the human milk fat globule and summarizes the current understanding of the mechanisms underlying this process in infants. We first discuss the partial hydrolysis of milk fat in the stomach, which leads to rearrangement of lipid droplets, creating a lipid-water interface necessary for duodenal lipolysis. In the first few months of life, secretion of pancreatic triglyceride lipase, phospholipase A2, and bile salts is immature. The dominant lipases aiding fat digestion in the newborn small intestine are therefore pancreatic lipase-related protein 2 and bile salt-stimulated lipase from both the exocrine pancreas and milk. We summarize the interaction between ionic fatty acids and cations to form insoluble fatty acid soaps and how it is influenced by various factors, including cation availability, pH, and bile salt concentration, as well as saturation and chain length of fatty acids. We further argue that the formation of the soap complex does not contribute to lipid bioavailability. Next, the possible roles that the gut microbiota plays in lipid digestion and absorption are discussed. Finally, we provide a perspective on how the manufacturing process of infant formula and dairy products may alter the physical properties and structure of lipid droplets, thereby altering the rate of lipolysis.Obesity and metabolic syndrome are important health problems that can lead to significant morbidity/mortality as well as subsequent health concerns. Alterations in the gut microbiota have been implicated in both obesity and metabolic syndrome. Fecal Microbiota Transplantation (FMT) has emerged as a new promising therapeutic approach aimed at manipulating the gut microbiota in various chronic diseases. Randomized clinical trials assessing the use of FMT in obese and metabolic syndrome patients have been reported. The purpose of this systematic review with meta-analysis using randomized clinical trials (RCT) is to evaluate the role of FMT for the treatment of obesity and metabolic syndrome and its impact on clinically relevant parameters. We searched the main databases, as well as the gray literature, to identify RCTs comparing FMT from lean donor(s) vs placebo for obese/metabolic syndrome patients. We included all studies that utilized any form of placebo (sham, saline, autologous FMT, or placebo capsules). Six studies met the inclusion criteria and were included for final analysis with a total of 154 patients. We looked for clinically significant parameters related to obesity and metabolic syndrome and organized the findings into early (2-6 weeks after intervention) and late (12 weeks after intervention) outcomes. Two to 6 weeks after intervention, mean HbA1c was lower in the FMT group (MD = -1.69 mmol/L, CI [-2.88, -0.56], P = .003) and mean HDL cholesterol was higher in the FMT group (MD = 0.09 mmol/L, CI [0.02, 0.15], P = .008). There was no difference in obesity parameters 6 to 12 weeks after intervention. No serious adverse events were reported. The findings for this meta-analysis show that FMT may have a role for the treatment of metabolic syndrome, but there is currently not enough evidence to support its use in clinical practice. High-quality well-powered RCTS with longer follow-up are necessary to clarify the role of FMT in this patient cohort.

Antibodies labeled with alpha-emitter astatine-211 have previously shown effective in intraperitoneal (i.p.) treatments of ovarian cancer. In the present work we explore the use of investigational farletuzumab, aimed at the folate receptor alpha. The aim was to evaluate the biodistribution and therapeutic effect of

At-farletuzumab in in-vitro and in-vivo experiments and, using models for radiation dosimetry, to translate the findings to expected clinical result. The activity concentration used for therapy in mice (170 kBq/mL) was chosen to be in agreement with an activity concentration that is anticipated to be clinically relevant in patients (200 MBq/L).

For biodistribution, using intravenous injections and mice carrying subcutaneous (s.c.) tumors, the animals were administered either

At-farletuzumab (n = 16); or with a combination of

I-farletuzumab and

At-MX35 (n = 12). At 1, 3, 10 and 22 h, mice were euthanized and s.c.-tumors and organs weighted and measured for radioactivity. To evaluate therse (treated versus controls) in antitumor efficacy. This observation warrants further clinical testing.

The current investigation of intraperitoneal therapy with 211At-farletuzumab, delivered at clinically relevant 211At-mAb radioactivity concentrations and specific activities, showed a 6 to 10-fold increase (treated versus controls) in antitumor efficacy. This observation warrants further clinical testing.

Cognitive preparation plays a crucial role in CBT with exposure for panic disorder and agoraphobia. High emotional arousal while developing the exposure rationale might impair patients’ cognitive capacities for processing information about treatment and impede therapeutic outcome.

This study investigates whether patients’ vocally encoded emotional arousal, assessed by fundamental frequency (f

), during rationale development is associated with premature treatment dropout, insight into the rationale, and symptom reduction.

Patients’ (N=197, mean age 36.1 years, 79.2% female) f

during rationale development was measured based on treatment videos from a randomized controlled trial of CBT for panic disorder and agoraphobia. Insight was rater assessed. Symptom severity was self- and rater assessed at the beginning and end of therapy.

Higher f

mean during rationale development was associated with lower probability of insight and less reduction in avoidance behavior. f

was not associated with dropout. Insight was associated with lower probability of dropout and partially mediated the association between f

and avoidance reduction.

This study highlights the importance of emotional arousal during cognitive preparation for exposure. Therapists should ensure that patients are not too highly aroused while learning about the exposure rationale as an important step in treatment.

This study highlights the importance of emotional arousal during cognitive preparation for exposure. Therapists should ensure that patients are not too highly aroused while learning about the exposure rationale as an important step in treatment.Analysis of condom evidence commonly focusses on the detection of silicone-based lubricants, such as polydimethylsiloxane. However, water-based compounds such as propylene glycol or glycerin can also be used as condom lubricants and may, therefore, be detected as transferred traces. Evaluation of the variability amongst a large sample set from an international market is needed to determine what are the most likely compounds that may be detected in casework. In this study, 165 condoms, personal hygiene products, lubricants, creams and oils were analysed using gas-chromatography coupled to a mass spectrometer detector (GCMS). The resulting compounds were identified using mass spectral databases, then the data were extracted and evaluated using established multivariate statistical techniques, such as principal component analysis and discriminant analysis. Qualitative visual inspection, as well as statistical analysis, revealed at least twelve different groupings within the dataset. Discrimination was based on variations in the concentration of major compounds, as well as the presence or absence of minor compounds, such as anaesthetics. For the 127 condoms examined, 2 were exclusively water-based lubricated (1.5 %) and 6 contained silicone and water-based components (4.7 %). All the others were only silicone-based (119 condoms, 93.7 %). Strong variation was observed between the different sources of products. Personal hygiene products (PHP), creams, lubricating oils, personal lubricants, and condoms were found to have different chemical compositions. Hence GCMS can be used to assist in the differentiation of water-based residues for investigative purposes.The aim of this work was to study the biological catalysts and possible substrate conversion routes in mesophilic dark fermentation reactors aimed at producing H2 from olive mill wastewater. Bacillus and Clostridium were the most abundant phylotypes during the rapid stage of H2 production. Chemical analyses combined with predictive functional profiling of the bacterial communities indicated that the lactate fermentation was the main H2-producing route. In fact, during the fermentation process, lactate and acetate were consumed, while H2 and butyrate were being produced. The fermentation process was rich in genes that encode enzymes for lactate generation from pyruvate. Lactate conversion to butyrate through the generation of pyruvate produced H2 through the recycling of electron carriers via the pyruvate ferredoxin oxydoreductase pathway. Overall, these findings showed the synergy among lactate-, acetate- and H2-producing bacteria, which complex interactions determine the H2 production routes in the bioreactors.An enhanced sequencing batch reactor (SBR) system was developed to treat synthetic wastewater rich in 600 mg/L aniline. The aniline degradation efficiency was almost 100%, and the total nitrogen (TN) removal rate was more than 50%. Metagenomics technology revealed the community structure, functional genes and metabolic mechanism during the start-up of the enhanced reactor. Sequencing results showed that Proteobacteria, Bacteroidetes, Chloroflexi and Actinobacteria were dominant phylum. The proportion of degradation of aromatic compounds function increased gradually, but the proportion of nitrogen metabolism function changed little. Functional genes involved in aniline degradation including benA-xylX and dmpB/xylE were detected. The functional genes of nitrogen metabolism were involved in complete nitrification, traditional denitrification, assimilation nitrate reduction and dissimilation nitrate reduction. The functional contribution analysis and network analysis showed that the cooperation and competition of Thauera, Delftia, Diaphorobacter, Micavibrio and Azoarcus ensured the effective removal of aniline and nitrogen.This study investigated oxytetracycline (OTC) effects on nitrogen (N) transformation and bacterial community diversity during chicken manure composting. The addition of OTC inhibited nitrifying bacteria, resulted in a decrease in the transformation of NH4+-N to NO3–N during composting, and affected in the order T3 (32.76%) > T2 (28.76%) > T1 (17.02%) > CK. The OTC could act as an inhibitor against core microbial growth, leading to a delay effect during composting. 16S rRNA sequencing was employed for the functional prediction, and results indicated the bacterial community related to N transformation reconstructed under OTC stress. The core microorganisms were changed after OTC addition, with the emergence of Bacillus and Thermobifida, which could inhibit the N transformation by network analysis. Therefore, core microorganisms could be regulated to reduce the negative of OTC impacts on N transformation and thus reduce N loss during composting.Co-digestion of substrates can improve hydrogen yield (HY) by adjusting carbon nitrogen ratio (C/N) of fermentation substrates. This study evaluated the enhancement of hydrogen production from co-digestion of duckweed and corn straw via photo-fermentation. The maximum HY of 78.0 mL/g Total solid (TS) was obtained from the mixed ratio of 51 (C/N of 13.2), which was 25.4% and 29.6% higher than those of single substrate of duckweed and corn straw, respectively. The effects of initial pH and inoculation volume ratio (IVR) on co-digestion photo-fermentative hydrogen production (CD-PFHP) from duckweed and corn straw were further studied. A maximum HY of 85.6 mL/g TS was achieved under the optimal condition (initial pH 8, IVR 20%, mix ratio of duckweed and corn straw of 51). Additionally, both mix ratio and initial pH showed statistical difference (p less then 0.05). Acetic acid and butyric acid were found to be the main metabolic by-products during CD-PFHP.While memory T-cells represent a hallmark of adaptive immunity, little is known about the genetic mechanisms regulating the longevity of memory CD4 T cells. Here, we studied the dynamics of gene expression in antigen specific CD4 T cells during infection, memory differentiation, and long-term survival up to nearly a year in mice. We observed that differentiation into long lived memory cells is associated with increased expression of genes inhibiting cell proliferation and apoptosis as well as genes promoting DNA repair response, lipid metabolism, and insulin resistance. We identified several transmembrane proteins in long-lived murine memory CD4 T cells, which co-localized exclusively within the responding antigen-specific memory CD4 T cells in human. The unique gene signatures of long-lived memory CD4 T cells, along with the new markers that we have defined, will enable a deeper understanding of memory CD4 T cell biology and allow for designing novel vaccines and therapeutics.Neuroinflammation and periphery-to-CNS neuroimmune cross-talk in patients with painful knee osteoarthritis (OA) are poorly understood. We utilized proximity extension assay to measure the level of 91 inflammatory proteins in CSF and serum from OA patients and controls. The patients had elevated levels of 48 proteins in CSF indicating neuroinflammation. Ten proteins were correlated between CSF and serum and potentially involved in periphery-to-CNS neuroimmune cross-talk. Seven CSF proteins, all with previously reported neuroprotective effects, were associated with lower pain intensity and milder knee-related symptoms. Our findings indicate that neuroinflammation in OA could be protective and associated with less severe symptoms.Primary cell culture in vitro suffers from cellular senescence. We hypothesized that expansion on decellularized extracellular matrix (dECM) deposited by simian virus 40 large T antigen (SV40LT) transduced autologous infrapatellar fat pad stem cells (IPFSCs) could rejuvenate high-passage IPFSCs in both proliferation and chondrogenic differentiation. In the study, we found that SV40LT transduced IPFSCs exhibited increased proliferation and adipogenic potential but decreased chondrogenic potential. Expansion on dECMs deposited by passage 5 IPFSCs yielded IPFSCs with dramatically increased proliferation and chondrogenic differentiation capacity; however, this enhanced capacity diminished if IPFSCs were grown on dECM deposited by passage 15 IPFSCs. Interestingly, expansion on dECM deposited by SV40LT transduced IPFSCs yielded IPFSCs with enhanced proliferation and chondrogenic capacity but decreased adipogenic potential, particularly for the dECM group derived from SV40LT transduced passage 15 cells. Our immunofluorescence staining and proteomics data identify matrix components such as basement membrane proteins as top candidates for matrix mediated IPFSC rejuvenation. Both cell proliferation and differentiation were endorsed by transcripts measured by RNASeq during the process. This study provides a promising model for in-depth investigation of the matrix protein influence on surrounding stem cell differentiation.A variety of targeted nanoparticles were developed for the diagnosis and therapy of orthotopic and metastatic bone tumors during the past decade. This critical review will focus on principles and methods in the design of these bone-targeted nanoparticles. Ligands including bisphosphonates, aspartic acid-rich peptides and synthetic polymers were grafted on nanoparticles such as PLGA nanoparticles, liposomes, dendrimers and inorganic nanoparticles for bone targeting. Besides, other ligands such as monoclonal antibodies, peptides and aptamers targeting biomarkers on tumor/bone cells were identified for targeted diagnosis and therapy. Examples of targeted nanoparticles for the early detection of bone metastatic tumors and the ablation of cancer via chemotherapy, photothermal therapy, gene therapy and combination therapy will be intensively reviewed. The development of multifunctional nanoparticles to break down the „vicious” cycle between tumor cell proliferation and bone resorption, and the challenges and perspectives in this area will be discussed.Liver tissue engineering offers a promising strategy for liver failure patients. Since transplantation rejection resulting in vessel thrombosis is regarded as a major hurdle, vascular reconstruction is one of indispensable requirements of whole organ engineering. Here we demonstrated a novel strategy for reconstruction of a vascularized bioengineered human liver (VBHL) using decellularized liver scaffolds in an efficient manner. First we achieved fully functional endothelial coverage of scaffolds by adopting the anti-CD31 aptamer as a potent coating agent for re-endothelialization. Through an ex vivo human blood perfusion that recapitulates the blood coagulation response in humans, we demonstrated significantly reduced platelet aggregation in anti-CD31 aptamer coated scaffolds. We then produced VBHL constructs using liver parenchymal cells and nonparenchymal cells, properly organized into liver-like structures with an aligned vasculature. Interestingly, VBHL constructs displayed prominently enhanced long-term liver-specific functions that are affected by vascular functionality. The VBHL constructs formed perfusable vessel networks in vivo as evidenced by the direct vascular connection between the VBHL constructs and the renal circulation. Furthermore, heterotopic transplantation of VBHL constructs supported liver functions in a rat model of liver fibrosis. Overall, we proposed a new strategy to generate transplantable bioengineered livers characterized by highly functional vascular reconstruction.A lysosomal-targeted near infrared (NIR) fluorescent probe for reactive oxygen species (ROS) was developed with highly sensitive ability. The different responding activity toward H2O2, OH, and HClO were investigated. Meanwhile, the probe has been successfully applied in detecting and imaging reactive oxygen species both in cells and in vivo.In this work, a novel phenoxazine-based fluorescent probe BPO-N3 was developed to detect H2S. The results showed that the probe had high selectivity and sensitivity toward H2S, and its detection mechanism was based the ratio between green and red fluorescence signals; its detection limit was as low as 30 nM. The fluorescent imaging experiments further showed that the probe BPO-N3 could successfully detect endogenous and exogenous H2S in living cells. This probe can be used as a powerful tool for in-depth study of H2S function in various physiological processes.