In conclusion, this miRNA signature could predict TMB level in endometrial cancer and might have some merits in providing guidance for immunotherapy in endometrial cancer.Health literacy plays an important role in personal and community health. Since university is a turning point when young adults begin to take responsibility for their own health, understanding university students’ health literacy levels is crucial. To this end, we aimed to explore health literacy and its associated factors among Palestinian university students. We conducted a cross-sectional study at Birzeit University in the Ramallah district. We recruited 472 students using convenience sampling at six on-campus cafeterias. The 44-item Arabic version of the Health Literacy Questionnaire was used to measure students’ health literacy levels, while a locally developed distress scale was used to measure students’ distress levels. We stratified the multiple regression model for the health literacy score by gender. Students’ average total health literacy score was 135.3 (SD 20.9), with male students scoring significantly higher than female students. A higher health literacy score was significantly associated with having a father with a higher level of education, a higher frequency of medical checkups, higher self-reported health status, and consulting a higher number of sources for health-related information. High distress levels were associated with lower levels of health literacy, especially among female students. This study provides the first evidence on Palestinian university students’ health literacy levels. Tailored health education and promotion are required for students with low parental education and moderate to high distress. Future research is required to explain the gender differences in health literacy and distress among university students.

Genetic variants in SLC16A2, encoding the thyroid hormone transporter MCT8, can cause intellectual and motor disability and abnormal serum thyroid function tests, known as MCT8 deficiency. The C-terminal domain of MCT8 is poorly conserved, which complicates prediction of the deleteriousness of variants in this region. We studied the functional consequences of 5 novel variants within this domain and their relation to the clinical phenotypes.

We enrolled male subjects with intellectual disability in whom genetic variants were identified in exon 6 of SLC16A2. The impact of identified variants was evaluated in transiently transfected cell lines and patient-derived fibroblasts.

Seven individuals from 5 families harbored potentially deleterious variants affecting the C-terminal domain of MCT8. Two boys with clinical features considered atypical for MCT8 deficiency had a missense variant [c.1724A>G;p.(His575Arg) or c.1796A>G;p.(Asn599Ser)] that did not affect MCT8 function in transfected cells or patiente clinical guidance in the assessment of the pathogenicity of variants within the C-terminal domain of MCT8.

To highlight geographic differences and the socio-structural determinants of SARS-CoV-2 test positivity within Los Angeles County (LAC).

A geographic information system was used to integrate, map, and analyze SARS-CoV-2 testing data reported by LAC DPH, and data from the American Community Survey. Structural determinants included race/ethnicity, poverty, insurance status, education, population and household density. We examined which factors were associated with positivity rates, using a 5% test positivity threshold, with spatial analysis and spatial regression.

Between 1 March and 30 June 2020 there were 843,440 SARS-CoV-2 tests and 86,383 diagnoses reported, for an overall positivity rate of 10.2% within the study area. Communities with high proportions of Latino/a residents, those living below the federal poverty line and with high household densities had higher crude positivity rates. Age- adjusted diagnosis rates were significantly associated with the proportion of Latino/as, individuals living below the poverty line, population, and household density.

There are significant local variations in test positivity within LAC and several socio-structural determinants contribute to ongoing disparities. Public health interventions, beyond shelter in place, are needed to address and target such disparities.

There are significant local variations in test positivity within LAC and several socio-structural determinants contribute to ongoing disparities. Public health interventions, beyond shelter in place, are needed to address and target such disparities.

Higher maternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is associated with adverse long-term outcomes for offspring, including obesity, poorer cognitive and social abilities, and increased risk of psychiatric disorders. Less clear is whether higher maternal BMI disrupts fetal growth and brain development.

To investigate the association of maternal prepregnancy BMI with fetal growth and neonatal functional connectivity.

This prospective longitudinal cohort study was conducted from 2012 to 2017. Participants included nulliparous pregnant adolescent and young adult women, aged 14 to 19 years who were recruited in the second trimester through Columbia University Irving Medical Center and Weill Cornell Medical College. Women received routine prenatal care and had no major health problems at the time of recruitment. Data were analyzed from January 2018 to March 2020.

Maternal prepregnancy BMI.

The main outcomes were fetal growth, measured anal BMI was associated with greater local thalamic (both hemispheres) and lower frontothalamic connectivity.

These results suggest that maternal prepregnancy BMI was associated with the development of regulation of body weight and thalamic functional brain connectivity in offspring even during fetal development.

These results suggest that maternal prepregnancy BMI was associated with the development of regulation of body weight and thalamic functional brain connectivity in offspring even during fetal development.

Machine-learning algorithms offer better predictive accuracy than traditional prognostic models but are too complex and opaque for clinical use.

To compare different machine learning methods in predicting overall mortality in cirrhosis and to use machine learning to select easily scored clinical variables for a novel cirrhosis prognostic model.

This prognostic study used a retrospective cohort of adult patients with cirrhosis or its complications seen in 130 hospitals and affiliated ambulatory clinics in the integrated, national Veterans Affairs health care system from October 1, 2011, to September 30, 2015. Patients were followed up through December 31, 2018. Data were analyzed from October 1, 2017, to May 31, 2020.

Potential predictors included demographic characteristics; liver disease etiology, severity, and complications; use of health care resources; comorbid conditions; and comprehensive laboratory and medication data. Patients were randomly selected for model development (66.7%) and validationanced ensemble gradient boosting. Using the clinical variables identified from simple machine learning in a cirrhosis mortality model produced a new score more transparent than machine learning and more predictive than the MELD-Na score.

The association between poverty and unfavorable cognitive outcomes is robust, but most research has focused on individual household socioeconomic status (SES). There is increasing evidence that neighborhood context explains unique variance not accounted for by household SES.

To evaluate whether neighborhood poverty (NP) is associated with cognitive function and prefrontal and hippocampal brain structure in ways that are dissociable from household SES.

This cross-sectional study used a baseline sample of the ongoing longitudinal Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study will follow participants for assessments each year for 10 years. Data were collected at 21 US sites, mostly within urban and suburban areas, between September 2019 and October 2018. School-based recruitment was used to create a participant sample reflecting the US population. Data analysis was conducted from March to June 2019.

NP and household SES were included as factors potentially associated with National Icabulary estimate [SE], -0.01 [0.004]; P < .001) and episodic memory (picture sequence estimate [SE], -0.01 [0.004]; P < 0.001).

In this study, NP accounted for unique variance in cognitive function and prefrontal and right hippocampal brain volume. These findings demonstrate the importance of including broader environmental influences when conceptualizing early life adversity.

In this study, NP accounted for unique variance in cognitive function and prefrontal and right hippocampal brain volume. These findings demonstrate the importance of including broader environmental influences when conceptualizing early life adversity.

More than half of US cardiothoracic surgeons are older than 55 years, and the association between surgeon number of years in practice and surgical outcomes remains unclear.

To assess the association between cardiac surgeons’ time in practice and operative outcomes for coronary artery bypass grafting (CABG) and valve surgery.

Cross-sectional analysis performed of surgeon-level outcomes data from the 2014-2016 New York State Cardiac Data Reporting System across the 38 New York cardiac surgery centers. Years in practice were characterized as early career (<10 years) and late career (≥10 years). Participants were 120 cardiothoracic surgeons who performed CABG and 112 cardiothoracic surgeons who performed valve procedures between 2014 and 2016. Data were analyzed in April 2020. Surgeons who trained outside of the United States or had unclear training history were excluded.

Risk-adjusted operative mortality rate (RAMR). Mortality was defined as all-cause death within 30 days of surgery or within the indere associated with worse risk-adjusted outcomes for valve operations but not for CABG. This finding suggests certain competence deficiency for valve surgery early after finishing training in cardiac surgery.

Lung cancer screening has been widely implemented in Europe and the US. However, there is little evidence on participation and diagnostic yields in population-based lung cancer screening in China.

To assess the participation rate and detection rate of lung cancer in a population-based screening program and the factors associated with participation.

This cross-sectional study used data from the Cancer Screening Program in Urban China from October 2013 to October 2019, with follow-up until March 10, 2020. The program is conducted at centers in 8 cities in Henan Province, China. Eligible participants were aged 40 to 74 and were evaluated for a high risk for lung cancer using an established risk score system.

Overall and group-specific participation rates by common factors, such as age, sex, and educational level, were calculated. Differences in participation rates between those groups were compared. The diagnostic yield of both screening and nonscreening groups was calculated.

The study recruited 282 3esigning effective population-based lung cancer screening strategies in the future.

The low participations rate in the program studied suggests that an improved strategy is needed. These findings may provide useful information for designing effective population-based lung cancer screening strategies in the future.Purposes Several studies have reported that elevated red cell distribution width (RDW) is related to poor prognosis in several cancers; however, the prognostic significance of perioperative RDW in rectal cancer patients which received neoadjuvant chemoradiation therapy (NACRT) is unclear. Methods A total of 120 rectal cancer patients who received NACRT followed surgery were retrospectively reviewed from Affiliated Cancer Hospital of Zhengzhou University between 2013 to 2015. Data for peripheral blood tests prior to the initiation of NACRT，before surgery and first chemotherapy after surgery were collected，respectively. The optimal cutoff values of RDW was determined by ROC analysis, respectively. The relationship between RDW and the prognosis of patients was evaluated by, respectively. Results The post-operative RDWHigh (≥15.55) patients had significantly worse five-year overall survival (OS, P=0.001) and disease-free survival (DFS, P=0.001) than the post-operative RDWLow ( less then 15.55) patients, respectively. Whereas high pre-operative RDW (≥16.45) was the only marker correlated with worse DFS (P=0.005) than the pre-operative RDWLow ( less then 16.45)patients, no relationship was found between pre-RDW and prognosis(OS, P=0.069; DFS, P=0.133). Multivariate analysis showed post-operative RDW had better predictive value than pre-RDW and pre-operative RDW. Conclusion Post-operative RDW might be a useful prognostic indicator in rectal cancer patients received neoadjuvant chemoradiation.Behavioural disinhibition is a common feature of the syndromes associated with frontotemporal lobar degeneration (FTLD). It is associated with high morbidity and lacks proven symptomatic treatments. A potential therapeutic strategy is to correct the neurotransmitter deficits associated with FTLD, thereby improving behaviour. Reductions in the neurotransmitters glutamate and GABA correlate with impulsive behaviour in several neuropsychiatric diseases and there is post-mortem evidence of their deficit in FTLD. Here, we tested the hypothesis that prefrontal glutamate and GABA levels are reduced by FTLD in vivo, and that their deficit is associated with impaired response inhibition. Thirty-three participants with a syndrome associated with FTLD (15 patients with behavioural variant frontotemporal dementia and 18 with progressive supranuclear palsy, including both Richardson’s syndrome and progressive supranuclear palsy-frontal subtypes) and 20 healthy control subjects were included. Participants undertook ultra-htransmitter. We conclude that the glutamatergic and GABAergic deficits in the frontal lobe are potential targets for symptomatic drug treatment of frontotemporal dementia and progressive supranuclear palsy.6-Phosphofructokinase-1-kinase (PFK) tetramers catalyse the phosphorylation of fructose 6-phosphate (F6P) to fructose 1,6-bisphosphate (F16BP). Vertebrates have three PFK isoforms (PFK-M, PFK-L, and PFK-P). This study is the first to compare the kinetics, structures, and transcript levels of recombinant human PFK isoforms. Under the conditions tested PFK-M has the highest affinities for F6P and ATP (K0.5ATP 152 µM; K0.5F6P 147 µM), PFK-P the lowest affinities (K0.5ATP 276 µM; K0.5F6P 1333 µM), and PFK-L demonstrates a mixed picture of high ATP affinity and low F6P affinity (K0.5ATP 160 µM; K0.5F6P 1360 µM). PFK-M is more resistant to ATP inhibition compared with PFK-L and PFK-P (respectively, 23%, 31%, 50% decreases in specificity constants). GTP is an alternate phospho donor. Interface 2, which regulates the inactive dimer to active tetramer equilibrium, differs between isoforms, resulting in varying tetrameric stability. Under the conditions tested PFK-M is less sensitive to fructose 2,6-bisphosphate (F26BP) allosteric modulation than PFK-L or PFK-P (allosteric constants [K0.5ATP+F26BP/K0.5ATP] 1.10, 0.92, 0.54, respectively). Structural analysis of two allosteric sites reveals one may be specialised for AMP/ADP and the other for smaller/flexible regulators (citrate or phosphoenolpyruvate). Correlations between PFK-L and PFK-P transcript levels indicate that simultaneous expression may expand metabolic capacity for F16BP production whilst preserving regulatory capabilities. Analysis of cancer samples reveals intriguing parallels between PFK-P and PKM2 (pyruvate kinase M2), and simultaneous increases in PFK-P and PFKFB3 (responsible for F26BP production) transcript levels, suggesting prioritisation of metabolic flexibility in cancers. Our results describe the kinetic and transcript level differences between the three PFK isoforms, explaining how each isoform may be optimised for distinct roles.

Pulmonary vein isolation (PVI) has become a cornerstone of the invasive treatment of atrial fibrillation. Severe complications are reported in 1-3% of patients. This study aims to compare complications and follow-up outcome of PVI in patients with atrial fibrillation.

The data were extracted from the Netherlands Heart Registration. Procedural and follow-up outcomes in patients treated with conventional radiofrequency (C-RF), multielectrode phased RF (Ph-RF), or cryoballoon (CB) ablation from 2012 to 2017 were compared. Subgroup analysis was performed to identify variables associated with complications and repeat ablations. In total, 13 823 patients (69% male) were included. The reported complication incidence was 3.6%. Patients treated with C-RF developed more cardiac tamponades (C-RF 0.8% vs. Ph-RF 0.3% vs. CB 0.3%, P ≤ 0.001) and vascular complications (C-RF 1.7% vs. Ph-RF 1.2% vs. CB 1.3%, P ≤ 0.001). Ph-RF was associated with fewer bleeding complications (C-RF 1.0% vs. Ph-RF 0.4% vs. CB 0.7%, P = 0.020). Phrenic nerve palsy mainly occurred in patients treated with CB (C-RF 0.1% vs. Ph-RF 0.2% vs. CB 1.5%, P ≤ 0.001). In total, 18.4% of patients were referred for repeat ablation within 1 year. Female sex, age, and CHA2DS2-VASc were independent risk factors for cardiac tamponade and bleeding complications, with an adjusted OR for female patients of 2.97 (95% CI 1.98-4.45) and 2.02 (95% CI 1.03-4.00) respectively.

The reported complication rate during PVI was low. Patients treated with C-RF ablation were more likely to develop cardiac tamponades and vascular complications. Female sex was associated with more cardiac tamponade and bleeding complications.

The reported complication rate during PVI was low. Patients treated with C-RF ablation were more likely to develop cardiac tamponades and vascular complications. Female sex was associated with more cardiac tamponade and bleeding complications.We have previously reported that PET with 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) provides a non-invasive assessment of cell proliferation in vivo in meningiomas. The purpose of this prospective study was to evaluate the potential of 18F-FLT PET in predicting subsequent tumour progression in asymptomatic meningiomas. Forty-three adult patients harbouring 46 MRI-presumed (n = 40) and residual meningiomas from previous surgery (n = 6) underwent a 60-min dynamic 18F-FLT PET scan prior to radiological surveillance. Maximum and mean tumour-to-blood ratios (TBRmax, TBRmean) of tracer radioactivity were calculated. Tumour progression was defined according to the latest published trial end-point criteria for bidimensional (2D) and corresponding yet exploratory volumetric measurements from the Response Assessment of Neuro-Oncology (RANO) workgroup. Independent-sample t-test, Pearson correlation coefficient, Cox regression, and receiver operating characteristic (ROC) curve analyses were used whenever appropriate. The Moreover, positive correlations were found between absolute and relative tumour growth rates and 18F-FLT uptake (r  less then  0.513, P  less then  0.015) that remained similar when excluding patients with residual meningioma or patients with stable disease and shorter follow-up period. Diagnostic accuracies were slightly inferior at 76% when assessing disease progression using volumetric criteria, while the thresholds remained unchanged. Multivariate analysis revealed that TBRmax was the only independent predictor of tumour progression (P  less then  0.046), while age, gender, baseline tumour size, tumour location, peritumoural oedema, and residual meningioma had no influence. The study reveals that 18F-FLT PET is a promising surrogate imaging biomarker for predicting subsequent tumour progression in treatment-naïve and asymptomatic residual meningiomas.

The aim of the study was to investigate differences in clinical outcomes and complication rates among European atrial fibrillation (AF) ablation centres related to the volume of AF ablations performed.

Data for this analysis were extracted from the ESC EHRA EORP European AF Ablation Long-Term Study Registry. Based on 33rd and 67th percentiles of number of AF ablations performed, the participating centres were classified into high volume (HV) (≥ 180 procedures/year), medium volume (MV) (<180 and ≥74/year), and low volume (LV) (<74/year). A total of 91 centres in 26 European countries enrolled in 3368 patients. There was a significantly higher reporting of cardiovascular complications and stroke incidence in LV centres compared with HV and MV (P = 0.039 and 0.008, respectively) and a lower success rate after AF ablation (55.3% in HV vs. 57.2% in LV vs. 67.4% in MV centres, P < 0.001), despite lower CHA2DS2-VASc score of patients, enrolled in LVs and less complex ablation techniques used. Adjustment among different volume centres, a fact reflecting the heterogeneity of patient and procedural profiles, and a counterbalance between expertise and risk level among participating centres.

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of low-trauma fractures. However, the effect of antidiabetic medication in relation to glycemic control on the risk of fracture is poorly understood.

This work aimed to evaluate the association between the level of glycemic control, use of antidiabetic medication, and risk of low-trauma fractures in patients with newly diagnosed T2DM.

We conducted a nested case-control analysis among individuals registered in the Clinical Practice Research Datalink. The base population consisted of patients with newly diagnosed T2DM from 1995 to 2017. Cases were patients with a low-trauma fracture after T2DM diagnosis. We matched 4 controls to each case. Exposures of interest were glycemic control (last glycated hemoglobin [HbA1c] level before fracture) and type of diabetes treatment. We conducted conditional logistic regression analyses adjusted for several confounders.

We identified 8809 cases and 35 219 controls. Patients with current metformin use and HbA1c levels of less than 7.0% and between 7.0-8.0% had a reduced risk of fractures (adjusted odds ratio 0.89; 95% CI, 0.83-0.96 and 0.81; 95% CI, 0.73-0.90, respectively) compared with untreated patients. However, in patients receiving metformin plus 1 or 2 other antidiabetic drugs, or insulin (alone or in addition to other antidiabetic medication), the level of glycemic control was not associated with the risk of fracture compared with untreated patients.

While patients with good or medium glycemic control receiving current metformin monotherapy had a lower risk of fracture compared with untreated patients, glycemic control in patients receiving treatment other than metformin was not associated with risk of fracture.

While patients with good or medium glycemic control receiving current metformin monotherapy had a lower risk of fracture compared with untreated patients, glycemic control in patients receiving treatment other than metformin was not associated with risk of fracture.The synthesis and release of LH and FSH in the pituitary of vertebrates are differentially regulated during gonadal development and maturation. However, the underlying neuroendocrine mechanisms remain to be fully elucidated. The present study examined the possible involvement of isotocin (Ist), an oxytocin-like neuropeptide, in the regulation of Lh and Fsh in a teleost, the ricefield eel Monopterus albus. The immunoreactive isotocin receptor 2 (Istr2) was shown to be localized to Lh but not Fsh cells. In contrast, immunoreactive isotocin receptor 1 (Istr1) was not observed in either Lh or Fsh cells in the pituitary. Interestingly, Lh cells in female ricefield eels expressed Istr2 and secreted Lh in response to Ist challenge stage-dependently and in correlation with ovarian vitellogenesis. Moreover, Ist decreased Lh contents in the pituitary of female fish, indicating its stimulatory roles on Lh release in vivo. The induction of Lh release by Ist in dispersed pituitary cells was blocked by a PLC or IP3R inhibitor but not by a PKA or PKC inhibitor, indicating the involvement of the IP3/Ca2+ pathway. Collectively, the above results indicate that isotocin may bind to Istr2 to stimulate Lh release via the IP3/Ca2+ pathway, and play important roles in the ovarian maturation in ricefield eels. Furthermore, the present study suggests a novel neuroendocrine mechanism underlying the differential regulation of Lh and Fsh in vertebrates.

Recent neural approaches on event extraction from text mainly focus on flat events in general domain, while there are less attempts to detect nested and overlapping events. These existing systems are built on given entities and they depend on external syntactic tools.

We propose an end-to-end neural nested event extraction model named DeepEventMine that extracts multiple overlapping directed acyclic graph structures from a raw sentence. On the top of the bidirectional encoder representations from transformers model, our model detects nested entities and triggers, roles, nested events and their modifications in an end-to-end manner without any syntactic tools. Our DeepEventMine model achieves the new state-of-the-art performance on seven biomedical nested event extraction tasks. Even when gold entities are unavailable, our model can detect events from raw text with promising performance.

Our codes and models to reproduce the results are available at https//github.com/aistairc/DeepEventMine.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.In Parkinson’s disease, striatal dopamine depletion produces profound alterations in the neural activity of the cortico-basal ganglia motor loop, leading to dysfunctional motor output and parkinsonism. A key regulator of motor output is the balance between excitation and inhibition in the primary motor cortex, which can be assessed in humans with transcranial magnetic stimulation techniques. Despite decades of research, the functional state of cortical inhibition in Parkinson’s disease remains uncertain. Towards resolving this issue, we applied paired-pulse transcranial magnetic stimulation protocols in 166 patients with Parkinson’s disease (57 levodopa-naïve, 50 non-dyskinetic, 59 dyskinetic) and 40 healthy controls (age-matched with the levodopa-naïve group). All patients were studied OFF medication. All analyses were performed with fully automatic procedures to avoid confirmation bias, and we systematically considered and excluded several potential confounding factors such as age, gender, resting motor thrr 1, n = 23). These results suggest that cortical disinhibition is a very early, possibly prodromal feature of Parkinson’s disease.Impaired oxygen and cellular metabolism is a hallmark of ischaemic injury in acute stroke. Magnetic resonance spectroscopic imaging (MRSI) has long been recognized as a potentially powerful tool for non-invasive metabolic imaging. Nonetheless, long acquisition time, poor spatial resolution, and narrow coverage have limited its clinical application. Here we investigated the feasibility and potential clinical utility of rapid, high spatial resolution, near whole-brain 3D metabolic imaging based on a novel MRSI technology. In an 8-min scan, we simultaneously obtained 3D maps of N-acetylaspartate and lactate at a nominal spatial resolution of 2.0 × 3.0 × 3.0 mm3 with near whole-brain coverage from a cohort of 18 patients with acute ischaemic stroke. Serial structural and perfusion MRI was used to define detailed spatial maps of tissue-level outcomes against which high-resolution metabolic changes were evaluated. Within hypoperfused tissue, the lactate signal was higher in areas that ultimately infarcted compared with those that recovered (P  less then  0.0001). Both lactate (P  less then  0.0001) and N-acetylaspartate (P  less then  0.001) differed between infarcted and other regions. Within the areas of diffusion-weighted abnormality, lactate was lower where recovery was observed compared with elsewhere (P  less then  0.001). This feasibility study supports further investigation of fast high-resolution MRSI in acute stroke.Amphiphilic polyoxometalate (POM) surfactants were prepared by covalently grafting double hydrophobic tails with chain lengths C12H25, C14H29, C16H33 or C18H37 onto the lacunary Wells-Dawson P2W17O61 headgroup. The critical micelle concentrations (CMCs) of these novel surfactants in aqueous solutions were determined by conductivity, and micelle formation was studied by small angle neutron scattering (SANS). Surprisingly, the amphiphiles with longer hydrophobic tails tend to form less elongated and more globular micelles in water. The self-assembled amphiphilic polyoxometalates were used as templates in the hydrothermal synthesis of mesoporous TiO2 containing dispersed, immobilised P2W17O61 units, which showed enhanced activity for the photodegradation of rhodamine B (RhB). The catalyst was recycled eight times with no loss of efficiency, demonstrating the stability of the hybrid structure. The amphiphilic polyoxometalates, therefore have excellent potential for the synthesis of various types of catalytically active porous materials.Bone plays an increasingly critical role in human health and disease. More noninvasive multi-scale imaging techniques are urgently required for investigations on the substructures and biological functions of bones. Our results firstly revealed that SWIR QDs prepared by us acted as a bone-specific imaging contrast to achieve real-time observation of bone structures both in vivo and ex vivo. The major bone structures of both Balb/C nude mice and Balb/C mice including their skull, spine, pelvis, limbs, and sternum could be rapidly and gradually identified via blood circulation after QD injection in vivo. More importantly, the binding capability of our QDs mainly depended on the biological activities of bone tissues, suggesting that our technique is suitable for in vivo live imaging. In addition, the cell imaging results suggested that the potential mechanism of our bone imaging could be ascribed to the highly specific interaction between QDs and MC3T3-E1 cells. In a word, the skeletal structures and biological activities of bones are anticipated to be observed and monitored with this QD-guided SWIR imaging strategy, respectively. This radiation-free QD-guided SWIR live imaging of bone can add new insights into a comprehensive study of bones in vivo and provide a basis for early diagnosis of bone diseases.The rapid capacity loss caused by the shuttling effect of polysulfides is one of the great challenges of Li-S batteries. In this work, we adopted a simple solid-phase sintering method to synthesize titanium disulfide (TiS2) and further demonstrated it as a superior modifier of separators for Li-S batteries. Two commonly adopted modification processes of separators, including vacuum filtration (VF) and slurry casting (SC) have been used to prepare TiS2/Celgard separators. TiS2-VF/Celgard can better restrain the polysulfide shuttling effect compared with TiS2-SC/Celgard. A TiS2-VF/Celgard-based Li-S battery has a reversible capacity of 771.6 mA h g-1, with a capacity retention of 645.6 mA h g-1 after 500 cycles at 2.0 C, corresponding to a capacity fading rate of ∼0.033% per cycle. This study has shown the potential of TiS2 as a multifunctional modifier of separators for high performance and long cycle life Li-S batteries.A set of cascade benzannulations of readily accessible chromone-3-carboxaldehydes and γ-nitroaldehydes for synthesizing biologically relevant 2-hydroxybenzophenones has been developed. The cascade was found to provide a transition-metal-free strategy for synthesizing 2-hydroxybenzophenones in acceptable yields (up to 57%).This present study describes the synthesis of ultrafine Bi-Sn nanoparticles decorated on carbon aerogels (Bi-Sn NP/CAG) as a nanocomposite for the electrochemical simultaneous determination of dopamine (DA) and clozapine (CLZ). The typical characterization techniques, such as XRD, Raman, BET, FT-IR, TGA, XPS, and FE-SEM/TEM, showed useful insights into the crystal phase and morphology of Bi-Sn NP/CAG. Integrated Bi-Sn NP/CAG built into a cost-effective screen printed carbon electrode (SPCE) offers a high electrochemical surface area (ECSA) compared to unmodified, Bi-Sn, and CAG/SPCEs, such that it favourably allowed the binding of DA and CLZ molecules onto the surface at the Bi-Sn/CAG, which was demonstrated by cyclic and differential pulse voltammetry techniques. As a result, the DA and CLZ sensing exhibited low detection limits (DL, 4.6 and 97.6 nM (S/N = 3)), and sensitivity (3.402 and 0.4 μA μM-1 cm-2) over a wide linear range (0.02-97.59 and 0.5-2092 μM), respectively. To go a step further, the Bi-Sn NP/CAG/SPCE was applied for the simultaneous determination of DA and CLZ which featured lower DL (23.1 and 31.3 nM (S/N = 3)), and sensitivity (0.4979 and 0.04 μA μM-1 cm-2) over a wide linear range (2-182 and 10-910 μM), respectively. The selectivity for DA and CLZ in the presence of a 10-fold concentration of their potentially interfering active species was demonstrated. Finally, this sensing methodology enables the rapid electrochemical determination of the amount of DA and CLZ in a rat brain region serum sample with successful recovery outcomes.Protein bioconjugation is an increasingly important field of research, with wide-ranging applications in areas such as therapeutics and biomaterials. Traditional cysteine and lysine bioconjugation strategies are widely used and have been extensively researched, but in some cases they are not appropriate and alternatives are needed or they are not compatible with one another to enable the formation of dually (and distinctly) modified dual-conjugates (an increasingly desired class of bioconjugates). Here we review the heretofore less explored approach of tyrosine bioconjugation, which is rapidly becoming a constructive alternative/complement to the more well-established strategies. Herein we present an overview of the field, and then focus on promising recent methods that can achieve high conversion and chemoselectivity. This suggests that not only can tyrosine bioconjugation be used in conjunction with cysteine and lysine modification to obtain proteins with multiple different modifications, it is also becoming a stand-alone alternative to these more traditional methods.Burchellin and its analogues are a class of neolignan natural products containing a rare core with three contiguous stereogenic centers. In previous reports, racemic burchellin was synthesized without accessing each of the enantiomers. In this paper, a concise and efficient total synthetic route to divergently access the enantiomers of burchellin and those of its 1′-epi-diastereoisomer over six steps for each is disclosed, where each of the enantiomers was obtained by preparative chiral phase HPLC purification. The key steps include the construction of a 2,3-dihydrobenzofuran moiety by two Claisen rearrangements and a one-step rearrangement/cyclization and subsequent tandem ester hydrolysis/oxy-Cope rearrangement/methylation to furnish the basic skeleton of burchellin. The structures and absolute configurations of the four stereoisomers were determined using spectroscopic data analyses and comparison of experimental and calculated electronic circular dichroism data. These stereoisomers were found to have potent antiviral effects against coxsackie virus B3, and is the first time that bioactivity has been reported for these compounds.We find that the use of Au substrate allows fast, self-limited WS2 monolayer growth using a simple sequential exposure pattern of low cost, low toxicity precursors, namely tungsten hexacarbonyl and dimethylsulfide (DMS). We use this model reaction system to fingerprint the technologically important metal organic chemical vapour deposition process by operando X-ray photoelectron spectroscopy (XPS) to address the current lack of understanding of the underlying fundamental growth mechanisms for WS2 and related transition metal dichalcogenides. Au effectively promotes the sulfidation of W with simple organosulfides, enabling WS2 growth with low DMS pressure ( less then 1 mbar) and a suppression of carbon contamination of as-grown WS2, which to date has been a major challenge with this precursor chemistry. Full WS2 coverage can be achieved by one exposure cycle of 10 minutes at 700 °C. We discuss our findings in the wider context of previous literature on heterogeneous catalysis, 2D crystal growth, and overlapping process technologies such as atomic layer deposition (ALD) and direct metal conversion, linking to future integrated manufacturing processes for transition metal dichalcogenide layers.Carbon nanobubbles are regarded as one of the most promising carbon-based anode materials for lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs), with significantly improved capacity and superior cycling stability. The wet-chemistry method is a cost-effective and readily scalable method of preparing carbon nanobubbles when compared to common pyrolysis, but balancing the relationship between high capacity and low initial coulombic efficiency still remains challenging. Herein, we present a solution-polymerization method associated with a removable template to realize the controllable synthesis of N-doped carbon nanobubbles (NCN). The obtained NCN material delivers impressive high specific capacity as an anode for both LIBs and SIBs (799 mA h g-1 at 0.8 A g-1 for 385 cycles in LIBs; 248 mA h g-1 at 0.3 A g-1 for 200 cycles in SIBs). Meanwhile, the NCN anode exhibits an initial coulombic efficiency of nearly 80% for both LIBs and SIBs, which is ascribed to the moderate specific surface area and rational structure design.Covering 2007 to 2020 Selaginellins are a small group of pigments exclusively found in the ancient genus Selaginella. Since the first report of selaginellin from S. sinensis in 2007, more than 110 selaginellins with diverse polyphenolic skeletons have been reported. This review provides extensive coverage of the selaginellins discovered from 2007 to 2020, including 61 natural ones and 52 synthetic analogues. The isolation, chemical structures, plausible biosynthetic pathways, bioactivity, and total synthesis of these selaginellins have been summarized for the first time, and this highlights the fact that the vast uninvestigated Selaginella species may serve as a potential treasure trove of chemically diverse selaginellins waiting to be discovered.Second near-infrared (NIR-II) window responsive phototheranostic agents have a precise spatiotemporal potential for the diagnosis and treatment of cancer. In this study, a full-spectrum responsive ZrO2-based phototheranostic agent was found to achieve NIR-II photoacoustic (PA) imaging-guided tumour-targeting phototherapy. Initially, the ZrO2-based phototheranostic agent was fabricated through NaBH4 reduction to form boron-doped oxygen-deficient zirconia (ZrO2-x-B), an amino-functionalised SiO2 shell and a further covalent connection with hyaluronic acid (HA), namely, ZrO2-x-B@SiO2-HA. In the ZrO2-x-B@SiO2-HA system, the oxygen vacancy and boron doping resulted in full-spectrum absorption, enabling a high NIR-II photothermal conversion, high-resolution PA imaging ability and a remarkable production of reactive oxygen species (ROS). The surface modification of HA provided ZrO2-x-B@SiO2-HA with water dispersibility and a targeting capability for CD44 overexpressed cancer cells. Furthermore, in vitro and in vivo experiments showed that NIR-II activated ZrO2-x-B@SiO2-HA had a targeted photothermal/photodynamic effect for cancer elimination under the real-time guidance of NIR-II PAs. Hence, ZrO2-x-B@SiO2-HA displays a precise NIR-II radiation-activated phototheranostic potential for PA imaging-guided cancer-targeting photothermal/photodynamic therapy.Though a large amount of literature has been reported on outlining the biological significance of zinc(ii) Schiff base complexes, yet none of them have explored the influence of nuclearity on their properties. This report elaborates the targeted syntheses of two different hemi-salen ligands for their ability to produce Zn(ii)-complexes with different nuclearity. Herein, one dimeric, [Zn2L12(N3)2] (1) and one trimeric [Zn3L22(N3)4] (2) [HL1 = (2-(((2-(diethylamino)ethyl)imino)methyl)phenol, HL2 = 2-(((3-(dimethylamino)-2,2-dimethylpropyl)imino)methyl)-6-methoxyphenol] complexes of hemi-salen ligands have been thoroughly screened for various biological studies including cytotoxic assay, DNA/protein-complex interplay, fluorescence imaging, and antibacterial pathogen tests. The trimer features the IC50 value of 9.651 ± 0.026 μM against the HeLa cancer cell line, one of the best figure by any Zn(ii) hemi-salen complex to date. How the nuclearity dependency affects the supramolecular interactions is also a key point of interest in this study. The compounds exhibit strong DNA binding affinity and the dimer 1 predominantly binds to the minor grooves of DNA (binding energy = -5.8 kcal mol-1), whereas trimer 2 prefers the intercalative mode (binding energy = -7.1 kcal mol-1) in contrast to groove binding (binding energy = -6.2 kcal mol-1). The atypical phenomenon behind the conformational changes of biomolecules by these zinc complexes has been investigated through experimental procedures and further corroborated theoretically. Apart from this, it has been found that even at very low concentration (≤10 μM) of the ligand, HL1 and complexes can be effective for live cell imaging. It is worth mentioning that HL1 could be useful for the specific staining of the cell cytoplasm. Furthermore, the complexes have shown promising anti-bacterial activity; thus, they can be convenient for multiple biological applications.Developing a mass spectrometry-based assay for the ovarian cancer biomarker CA125 (MUC16) is a desirable goal, because it may enable detection of molecular regions that are not recognized by antibodies and are therefore analytically silent in the current immunoassay. Additionally, the ability to characterize the CA125 proteoforms expressed by individuals may offer clinical insight. Enrichment of CA125 from malignant ascites may provide a high-quality source of this important ovarian cancer biomarker, but a reliable strategy for such enrichment is currently lacking. Beginning with crude ascites isolated from three individual patients with high grade serous ovarian cancer, we enriched for MUC16 using filtration, ion exchange, and size exclusion chromatography and then performed bottom-up proteomics on the isolated proteins. This approach of enrichment and analysis reveals that the peptides detected via mass spectrometry map to the SEA domain and C-loop regions within the tandem repeat domains of CA125 and that peptide abundance correlates with clinical CA125 counts.Here we evaluate a quick and easy tool for determination of epitope configuration using immunocapture and liquid chromatography mass spectrometry (LC-MS) subsequent to pre-treatment of the target protein to disrupt its three-dimensional structure. The approach can be a valuable screening tool to identify antibodies that can be used in peptide capture by anti-protein antibodies. The experimental set-up was established using seven monoclonal antibodies (mAbs) with known linear or conformational epitope recognition. The mAbs were developed to target either of the two biomarkers, progastrin releasing peptide (ProGRP) or human chorionic gonadotropin (hCG). Best coherence with established epitope configuration was seen when using both denaturation, reduction and alkylation as pre-treatment method of the proteins (≥70% reduction in MS signal intensity compared to control) prior to immunocapture and LC-MS determination. The final method was used to determine the epitope configuration of four anti-thyroglobulin mAbs with unknown epitope configuration; all four mAbs showed configurational epitope recognition. These results were also supported by western blots of native, and reduced and alkylated protein using three of the evaluated mAbs, and by analysis native, and reduced and alkylated protein in a routine immunofluorometric assay employing the four evaluated antibodies.Three copper(ii) complexes, [Cu(L1)(NCS)]n (1), [Cu(L1)(N3)]n (2) and [Cu(L2)(N3)] (3) were synthesized from one Schiff base ligand and one reduced Schiff base ligand, (E)-4-chloro-2-[(2-propylaminoethylimino)methyl]phenol (HL1) and 4-chloro-2-[(2-(propylaminoethylamino) methyl]phenol (HL2), respectively. All complexes were characterized by various physicochemical studies, such as FT-IR, UV-Vis, ESI-MS, EPR and single crystal X-ray diffraction. Complexes 1 and 2 have 1D polymeric chain-like structures bridging through thiocyanate and azide anions, whereas complex 3 has a mononuclear structure in the solid state. All the complexes are active towards mimicking two well-known proteins, phosphatase and phenoxazinone synthase, using the disodium salt of 4-nitrophenylphosphate (4-NPP) and 2-aminophenol (OAP) as the substrate in DMF medium. Complexes 2 and 3 show the highest activity towards phosphatase and phenoxazinone synthase activity with kcat values of 22.6 s-1 and 134.4 h-1, respectively. EPR studies confirmed that for complex 1, the OAP oxidation goes through the generation of an organic radical at g = 1.99, which is due to an imine radical formation, whereas the metal center redox pathway is followed for complex 3. Extensive DFT calculations have been performed for both catalytic studies to put forward the most probable mechanistic pathways.A simple and easy surface sensitive spectroscopic method using hard X-rays has been developed and applied to observe the surface oxide reduction reaction. The method named TREXS, Total REflection X-ray Spectroscopy, records the total reflection of incident X-rays at sample surfaces. The surface reduction reaction of Co oxide (Co3O4) to Co metal was successfully observed by in situ TREXS measurements with a surface sensitivity of ∼2 nm. The in situ TREXS measurements were performed under H2 flow of N2 balanced atmospheric pressure with increasing temperature. This method, in situ TREXS, will be a suitable and powerful tool to observe a variety of surface chemical reactions and consequently to understand catalytic processes under realistic operating conditions.A nickel-catalyzed reductive cyclization of 1,1-dichloroalkenyl silanes is reported. The products of this reaction are unsaturated five- or six-membered silacycles. Intermolecular variants are also described, providing access to trisubstituted vinyl silanes that are not accessible by alkyne hydrosilylation or sila-Heck-type processes. A variety of silanes can be utilized, including those that serve as nucleophilic partners in Hiyama cross-coupling reactions. Mechanistic studies using deuterium-labelled silanes are described.Two series of lanthanide-based metal-organic frameworks, namely [Ln(BIPA-TC)0.5(DMA)2(NO3)]·DMA·H2On (1-Ln, Ln = Eu, Dy, Sm, Nd) and [Ln2(BIPA-TC)1.5(DMA)3(H2O)2]·2DMA·2H2On (2-Ln, Ln = Eu, Dy, Sm, Nd), were successfully constructed via a solvent regulation strategy based on a π-electron rich tetra-carboxylate ligand (H4BIPA-TC). 1-Ln shows a 4-connected lvt topology with the point symbol of 42·84, but 2-Ln displays a new 4,4,6-connected wxk1 topology with the point symbol of 43·83446·66·83286. The solid-state luminescence property and the microporous nature of Eu-MOFs (1-Eu and 2-Eu) indicate that they can potentially be used as luminescent sensors. Fluorescence measurements indicate that Fe3+ exhibits the quenching effect for 1-Eu with the quenching efficiency of 93.1%. 2-Eu is the first MOF sensor for Mg2+ with the lowest detection limit of 1.53 × 10-10 mol L-1 and displays good recyclable capability. Simultaneously, in the presence of other metal ions (Ca2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Pd2+, Al3+, Cr3+and Fe3+), 2-Eu can maintain the selective sensing of Mg2+, indicating its potential for Mg2+ turn-on sensing.A novel ligand (6) for copper-catalyzed azide-alkyne cycloaddition (CuAAC) in bioconjugation has been developed. Both in vitro and in vivo experiments indicate that 6 is more efficient and less cytotoxic than the canonical CuAAC ligands. Besides, 6 is easily accessible and can be prepared at gram scale. Our study reveals that 6 might be an ideal CuAAC ligand for bioconjugations.Metal complexes of mesoionic carbene (MIC) ligands are known to catalyze a variety of chemical transformations. In this contribution, we report on the synthesis of a dicationic dicopper(i) complex containing a di-MIC ligand. Two routes are presented for the synthesis of the dicopper complex Ag-mediated transmetalation and direct deprotonation. For the Ag-mediated transmetalation route, the detection and isolation of several Ag-containing intermediates that are relevant for the final formation of the aforementioned dicopper complex are reported. We then investigate a series of copper(i) complexes based on MIC ligands as precatalysts for the azide halo-alkyne (Click) cycloaddition reaction. In a comparative study, three different halide-containing (I, Br, Cl) substrates have been investigated with different catalysts to survey the behaviour for mono/di-copper-MIC complexes as well as neutral, mono- and di-cationic complexes. The cationic complexes proved to have superior activities compared to the neutral species. These are the first reports on the use of Cu-MIC complexes as precatalysts for the halo-Click reaction.Non-destructive methods that allow the quantification of bioproducts in a simple and quick manner during fermentation are extremely desirable from a practical point of view. Therefore, a 9 day fermentation experiment with Schizophyllum commune was carried out to investigate the possibility of using ATR-FTIR to quantify the schizophyllan biopolymer (SPG) directly from the culture medium. On each day, aliquots of the fermentation were taken, and the cell-free supernatant was analyzed by ATR-FTIR. The main objective of this step was to evaluate whether FTIR would be able to detect the appearance of specific peaks related to the production of SPG. The results of the PCA analysis showed that there was a reasonable separation of the days through the FTIR spectra. Then PCA-LDA was applied to the same dataset, which confirmed the formation of groups for each day of fermentation, after which, a calibration and test set was developed. Through a matrix generated by an experimental design with 2 factors and 5 levels, 25 samples were created with variations in the concentration of the culture medium and SPG.