The above phenomenon was reversed by a 4-week aerobic exercise intervention. Therefore, this study suggests that the mechanism by which aerobic exercise improves PD-related motor dysfunction may be related to that the aerobic exercise intervention alleviates the activity of extracellular signal-regulated kinase/mitogen-activated protein kinases (Erk/MAPK) signaling pathway in striatal medium spiny neurons expressing D2-like receptors (D2-MSNs) of PD mice by regulating the striatal DA and Glu signaling.The immune system is a human defense system that can be adapted to external conditions and is present ubiquitously throughout the organism. Its main purpose is to prevent damage caused by pathogens or toxins. In addition, it is capable of recognizing and destroying defective or degenerated endogenous cells. The immunological network in the body consists of various organs and organ systems, different immunoactive cell types as well as extra- and intracellular signaling molecules and signal complexes. The immune system is divided into the innate immune system and the acquired immune system. Pathological conditions, which may be short- or long-lasting, range from the congenital disorders of autoinflammation to the numerous autoimmune diseases, triggered by various stimuli. From a treatment perspective, nonspecific immunosuppressants or direct immune cell inhibitors or antibodies can be used for excessive reactions.

To develop and validate anomogram to predict distant metastasis-free survival of patients with locoregionally advanced nasopharyngeal carcinoma.

We collected the total clinical data of 820nasopharyngeal carcinoma (NPC) patients, of whom 482formed the training cohort from one hospital and 328made up the validation cohort from another hospital. By analyzing the prognosis of all patients after intensity-modulated radiotherapy by univariate and multivariate Cox regression models, anomogram related to DMFS was created in the training cohort. The discriminatory and calibration power of the nomogram was successively assessed in the training and validation cohorts by the C‑index and calibration curve. The predictive ability for 3‑year DMFS was compared between the nomogram and TNM stage using ROC curves. Patients were divided into different risk groups based on scores calculated from the nomogram.

Age, lymph node gross tumor volume (GTVnd), and gross tumor volume of the nasopharynx (GTVnx) were the factors included in the nomogram. The C‑index of the nomogram was 0.721 in the training cohort and 0.750 in the validation cohort. The calibration curves were satisfactory. Patients in the high-risk group were more likely to develop metastases.

Anomogram incorporating age, GTVnd, and GTVnx showed good performance for predicting DMFS in patients with locoregionally advanced NPC.

A nomogram incorporating age, GTVnd, and GTVnx showed good performance for predicting DMFS in patients with locoregionally advanced NPC.The objective of this study is to clarify the clinical features and risk factors of venous thromboembolism (VTE) in patients with rheumatoid arthritis (RA). We retrospectively reviewed the prevalence of VTE in RA patients who visited Hokkaido University Hospital from 2010 to 2019 and had more than 2 years of follow-up. To explore the risk to develop VTE, we selected 260 RA patients without VTE (non-VTE) via density sampling and identified the risk factors for VTE by multivariate logistic regression analysis. Univariate conditional logistic regression analysis showed older age (p  less then  0.0001, Odds Ratio [OR] 1.08, 95% Confidence Interval [CI] 1.04-1.14), increase of the body mass index (BMI) (p = 0.001, OR 1.17, 95% CI 1.06-1.31), higher prevalence of RA-associated lung disease (p = 0.002, OR 2.10, 95% CI 1.33-3.30) and more frequent glucocorticoid usage (p = 0.001, OR 2.09, 95% CI 1.34-3.51) in RA patients was associated with the development of VTE significantly. Furthermore, patients with higher time-averaged disease activity score 28 (DAS28) CRP were at elevated risk (p  less then  0.0001, OR 3.25, 95% CI 1.94-6.12). In conditional multivariate logistic regression analysis, time averaged DAS28CRP was significantly associated with the development of VTE (p = 0.0001, adjusted OR 3.40, 95% CI 1.77-7.85). Disease activity was identified as a major risk factor of VTE in patients with RA, suggesting that sustained clinical remission could be beneficial for decrease the risk of VTE.The need for biosensors has evolved in the detection of molecules, diseases, and pollution from various sources. This requirement has headed to the development of accurate and powerful equipment for analysis using biological sensing component as a biosensor. Biosensors have the advantage of rapid detection that can beat the conventional methods for the detection of the same molecules. Bio-chemiluminescence-based sensors are very sensitive during use in biological immune assay systems. Optical biosensors are emerging with time as they have the advantage that they act with a change in the refractive index. Carbon nanotube-based sensors are another area that has an important role in the biosensor field. Bioluminescence gives much higher quantum yields than classical chemiluminescence. Electro-generated bioluminescence has the advantage of miniature size and can produce a high signal-to-noise ratio and the controlled emission. Recent advances in biological techniques and instrumentation involving fluorescence tag to nanomaterials have increased the sensitivity limit of biosensors. Integrated approaches provided a better perspective for developing specific and sensitive biosensors with high regenerative potentials. This paper mainly focuses on sensors that are important for the detection of multiple molecules related to clinical and environmental applications. KEY POINTS • The review focusses on the applications of luminescence-based, surface plasmon resonance-based, carbon nanotube-based, and graphene-based biosensors • Potential clinical, environmental, agricultural, and food industry applications/uses of biosensors have been critically reviewed • The current limitations in this field are discussed, as well as the prospects for future advancement.Multidrug resistance (MDR) has significantly increased in the past decades and the use of nanotechnology has opened new venues for novel treatments. Nanosulfur is a potent antimicrobial agent and a cheaper alternative to other nanomaterials. However, very few studies have been published on its activity against MDR organisms. Therefore, the goal of this in vitro study was to assess cytotoxicity, antimicrobial, and anti-biofilm activity of nanosulfur (47 nm, orthorhombic) against clinical isolates of MDR Staphylococcus pseudintermedius (SP) and Pseudomonas aeruginosa (PA) in planktonic and biofilm state using canine skin explants. Nanosilver (50 nm, spherical) was tested as a comparative control. Concentrations between 1866.7 and 0.11 μg/mL of both nanoparticles were tested. The ultrastructure of nanosulfur was assessed via electron microscopy. Both types of nanoparticles showed no direct cytotoxicity on a canine keratinocyte cell line. In the planktonic phase, nanosulfur was able to inhibit or kill (6-log10 reduction of CFU) 7 of 10 MDR-SP isolates at 233.3 μg/mL, whereas, when in biofilm state, 6 of 10 isolates were killed at different concentrations (233.33 to 1866.7 μg/mL). Nanosilver did not show any antimicrobial or anti-biofilm activity at any concentrations tested. Both types of nanoparticles were ineffective against MDR-PA in either state. Ultrastructurally, nanosulfur was present in individual nanoparticles as well as forming larger nanoclusters. This is the first study showing an antimicrobial and anti-biofilm activity of nanosulfur for MDR-SP in absence of cytotoxicity. Nanosulfur has the potential to be used in veterinary and human medicine as effective, safe, and cheap alternative to antimicrobials and anti-biofilm agents currently available. KEY POINTS • Nanosulfur is a better alternative than nanosilver to treat MDR-Staphylococci. • Nanosulfur is an effective agent against MDR-Staphyloccocal biofilm. • Canine skin explant model is reliable for testing anti-biofilm agents.Methanotrophs capable of converting C1-based substrates play an important role in the global carbon cycle. As one of the essential macronutrient components in the medium, the uptake of nitrogen sources severely regulates the cell’s metabolism. Although the feasibility of utilizing nitrogen gas (N2) by methanotrophs has been predicted, the mechanism remains unclear. Herein, the regulation of nitrogen fixation by an essential nitrogen-fixing regulator (NifA) was explored based on transcriptomic analyses of Methylomicrobium buryatense 5GB1. A deletion mutant of the nitrogen global regulator NifA was constructed, and the growth of M. buryatense 5GB1ΔnifA exhibited significant growth inhibition compared with wild-type strain after the depletion of nitrate source in the medium. Our transcriptome analyses elucidated that 22.0% of the genome was affected in expression by NifA in M. buryatense 5GB1. Besides genes associated with nitrogen assimilation such as nitrogenase structural genes, genes related to cofactor biosynthesis, electron transport, and post-transcriptional modification were significantly upregulated in the presence of NifA to enhance N2 fixation; other genes related to carbon metabolism, energy metabolism, membrane transport, and cell motility were strongly modulated by NifA to facilitate cell metabolisms. This study not only lays a comprehensive understanding of the physiological characteristics and nitrogen metabolism of methanotrophs, but also provides a potentially efficient strategy to achieve carbon and nitrogen co-utilization.Key points• N2 fixation ability of M. buryatense 5GB1 was demonstrated for the first time in experiments by regulating the supply of N2.• NifA positively regulates nif-related genes to facilitate the uptake of N2 in M. buryatense 5GB1.• NifA regulates a broad range of cellular functions beyond nif genes in M. buryatense 5GB1.In this study, we evaluated a new biopesticide containing different combinations of Photorhabdus luminescens (ATCC 29,999; Pl) and Bacillus thuringiensis subsp. aizawai (Bt) to leverage their insecticidal activity against Plutella xylostella. Mixtures containing proteins of various sizes were assayed to determine which combination of the two bacteria would yield the maximum insecticidal activity. A histopathologic slide revealed vacuole formations and rifts near the apical membrane (a symptom of Bt) and severe thinning of the intestinal wall (a symptom of Pl). When the two bacteria were cultured separately and then mixed, the insecticidal activity of the treatment reached 83.33% ± 8.82%. The insecticidal activity was elevated and significantly accelerated when Bt was mixed with both the Pl supernatant and the isolated protein with a molecular mass [Formula see text] 100 kDa of Pl. These results highlight the potential of Pl as a potent bioinsecticide to economically and sustainably control Pl. xylostella and other lepidopteran pests. KEY POINTS • Growth inhibition by Bacillus thuringiensis exerted a significant effect on insecticidal activity. • Large Photorhabdus luminescens proteins can accelerate the synergistic insecticidal effect on Plutella xylostella.