Crystal Structures of Membrane Transporter MmpL3, an Anti-TB Drug Target.

Despite intensive efforts to discover highly effective treatments to eradicate tuberculosis (TB), it remains as a major threat to global human health. For this reason, new TB drugs directed toward new targets are highly coveted. MmpLs (Mycobacterial membrane proteins Large), which play crucial roles in transporting lipids, polymers and immunomodulators and which also extrude therapeutic drugs, are among the most important therapeutic drug targets to emerge in recent times. Here, crystal structures of mycobacterial MmpL3 alone and in complex with four TB drug candidates, including SQ109 (in Phase 2b-3 clinical trials), are reported. MmpL3 consists of a periplasmic pore domain and a twelve-helix transmembrane domain. Two Asp-Tyr pairs centrally located in this domain appear to be key facilitators of proton-translocation. SQ109, AU1235, ICA38, and rimonabant bind inside the transmembrane region and disrupt these Asp-Tyr pairs. This structural data will greatly advance the development of MmpL3 inhibitors as new TB drugs.

Molecular recognition of trehalose and trehalose analogues by Mycobacterium tuberculosis LpqY-SugABC.

Trehalose plays a crucial role in the survival and virulence of the deadly human pathogen Mycobacterium tuberculosis (Mtb). The type I ATP-binding cassette (ABC) transporter LpqY-SugABC is the sole pathway for trehalose to enter Mtb. The substrate-binding protein, LpqY, which forms a stable complex with the translocator SugABC, recognizes and captures trehalose and its analogues in the periplasmic space, but the precise molecular mechanism for this process is still not well understood. This study reports a 3.02-Å cryoelectron microscopy structure of trehalose-bound Mtb LpqY-SugABC in the pretranslocation state, a crystal structure of Mtb LpqY in a closed form with trehalose bound and five crystal structures of Mtb LpqY in complex with different trehalose analogues. These structures, accompanied by substrate-stimulated ATPase activity data, reveal how LpqY recognizes and binds trehalose and its analogues, and highlight the flexibility in the substrate binding pocket of LpqY. These data provide critical insights into the design of trehalose analogues that could serve as potential molecular probe tools or as anti-TB drugs.

Genome-wide association study of exercise-induced skeletal muscle hypertrophy and the construction of predictive model.

The aim of the current study was to investigate interindividual differences in muscle thickness of the rectus femoris (MTRF) following 12 wk of resistance training (RT) or high-intensity interval training (HIIT) to explore the genetic architecture underlying skeletal muscle hypertrophy and to construct predictive models. We conducted musculoskeletal ultrasound assessments of the MTRF response in 440 physically inactive adults after the 12-wk exercise period. A genome-wide association study was used to identify variants associated with the MTRF response, separately for RT and HIIT. Using the polygenic predictor score (PPS), we estimated the genetic contribution to exercise-induced hypertrophy. Predictive models for the MTRF response were constructed using random forest (RF), support vector mac (SVM), and generalized linear model (GLM) in 10 cross-validated approaches. MTRF increased significantly after both RT (8.8%, P < 0.05) and HIIT (5.3%, P < 0.05), but with considerable interindividual differences (RT: -13.5 to 38.4%, HIIT: -14.2 to 30.7%). Eleven lead single-nucleotide polymorphisms in RT and eight lead single-nucleotide polymorphisms in HIIT were identified at a significance level of P < 1 × 10-5. The PPS was associated with the MTRF response, explaining 47.2% of the variation in response to RT and 38.3% of the variation in response to HIIT. Notably, the GLM and SVM predictive models exhibited superior performance compared with RF models (P < 0.05), and the GLM demonstrated optimal performance with an area under curve of 0.809 (95% confidence interval: 0.669-0.949). Factors such as PPS, baseline MTRF, and exercise protocol exerted influence on the MTRF response to exercise, with PPS being the primary contributor. The GLM and SVM predictive model, incorporating both genetic and phenotypic factors, emerged as promising tools for predicting exercise-induced skeletal muscle hypertrophy.NEW & NOTEWORTHY The interindividual variability induced muscle hypertrophy by resistance training (RT) or high-intensity interval training (HIIT) and the associated genetic architecture remain uncertain. We identified genetic variants that underlie RT- or HIIT-induced muscle hypertrophy and established them as pivotal factors influencing the response regardless of the training type. The genetic-phenotype predictive model developed has the potential to identify nonresponders or individuals with low responsiveness before engaging in exercise training.

Differential regulation of phosphorylation, structure, and stability of circadian clock protein FRQ isoforms.

Neurospora crassa is an important model organism for circadian clock research. The Neurospora core circadian component FRQ protein has two isoforms, large FRQ (l-FRQ) and small FRQ (s-FRQ), of which l-FRQ bears an additional N-terminal 99-amino acid fragment. However, how the FRQ isoforms operate differentially in regulating the circadian clock remains elusive. Here, we show l-FRQ and s-FRQ play different roles in regulating the circadian negative feedback loop. Compared to s-FRQ, l-FRQ is less stable and undergoes hypophosphorylation and faster degradation. The phosphorylation of the C-terminal l-FRQ 794-aa fragment was markedly higher than that of s-FRQ, suggesting the l-FRQ N-terminal 99-aa region may regulate the phosphorylation of the entire FRQ protein. Quantitative label-free LC/MS analysis identified several peptides that were differentially phosphorylated between l-FRQ and s-FRQ, which were distributed in FRQ in an interlaced fashion. Furthermore, we identified two novel phosphorylation sites, S765 and T781; mutations S765A and T781A showed no significant effects on conidiation rhythmicity, although T781 conferred FRQ stability. These findings demonstrate that FRQ isoforms play differential roles in the circadian negative feedback loop and undergo different regulations of phosphorylation, structure, and stability. The l-FRQ N-terminal 99-aa region plays an important role in regulating the phosphorylation, stability, conformation, and function of the FRQ protein. As the FRQ circadian clock counterparts in other species also have isoforms or paralogues, these findings will also further our understanding of the underlying regulatory mechanisms of the circadian clock in other organisms based on the high conservation of circadian clocks in eukaryotes.

Automatic Electrochemiluminescence Method for the Detection of Cancerous Exosomes Incorporating Specific Aptamer-Magnetic Beads and Signal Nanoprobes.

Exosomes, as an emerging biomarker, have exhibited remarkable promise in early cancer diagnosis. Here, a highly sensitive, selective, and automatic electrochemiluminescence (ECL) method for the detection of cancerous exosomes was developed. Specific aptamer-(EK)4 peptide-tagged magnetic beads (MBs-(EK)4-aptamer) were designed as a magnetic capture probe in which the (EK)4 peptide was used to reduce the steric binding hindrance of cancerous exosomes with a specific aptamer. One new universal ECL signal nanoprobe (CD9 Ab-PEG@SiO2ϵRu(bpy)32+) was designed and synthesized by using microporous SiO2 nanoparticles as the carrier for loading ECL reagent Ru(bpy)32+, polyethylene glycol (PEG) layer, and anticluster of differentiation 9 antibody (CD9 Ab). A "sandwich" biocomplex was formed on the surface of the magnetic capture probe after mixing the capture probe, target exosomes, and ECL signal nanoprobe, and then it was introduced into an automated ECL analyzer for rapid and automatic ECL measurement. It was found that the designed signal nanoprobe shows a 270-fold improvement in the signal-to-noise ratio than that of the ruthenium complex-labeled CD9 antibody signal probe. The relative ECL intensity was proportional to MCF-7 exosomes as a model in the range of 102 to 104 particle/µL, with a detection limit of 11 particle/µL. Furthermore, the ECL method was employed to discriminate cancerous exosomes based on fingerprint responses using the designed multiple magnetic capture probes and the universal ECL signal nanoprobe. This work demonstrates that the utilization of a designed automated ECL tactic using the MBs-(EK)4-aptamer capture probe and the CD9 Ab-PEG@SiO2ϵRu(bpy)32+ signal nanoprobe will provide a unique and robust method for the detection and discrimination of cancerous exosomes.

Nomogram to predict overall survival of patients receiving radical gastrectomy and incomplete peri-operative adjuvant chemotherapy for stage II/III gastric cancer: a retrospective bi-center cohort study.

BACKGROUND: To establish a nomogram to predict the probability of survival of patients with stage II/III gastric cancer (GC) who received incomplete peri-operative adjuvant chemotherapy (PAC). METHODS: The medical records of stage II/III GC patients who received curative resection and 1 to 5 cycles of PAC from two tertiary hospitals were retrospectively reviewed. Patients were randomly classified into either a training group or validation group at a ratio of 7:3. The nomogram was constructed based on various prognostic factors using Cox regression analysis in the training cohort, and was validated by the validation group. Concordance index and calibration curves were used to evaluate the discrimination and calibration of the nomogram. Additionally, decision curve analysis (DCA) was used to compare the net clinical benefits of the nomogram and eighth version of TNM staging system. RESULTS: A total of 1,070 consecutive patients were included and 749 patients were enrolled into the training group. Lower body mass index (< 18.5 kg/m2), total gastrectomy, stage III disease and fewer cycles of PAC were identified to be independent predictors for poorer survival. The area under the curve (AUC) values of receiver operating characteristics (ROC) curve predicting 5-year survival probabilities and C-index were 0.768 and 0.742, 0.700 (95%CI: 0.674-0.726) and 0.689 (95%CI: 0.646-0.732) in the training and validation groups, respectively. The calibration curves in the validation cohort showed good agreement between the prediction and observation of 1-, 3- and 5-year survival probabilities. Furthermore, DCA showed that our model has a better net benefit than that of TNM staging system. CONCLUSIONS: The findings emphasize the value of completing PAC. The nomogram which was established to predict survival probability in patients with stage II/III GC receiving radical gastrectomy and incomplete PAC had good accuracy and was verified through both internal and external validation.

The opportunities and challenges of the disease-modifying immunotherapy for type 1 diabetes: A systematic review and meta-analysis.

There are multiple disease-modifying immunotherapies showing the potential of preventing or delaying the progression of type 1 diabetes (T1D). We designed and performed this systematic review and meta-analysis to gain an overview of what a role immunotherapy plays in the treatment of T1D. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to December 2023. We included clinical trials of immunotherapy conducted in patients with T1D that reported the incidence of hypoglycemia or changes from baseline in at least one of following outcomes: 2 h and 4 h mixed-meal-stimulated C-peptide area under the curve (AUC), fasting C-peptide, daily insulin dosage, glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG). The results were computed as the weighted mean differences (WMDs) or odds ratios (ORs) and 95% confidence intervals (CIs) in random-effect model. In all, 34 clinical trials were included. When compared with control groups, 2 h C-peptide AUC was marginally higher in patient treated with nonantigen-based immunotherapies (WMD, 0.04nmol/L, 95% CI, 0.00-0.09 nmol/L, P=0.05), which was mainly driven by the effects of T cell-targeted therapy. A greater preservation in 4 h C-peptide AUC was observed in patients with nonantigen-based immunotherapies (WMD, 0.10nmol/L, 95% CI, 0.04-0.16 nmol/L, P=0.0007), which was mainly driven by the effects of tumor necrosis factor α (TNF-α) inhibitor and T cell-targeted therapy. After excluding small-sample trials, less daily insulin dosage was observed in patient treated with nonantigen-based immunotherapies when compared with control groups (WMD, -0.07units/kg/day, 95% CI, -0.11 to -0.03units/kg/day, P=0.0004). The use of antigen-based immunotherapies was also associated with a lower daily insulin dosage versus control groups (WMD, -0.11units/kg/day, 95% CI, -0.23 to -0.00units/kg/day, P=0.05). However, changes of HbA1c or FPG were comparable between nonantigen-based immunotherapies or antigen-based immunotherapies and control groups. The risk of hypoglycemia was not increased in patients treated with nonantigen-based immunotherapies or patients treated with antigen-based immunotherapies when compared with control groups. In conclusion, nonantigen-based immunotherapies were associated with a preservation of 2 h and 4 h C-peptide AUC in patients with T1D when compared with the controls, which was mainly driven by the effects of TNF-a inhibitor and T cell-targeted therapy. Both nonantigen-based immunotherapies and antigen-based immunotherapies tended to reduce the daily insulin dosage in patients with T1D when compared with the controls. However, they did not contribute to a substantial improvement in HbA1c or FPG. Both nonantigen-based immunotherapies and antigen-based immunotherapies were well tolerated with not increased risk of hypoglycemia in patients with T1D.

Diffusion spectrum imaging in patients with idiopathic normal pressure hydrocephalus: correlation with ventricular enlargement.

BACKGROUND: To investigate the association between white matter changes and ventricular expansion in idiopathic normal pressure hydrocephalus (iNPH) based on diffusion spectrum imaging (DSI). METHODS: We included 32 patients with iNPH who underwent DSI using a 3T MRI scanner. The lateral ventricles were manually segmented, and ventricular volumes were measured. Two methods were utilised in the study: manual region-of-interest (ROI) delineation and tract diffusion profile analysis. General fractional anisotropy (GFA) and fractional anisotropy (FA) were extracted in different white matter regions, including the bilateral internal capsule (anterior and posterior limbs) and corpus callosum (body, genu, and splenium) with manual ROI delineation. The 18 main tracts in the brain of each patient were extracted; the diffusion metrics of 100 equidistant nodes on each fibre were calculated, and Spearman's correlation coefficient was used to determine the correlation between diffusion measures and ventricular volume of iNPH patients. RESULTS: The GFA and FA of all ROI showed no significant correlation with lateral ventricular volume. However, in the tract diffusion profile analysis, lateral ventricular volume was positively correlated with part of the cingulum bundle, left corticospinal tract, and bilateral thalamic radiation posterior, whereas it was negatively correlated with the bilateral cingulum parahippocampal (all p < 0.05). CONCLUSIONS: The effect of ventricular enlargement in iNPH on some white matter fibre tracts around the ventricles was limited and polarizing, and most white matter fibre tract integrity changes were not associated with ventricular enlargement; this reflects that multiple pathological mechanisms may have been combined to cause white matter alterations in iNPH.

Electrochemical oxidative thioetherification of aldehyde hydrazones with thiophenols.

An electrochemically promoted oxidative dehydrogenation cross-coupling reaction between aldehyde hydrazones and thiophenols is demonstrated for the first time, which resulted in a variety of (Z)-thioetherified products in moderate to excellent yields. This strategy can be carried out under an air atmosphere, featuring scalability and excellent stereoselectivity. In addition, the transformation efficiently produces readily recyclable disulfide as a by-product with high yields, which significantly reduces the environmental pollution caused by thioetherification.

Novel glycosidase from Paenibacillus lactis 154 hydrolyzing the 28-O-ß-D-glucopyranosyl ester bond of oleanane-type saponins.

Oleanane-type ginsenosides are a class of compounds with remarkable pharmacological activities. However, the lack of effective preparation methods for specific rare ginsenosides has hindered the exploration of their pharmacological properties. In this study, a novel glycoside hydrolase PlGH3 was cloned from Paenibacillus lactis 154 and heterologous expressed in Escherichia coli. Sequence analysis revealed that PlGH3 consists of 749 amino acids with a molecular weight of 89.5 kDa, exhibiting the characteristic features of the glycoside hydrolase 3 family. The enzymatic characterization results of PlGH3 showed that the optimal reaction pH and temperature was 8 and 50 °C by using p-nitrophenyl-ß-D-glucopyranoside as a substrate, respectively. The Km and kcat values towards ginsenoside Ro were 79.59 ± 3.42 µM and 18.52 s-1, respectively. PlGH3 exhibits a highly specific activity on hydrolyzing the 28-O-ß-D-glucopyranosyl ester bond of oleanane-type saponins. The mechanism of hydrolysis specificity was then presumably elucidated through molecular docking. Eventually, four kinds of rare oleanane-type ginsenosides (calenduloside E, pseudoginsenoside RP1, zingibroside R1, and tarasaponin VI) were successfully prepared by biotransforming total saponins extracted from Panax japonicus. This study contributes to understanding the mechanism of enzymatic hydrolysis of the GH3 family and provides a practical route for the preparation of rare oleanane-type ginsenosides through biotransformation. KEY POINTS: • The glucose at C-28 in oleanane-type saponins can be directionally hydrolyzed. • Mechanisms to interpret PlGH3 substrate specificity by molecular docking. • Case of preparation of low-sugar alternative saponins by directed hydrolysis.

Psychometric evaluation of the Chinese version of the stressors in breast cancer scale: a translation and validation study.

OBJECTIVE: To translate the Stressors in Breast Cancer Scale (SBCS) from English to Chinese and assess its psychometric properties. METHODS: The Brislin's translation model was applied to perform forward translation, back translation, cross-cultural adaptation, Whereas the Chinese version of the SBCS was formed by conducting pre-testing. A cohort of 878 breast cancer patients participated in this methodological study. Content validity, construct validity, convergent validity, discriminant validity, and criterion-related validity were used to establish validity. Internal consistency reliability, split-half reliability, and test-retest reliability were used to establish reliability. RESULTS: The final scale contained five dimensions and 24 items, including interpersonal relationship and healthcare strains, worries and concerns about the future, physical appearance and sex strains, daily difficulties and health. The average content validity index of the scale was 0.975. The goodness-of-fit index (χ2/DF = 2.416, RMSEA = 0.057, GFI = 0.896, CFI = 0.947, IFI = 0.947, and TLI = 0.939) indicated that the model was well-fitted. The composite reliability (CR) of the dimensions ranged from 0.825 to 0.934, the average variance extracted (AVE) ranged from 0.539 to 0.712, and the correlation coefficients of each dimension with the other dimensions were less than the square root of the AVE for that dimension. The Criterion-related validity was 0.511. The Cronbach's alpha was 0.938, and the dimensions ranged from 0.779 to 0.900. Split-half reliability was 0.853, with dimensions ranging from 0.761 to 0.892. Test-retest reliability was 0.855. CONCLUSIONS: The Chinese version of the SBCS has good reliability and validity, which can be applied to the assessment of stressors in breast cancer patients in China.

The effect of sodium bicarbonate mini-tablets ingested in a carbohydrate hydrogel system on 40 km cycling time trial performance and metabolism in trained male cyclists.

INTRODUCTION: Sodium bicarbonate (NaHCO3) ingestion has been found to be ergogenic in high-intensity exercise that ranges from 1 to 10 min; however, limited studies have investigated high-intensity exercise beyond this duration. PURPOSE: The present study aimed to determine the effect of NaHCO3 ingested using a carbohydrate hydrogel delivery system on 40 km time trial (TT) performance in trained male cyclists. METHODS: Fourteen trained male cyclists ingested 0.3 g kg-1 BM NaHCO3 (Maurten AB, Sweden) to determine individualised peak alkalosis, which established time of ingestion prior to exercise. Participants completed a 40 km familiarisation TT, and two 40 km experimental TTs after ingestion of either NaHCO3 or placebo in a randomised, double-blind, crossover design. RESULTS: NaHCO3 supplementation improved performance (mean improvement = 54.14 s ± 18.16 s; p = 0.002, g = 0.22) and increased blood buffering capacity prior to (HCO3- mean increase = 5.6 ± 0.2 mmol L-1, p < 0.001) and throughout exercise (f = 84.82, p < 0.001, pη2 = 0.87) compared to placebo. There were no differences in total gastrointestinal symptoms (GIS) between conditions either pre- (NaHCO3, 22 AU; Placebo, 44 AU; p = 0.088, r = 0.46) or post-exercise (NaHCO3, 76 AU; Placebo, 63 AU; p = 0.606, r = 0.14). CONCLUSION: The present study suggests that ingesting NaHCO3 mini-tablets in a carbohydrate hydrogel can enhance 40 km TT performance in trained male cyclists, with minimal GIS. This ingestion strategy could therefore be considered by cyclists looking for a performance enhancing ergogenic aid.

Architecture of the mycobacterial succinate dehydrogenase with a membrane-embedded Rieske FeS cluster.

Complex II, also known as succinate dehydrogenase (SQR) or fumarate reductase (QFR), is an enzyme involved in both the Krebs cycle and oxidative phosphorylation. Mycobacterial Sdh1 has recently been identified as a new class of respiratory complex II (type F) but with an unknown electron transfer mechanism. Here, using cryoelectron microscopy, we have determined the structure of Mycobacterium smegmatis Sdh1 in the presence and absence of the substrate, ubiquinone-1, at 2.53-Å and 2.88-Å resolution, respectively. Sdh1 comprises three subunits, two that are water soluble, SdhA and SdhB, and one that is membrane spanning, SdhC. Within these subunits we identified a quinone-binding site and a rarely observed Rieske-type [2Fe-2S] cluster, the latter being embedded in the transmembrane region. A mutant, where two His ligands of the Rieske-type [2Fe-2S] were changed to alanine, abolished the quinone reduction activity of the Sdh1. Our structures allow the proposal of an electron transfer pathway that connects the substrate-binding and quinone-binding sites. Given the unique features of Sdh1 and its essential role in Mycobacteria, these structures will facilitate antituberculosis drug discovery efforts that specifically target this complex.

A Genotype-Phenotype Model for Predicting Resistance Training Effects on Leg Press Performance.

This study develops a comprehensive genotype-phenotype model for predicting the effects of resistance training on leg press performance. A cohort of physically inactive adults (N=193) underwent 12 weeks of resistance training, and measurements of maximum isokinetic leg press peak force, muscle mass, and thickness were taken before and after the intervention. Whole-genome genotyping was performed, and genome-wide association analysis identified 85 novel SNPs significantly associated with changes in leg press strength after training. A prediction model was constructed using stepwise linear regression, incorporating seven lead SNPs that explained 40.4% of the training effect variance. The polygenic score showed a significant positive correlation with changes in leg press strength. By integrating genomic markers and phenotypic indicators, the comprehensive prediction model explained 75.4% of the variance in the training effect. Additionally, five SNPs were found to potentially impact muscle contraction, metabolism, growth, and development through their association with REACTOME pathways. Individual responses to resistance training varied, with changes in leg press strength ranging from -55.83% to 151.20%. The study highlights the importance of genetic factors in predicting training outcomes and provides insights into the potential biological functions underlying resistance training effects. The comprehensive model offers valuable guidance for personalized fitness programs based on individual genetic profiles and phenotypic characteristics.

Longitudinal associations of participation in organized and unorganized sports in youth with physical activity in mid-adulthood: The Young Finns Study.

We investigated the longitudinal associations between sports participation patterns in youth and physical activity (PA) in adulthood. PA was self-reported triannually between ages 9-18 (n = 2550, 52% females) and measured by accelerometers in mid-adulthood (n = 1002, 61% females, aged 48 ± 4 years). Three latent classes of youth sports participation emerged for both genders: 1) "organized sports" (persistent high PA with regular sports club activities), 2) "unorganized sports" (persistent high PA without sports club activities and 3) "low activity" (low PA with decreasing sports involvement). These groups comprised 29%, 34% and 37% of males, and 23%, 27% and 50% of females, respectively. Youth "organized sports" was associated with higher adult PA in both males (+1166 steps/day, p = 0.012) and females (+15 min/day moderate-to-vigorous PA [MVPA], +1064 steps/day, +1066 leisure-time steps/day; p ≤ 0.005) compared to "low activity". In males, youth "organized sports" was associated with higher adult PA (+1103 steps/day, -26 min/day sedentary time and +133 counts/minute higher total PA, p ≤ 0.039) compared to "unorganized sports". In females, "unorganized sports" in youth was related to higher adult PA (+10 min/day MVPA, p = 0.034) when compared to "low activity". Sustained participation in youth organized sports, and for females, also in unorganized sports, is positively linked with adult PA.

Quantitative Detection of Pipeline Cracks Based on Ultrasonic Guided Waves and Convolutional Neural Network.

In this study, a quantitative detection method of pipeline cracks based on a one-dimensional convolutional neural network (1D-CNN) was developed using the time-domain signal of ultrasonic guided waves and the crack size of the pipeline as the input and output, respectively. Pipeline ultrasonic guided wave detection signals under different crack defect conditions were obtained via numerical simulations and experiments, and these signals were input as features into a multi-layer perceptron and one-dimensional convolutional neural network (1D-CNN) for training. The results revealed that the 1D-CNN performed better in the quantitative analysis of pipeline crack defects, with an error of less than 2% in the simulated and experimental data, and it could effectively evaluate the size of crack defects from the echo signals under different frequency excitations. Thus, by combining the ultrasonic guided wave detection technology and CNN, a quantitative analysis of pipeline crack defects can be effectively realized.

Transcriptomic Analysis of the CNL Gene Family in the Resistant Rice Cultivar IR28 in Response to Ustilaginoidea virens Infection.

Rice false smut, caused by Ustilaginoidea virens, threatens rice production by reducing yields and contaminating grains with harmful ustiloxins. However, studies on resistance genes are scarce. In this study, the resistance level of IR28 (resistant cultivar) to U. virens was validated through artificial inoculation. Notably, a reactivation of resistance genes after transient down-regulation during the first 3 to 5 dpi was observed in IR28 compared to WX98 (susceptible cultivar). Cluster results of a principal component analysis and hierarchical cluster analysis of differentially expressed genes (DEGs) in the transcriptome exhibited longer expression patterns in the early infection phase of IR28, consistent with its sustained resistance response. Results of GO and KEGG enrichment analyses highlighted the suppression of immune pathways when the hyphae first invade stamen filaments at 5 dpi, but sustained up-regulated DEGs were linked to the 'Plant-pathogen interaction' (osa04626) pathway, notably disease-resistant protein RPM1 (K13457, CNLs, coil-coiled NLR). An analysis of CNLs identified 245 proteins containing Rx-CC and NB-ARC domains in the Oryza sativa Indica genome. Partial candidate CNLs were shown to exhibit up-regulation at both 1 and 5 dpi in IR28. This study provides insights into CNLs' responses to U. virens in IR28, potentially informing resistance mechanisms and genetic breeding targets.

Diversified crop rotations improve soil microbial communities and functions in a six-year field experiment.

Diversified crop rotations can help mitigate the negative impacts of increased agricultural intensity on the sustainability of agroecosystems. However, the impact of crop rotation diversity on the complexity of soil microbial association networks and ecological functions is still not well understood. In this study, a 6-year field experiment was conducted to evaluate how six different crop rotations change the composition and network complexity of soil microbial communities, as well as their related ecological functions. Microbial traits were measured in six crop rotations with different crop diversity index (CDI) during 2016-2022, including winter wheat-summer maize (CDI 1, WM) as the control, sweet potato→winter wheat-summer maize (CDI 1.5, SpWM), peanut→winter wheat-summer maize (CDI 1.5, PWM), soybean→winter wheat-summer maize (CDI 1.5, SWM), spring maize→winter wheat-summer maize (CDI 1.5, SmWM), and ryegrass-sweet sorghum→winter wheat-summer maize (CDI 2, RSWM). The study findings indicated that diversified crop rotations significantly increased ASV richness of both bacterial and fungal communities after 6-year treatments, and the ß-diversity profiles of bacterial and fungal communities significantly distinguished at the year of 2022 from 2016. The relative abundance of Acidobacteria and Chloroflexi was significantly enriched in SpWM rotation at 2022, while Basidiomycota significantly declined in five diversified rotations compared to WM. Diversified crop rotations at 2022 increased the complexity and density of bacterial and fungal networks than 2016. SpWM and PWM rotations had the highest functional groups involved in chemoheterotrophy and saprotroph, respectively. Structural equation modelling (SEM) also revealed that diversified crop rotations increased soil nutrients through improving the composition of bacterial communities and the augmented intricacy of the interconnections within both bacterial and fungal communities. This research underscores the importance of preserving the diversity and ecological functions of soil microorganisms in the nutrient-recycling processes for efficient agricultural practices.

Relationship between Sociodemographic and Health-Related Factors and Sedentary Time in Middle-Aged and Older Adults in Taiwan.

Background and Objectives: This study aimed to investigate the associations between sociodemographic and health-related factors and sedentary time in middle-aged and older Taiwanese adults. Materials and Methods: A total of 1031 participants (460 men, 571 women; mean age 65.0 years ± 7.8 years; range 55 to 93 years) were randomly recruited from the National Computer Assessment Telephone Interview, Taiwan, in 2013. Sedentary time, TV viewing, physical activity, and sociodemographic factors were assessed through questionnaires. Body mass index was self-reported and calculated to evaluate obesity. In 2023, the associations between sedentary time and sociodemographic and health-related factors were analyzed using Pearson's correlation, cross tabulation, and logistic regression and were stratified by gender. Results: Over 47% of participants reported spending more than 2 h watching TV, and more than 33% reported engaging in over 6 h of total sedentary activities. Men and women with insufficient physical activity had a higher probability of prolonged sedentary time than their physically active counterparts (p = 0.032 for men, p = 0.024 for women). Both men and women who spent more than 2 h watching TV daily were more likely to have high sedentary time compared to those with shorter TV viewing durations (both p < 0.001). Highly educated and unmarried women exhibited a higher likelihood of prolonged sedentary time than their less educated and married counterparts (p = 0.021 and p = 0.01, respectively). Conclusions: Sedentary time showed significant and positive associations with both insufficient physical activity and prolonged TV viewing in both genders. Additionally, significant associations were observed between sedentary time and high education and unmarried status in women. These findings emphasize the importance of implementing gender-specific approaches in future interventions and policy initiatives aimed at reducing sedentary behavior among middle-aged and older adults.

Genetic markers and predictive model for individual differences in countermovement jump enhancement after resistance training.

This study aims to utilize Genome-Wide Association Analysis (GWAS) to identify genetic markers associated with enhanced power resulting from resistance training. Additionally, we analyze the potential biological effects of these markers and establish a predictive model for training outcomes. 193 Han Chinese adults (age: 20 ± 1 years) underwent resistance training involving squats and bench presses at 70% 1RM, twice weekly, 5 sets × 10 repetitions, for 12 weeks. Whole-genome genotyping was conducted, and participants' countermovement jump (CMJ) height, lower limb muscle strength, and body muscle mass were assessed. CMJ height change was used to assess changes in power and subjected to Genome-Wide Association Analysis (GWAS) against genotypes. Employing Polygenic Score (PGS) calculations and stepwise linear regression, a predictive model for training effects was constructed. The results revealed a significant increase in CMJ height among participants following the resistance training intervention (Δ% = 16.53%, p < 0.01), with individual differences ranging from -35.90% to 125.71%. 38 lead SNPs, including PCTP rs9907859 (p < 1 × 10-8), showed significant associations with the percentage change in CMJ height after training (p < 1 × 10-5). The explanatory power of the predictive model for training outcomes, established using PGS and phenotypic indicators, was 62.6%, comprising 13.0% from PGS and 49.6% from phenotypic indicators. SNPs associated with power resistance training were found to participate in the biological processes of musculoskeletal movement and the Striated muscle contraction pathway. These findings indicate that individual differences in the training effect of CMJ exist after resistance training, partially explained by genetic markers and phenotypic indicators (62.6%).