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Abstract The decrease in sperm count and infertility is a global issue that remains unresolved. By screening environmental bacterial isolates, we have found that a novel lactic acid bacterium, Lactiplantibacillus plantarum SNI3, increased testis size, testosterone levels, sperm count, sexual activity and fertility in mice that have consumed the bacteria for four weeks. The abundance of L. plantarum in the colon microbiome was positively associated with sperm count. Fecal microbiota transplantation (FMT) from L. plantarum SNI3-dosed mice improved testicular functions in microbiome-attenuated recipient animals. To identify mediators that confer pro-reproductive effects on the host, untargeted in situ mass spectrometry metabolomics was performed on testis samples of L. plantarum SNI3-treated and control mice. Enrichment pathway analysis revealed several perturbed metabolic pathways in the testis of treated mice. Within the testis, a dipeptide, glutamyl-glutamate (GluGlu) was the most upregulated metabolite following L. plantarum SNI3 administration. To validate the pro-reproductive feature of GluGlu, systemic and local injections of the dipeptide have been performed. γ-GluGlu increased sperm count but had no effect on testosterone. These findings highlight the role of γ-GluGlu in mediating spermatogenetic effects of L. plantarum on the male mouse host and –following relevant human clinical trials- may provide future tools for treating certain forms of male infertility.

Abstract Backgrounds The use of large language models (LLMs) in medicine can help physicians improve the quality and effectiveness of health care by increasing the efficiency of medical information management, patient care, medical research, and clinical decision-making. Methods We collected 34 frequently asked questions about glucocorticoid-induced osteoporosis (GIOP), covering topics related to the disease’s clinical manifestations, pathogenesis, diagnosis, treatment, prevention, and risk factors. We also generated 25 questions based on the 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis (2022 ACR-GIOP Guideline). Each question was posed to the LLM (ChatGPT-3.5, ChatGPT-4, and Google Gemini), and three senior orthopedic surgeons independently rated the responses generated by the LLMs. Three senior orthopedic surgeons independently rated the answers based on responses ranging between 1 and 4 points. A total score (TS) > 9 indicated ‘good’ responses, 6 ≤ TS ≤ 9 indicated ‘moderate’ responses, and TS

Abstract With the rapid development of social networks, short videos have become a popular form of content, especially dance videos. In this context, research on automatically generating music for dance videos shows significant practical value. However, existing studies face challenges such as limited richness in music timbre and lack of synchronization with dance movements. In this paper, we propose Dance2Music-Diffusion, a novel framework for music generation from dance videos using latent diffusion models. Our approach includes a motion encoder module for extracting motion features and a music diffusion generation module for generating latent music representations. By integrating dance type monitoring and latent diffusion techniques, our framework outperforms existing methods in generating complex and rich dance music. We conducted objective and subjective evaluations of the results produced by various existing models on the AIST++ dataset. Our framework shows outstanding performance in terms of beat recall rate, consistency with GT beats, and coordination with dance movements. This work represents the state of the art in automatic music generation from dance videos, is easy to train, and has implications for enhancing entertainment experiences and inspiring innovative dance productions. Sample videos of our generated music and dance can be viewed at https://youtu.be/eCvLdLdkX-Y . The code is available at https://github.com/hellto/dance2music-diffusion .

Abstract To reveal the influence of the diversity of precursors on the formation of environmental persistent free radicals (EPFRs), pomelo peel (PP) and its physically divided portion, pomelo cuticle (PC), and white fiber (WF) were used as precursors to prepare six hydrochars: PPH-Fe, PCH-Fe, WFH-Fe, PPH, PCH, and WFH with and without Fe(III) addition during hydrothermal carbonization (HTC). PPH-Fe and WFH-Fe had higher EPFRs content (9.11 × 1018 and 8.25 × 1018 spins·g−1) compared to PPH and WFH (3.33 × 1018 and 2.96 × 1018 spins·g−1), indicating that iron-doping favored EPFRs formation. However, PCH-Fe had lower EPFRs content (2.78 × 1018 spins·g−1) than PCH (7.95 × 1018 spins·g−1), possibly due to excessive iron leading to the consumption of the generated EPFRs. For another reason, the required Fe(III) amount for EPFRs formation might vary among different precursors. PC has a lower concentration of phenolic compounds but 68–97% fatty acids, while WF and PP are rich in cellulose and lignin. In the Fenton-like reaction, oxygen-centered radicals of hydrochar played a significant role in activating H2O2 and efficiently degrading bisphenol A (BPA). Mechanisms of reactive oxygen species (ROS) generation in hydrochar/H2O2 system were proposed. EPFRs on hydrochar activate H2O2 via electron transfer, creating ·OH and 1O2, leading to BPA degradation. More importantly, the embedded EPFRs on the hydrochar's inner surface contributed to the prolonged Fenton-like reactivity of PPH-Fe stored for 45 days. This study demonstrates that by optimizing precursor selection and iron doping, hydrochars can be engineered to maximize their EPFRs content and reactivity, providing a cost-effective solution for the degradation of hazardous pollutants. Graphical abstract

ObjectiveDeveloping and validating a clinical prediction nomogram of 28-day mortality in critically ill patients with acute gastrointestinal injury (AGI).MethodsFirstly, the construction of a clinical prediction model was developed using data obtained from a prospective observational study from May 2023 to April 2024. Then, data from a prospective multicenter observational study conducted in the intensive care units of 12 teaching hospitals in 2014 were utilized to independently and externally validate the clinical prediction model developed in the first part. We first screened the covariates of the development cohort by univariate cox regression, and then carried out cox regression analysis on the development cohort by backward stepwise regression to determine the optimal fitting model. Subsequently, a nomogram was derived from this model.ResultsA total of 1102 and 379 patients, 28-day mortality occurred in 20.3% and 15.8% of patients respectively, were included in the development and validation cohort, respectively. We developed a nomogram in critically ill patients with AGI and the AGI grade, APACHE II score, Mechanical ventilation (MV), Feeding intolerance (FI) and daily calorie intake (DCI) in 72 h, were independent predictors of 28-day mortality, with the OR of the AGI grade was 1.910 (95% CI, 1.588–2.298; P < 0.001), the OR of APACHE II score was 1.099 (95% CI, 1.069–1.130; P < 0.001), the OR of MV was 1.880 (95% CI, 1.215–2.911; P = 0.005), the OR of FI was 3.453 (95% CI, 2.414–4.939; P < 0.001) and the DCI > 0.7 or < 0.5 of calorie target is associated with increased 28-day mortality, with OR of 1.566 (95% CI, 1.024–2.395; P = 0.039) and 1.769 (95% CI, 1.170–2.674; P = 0.007), respectively. Independent external validation of the prediction model was performed. This model has good discrimination and calibration. The DCA and CIC also validated the good clinical utility of the nomogram.ConclusionThe prediction of 28-day mortality can be conveniently facilitated by the nomogram that integrates AGI grade, APACHE II score, MV, FI and DCI in 72 h in critically ill patients with AGI.

The flower buds of Sophora japonica L. (FBSJ) have long been applied as Traditional Chinese Medicine (TCM) and functional food in East Asia. In this study, extracts of FBSJ from 11 different locations were analyzed using the HPLC method to establish their HPLC fingerprints. By determining the IC50 on tyrosinase activity, it was discovered that the extract from Kunming, Yunnan Province exhibited the strongest inhibitory activity. Further analysis, including partial least squares regression coefficient analysis and grey correlation analysis, regarded kaempferol, isorhamnetin, and quercetin as the compounds with significant tyrosinase inhibitory activities. To understand the inhibition mechanism of tyrosinase activity, various analytical techniques such as enzymatic kinetic analysis, fluorescence quenching, circular dichroism (CD), molecular docking, and molecular dynamics simulation were employed. The results revealed that quercetin, isorhamnetin, and kaempferol exhibited higher inhibitory activity and binding energy compared with kojic acid, indicating their potential value as natural tyrosinase inhibitors. This research provides a solid theoretical foundation for studying the application and mechanism of flavonoids against tyrosinase in FBSJ.

ABSTRACT Glaesserella parasuis is a commensal bacterial organism found in the upper respiratory tract of healthy pigs and the etiological agent of Glässer’s disease, which causes severe economic losses in the swine industry. This study aimed to better understand the epidemiological characteristics of this opportunistic pathogen. We investigated the prevalence and distribution of sequence types (STs), serovars, antimicrobial resistance genes (ARGs), and potential virulence factors (VFs) in 764 G. parasuis isolates collected from diseased and healthy pigs from 19 countries, including China. Multilocus sequence typing showed a high degree of variation with 334 STs, of which 93 were not previously recognized. Phylogenetic analysis revealed two major clades distinguished by isolation year, source, country, and serovar. The dominant serovars of G. parasuis were serovars 4 (19.50%), 7 (15.97%), 5/12 (13.87%), and 13 (12.30%). Serovar 7 gradually became one of the dominant serovars in G. parasuis with more VFs and fewer ARGs. Serovars 4 and 5/12 were the most frequent serovars in diseased pigs, whereas serovars 2, 8, and 11 were predominant in healthy pigs. Serovars 7 and 13 possessed more VFs than the other serovars. This study provides novel insights into the global prevalence and epidemiology of G. parasuis and valuable clues for further investigation into the pathogenicity of G. parasuis, which will facilitate the development of effective vaccines.IMPORTANCEGlaesserella parasuis is a clinically important gram-negative opportunistic pathogen, which causes serious financial losses in swine industry on a global scale. No vaccine is known that provides cross-protection against all 15 serovars; furthermore, the correlation between serovar and virulence is largely unknown. This study provides a large number of sequenced strains in 19 countries and compares the genomic diversity of G. parasuis between diseased and healthy pigs. We found a slight change in the dominant serovar of G. parasuis in the world, with serovar 7 gradually emerging as one of the predominant serovars. The observed higher average number of VFs in this particular serovar strain challenges the previously held notion that serovar 7 is non-virulent, indicating a more complex virulence landscape than previously understood. Our analysis indicating that six ARGs [tet(B), sul2, aph(3')-Ia, aph (6)-Id, blaROB-1, and aph(3'')-Ib] are likely to be transmitted horizontally in their entirety. By analyzing VFs, we provided an improved understanding of the virulence of G. parasuis, and these key findings suggest that vaccine development will be challenging.

Background: Osteoarthritis (OA) is a chronic and degenerative condition that persists and progresses over time. Sipeimine (Sip), a steroidal alkaloid derived from Fritillariae Cirrhosae Bulbus, has attracted considerable attention due to its exceptional anti-inflammatory, analgesic, antioxidant, and anti-cancer characteristics. However, Sip's effects on OA and its mechanism still need further research. Methods: This study utilized network pharmacology to identify initial targets for Sip. Functional associations of Sip in OA were clarified through Gene Ontology (GO) enrichment analysis, bioinformatically analyzing a list of targets. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis assessed pathways linked to Sip's therapeutic efficacy in OA. Molecular docking techniques explored Sip's binding affinity with key targets. In vitro experiments assessed Sip's impact on lipopolysaccharide (LPS)-induced pro-inflammatory factors and its protective effects on collagen-II and aggrecan degradation within the extracellular matrix (ECM). Western blotting and fluorescence analyses were conducted to determine Sip-mediated signaling pathways. Moreover, in vivo experiments using a mouse OA model validated Sip's therapeutic efficacy. Results: The results from network pharmacology revealed a total of 57 candidate targets for Sip in OA treatment. GO enrichment analysis demonstrated a robust correlation between Sip and inflammatory response, response to LPS and NF-κB-inducing kinase activity in OA. KEGG enrichment analysis highlighted the significance of NF-κB and PI3K-AKT pathways in Sip's therapeutic potential for OA. Furthermore, molecular docking results demonstrated Sip's robust binding affinity with p65 and PI3K. In vitro experiments demonstrated Sip's effectively suppressed the expression of pro-inflammatory factors induced by LPS, such as COX-2, iNOS, IL-1β, and IL-18. Besides, Sip counteracted the degradation of collagen-II and aggrecan within the ECM and the expression of MMP-13 and ADAMTS-5 mediated by LPS. The safeguarding effects of Sip were ascribed to its inhibition of PI3K/AKT/NF-κB pathway and NLRP3 inflammasome mediated pyroptosis. Additionally, in vivo experiments revealed that Sip could alleviate the subchondral remodeling, cartilage degeneration, synovitis as well as ECM degradation a mouse model of OA. Conclusion: Sip exhibited potential in attenuating OA progression by suppressing the PI3K/AKT/NF-κB pathway, consequently inhibiting the activation of NLRP3 inflammasome and pyroptosis. The translational potential statement: The translational potential of this articleThis study provides a biological rationale for the use of Sip as a potential candidate for OA treatment, provide a new concept for the cartilage targeted application of natural compounds.

Abstract Background Neovascular age-related macular degeneration (nAMD), accounts for up to 90% of AMD-associated vision loss, ultimately resulting in the formation of fibrotic scar in the macular region. The pathogenesis of subretinal fibrosis in nAMD involves the process of epithelial–mesenchymal transition (EMT) occurring in retinal pigment epithelium (RPE). Here, we aim to investigate the underlying mechanisms involved in the Wnt signaling during the EMT of RPE cells and in the pathological process of subretinal fibrosis secondary to nAMD. Methods In vivo, the induction of subretinal fibrosis was performed in male C57BL/6J mice through laser photocoagulation. Either FH535 (a β-catenin inhibitor) or Box5 (a Wnt5a inhibitor) was intravitreally administered on the same day or 14 days following laser induction. The RPE-Bruch's membrane-choriocapillaris complex (RBCC) tissues were collected and subjected to Western blot analysis and immunofluorescence to examine fibrovascular and Wnt-related markers. In vitro, transforming growth factor beta 1 (TGFβ1)-treated ARPE-19 cells were co-incubated with or without FH535, Foxy-5 (a Wnt5a-mimicking peptide), Box5, or Wnt5a shRNA, respectively. The changes in EMT- and Wnt-related signaling molecules, as well as cell functions were assessed using qRT-PCR, nuclear-cytoplasmic fractionation assay, Western blot, immunofluorescence, scratch assay or transwell migration assay. The cell viability of ARPE-19 cells was determined using Cell Counting Kit (CCK)-8. Results The in vivo analysis demonstrated Wnt5a/ROR1, but not Wnt3a, was upregulated in the RBCCs of the laser-induced CNV mice compared to the normal control group. Intravitreal injection of FH535 effectively reduced Wnt5a protein expression. Both FH535 and Box5 effectively attenuated subretinal fibrosis and EMT, as well as the activation of β-catenin in laser-induced CNV mice, as evidenced by the significant reduction in areas positive for fibronectin, alpha-smooth muscle actin (α-SMA), collagen I, and active β-catenin labeling. In vitro, Wnt5a/ROR1, active β-catenin, and some other Wnt signaling molecules were upregulated in the TGFβ1-induced EMT cell model using ARPE-19 cells. Co-treatment with FH535, Box5, or Wnt5a shRNA markedly suppressed the activation of Wnt5a, nuclear translocation of active β-catenin, as well as the EMT in TGFβ1-treated ARPE-19 cells. Conversely, treatment with Foxy-5 independently resulted in the activation of abovementioned molecules and subsequent induction of EMT in ARPE-19 cells. Conclusions Our study reveals a reciprocal activation between Wnt5a and β-catenin to mediate EMT as a pivotal driver of subretinal fibrosis in nAMD. This positive feedback loop provides valuable insights into potential therapeutic strategies to treat subretinal fibrosis in nAMD patients.

Motivated by the excellent detonation performance of octanitrocubane, prismane is another potential backbone with high strain energy in energetic molecule design. In this work, we aim to screen out candidates of highly energetic molecules from the space of prismane derivatives. The high-throughput computation (HTC) is performed based on 200 molecules derived from the molecule space of 1503 prismane derivatives with four substituents. Based on the calculated results, the machine learning (ML) models of density, detonation velocity, detonation pressure, heat of formation and detonation heat are established, and thereby the performances of the remaining 1303 samples are predicted. It is found that the –NHNO2 group increases density, while both –NO2 and –C(NO2)3 groups promote detonation performances. Based on the detonation velocity and bond dissociation energy as criteria representing energy and molecular stability, four molecules were screened out with good detonation performance and acceptable thermal stability. This work demonstrates the efficiency of HTC and ML combined strategy for screening high-quality energetic molecules.

BackgroundTo assess the bioequivalence between Gan & Lee (GL) glargine U300 and Toujeo® regarding pharmacokinetics (PK), pharmacodynamics (PD), and safety in Chinese healthy male participants.MethodsA single-center, randomized, double-blind, single-dose, two-preparation, two-sequence, four-cycle repeated crossover design study was performed to compare GL glargine U300 and Toujeo® in 40 healthy participants. The primary PK endpoints were the area under the curve of glargine metabolites, M1 concentration from 0 to 24 hours (AUC0-24h), and the maximum glargine concentration within 24 hours post-dose (Cmax). The primary PD endpoints were the area under the glucose infusion rate (GIR) curve from 0 to 24 hours (AUCGIR.0-24h) and the maximum GIR within 24 hours post-dose (GIRmax).ResultsGL Glargine U300 demonstrated comparable PK parameters (AUC0–24h, Cmax, AUC0–12h, and AUC12–24h of M1) and PD responses [AUCGIR.0–24h, GIRmax, AUCGIR.0–12h, and AUCGIR.12–24h] to those of Toujeo®, as indicated by 90% confidence intervals ranging from 80% to 125%. No significant disparities in safety profiles were observed between the two treatment groups, and there were no reported instances of serious adverse events.ConclusionThe PK, PD, and safety of GL glargine U300 were bioequivalent to that of Toujeo®.Clinical trial registrationhttps://www.chinadrugtrials.org.cn/, identifier CTR20212419.

Abstract Developing functional additive resistant to space atomic oxygen (AO) irradiation through simple molecular design and chemical synthesis to enhance the lubricating performance of multialkylated cyclopentanes (MACs) oil is a significant challenge. Herein, sulfur-containing polyhedral oligomere silsesquioxane (POSS) were synthesize via a click-chemistry reaction of octavinyl polyhedral oligomeric with alkyl sulfide. The reduce-friction (RF), anti-wear (AW) properties and anti-AO irradiation of POSS-S-R as MACs base oil additives in atmospheric and simulated space environments were systematically investigated for the first time. Results demonstrate that POSS-S-R not only possesses outstanding anti-AO irradiation capacity but also effectively improves the RF and AW of MACs in atmospheric or simulated space surroundings. This improvement is due to the excellent anti-AO irradiation properties of the POSS structure itself and the high load-carrying ability of silicon-containing and sulfur-containing compounds generated by tribo-chemical reactions, which effectively separates the direct contact of the friction interface. We believe that this synthesized POSS-S-R is a promising additive for space lubricants.

Abstract Background Supraclavicular nodal (SCL) irradiation is commonly used for patients with high-risk breast cancer after breast surgery. The Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) breast contouring atlases delineate the medial part of the SCL region, while excluding the posterolateral part. However, recent studies have found that a substantial proportion of SCL failures are located in the posterolateral SCL region, outside of the RTOG/ESTRO-defined SCL target volumes. Consequently, many radiation oncologists advocate for enlarging the SCL irradiation target volume to include both the medial and posterolateral SCL regions. Nevertheless, it remains uncertain whether adding the posterolateral SCL irradiation improves survival outcomes for high-risk breast cancer patients. Methods The SUCLANODE trial is an open-label, multicenter, randomized, phase 3 trial comparing the efficacy and adverse events of medial SCL irradiation (M-SCLI group) and medial plus posterolateral SCL irradiation (entire SCL irradiation, E-SCLI group) in high-risk breast cancer patients who underwent breast conserving-surgery or mastectomy. Patients with pathological N2-3b disease following initial surgery, or clinical stage III or pathological N1-3b if receiving neoadjuvant systemic therapy, are eligible and randomly assigned (1:1) to M-SCLI group and E-SCLI group. Stratification is by chemotherapy sequence (neoadjuvant vs. adjuvant), T stage (T3-4 vs. T1-2), N stage (N1-2 vs. N3), and ER status (positive vs. negative). Other radiation volumes are identical in the two arms, including breast/chest wall, undissected axillary lymph node, and internal mammary node. Advanced intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), or tomotherapy techniques are recommended. Both hypofractionated and conventional fractionation schedules are permitted. The primary end point is invasive disease-free survival, and secondary end points included overall survival, SCL recurrence, local-regional recurrence, distance recurrence, safety outcome, and patient-reported outcomes. The target sample size is 1650 participants. Discussion The results of the SUCLANODE trial will provide high-level evidence regarding whether adding posterolateral SCL irradiation to medial SCL target volume provides survival benefit in patients with high-risk breast cancer. Trial registration ClinicalTrials.gov Identifier: NCT05059379. Registered 28 September 2021, https://www.clinicaltrials.gov/ct2/show/NCT05059379 .

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common chronic liver diseases. Over time, there has been a significant increase in the prevalence of MASLD. It has become one of the leading causes of hepatocellular carcinoma (HCC) in the United States, France, and the United Kingdom. Globally, the incidence of HCC related to MASLD may further increase with the growing prevalence of obesity. Non-alcoholic steatohepatitis (NASH) is an important stage of MASLD, which is more likely to cause cirrhosis and even HCC. And patients with NASH cirrhosis have a much higher incidence of hepatocellular cancer than patients with non-cirrhotic MASLD. As a result, it is critical to investigate the targets of MASLD therapy in HCC. This article reviews therapeutic targets of MASLD, such as farnesoid X receptor (FXR), peroxisome proliferator activated receptor (PPAR), fibroblast growth factor-21 (FGF-21), etc., and introduces the drugs related to these targets and their mechanisms of action in HCC. In addition, the developmental process and pathogenesis of MASLD, as well as risk factors for HCC development, are discussed. These are of great significance for the prevention and treatment of HCC.

1,1-dinitro-2,2-diamino ethylene (FOX-7) is typically representative of low sensitivity and high energy compound. In this work, analogues of FOX-7 are screened using a combined method of high-throughput computation (HTC) and machine learning (ML). The molecules are generated with typical unsaturated hydrocarbons backbones and random combination of substituents -H, -NH2 and -NO2, then HTC is performed based on 200 sample molecules. ML models are established based on the HTC results, with detonation parameters predicted using the most accurate model of extreme gradient boosting (XGB). Finally, stability of the filtered high energy molecules are confirmed by quantum chemistry calculations, and besides FOX-7, 8 more energetic molecules with high energy as well as high stability (detonation velocity ≥ 8841.1 m/s, detonation pressure ≥ 34.6 GPa and stability parameter bond dissociation energy ≥ 201.7 kJ/mol) are achieved. This work has shown the efficiency of HTC and ML methods in searching new target molecules.

The purpose of this paper is to construct an evaluation system for AI painting software based on generative adversarial network (GAN) technology, which optimizes the performance of the related software in terms of functionality, ease of use, system performance, and safety. The results of the questionnaires are statistically analyzed. In addition, an exploratory factor analysis was conducted to extract the data of the study, which were ultimately used to calculate the weight and importance of each index using the fuzzy hierarchical analysis method. This study constructed an evaluation system for AI painting software based on GAN technology, including 16 indicators of functionality, 16 indicators of ease of use, 7 indicators of system performance, and 8 indicators of safety, respectively, whose alpha coefficients were 0.882, 0.962, 0.932, 0.932, and 0.932, respectively. In addition, the accumulated explanatory variances of their coefficients were 84.405%, 84.897%, 84.013%, 72.606%, 73.013%, and 72.606%, respectively. It is clear that the items included in each of the indicators are homogeneous, with a high degree of internal consistency. This paper suggests that the development of AI painting software focusing on functionality, ease of use, system performance, and safety can enhance the market competitiveness of the software.

ObjectiveThis study aims to compare gray matter volume changes in patients with chronic kidney disease (CKD) undergoing peritoneal dialysis (PD) and hemodialysis (HD) using voxel-based morphometry (VBM).MethodsA total of 27 PD patients, 25 HD patients, and 42 healthy controls were included. VBM analysis was performed, and cognitive function was assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment Scale (MoCA). The correlation between cognitive function and changes in brain gray matter volume was analyzed.ResultsBoth peritoneal dialysis and hemodialysis patients had partial gray matter volume reduction compared to the controls, but the affected brain regions were not uniform. The hemodialysis patients had greater volume reduction in certain brain regions than the PD patients. The MMSE and MoCA scores were positively correlated with gray matter volume changes.ConclusionDifferent dialysis modalities cause damage to specific areas of the brain, which can be detected using VBM. VBM, combined with cognitive function assessment, can help detect structural brain changes and cognitive impairment in patients with different dialysis modalities. The comprehensive application of VBM in the field of neurological function deserves further exploration.

Objective: To develop an algorithm using deep learning methods to calculate the volume of intraretinal and subretinal fluid in optical coherence tomography (OCT) images for assessing diabetic macular edema (DME) patients’ condition changes. Design: Cross-sectional study. Participants: Treatment-naive patients diagnosed with DME recruited from April 2020 to November 2021. Methods: The deep learning network, which was built for autonomous segmentation utilizing an encoder-decoder network based on the U-Net architecture, was used to calculate the volume of intraretinal fluid (IRF) and subretinal fluid (SRF). The alterations of retinal vessel density and thickness, and the correlation between best-corrected visual acuity (BCVA) and OCT parameters were analyzed. Results: 2,955 OCT images of fourteen eyes from DME patients with IRF and SRF who received anti-vascular endothelial growth factor (VEGF) agents were obtained. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the algorithm was 0.993 for IRF and 0.998 for SRF. The volumes of IRF and SRF were significantly decreased from 1.93 ± 0.58 /1.14 ± 0.25 mm3 (baseline) to 0.26 ± 0.13 /0.26 ± 0.18 mm3 (post-injection), respectively (p = 0.0170 for IRF, and p = 0.0004 for SRF). The Spearman correlation demonstrated that the reduction of IRF volume was negatively correlated with age (coefficient = −0.698, p = 0.006). Conclusion: We developed a deep learning assisted fluid volume calculation algorithm with high sensitivity and specificity for assessing the volume of IRF and SRF in DME patients. Key words: deep learning; diabetic macular edema; optical coherence tomography.

In this study, the effect of different amounts of molybdenum disulfide (MoS2) content on the microstructure and mechanical properties of Cu–10Al–4Ni–4.8Fe powder alloys was investigated. The results showed that the alloy initially consisted of KⅠ, KⅡ, KⅢ, and α phases without MoS2. However, when 2% MoS2 content was added, the lamellar Cu1.84Mo6S8 phase appeared in the alloy, and with increasing MoS2 content, the lamellar Cu1.84Mo6S8 phase and the number of pores increased. A gradual increase in the MoS2 content initially increased the sintered density, hardness, and yield strength of the alloy and then decreased. The sintered density and hardness reached their maximum values at 2% MoS2 content, while the yield strength reached its maximum value at 4% MoS2 content. With increasing MoS2 content, the friction coefficient fluctuated, while the wear loss decreased after first increasing. By applying the study results, the wear resistance of aluminum-bronze powder alloys can be improved to meet its rapidly growing industrial requirements.

Introducing an additive is a practical approach to improve the lubrication performance of base oil in the field of tribology. Herein, a series of sulfoximine derivatives was synthesized and incorporated into base oil A51 as additives. The tribological properties of these lubricants were evaluated at both room and high temperatures, and the result demonstrated that they displayed excellent friction reduction and wear resistance in the friction process under both test conditions. Moreover, the chemical composition of the worn scar surface was inspected using EDS, XPS and TOF-SIMS to explore the lubricating mechanism. It is reasonable to conclude that the synergistic interaction between the aromatic ring scaffolds and elements like N, F, and S facilitated the adsorption of lubricant on the steel block surfaces and forming a tribofilm during the friction process. This tribofilm has a dominant impact on the system’s lubrication performance. This research provides novel oil-soluble lubricant additives, offering a facile approach to formulating high-quality lubricants.

Potassium-ion batteries (PIBs) have been widely studied owing to the abundant reserves, widespread distribution, and easy extraction of potassium (K) resources. Molybdenum disulfide (MoS2) has received a great deal of attention as a key anode material for PIBs owing to its two-dimensional diffusion channels for K+ ions. However, due to its poor electronic conductivity and the huge influence of embedded K+ ions (with a large ionic radius of 3.6 Å) on MoS2 layer, MoS2 anodes exhibit a poor rate performance and easily collapsed structure. To address these issues, the common strategies are enlarging the interlayer spacing to reduce the mechanical strain and increasing the electronic conductivity by adding conductive agents. However, simultaneous implementation of the above strategies by simple methods is currently still a challenge. Herein, MoS2 anodes on reduced graphene oxide (MoS2/rGO) composite were prepared using one-step hydrothermal methods. Owing to the presence of rGO in the synthesis process, MoS2 possesses a unique scaled structure with large layer spacing, and the intrinsic conductivity of MoS2 is proved. As a result, MoS2/rGO composite anodes exhibit a larger rate performance and better cycle stability than that of anodes based on pure MoS2, and the direct mixtures of MoS2 and graphene oxide (MoS2-GO). This work suggests that the composite material of MoS2/rGO has infinite possibilities as a high-quality anode material for PIBs.

Abstract Leaf color mutants are important materials for studying chloroplast and photomorphogenesis, and can function as basic germplasms for genetic breeding. In an ethylmethanesulfonate mutagenesis population of watermelon cultivar “703”, a chlorophyll-deficient mutant with yellow leaf (Yl2) color was identified. The contents of chlorophyll a, chlorophyll b, and carotenoids in Yl2 leaves were lower than those in wild-type (WT) leaves. The chloroplast ultrastructure in the leaves revealed that the chloroplasts in Yl2 were degraded. The numbers of chloroplasts and thylakoids in the Yl2 mutant were lower, resulting in lower photosynthetic parameters. Transcriptomic analysis identified 1292 differentially expressed genes, including1002 upregulated and 290 downregulated genes. The genes involved in chlorophyll biosynthesis (HEMA, HEMD, CHL1, CHLM, and CAO) were significantly downregulated in the Yl2 mutant, which may explain why chlorophyll pigment content was lower than that in the WT. Chlorophyll metabolism genes such as PDS, ZDS and VDE, were upregulated, which form the xanthophyll cycle and may protect the yellow‒leaves plants from photodamage. Taken together, our findings provide insight into the molecular mechanisms of leading to leaf color formation and chloroplast development in watermelon.

Photo-induced decay may serve as a way to decompose energetic materials under some special conditions, and understanding the related mechanism is crucial to guide the determination of storage, transport and use conditions. In this work, we confirm the photo-induced intramolecular hydrogen transfer (HT) of 2,4,6-trinitrotoluene (TNT) by matrix-isolation infrared spectroscopy method; meanwhile, no backing of the H transferred isomer to the original TNT molecule is found when annealed and it exhibits an irreversible HT. With time-dependent density functional theory and state-averaged complete-active-space self-consistent-field calculations, we propose a photoisomerization path that occurs in the T1 state. This is because the H transferred isomer can readily back to the ground state (S0 state) by means of intersystem crossing (T1/S0), with a rather high energy barrier required to overcome for the reverse reaction to the original TNT molecule. Thereby, the irreversible HT when annealed is understandable.

Abstract Background Both Kinesio Tape (KT) and Compression Sleeves (CS) can relieve Delayed Onset Muscle Soreness (DOMS) to a certain extent, but there is no study report on the difference in the effectiveness of the KT and CS whether the effect is better when used at the same time. The purpose of this study was to compare the effects of KT and CS on the recovery of muscle soreness, isokinetic strength, and body fatigue after DOMS. Methods In this single-blinded randomized controlled trial, 32 participants aged 18 to 24 years were randomly divided into Control group (CG), Compression Sleeves group (CSG), Kinesio Tape group (KTG), Compression Sleeves and Kinesio Tape group (CSKTG), between October 2021 and January 2022. KTG uses Kinesio Tape, CSG wears Compression Sleeves, and CSKTG uses both Compression Sleeves and Kinesio Tape. Outcomes were performed at five-time points (baseline, 0 h, 24 h, 48 h, 72 h), Primary outcome was pain level Visual Analogue Scale (VAS), and Secondary outcomes were Interleukin 6, Peak Torque/Body Weight, Work Fatigue. Statistical analyses were performed using the repeated measures analysis of variance method. Setting: Laboratory. Results After the intervention, VAS reached the highest at 24 h after exercise-induced muscle soreness, while the KTG and CSG at each time point were less than CG, and the scores of CSKTG at 24 h and 48 h were less than those of KTG and CSG in the same period (P

Irritable Bowel Syndrome (IBS) is a complex functional gastrointestinal disorder primarily characterized by chronic abdominal pain, bloating, and altered bowel habits. Chronic abdominal pain caused by visceral Hypersensitivity (VH) is the main reason why patients with IBS seek medication. Significant research effort has been devoted to the efficacy of acupuncture as a non-drug alternative therapy for visceral-hyperalgesia-induced IBS. Herein, we examined the central and peripheral analgesic mechanisms of acupuncture in IBS treatment. Acupuncture can improve inflammation and relieve pain by reducing 5-hydroxytryptamine and 5-HT3A receptor expression and increasing 5-HT4 receptor expression in peripheral intestinal sensory endings. Moreover, acupuncture can also activate the transient receptor potential vanillin 1 channel, block the activity of intestinal glial cells, and reduce the secretion of local pain-related neurotransmitters, thereby weakening peripheral sensitization. Moreover, by inhibiting the activation of N-methyl-D-aspartate receptor ion channels in the dorsal horn of the spinal cord and anterior cingulate cortex or releasing opioids, acupuncture can block excessive stimulation of abnormal pain signals in the brain and spinal cord. It can also stimulate glial cells (through the P2X7 and prokinetic protein pathways) to block VH pain perception and cognition. Furthermore, acupuncture can regulate the emotional components of IBS by targeting hypothalamic-pituitary-adrenal axis-related hormones and neurotransmitters via relevant brain nuclei, hence improving the IBS-induced VH response. These findings provide a scientific basis for acupuncture as an effective clinical adjuvant therapy for IBS pain.

Age-related macular degeneration (AMD) is a leading cause of vision loss among elderly people in developed countries. Neovascular AMD (nAMD) accounts for more than 90% of AMD-related vision loss. At present, intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is widely used as the first-line therapy to decrease the choroidal and retinal neovascularizations, and thus to improve or maintain the visual acuity of the patients with nAMD. However, about 1/3 patients still progress to irreversible visual impairment due to subretinal fibrosis even with adequate anti-VEGF treatment. Extensive literatures support the critical role of epithelial-mesenchymal transformation (EMT) of retinal pigment epithelium (RPE) in the pathogenesis of subretinal fibrosis in nAMD, but the underlying mechanisms still remain largely unknown. This review summarized the molecular pathogenesis of subretinal fibrosis in nAMD, especially focusing on the transforming growth factor-β (TGF-β)-induced EMT pathways. It was also discussed how these pathways crosstalk and respond to signals from the microenvironment to mediate EMT and contribute to the progression of nAMD-related subretinal fibrosis. Targeting EMT signaling pathways might provide a promising and effective therapeutic strategy to treat subretinal fibrosis secondary to nAMD.

The high spatial-temporal variability of soil moisture necessitates monitoring at a high resolution in order to improve our understanding of Earth system processes. Current large-scale soil moistures inferred from the microwave satellites have limited spatial resolution, typically in the range of tens of kilometers. Recent studies have revealed that synthetic aperture radar (SAR) backscatter exhibits qualitative relationships with soil moisture, suggesting the potential for large-scale high-resolution mapping of soil moisture. Here, we proposed a method for directly estimating soil moisture content based on the advanced integral equation model and Mironov dielectric model. The approach involves establishing a series of semiempirical models, independent of preceding surface roughness determination, using two Envisat advanced synthetic aperture radar (ASAR) alternating polarization (AP) model precision products. We generate a time series of high-resolution soil moisture using Envisat ASAR AP data acquired from 2004 to 2011, with an uncertainty of approximately 0.05 m3/m3. Our soil moisture retrievals demonstrate very good agreement with European Space Agency Climate Change Initiative soil moisture products and the European Centre for Medium-Range Weather Forecasts ERA5 reanalysis hourly products, even in the absence of synchronous ground measurements. Furthermore, our study reveals good temporal coherence between drought and heavy rainfall events, and SAR-derived soil moisture, which suggests a potential to capture heavy rainfall and drought events. We conclude that SAR-derived soil moisture is a more direct and efficient method in quantifying soil moisture at a high spatial resolution, making it more suitable for watershed scale hydrological studies.

Abstract Autophagy dysfunction is one of the common causes of tumor formation and plays an important role in uveal melanoma (UM). However, little is known about the regulatory mechanisms of autophagy in UM. Here, we show that PTK6 can promote the proliferation, migration, and invasion of UM cells by inhibiting autophagy. SOCS3 can inhibit the proliferation, migration, and invasion of UM cells. Overexpression of SOCS3 can partially rescue the PTK6-induced promotion of UM cell proliferation, migration, and invasion. Mechanistically, PTK6 can bind to SOCS3, and SOCS3 can downregulate the expression of PTK6. Furthermore, PTK6 can upregulate the phosphorylation of mTOR to inhibit autophagy. Taken together, our findings demonstrate the functions of PTK6 and SOCS3 in UM cells and targeting the SOCS3-PTK6 signaling axis might be a novel and promising therapeutic strategy for patients with UM.

Abstract Background Maintaining osmotic equilibrium plays an important role in the survival of cold-water fishes. Heat stress has been proven to reduce the activity of Na+/K+-ATPase in the gill tissue, leading to destruction of the osmotic equilibrium. However, the mechanism of megatemperature affecting gill osmoregulation has not been fully elucidated. Results In this study, Siberian sturgeon (Acipenser baerii) was used to analyze histopathological change, plasma ion level, and transcriptome of gill tissue subjected to 20℃, 24℃and 28℃. The results showed that ROS level and damage were increased in gill tissue with the increasing of heat stress temperature. Plasma Cl− level at 28℃ was distinctly lower than that at 20℃ and 24℃, while no significant difference was found in Na+ and K+ ion levels among different groups. Transcriptome analysis displayed that osmoregulation-, DNA-repair- and apoptosis-related terms or pathways were enriched in GO and KEGG analysis. Moreover, 194 osmoregulation-related genes were identified. Amongst, the expression of genes limiting ion outflow, occluding (OCLN), and ion absorption, solute carrier family 4, member 2 (AE2) solute carrier family 9, member 3 (NHE3) chloride channel 2 (CLC-2) were increased, while Na+/K+-ATPase alpha (NKA-a) expression was decreased after heat stress. Conclusions This study reveals for the first time that the effect of heat stress on damage and osmotic regulation in gill tissue of cold-water fishes. Heat stress increases the permeability of fish’s gill tissue, and induces the gill tissue to keep ion balance through active ion absorption and passive ion outflow. Our study will contribute to research of global-warming-caused effects on cold-water fishes.

In recent years, AMPK channel has gained considerable attention in a variety of research areas, and several academic journals have published articles on AMPK research. However, few attempts have been made to thoroughly assess the scientific output and current status systematically in this topic from a worldwide viewpoint. As a result, it is critical to adopt an appropriate visualization method to reveal the global status, future research trends, and hotspots in AMPK channel research. To investigate research hotspots/frontiers in certain domains, bibliometric analysis has been frequently utilized to determine the productivity of nations, institutions, authors, and the frequency of keywords. In this work, we used CiteSpace and VOSviewer to conduct a bibliometric analysis of AMPK channel studies from 2012 to 2021 in order to perform researchers with some directions for AMPK channel research.

Pumpkin (Cucurbita moschata) has been widely used as cucumber (Cucumis sativus L.) rootstock to defend against Fusarium wilt (FW) and increase cucumber yields and profits. However, the resistance genes and mechanisms underlying the FW tolerance in pumpkin are poorly understood. Here we analyzed the transcriptome of pumpkin inoculated with the cucumber FW causal agent Fusarium oxysporum f. sp. cucumerinum (Foc), and obtained 3 152 and 4 735 upregulated genes induced by Foc at 24 h after Foc inoculation compared with at 0 h and 24 h non-inoculated control, respectively. Next, 404 common differentially expressed genes (DEGs) were screened using the criterion log2 FPKM (fold change) ≥ 2. In total, 206 of 404 DEGs were predominantly expressed in roots, which is the first tissue that Foc contacts and invades. 140 DEGs were selected and classified into four groups (pathogenesis resistance, secondary metabolism-related, transcription factor and signal binding) based on their functional descriptions. Then, 29 genes having high expression levels were selected to investigate the expression patterns induced by a Foc inoculation. Among them, 16 genes were significantly induced by Foc and showed high expression levels at various treatment time points. These candidate genes may act as positive regulators of FW resistance in pumpkin and provide effective resources for improving cucumber FW resistance through breeding programs.

With increasing requirements for environmental protection and energy conservation, Al–Cu powder alloys play an important role in machine weight reduction. During the preparation of the Al–Cu powder alloy, an appropriate sintering temperature helps improve the comprehensive performance of the alloys. In this study, powder metallurgy was used to prepare Al–7.5Cu–1Si alloys, and the effects of different sintering temperatures on their relative sintering density, hardness, and tensile strength were studied. The microstructure and phase composition of the alloy were observed and analyzed by scanning electron microscopy and x-ray diffraction, and the mechanical properties of the alloy were studied using a Brinell hardness tester and a universal material testing machine. By analyzing the microstructural changes of the alloys at different sintering temperatures, the optimal sintering temperature of the alloy was determined to obtain the best properties. The results demonstrated that the sintering temperature significantly affected the diffusion and migration of the metal particles inside the alloy. When the temperature was low, numerous pores were present in the alloy, and the degree of bonding between the metal particles was poor. As the temperature increased, the number of pores in the alloy decreased, and good metallurgical bonding occurred between the particles. The relative densities and mechanical properties of the alloys were significantly affected by the sintering temperature. When the temperature was below 570 °C, the relative density and mechanical properties were low. At 590 °C, the alloy underwent deformation and was in an over-sintered state. The best sintering temperature was 570 °C. This is because at this temperature, the relative sintering density, hardness, and tensile strength of the alloy all reached maximum values, which were 98.6%, 71 HB, and 153 MPa, respectively.

Chronic heat stress caused by global warming can have serious implications for fish survival. The kidney plays a central role in many homeostatic functions, including water and electrolyte regulation. However, there is limited knowledge about the effect of heat stress on fish kidneys. In this study, water temperatures were increased from 20 °C to 24 °C and 28 °C in 8 days at a warming rate of 1 °C/d, and then maintained for 12 days. We investigated the effects of mild heat stress (24 °C) and high heat stress (28 °C) on Siberian Sturgeon (Acipenser baerii) kidneys using histological observation, flow cytometry detection, and RT-qPCR. Our histological observations revealed that heat stress caused significant infiltration of inflammatory cells in the kidney, especially at 28 °C. The flow cytometry assay demonstrated a significant increase in the number of apoptotic cells after heat stress at 28 °C compared to a control group at 20 °C (p = 0.033). The level of plasma creatinine was significantly increased in the 28 °C group compared to the control group (p = 0.001). In addition, the mRNA expression levels of heat shock protein GRP75 increased (p = 0.009). The results indicate that heat stress at 28 °C caused damage to the kidneys of A. baerii and triggered the protective response of heat shock proteins. In conclusion, this study contributes to the understanding of the coping strategies of the kidney of A. baerii for chronic heat stress.

Abstract A new type of lubricating material (BTA-P4444-Lig) was synthesized by combining lignin with tetrabutylphosphorus and benzotriazole. The tribological properties, corrosion resistance, and anti-oxidation properties of BTA-P4444-Lig as a lubricant were investigated. The lubricating material exhibits excellent friction reduction and wear resistance, as well as good thermal stability and excellent oxidation resistance. Mechanistic analysis reveals that the active elements N and P in the lubricating material react with the metal substrate, and the reaction film effectively blocks direct contact between the friction pairs, affording excellent friction reduction and wear resistance. At the same time, the phenolic hydroxyl group in lignin reacts with oxygen free radicals to form a resonance-stable semi-quinone free radical, which interrupts the chain reaction and affords good anti-oxidant activity.

The addition of active metallic particles to common explosives can greatly extend high-temperature and high-pressure time of explosion, as the so-called thermobaric effect. However, the atomic details for this effect remain unclear. This work presents an atomic insight into the thermobaric explosion including anaerobic and aerobic stages by molecular dynamics simulations with a thermobaric explosive (TBX) model consisting of Al@Al2O3 nanoparticle and RDX. It is found that the thermobaric effect is originated from the Al oxidation by the intermediates and products of the RDX decomposition in the first anaerobic stage with a lot of Al-O, Al-H, Al-C and Al-N bonds formed, and the further oxidation by O2 in the aerobic stage with many C, H and N atoms extruded from the Al clusters. Interestingly, in terms of the components and structures of the final products, as well as the total heat release, the whole thermobaric explosion of the RDX-Al system can be regarded as the sum of the RDX decomposition and the Al oxidation in O2. Thereby, the energy design of a TBX can be simplified by considering the sum of the decomposition heat of the energetic compound involved and the combustion heat of the active metal. Regarding RDX, it plays a role in forming a high temperature and high pressure environment to promote the dispersion and combustion of Al particles. This work presents the atomic details responsible for the thermobaric effect and it is expected to pave a way to understand this effect.

BackgroundGrowing evidence suggests that gait training can improve stroke patients’ balance outcomes. However, it remains unclear which type of gait training is more effective in improving certain types of balance outcomes in patients with stroke. Thus, this network meta-analysis (NMA) included six types of gait training (treadmill, body-weight-supported treadmill, virtual reality gait training, robotic-assisted gait training, overground walking training, and conventional gait training) and four types of balance outcomes (static steady-state balance, dynamic steady-state balance, proactive balance, and balance test batteries), aiming to compare the efficacy of different gait training on specific types of balance outcomes in stroke patients and determine the most effective gait training.MethodWe searched PubMed, Embase, Medline, Web of Science, and Cochrane Library databases from inception until 25 April 2022. Randomized controlled trials (RCTs) of gait training for the treatment of balance outcomes after stroke were included. RoB2 was used to assess the risk of bias in the included studies. Frequentist random-effects network meta-analysis (NMA) was used to evaluate the effect of gait training on four categories of balance outcomes.ResultA total of 61 RCTs from 2,551 citations, encompassing 2,328 stroke patients, were included in this study. Pooled results showed that body-weight-support treadmill (SMD = 0.30, 95% CI [0.01, 0.58]) and treadmill (SMD = 0.25, 95% CI [0.00, 0.49]) could improve the dynamic steady-state balance. Virtual reality gait training (SMD = 0.41, 95% CI [0.10, 0.71]) and body-weight-supported treadmill (SMD = 0.41, 95% CI [0.02, 0.80]) demonstrated better effects in improving balance test batteries. However, none of included gait training showed a significant effect on static steady-state balance and proactive balance.ConclusionGait training is an effective treatment for improving stroke patients’ dynamic steady-state balance and balance test batteries. However, gait training had no significant effect on static steady-state balance and proactive balance. To achieve maximum efficacy, clinicians should consider this evidence when recommending rehabilitation training to stroke patients. Considering body-weight-supported treadmill is not common for chronic stroke patients in clinical practice, the treadmill is recommended for those who want to improve dynamic steady-state balance, and virtual reality gait training is recommended for those who want to improve balance test batteries.LimitationMissing evidence in relation to some types of gait training is supposed to be taken into consideration. Moreover, we fail to assess reactive balance in this NMA since few included trials reported this outcome.Systematic Review RegistrationPROSPERO, identifier CRD42022349965.

One common problem in omics data analysis is missing values, which can arise due to various reasons, such as poor tissue quality and insufficient sample volumes. Instead of discarding missing values and related data, imputation approaches offer an alternative means of handling missing data. However, the imputation of missing omics data is a non-trivial task. Difficulties mainly come from high dimensionality, non-linear or non-monotonic relationships within features, technical variations introduced by sampling methods, sample heterogeneity, and the non-random missingness mechanism. Several advanced imputation methods, including deep learning-based methods, have been proposed to address these challenges. Due to its capability of modeling complex patterns and relationships in large and high-dimensional datasets, many researchers have adopted deep learning models to impute missing omics data. This review provides a comprehensive overview of the currently available deep learning-based methods for omics imputation from the perspective of deep generative model architectures such as autoencoder, variational autoencoder, generative adversarial networks, and Transformer, with an emphasis on multi-omics data imputation. In addition, this review also discusses the opportunities that deep learning brings and the challenges that it might face in this field.

Antimicrobial resistance is undoubtedly one of the greatest global health threats. The emergence of multidrug-resistant (MDR) Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), and β-lactamase-resistant Streptococcus pneumonia, has severely limited our antibiotic arsenal. Numerous ribosome-targeting antibiotics, especially pleuromutilins, oxazolidinones, and streptogramins, are viewed as promising alternatives against aggressive MDR pathogens. In this study, we identified a new adenosine triphosphate (ATP)-binding cassete (ABC)-F family determinant, srpA, in Streptococcus suis (S. suis) by means of a comparative analysis of the whole-genome sequences of tiamulin (TIA)-resistant and TIA-sensitive bacteria. Functional cloning confirmed that the deduced gene can mediate cross-resistance to pleuromutilins, lincosamides, and streptogramin A in S. suis and S. aureus. A sequence alignment revealed that SrpA shares the highest amino acid identity with Vga(E) (36%) and shows canonical characteristics of ABC-F family members. In SrpA-ribosome docked compounds, the extended loop region of SrpA approaches the valnemulin-binding pocket in the ribosome peptidyl-transferase center and competes with bound valnemulin. A detailed mutational analysis of the loop residues confirmed that this domain is crucial for SrpA activity, as substitutions or truncations of this region affect the efficiency and specificity of antibiotic resistance. Intracellular antibiotics accumulation indicated that SrpA does not act as an efflux pump, while a ribosome binding assay supported the protective effects of SrpA on the ribosome by preventing antibiotic binding as well as displacing bound drugs. These findings clarify the mechanisms underlying resistance to ribosomal antibiotics.

Abstract Background Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. Results To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when > 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30×. Conclusions Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS.

This study systematically investigated the causal relationship between gastroesophageal reflux disease (GERD) and major depression (MD). Single-nucleotide polymorphisms (SNPs) associated with disorders of interest were screened via the genome-wide association study (GWAS) enrolling individuals of European descent. Summary-level data for GERD and MD were extracted from the UK Biobank. The inverse-variance-weighted (IVW) method was utilized as the primary analysis. Sensitivity analyses were performed using the MR-Egger method, the Maximum likelihood method, the MR-pleiotropy residual sum outlier (MR-PRESSO) method, and MR-robust adjusted profile score (MR-RAPS) method. MR-Egger regression, heterogeneity tests, pleiotropy tests, and leave-one-out tests were also performed to analyze sensitivity. The MR Steiger test was used to verify the directionality of the exposure to the outcome. An available website tool (https://shiny.cnsgenomics.com/mRnd/) was used to calculate the statistical power of MR analysis. Meta-analysis was applied to test MD's average genetically predicted effect on GERD. Our MR study showed a bidirectional causal association between MD and GERD. Regarding MD to GERD, there was a positive association between them; the ORs were 1.500 (95% CI = 1.320-1.704; P = 4.91E-10) and 2.058 (95% CI = 1.868-2.267; P = 2.20E-48) in the IVW method, respectively. In addition, the meta-analysis also showed a strong positive causal association between MD and GERD. When exposure and outcome were reversed, genetic predisposition to GERD was significantly associated with the overall Risk of advanced MD (ieu-a-1187, OR = 1.982, 95% CI = 1.694-2.319, P = 1.41E-17; ieu-b-102, OR = 1.612, 95% CI = 1.530-2.700, P = 1.15E-70). Our study provides 100% power to detect the causal effect of MD on GERD and vice versa. Genetically predicted MD was positively associated with higher GERD risk, and vice versa. Our study reminds clinicians to pay attention to screening for GERD when diagnosing and treating MD and vice versa. Moreover, there may be positive feedback between MD and GERD when treating and preventing one disorder may benefit the treatment and prevention of the other.

PurposeIn individuals with chronic kidney disease (CKD), neurological damage is commonly observed. This neurodegeneration is closely linked to microstructural damage to the brain white matter due to the high incidence of cognitive dysfunction. However, the specific pathogenesis of CKD nephropathy caused by cognitive system developmental disorders remains unclear. This study aimed to examine the correlation between cognitive impairment and diffusion parameters obtained on diffusion tensor imaging (DTI) of abnormal white matter tracts in CKD patients.MethodsSixty-four patients with CKD were divided into the non-dialysis-dependent CKD (NDD-CKD) group (N = 26) and dialysis-dependent CKD (DD-CKD) group (N = 38) according to the estimated glomerular filtration rate, whereas 43 healthy control subjects (normal control [NC]) were included and underwent cranial magnetic resonance imaging during the same period. Differences in the abnormal white matter microstructure and correlations between them and cognitive scores were assessed using several parameters between the groups.ResultsThere were more extensive peri-lesions and distant white matter microstructural changes in the DD-CKD and NDD-CKD groups than in the NC group. DTI diffusion parameters in abnormal white matter regions were associated with impaired cognitive function in CKD patients. The DD-CKD group had worse cognitive function and more severe microstructural damage in the cerebral white matter than the NDD-CKD group.ConclusionCKD patients showed cognitive impairment and changes in the brain white matter microstructure; CKD can lead to extensive white matter tract damage. Additionally, diffusion parameters can be used as a complement to describe structural brain damage in CKD patients.

One novel catfish (Chinese called it ‘Gou nian’) widely cultured in China shares the same name with Ictalurus punctatus introduced from America, but is morphologically closed to genus Silurus. For years, the novel catfish was speculated to be an artificial hybrid of S. asotus and S. meridionalis. Therefore, we investigated the correct taxonomic status and origin of the novel catfish by means of morphological and molecular approaches. First, the novel ‘Gou nian’ could not be distinguished from S. asotus and S. meridionalis through anatomical observation, however, it was morphologically similar to S. asotus. Then, the novel ‘Gou nian’ was found not a hybrid of S. asotus and S. meridionalis based on the identification of ITS-2 and RAG-2, moreover, the analysis of COI barcoding found it more likely to be S. asotus. The phylogenic and population genetic analysis of Cyt b showed that the novel ‘Gou nian’ belonged to a taxonomic branch of S. asotus from the Liao River. The results convincingly indicated that the novel catfish is S. asotus and may originate from Northern China. The findings also provided useful implications for aquaculture management of the species.

Heat resistance is a basic and crucial characteristic of energetic materials (EMs), and always accounted in development and application. Compared with the clear origin of the high heat resistance of EMs, the mechanism for the low heat resistance remains still unclear. This work reveals the mechanism by carrying reactive molecular dynamics simulations on heating six less thermally stable EMs of nitroforms and pentaerythritol tetranitrate (PETN), as well as a more thermally stable EM of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) for comparison. Unexceptionally, all the nitroforms and PETN heated feature fast NO2 partition and further decomposition throng the oxidation of NO2 to form small fragments and final small stable product molecules, with fast heat release; while, the intermolecular reactions and the further clustering govern the initial steps in decomposing TATB. Therein the reactants also exhibit a rapid consumption; however, this fast consumption with clustering does not result in the low heat resistance of TATB. That is, some general indicators representative of thermostability, such as bond dissociation energy and the reactant consumption rate, are insufficient to assess it practically. Thus, the rapid fragmentation originally contributes to the low heat resistance. These insights are expected to present an overall perspective of understanding the thermal stability mechanism of EMs, and set a theoretical base and pave a way for designing EMs with desired heat resistance.

Association studies have linked alterations of blood‐derived microRNAs (miRNAs) with colorectal cancer (CRC). Here, we performed a microarray‐based comparison of the profiles of 2549 miRNAs in 80 blood samples from healthy donors and patients with colorectal adenomas, colorectal diverticulitis and CRC at different stages. Confirmation by quantitative real‐time PCR (RT‐PCR) was complemented by validation of identified molecules in another 36 blood samples. No variations in miRNA levels were observed in samples from patients with colorectal adenomas and diverticulitis or from healthy donors. However, there were 179 CRC‐associated miRNAs of differential abundance compared to healthy controls. Only three – miR‐1225‐5p, miR‐1207‐5p and miR‐4459 – exhibited increased levels at all CRC stages. Most deregulated miRNAs (128/179, 71%) specifically predicted metastatic CRC. Pathway analysis found several cancer‐related pathways to which the miRNAs contribute in various ways. In conclusion, miRNA levels in blood vary throughout CRC progression and affect cellular functions relevant to haematogenous CRC progression and dissemination. The identified biomarker and therapeutic candidates require further confirmation of their clinical relevance.

Abstract Background Stroke is the leading cause of death worldwide. China faces a similar risk of stroke as developed countries because of considerable changes in lifestyle, such as overeating and smoking. Tai Chi is a traditional form of mind-body exercise that has been widely practiced in China for thousands of years. However, there are few studies on the effect of Tai Chi on the cardiopulmonary function of stroke patients in the recovery phase. Therefore, it is necessary to observe the effect of Tai Chi on the cardiorespiratory fitness of patients after stroke. Methods This is a parallel-design, two-arm, analyst assessor-blinded, randomized controlled trial. A total of 226 stroke patients in the recovery phase will be recruited and assigned randomly to a control group or Tai Chi group at a 1:1 ratio. The patients in the Tai Chi group will perform the Tai Chi exercise. The patients in the control group will perform walking exercises. Patients in both groups will receive conventional treatments and healthy education. The primary outcomes will be VO2peak and scores on the MOS item short form health survey (SF-36) scale. Secondary outcomes will include vital capacity (VC), ejection fractions (EF), and cardiac output (CO). The assessments of the tests will be performed at three time points (before exercise, at the end of exercise, and 6 weeks after exercise). Adverse events will be recorded faithfully during the study. Discussion If the results are positive, this study will contribute to the establishment of further guided Tai Chi rehabilitation programs. Trial registration Chinese Clinical Trial Registry ChiCTR2000034719 . Registered on 16 July 2020.

PurposeThe study characterizes regional homogeneity (ReHo) and amplitude of low frequency fluctuations (ALFF) in abnormal regions of brain in patients of chronic kidney disease (CKD).Materials and methodsA total of 64 patients of CKD were divided into 26 cases of non-dialysis-dependent chronic kidney disease (NDD-CKD), and 38 cases of dialysis-dependent chronic kidney disease (DD-CKD). A total of 43 healthy controls (normal control, NC) were also included. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI). ALFF and ReHo data was processed for monitoring the differences in spontaneous brain activity between the three groups. ALFF and ReHo values of extracted differential brain regions were correlated to the clinical data and cognitive scores of CKD patients.ResultsNon-dialysis-dependent group has increased ALFF levels in 13 brain regions while that of DD group in 28 brain regions as compared with NC group. ReHo values are altered in six brain regions of DD group. ALFF is correlated with urea nitrogen and ReHo with urea nitrogen and creatinine. DD group has altered ReHo in two brain regions compared with NDD group. The differences are located in basal ganglia, cerebellar, and hippocampus regions.ConclusionAbnormal activity in basal ganglia, cerebellar, and hippocampal regions may be involved in the cognitive decline of CKD patients. This link can provide theoretical basis for understanding the cognitive decline.

Genotype imputation has a wide range of applications in genome-wide association study (GWAS), including increasing the statistical power of association tests, discovering trait-associated loci in meta-analyses, and prioritizing causal variants with fine-mapping. In recent years, deep learning (DL) based methods, such as sparse convolutional denoising autoencoder (SCDA), have been developed for genotype imputation. However, it remains a challenging task to optimize the learning process in DL-based methods to achieve high imputation accuracy. To address this challenge, we have developed a convolutional autoencoder (AE) model for genotype imputation and implemented a customized training loop by modifying the training process with a single batch loss rather than the average loss over batches. This modified AE imputation model was evaluated using a yeast dataset, the human leukocyte antigen (HLA) data from the 1,000 Genomes Project (1KGP), and our in-house genotype data from the Louisiana Osteoporosis Study (LOS). Our modified AE imputation model has achieved comparable or better performance than the existing SCDA model in terms of evaluation metrics such as the concordance rate (CR), the Hellinger score, the scaled Euclidean norm (SEN) score, and the imputation quality score (IQS) in all three datasets. Taking the imputation results from the HLA data as an example, the AE model achieved an average CR of 0.9468 and 0.9459, Hellinger score of 0.9765 and 0.9518, SEN score of 0.9977 and 0.9953, and IQS of 0.9515 and 0.9044 at missing ratios of 10% and 20%, respectively. As for the results of LOS data, it achieved an average CR of 0.9005, Hellinger score of 0.9384, SEN score of 0.9940, and IQS of 0.8681 at the missing ratio of 20%. In summary, our proposed method for genotype imputation has a great potential to increase the statistical power of GWAS and improve downstream post-GWAS analyses.

The leakage of the injection–production string is one of the important hidden dangers for the safe and efficient operation of underground salt cavern gas storage. Although distributed fiber optic temperature measurement system (DTS) can accurately locate the position of the string leakage port, how to establish the quantitative relationship between the temperature difference and leakage rate of the leakage port still needs further exploration. This paper proposes a new quantitative prediction model based on a DTS for the leakage monitoring of the injection–production string of salt cavern gas storage. The model takes into account the gas’s physical parameters, unstable temperature conditions, and the Joule–Thomson effect. In order to verify the accuracy of the model, a simulation experiment of string leakage based on a DTS was carried out. The test results show that the relative deviation between the predicted leakage rate and the measured value is less than 5% compared with the calculated value. When the leakage rate drops to 0.16 m3/h and the temperature range is less than 0.5 °C, it is difficult to accurately monitor the DTS. The results of this study help to improve the early warning time of underground salt cavern gas storage string leakage.

Large-scale mortality due to Aeromonas hydrophila (A. hydrophila) infection has considerably decreased the yield of the Chinese pond turtle (Mauremys reevesii). Purslane is a naturally active substance with a wide range of pharmacological functions, but its antibacterial effect on Chinese pond turtles infected by A. hydrophila infection is still unknown. In this study, we investigated the effect of purslane on intestinal morphology, digestion activity, and microbiome of Chinese pond turtles during A. hydrophila infection. The results showed that purslane promoted epidermal neogenesis of the limbs and increased the survival and feeding rates of Chinese pond turtles during A. hydrophila infection. Histopathological observation and enzyme activity assay indicated that purslane improved the intestinal morphology and digestive enzyme (α-amylase, lipase and pepsin) activities of Chinese pond turtle during A. hydrophila infection. Microbiome analysis revealed that purslane increased the diversity of intestinal microbiota with a significant decrease in the proportion of potentially pathogenic bacteria (such as Citrobacter freundii, Eimeria praecox, and Salmonella enterica) and an increase in the abundance of probiotics (such as uncultured Lactobacillus). In conclusion, our study uncovers that purslane improves intestinal health to protect Chinese pond turtles against A. hydrophila infection.