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Abstract Objective To evaluate the prognostic importance of sex in lupus nephritis (LN). Methods A retrospective cohort of 1048 biopsy-confirmed LN patients, diagnosed between January 1, 1996, and December 31, 2018, was analyzed. Demographics, clinical characteristics, laboratory findings, and renal pathology were assessed. The primary outcome was mortality, and the secondary outcomes included doubling of serum creatinine and end-stage renal disease (ESRD). Sex-associated risks were evaluated using Cox regression models. Results Among the1048 patients, 178 (17%) were male and 870 (83%) were female. Male patients exhibited more aggressive features: higher blood pressure, earlier disease onset, and elevated levels of serum creatinine (Scr), uric acid, blood urea nitrogen. Intriguingly, male patients also displayed more severe histopathological alterations, such as more total crescents, cellular crescents formations, higher level of glomerular leukocyte infiltration and Activity Index (AI), even when overall renal pathology was comparable between sexes. During a median follow-up of 112 months, mortality was registered in 141 patients (15.3%). Mortality rates were conspicuously higher in males (24.2% males vs. 13.4% females, p = 0.0029). Secondary outcomes did not show significant sex differences. Cox regression analysis highlighted male, age of renal biopsy, eGFR, and Chronicity Index (CI) as independent risk factors for survival in LN patients. Notably, infections emerged as the leading cause of mortality among LN patients, with a significant higher rate in male patients. Conclusion In our cohort with LN, there was a higher rate of all-cause mortality and proportion of infection-related death in male. Recognizing and further exploring these sex disparities is crucial for optimized LN patients care. Graphical Abstract

Abstract Populus cathayana × canadansis ‘Xinlin 1’ (‘P.‘xin lin 1’) with the characteristics of rapid growth and high yield, is frequently attacked by herbivorous insects. However, little is known about how it defenses against Hyphantria cunea (H. cunea) at molecular and biochemical levels. Differences in the transcriptome and metabolome were analyzed after ‘P. ‘xin lin 1’ leaves were fed to H. cunea for 0h, 2h, 4h, 8h, 16h and 24h. In the five comparison groups including 2h vs. CK, 4h vs. CK, 8h vs. CK, 16h vs. CK, and 24h vs. CK, a total of 8925 genes and 842 metabolites were differentially expressed. A total of 825 transcription factors (TFs) were identified, which encoded 56 TF families. The results showed that the top four families with the highest number of TFs were AP2/ERF, MYB, C2C2, bHLH. Analyses of leaves which were fed to H. cunea showed that the differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were significantly enriched in plant hormone signal transduction pathway, MAPK signaling pathway, flavonoid, flavone and flavonol and anthocyanin biosynthesis pathway. Additionally, there were a number of genes significantly up-regulated in MAPK signaling pathway. Some compounds involved in plant hormone signal transduction and flavonoid/flavone and flavonol/ anthocyanin pathways such as jasmonic acid (JA), jasmonoyl-L-Isoleucine (JA-Ile), kaempferol and cyanidin-3-O-glucoside were induced in infested ‘P.‘xin lin 1’. This study provides a new understanding for exploring the dynamic response mechanism of poplar to the infestation of H. cunea.

Abstract Background Nintedanib is a primary antifibrosing medication available for idiopathic pulmonary fibrosis, systemic sclerosis-interstitial lung disease, and progressive pulmonary fibrosis, with scattered report of drug-induced thrombocytopenia. Case report A 60-year-old Asian male with no history of thrombocytopenia was administered with nintedanib to treat progressive pulmonary fibrosis. The platelet count dropped rapidly after introduction of nintedanib and resolved gradually by withdrawal of the medication along with thrombopoietin receptor agonist. Conclusion Based on experience from the limited reports, nintedanib-induced thrombocytopenia is typically reversible and manageable. Close monitoring of platelet counts in patients receiving this medication should be warranted.

In the present work, the corrosion behaviour of 2A97 Al-Cu-Li alloy with different thermomechanical treatments is investigated using electron microscopy and electrochemical measurements. The various thermomechanical treatments allowed the assessment of the individual and synergistic influence of local plastic deformation and precipitation on the corrosion susceptibility and mechanism of the alloy. It is found that in NaCl solution, corrosion of the alloys in T3 and T4 tempers occurs in the form of intergranular corrosion, which is closely associated with stored energy distribution. By contrast, the alloys in T6 and T8 tempers exhibit mainly intragranular corrosion due to high volume fractions of precipitates formed by artificial ageing.

Diabetic wound healing presents a unique and complex challenge due to the impaired cellular and molecular functions associated with diabetes. Chronic wounds in diabetic patients are characterized by prolonged inflammation, reduced angiogenesis, and impaired collagen deposition, which significantly hinder the healing process. This comprehensive review focuses on the innovative applications of designer cytokines in precision therapy for diabetic wound healing, emphasizing the remarkable advancements made in overcoming the limitations of natural cytokines, such as their short half-life, potential cytotoxicity, and lack of specificity. We begin by detailing the intricate biological characteristics of diabetic wounds and the essential role that cytokines play in orchestrating the healing process. The review critically examines the constraints of natural cytokines and traces the evolution of synthetic alternatives, with a particular emphasis on peptide-based and nucleic acid-based artificial cytokines. Advanced strategies for designing these artificial cytokines are discussed, including molecular modifications, functional enhancements, and specificity improvements to better target pathological conditions in diabetic wounds. Furthermore, we explore the utilization of synthetic biology techniques to engineer effective cytokine-based therapies. The promising therapeutic potential of rationally designed cytokines is highlighted, showcasing their ability to modulate the wound microenvironment, enhance tissue regeneration, and reduce chronic inflammation. This review not only provides valuable perspectives on the future research directions but also offers insights into the potential clinical applications of these innovative therapies, aiming to significantly improve the outcomes for patients suffering from diabetic wounds.

Abstract Osteosarcomas are intricate cellular ecosystems, where heterotypic interactions significantly influence disease progression and therapeutic outcomes. Despite their importance, a detailed understanding of their cellular composition and organizational structure remains elusive. In this study, we provide a comprehensive single-cell and spatially resolved transcriptomics analysis of human osteosarcomas. We construct a cellular meta-map to dissect spatial transcriptomic data, unveiling a detailed atlas of osteosarcoma compositional subgroups. We meticulously characterize the unique gene signatures and functional states of each subgroup and investigate the impact of chemotherapy on these cellular subpopulations. Additionally, our spatial transcriptomics analysis identifies a distinct spatial niche, located at the forefront of tumor necrotic zones, potentially associated with chemotherapy resistance. We also delve into the crosstalk between different cellular subgroups. This study furnishes a comprehensive transcriptional atlas of osteosarcoma's cellular architecture, enriching our comprehension of its complexity and laying the groundwork for more targeted therapeutic approaches.

Abstract Aims Recent years, several studies have suggested that abnormal baseline left ventricular (LV) function and structure are associated with left ventricular thrombus (LVT) formation. Despite this, most studies have given less attention to the potential role of left ventricular reverse remodelling (LVRR), that is, the improvement of LV function and structure, in resolving LVT. In this study, we aim to investigate the clinical characteristics, prognosis, and LVT resolution in patients with LVRR. Methods and results This is a retrospective study conducted at The First Affiliated Hospital of Dalian Medical University. Our cohort consists of patients diagnosed with LVT between 1 November 2015 and 31 May 2020. Enrolled patients were categorized into two groups: LVRR and Failure of LVRR. The primary endpoints included LVT resolution and embolic events. A total of 84 patients were included in the study, with 59 patients in the LVRR group and 25 patients in the Failure of LVRR group. In our study, patients in the LVRR group experienced higher incidence of LVT resolution and a lower risk of embolic events. Multivariate logistic analysis revealed that Failure of LVRR was the only independent negative predictor for LVT resolution and positive predictor for embolic events. Conclusions Patients with LVRR experience higher incidence of LVT resolution and have lower risk of embolic events, highlighting the significance of identifying and mitigating risk factors that contribute to abnormal LV function and structure in management of patients with LVT.

As a promising material for marine engineering, the insufficient corrosion resistance of manganese aluminium bronze (MAB) alloy when exposed to the marine environment may limit its application. In the present work, micro-arc oxidation (MAO) of MAB alloy was conducted in an aluminate-based electrolyte with the influence of ultrasonic vibration (UV) examined. A porous ceramic film has been successfully produced on MAB via MAO, which exhibits dramatic increases in both film thickness and compactness after the introduction of UV. As a result, the ceramic film produced by ultrasound-assisted MAO (UMAO) exhibits an enhanced corrosion resistance relative to that via MAO, which also possesses a desired antifouling capability. Hence, the present work illustrates the influence of UV on the MAO behaviour of non-valve alloys and, more importantly, provides theoretical guidance for related surface modification strategies in marine engineering.

Objective MicroRNAs (miRNAs) are endogenous non-coding RNAs that can play a role in the post-transcriptional regulation of mammalian preadipocyte differentiation. However, the precise functional mechanism of its regulation of fat metabolism is not fully understood. Methods We identified bta-miR-365-3p, which specifically targets the 3′ untranslated region (3′UTR) of the FK506-binding protein 5 (FKBP5), and verified its mechanisms for regulating expression and involvement in adipogenesis. Results In this study, we found that the overexpression of bta-miR-365-3p significantly decreased the lipid accumulation and triglyceride content in the adipocytes. Compared to inhibiting bta-miR-36 5-3p group, overexpression of bta-miR-365-3p can inhibit the expression of adipocyte differentiation-related genes C/EBPα and PPARγ. The dual-luciferase reporter system further validated the targeting relationship between bta-miR-365-3p and FKBP5. FKBP5 mRNA and protein expression were detected by quantitative real-time polymerase chain reaction and Western blot. Overexpression of bta-miR-365-3p significantly down-regulated FKBP5 expression, while inhibition of bta-miR-365-3p showed the opposite, indicating that bta-miR-365-3p negatively regulates FKBP5. Adenosine 5′-monophosphate (AMP)-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway is closely related to the regulation of cell growth and is involved in the development of bovine adipocytes. In this study, overexpression of bta-miR-365-3p significantly inhibited mRNA and protein expression of AMPK, mTOR, and SREBP1 genes, while the inhibition of bta-miR-365-3p expression was contrary to these results. Overexpression of FKBP5 significantly upregulated AMPK, mTOR, and SREBP1 gene expression, while inhibition of FKBP5 expression was contrary to the above experimental results. Conclusion In conclusion, these results indicate that bta-miR-365-3p may be involved in the AMPK/mTOR signaling pathway in regulating Yanbian yellow cattle preadipocytes differentiation by targeting the FKBP5 gene.

Abstract Objectives To investigate whether reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with deep learning reconstruction (DLR) can improve the accuracy of evaluating muscle invasion using VI-RADS. Methods Eighty-six bladder cancer participants who were evaluated by conventional full field-of-view (fFOV) DWI, standard rFOV (rFOVSTA) DWI, and fast rFOV with DLR (rFOVDLR) DWI were included in this prospective study. Tumors were categorized according to the vesical imaging reporting and data system (VI-RADS). Qualitative image quality scoring, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and ADC value were evaluated. Friedman test with post hoc test revealed the difference across the three DWIs. Receiver operating characteristic analysis was performed to calculate the areas under the curve (AUCs). Results The AUC of the rFOVSTA DWI and rFOVDLR DWI were higher than that of fFOV DWI. rFOVDLR DWI reduced the acquisition time from 5:02 min to 3:25 min, and showed higher scores in overall image quality with higher CNR and SNR, compared to rFOVSTA DWI (p 0.05). Conclusions rFOV DWI with DLR can improve the diagnostic accuracy of fFOV DWI for evaluating muscle invasion. Applying DLR to rFOV DWI reduced the acquisition time and improved overall image quality while maintaining ADC value and diagnostic accuracy. Critical relevance statement The diagnostic performance and image quality of full field-of-view DWI, reduced field-of-view (rFOV) DWI with and without DLR were compared. DLR would benefit the wide clinical application of rFOV DWI by reducing the acquisition time and improving the image quality. Key Points Deep learning reconstruction (DLR) can reduce scan time and improve image quality. Reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with DLR showed better diagnostic performances than full field-of-view DWI. There was no difference of diagnostic accuracy between rFOV DWI with DLR and standard rFOV DWI. Graphical Abstract

Abstract Climate change and land use change caused by human activities have a profound impact on ecological security. Simulating the spatio-temporal changes in ecosystem service value and ecological security patterns under different carbon emission scenarios in the future is of great significance for formulating sustainable development policies. This study quantified the four major ecosystem services (habitat quality, water retention, soil erosion, and carbon storage) in Northeast China (NC), identified ecological source areas, and constructed a stable ecological security pattern. The results show that the spatial patterns of soil erosion, carbon storage, water retention, and habitat quality, the four major ecosystem services in NC, are relatively stable in the next 30 years, and there is no significant difference from the current spatial pattern distribution. The SSP1–2.6 carbon emission scenario is a priority model for the development of NC in the next 30 years. In this carbon emission scenario, the NC has the largest ecological resources (191,177 km2) and the least comprehensive resistance value (850.006 × 10−4). At the same time, the relative resistance of the corridor in this scenario is the smallest, and the area of the mandatory reserve pinch points is the least. The ecological corridors in the SSP1–2.6 scenario form a network distribution among the ecological sources, connecting several large ecological sources as a whole. This study fills the knowledge gap in building a stable ecological security pattern in NC under the background of global change, and provides a scientific basis for the decision-making of regional ecological security and land resource management.

On September 5, 2022, a strong earthquake with a magnitude of MS6.8 struck Luding County in Sichuan Province, China, triggering thousands of landslides along the Dadu River in the northwest-southeast (NW-SE) direction. We investigated the reactivation characteristics of historical landslides within the epicentral area of the Luding earthquake to identify the initiation mechanism of earthquake-induced landslides. Records of the two newly triggered and historical landslides were analyzed using manual and threshold methods; the spatial distribution of landslides was assessed in relation to topographical and geological factors using remote sensing images. This study sheds light on the spatial distribution patterns of landslides, especially those that occur above historical landslide areas. Our results revealed a similarity in the spatial distribution trends between historical landslides and new ones induced by earthquakes. These landslides tend to be concentrated within a range of 0.2 km from the river and 2 km from the fault. Notably, both rivers and faults predominantly influenced the reactivation of historical landslides. Remarkably, the reactivated landslides are characterized by their small to medium size and are predominantly situated in historical landslide zones. The number of reactivated landslides surpassed that of previously documented historical landslides within the study area. We provide insights into the critical factors responsible for historical landslides during the 2022 Luding earthquake, thereby enhancing our understanding of the potential implications for future co-seismic hazard assessments and mitigation strategies.

The influence of grain boundary segregation on corrosion behaviour of AA5083 alloy remains unclear. In the present work, the segregation in both as-received and sensitized AA5083 alloys was examined via transmission electron microscopy (TEM). The influence of TEM specimen preparation methods on grain boundary segregation detection was explored. It is revealed that focussed ion beam (FIB) is reliable for the detection of grain boundary segregation. Further, the influence of grain boundary segregation on intergranular corrosion (IGC) of AA5083 alloy was examined. It is indicated that Mg segregation at grain boundary is decisive for IGC development in AA5083-H116 alloy, which also benefits IGC development in sensitized AA5083-H116 alloy by increasing the continuity of grain boundary micro-chemistry.

IntroductionThe intricate roles of immune cells and inflammatory factors in cancer, particularly their association with the risk of bladder cancer, are not well understood.MethodsThis study aimed to clarify potential causal relationships between these elements and the development of bladder cancer using genome-wide association study (GWAS) summary statistics for 731 immune cell phenotypes and 91 circulating inflammatory factors (cases=2,053; controls=287,137). The primary analytical approach was Inverse Variance Weighting (IVW), supplemented by MR-Egger regression, weighted median, and weighted mode analyses. Sensitivity analyses included Cochran Q test, MR-Egger intercept test, and Leave-one-out test.ResultsThe findings indicated that monocytes are positively correlated with an increased risk of bladder cancer. On the contrary, double-negative (DN) T cells, HLA DR+CD8br, and CD28 on CD28+CD45RA+CD8br T cells exhibited an inverse correlation, suggesting a possible protective effect. Furthermore, inflammatory factors IL-20, IL-22RA1, and Eotaxin were significantly associated with an increased risk of bladder cancer.DiscussionThese results suggest that certain immune cell phenotypes and inflammatory factors may play a role in the development of bladder cancer and could serve as potential biomarkers for assessing tumor risk. The findings also offer new insights into the pathogenesis of bladder cancer, indicating a need for further investigation.

IntroductionMultiple myeloma (MM) is a leading cause of hematopoietic cancer-related mortality, accounting for 20% of deaths. MM-targeted therapies have demonstrated efficacy, and since 2015, the United States Food and Drug Administration (FDA) has approved five targeted drugs. However, their cardiovascular safety has not been comprehensively evaluated.ObjectiveThis study aimed to investigate the association between MM-targeted therapy and cardiovascular adverse events (AEs).MethodsDisproportionality analysis was conducted on reports from the FDA AE Reporting System database from 2014 to the second quarter of 2023. Cardiovascular AEs were grouped into nine narrow categories using the Standardized Medical Dictionary for Regulatory Activities Queries (SMQs).ResultsA total of 3,228 cardiovascular AE cases involving MM-targeted therapy were extracted and analyzed. Significant disproportionality was identified for daratumumab, elotuzumab, and isatuximab. Among the nine narrow SMQ categories, the three most reported cardiovascular AEs were cardiomyopathy, cardiac arrhythmias, and embolic and thrombotic events. Noninfectious myocarditis/pericarditis, cardiac arrhythmias, and embolic and thrombotic events exhibited the strongest signal strengths. The cardiovascular AE risk was higher within the first month and gradually decreased thereafter; however, it increased rapidly again after 1 year. This trend was observed for all cardiovascular AEs. The Kaplan–Meier curve and the log-rank test revealed that isatuximab and elotuzumab exhibited a significantly lower probability of cardiovascular AEs than daratumumab (p < 0.001).ConclusionsMM-targeted therapy is significantly associated with an increased risk of previously unknown cardiovascular AE profiles, with the range and onset differing among various drugs, thereby warranting specific monitoring and appropriate management.

ObjectiveThis systematic review and meta-analysis assessed the effects of three types of physical exercise (resistance exercise, aerobic exercise, and group exercise), different exercise intervention times (3 months, 6 months), and different exercise intensities (low, moderate, and high) on the improvement of depressive symptoms in older adults aged ≥60 years, as well as to explore the impact of the sustainability of these physical exercise intervention programs on depressive symptoms in older adults.MethodsThe randomized controlled trials (RCTs) on the effect of physical exercise on depressive symptoms in older adults were retrieved from Cochrane Library, Web of Science, PubMed, and Embase Data. The retrieval time limit is from establishing the database to January 7, 2024. We conducted a meta-analysis using a 95% confidence interval (95% CI) and the standardized mean differences (SMD). The I2 statistic was used to assess the heterogeneity of the outcomes of the studies. When I2 50%, we used the random-effects model. Subgroup and sensitivity analyses investigated heterogeneity origins.ResultsThere are 15 articles reported 20 studies, with a total of 1,346 patients, including 689 in the control group and 657 in the experimental group. The findings demonstrated a notable improvement in depression symptoms among older persons as an immediate result of engaging in physical exercise [SMD = −0.82, 95% CI (−1.19, −0.45)]. The subgroup analysis showed that moderate-intensity physical exercise [SMD = −0.25, 95% CI (−0.47, −0.03)], high-intensity physical exercise [SMD = −0.94, 95% CI (−1.37, −0.51)], resistance exercise [SMD = −0.70, 95% CI (−1.20, −0.20)], and group exercise [SMD = −0.97, 95% CI (−1.89, −0.05)], and the exercise intervention time was 3 months [SMD = −0.81, 95% CI (−1.38, −0.23)] or 6 months [SMD = −0.93, 95% CI (−1.46, −0.41)] were more effective in improving depressive symptoms in older adults.ConclusionThe sustainable resistance and group exercise have a better effect on improving depressive symptoms in older adults. Appropriate exercise intervention time can also ensure the sustainable improvement effect of exercise.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/record_email.php, identifier CRD42023405525.

BackgroundSeveral urinary biomarkers have good diagnostic value for diabetic kidney disease (DKD); however, the predictive value is limited with the use of single biomarkers. We investigated the clinical value of Luminex liquid suspension chip detection of several urinary biomarkers simultaneously.MethodsThe study included 737 patients: 585 with diabetes mellitus (DM) and 152 with DKD. Propensity score matching (PSM) of demographic and medical characteristics identified a subset of 78 patients (DM = 39, DKD = 39). Two Luminex liquid suspension chips were used to detect 11 urinary biomarkers according to their molecular weight and concentration. The biomarkers, including cystatin C (CysC), nephrin, epidermal growth factor (EGF), kidney injury molecule-1 (KIM-1), retinol-binding protein4 (RBP4), α1-microglobulin (α1-MG), β2-microglobulin (β2-MG), vitamin D binding protein (VDBP), tissue inhibitor of metalloproteinases-1 (TIMP-1), tumor necrosis factor receptor-1 (TNFR-1), and tumor necrosis factor receptor-2 (TNFR-2) were compared in the DM and DKD groups. The diagnostic values of single biomarkers and various biomarker combinations for early diagnosis of DKD were assessed using receiver operating characteristic (ROC) curve analysis.ResultsUrinary levels of VDBP, RBP4, and KIM-1 were markedly higher in the DKD group than in the DM group (p < 0.05), whereas the TIMP-1, TNFR-1, TNFR-2, α1-MG, β2-MG, CysC, nephrin, and EGF levels were not significantly different between the groups. RBP4, KIM-1, TNFR-2, and VDBP reached p < 0.01 in univariate analysis and were entered into the final analysis. VDBP had the highest AUC (0.780, p < 0.01), followed by RBP4 (0.711, p < 0.01), KIM-1 (0.640, p = 0.044), and TNFR-2 (0.615, p = 0.081). However, a combination of these four urinary biomarkers had the highest AUC (0.812), with a sensitivity of 0.742 and a specificity of 0.760.ConclusionsThe urinary levels of VDBP, RBP4, KIM-1, and TNFR-2 can be detected simultaneously using Luminex liquid suspension chip technology. The combination of these biomarkers, which reflect different mechanisms of kidney damage, had the highest diagnostic value for DKD. However, this finding should be explored further to understand the synergistic effects of these biomarkers.

ObjectiveTo comprehensively and quantitatively evaluate the impact of body weight support training (BWST) on balance and gait function in stroke patients based on an evidence-based basis and to identify the most effective intervention strategies.MethodsPubMed, Web of Science, The Cochrane Library, CNKI, Wanfang, and Chinese SinoMed Database were searched until November 25, 2023. Quality assessment and meta-analysis were performed using RevMan 5.2 and Stata 14.0 software.ResultsA total of 31 randomized controlled trials involving 1,918 patients were included in the study. The meta-analysis demonstrated that body weight support training (BWST) significantly improved Berg Balance Scale (BBS) scores (MD = 3.60; 95% CI: 1.23 to 5.98; p = 0.003), gait speed (SMD = 0.77; 95% CI: 0.38 to 1.15; p

Tetrodotoxin (TTX) is a highly potent and widely distributed ion-channel marine neurotoxin; it has no specific antidote and poses a great risk to human health. Therefore, detecting and quantifying TTX to effectively implement prevention strategies is important for food safety. The development of novel and highly sensitive, highly specific, rapid, and simple techniques for trace TTX detection has attracted widespread attention. This review summarizes the latest advances in the detection and quantitative analysis of TTX, covering detection methods based on biological and cellular sensors, immunoassays and immunosensors, aptamers, and liquid chromatography-mass spectrometry. It further discusses the advantages and applications of various detection technologies developed for TTX and focuses on the frontier areas and development directions of TTX detection, providing relevant information for further investigations.

Summary: Zebrafish and organoids, crucial for complex biological studies, necessitate an imaging system with deep tissue penetration, sample protection from environmental interference, and ample operational space. Traditional three-photon microscopy is constrained by short-working-distance objectives and falls short. Our long-working-distance high-collection-efficiency three-photon microscopy (LH-3PM) addresses these challenges, achieving a 58% fluorescence collection efficiency at a 20 mm working distance. LH-3PM significantly outperforms existing three-photon systems equipped with the same long working distance objective, enhancing fluorescence collection and dramatically reducing phototoxicity and photobleaching. These improvements facilitate accurate capture of neuronal activity and an enhanced detection of activity spikes, which are vital for comprehensive, long-term imaging. LH-3PM’s imaging of epileptic zebrafish not only showed sustained neuron activity over an hour but also highlighted increased neural synchronization and spike numbers, marking a notable shift in neural coding mechanisms. This breakthrough paves the way for new explorations of biological phenomena in small model organisms.

Background/purpose: This study aimed to summarize the survival and complication profiles of the compress® endoprosthesis (CPS) through a systematic review and meta-analysis. Methods: Online databases (PubMed, EMBASE and Web of Science) were searched from inception to November 2023. Trials were included that involved the use of CPS for endoprosthetic replacement in patients with massive segmental bone defects. Patients’ clinical characteristics and demographic data were extracted using a standardized form. The methodological quality of included 13 non-comparative studies was assessed on basis of the Methodological Index for Non-Randomized Studies (MINORS). All the available Kaplan-Meier curves in the included studies were digitized and combined using Engauge-Digitizer software and the R Project for Statistical Computing. Results: The meta-analysis of thirteen included studies indicated: the all-cause failure rates of CPS were 26.3 % after surgery, in which the occurrence rates of aseptic loosening were 5.8 %. And the incidences of other complications were as follows: soft tissue failure (1.8 %), structure failure (8.2 %), infection (9.5 %), tumor progression (1.1 %). The 1-, 4-, and 8-year overall survival rates for all-cause failure with 95 % CI were 89 % (86 %-92 %), 75 % (71 %-79 %) and 65 % (60 %-70 %), respectively. The estimated mean survival time of all-cause failure was 145 months (95 % CI, 127–148 months), and the estimated median survival time of all-cause failure was 187 months (95 % CI, 135–198 months). The 1-, 4-, and 8-year overall survival rates of aseptic loosening with 95 % CI were 96 % (94 %-98 %), 91 % (87 %-95 %) and 88 % (83 %-93 %), respectively. The estimated mean survival time of aseptic loosening was 148 months (95 % CI, 137–153 months). Conclusion: CPS’s innovative spring system promotes bone ingrowth by providing immediate and high-compression fixation, thereby reducing the risk of aseptic loosening caused by stress shielding and particle-induced osteolysis. CPS requires less residual bone mass for reconstructing massive segmental bone defects and facilitates easier revision due to its non-cemented fixation. In addition, the survival rate, estimated mean survival time, and complication rates of CPS are not inferior to those of common endoprosthesis.

Abstract Background The Vesical Imaging-Reporting and Data System (VI-RADS) has demonstrated effectiveness in predicting muscle invasion in bladder cancer before treatment. The urgent need currently is to evaluate the muscle invasion status after neoadjuvant chemotherapy (NAC) for bladder cancer. This study aims to ascertain the accuracy of VI-RADS in detecting muscle invasion post-NAC treatment and assess its diagnostic performance across readers with varying experience levels. Methods In this retrospective study, patients with muscle-invasive bladder cancer who underwent magnetic resonance imaging (MRI) after NAC from September 2015 to September 2018 were included. VI-RADS scores were independently assessed by five radiologists, consisting of three experienced in bladder MRI and two inexperienced radiologists. Comparison of VI-RADS scores was made with postoperative histopathological diagnosis. Receiver operating characteristic curve analysis (ROC) was used for evaluating diagnostic performance, calculating sensitivity, specificity, and area under ROC (AUC)). Interobserver agreement was assessed using the weighted kappa statistic. Results The final analysis included 46 patients (mean age: 61 years ± 9 [standard deviation]; age range: 39–70 years; 42 men). The pooled AUC for predicting muscle invasion was 0.945 (95% confidence interval (CI): 0.893–0.977) for experienced readers, and 0.910 (95% CI: 0.831–0.959) for inexperienced readers, and 0.932 (95% CI: 0.892–0.961) for all readers. At an optimal cut-off value ≥ 4, pooled sensitivity and specificity were 74.1% (range: 66.0–80.9%) and 94.1% (range: 88.6–97.7%) for experienced readers, and 63.9% (range: 59.6–68.1%) and 86.4% (range: 84.1–88.6%) for inexperienced readers. Interobserver agreement ranged from substantial to excellent between all readers (k = 0.79–0.92). Conclusions VI-RADS accurately assesses muscle invasion in bladder cancer patients after NAC and exhibits good diagnostic performance across readers with different experience levels.

Abstract Aims Rhythm control therapy has shown great benefits for patients with atrial fibrillation (AF) and heart failure (HF). However, few studies have evaluated the effects of rhythm control on left ventricular ejection fraction (LVEF) trajectory across the whole HF spectrum. Our study explored the prevalence and predictors of LVEF trajectory changes and their prognostic implications following rhythm control. Methods and results Depending on the treatment strategy, the cohort was classified into rhythm and rate control groups. Alterations in HF types and LVEF trajectory were recorded. The observational endpoints were all‐cause mortality and HF‐related admission. Predictors of LVEF trajectory improvement in the rhythm control group were evaluated. After matching, the two groups had similar age [mean age (years): rhythm/rate control: 63.96/65.13] and gender [male: rhythm/rate control: n = 228 (55.6%)/233 (56.8%)]. Based on baseline LVEF measurement, the post‐matched cohort had 490 HF with preserved ejection fraction (rhythm/rate control: n = 260/230; median LVEF: 58.00%/57.00%), 99 HF with mildly reduced ejection fraction (rhythm/rate control: n = 50/49; median LVEF: 45.00%/46.00%), and 231 HF with reduced ejection fraction (rhythm/rate control: n = 100/131; median LVEF: 32.50%/33.00%). Trajectory analysis found that the rhythm control group had a greater percentage of LVEF trajectory improvement than the rate control group [80 (53.3%) vs. 71 (39.4%), P = 0.012]. Cox regression analysis also showed that the rhythm control group was more likely to have improved LVEF trajectory compared with the rate control group {hazard ratio [HR] 1.671 [95% confidence interval (CI) 1.196–2.335], P = 0.003}. In the survival analysis, the rhythm control group experienced significant lower risks of all‐cause mortality [HR 0.600 (95% CI 0.366–0.983), P = 0.043] and HF‐related admission [HR 0.611 (95% CI 0.496–0.753), P

Abstract Wild medicinal plants are prominent in the field of Traditional Chinese Medicine (TCM), but their availability is being impacted by human activities and ecological degradation in China. To ensure sustainable use of these resources, it is crucial to scientifically plan areas for wild plant cultivation. Thesium chinense, a known plant antibiotic, has been overharvested in recent years, resulting in a sharp reduction in its wild resources. In this study, we employed three atmospheric circulation models and four socio-economic approaches (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5) to investigate the primary environmental factors influencing the distribution of T. chinense. We also examined changes in its suitable area using the Biomod2 package. Additionally, we utilized the PLUS model to project and analyze future land use changes in climate-stable regions for T. chinense. Our planning for wild tending areas of T. chinense was facilitated by the ZONATION software. Over the next century, the climate-stable regions for T. chinense in China is approximately 383.05 × 104 km2, while the natural habitat in this region will progressively decline. Under the current climate conditions, about 65.06% of the habitats in the high suitable areas of T. chinense are not affected by future land use changes in China. Through hotspot analysis, we identified 17 hotspot cities as ideal areas for the wild tending of T. chinense, including 6 core hotspot cities, 6 sub-hotspot cities, and 5 fringe hotspot cities. These findings contribute to a comprehensive research framework for the cultivation planning of T. chinense and other medicinal plants.

Abstract The dynamic protein corona formed on nanocarriers has been revealed to strongly affect their in vivo behaviors. Precisely manipulating the formation of protein corona on nanocarriers may provide an alternative impetus for specific drug delivery. Herein, we explore the role of glycosylated polyhydroxy polymer-modified nanovesicles (CP-LVs) with different amino/hydroxyl ratios in protein corona formation and evolution. CP-LVs with an amino/hydroxyl ratio of approximately 0.4 (CP1-LVs) are found to efficiently suppress immunoglobulin adsorption in blood and livers, resulting in prolonged circulation. Moreover, CP1-LVs adsorb abundant tumor distinctive proteins, such as CD44 and osteopontin in tumor interstitial fluids, mediating selective tumor cell internalization. The proteins corona transformation specific to the environment appears to be affected by the electrostatic interaction between CP-LVs and proteins with diverse isoelectric points. Benefiting from surface modification-mediated protein corona regulation, paclitaxel-loaded CP1-LVs demonstrate superior antitumor efficacy to PEGylated liposomes. Our work offers a perspective on rational surface-design of nanocarriers to modulate the protein corona formation for efficient drug delivery.

Abstract Airway epithelial transcriptome analysis of asthma patients with different severity was used to disentangle the immune infiltration mechanisms affecting asthma exacerbation, which may be advantageous to asthma treatment. Here we introduce various bioinformatics methods and develop two models: an OVA/CFA-induced neutrophil asthma mouse model and an LPS-induced human bronchial epithelial cell damage model. Our objective is to investigate the molecular mechanisms, potential targets, and therapeutic strategies associated with asthma severity. Multiple bioinformatics methods identify meaningful differences in the degree of neutrophil infiltration in asthma patients with different severity. Then, PTPRC, TLR2, MMP9, FCGR3B, TYROBP, CXCR1, S100A12, FPR1, CCR1 and CXCR2 are identified as the hub genes. Furthermore, the mRNA expression of 10 hub genes is determined in vivo and in vitro models. Reperixin is identified as a pivotal drug targeting CXCR1, CXCR2 and MMP9. We further test the potential efficiency of Reperixin in 16HBE cells, and conclude that Reperixin can attenuate LPS-induced cellular damage and inhibit the expression of them. In this study, we successfully identify and validate several neutrophilic signatures and targets associated with asthma severity. Notably, Reperixin displays the ability to target CXCR1, CXCR2, and MMP9, suggesting its potential therapeutic value for managing deteriorating asthma.

Abstract Aims We conducted a presentation on an 84‐year‐old male patient who has been diagnosed with TTRA81V (p. TTRA101V) hereditary transthyretin cardiac amyloidosis (hATTR‐CM). In order to establish its pathogenicity, we extensively investigated the biochemical and biophysical properties of the condition. Methods and results Transthyretin amyloid cardiomyopathy (ATTR‐CM) is an increasingly acknowledged progressive infiltrative cardiomyopathy that leads to heart failure and potentially fatal arrhythmias. Gaining a comprehensive understanding of the biochemical and biophysical characteristics of genetically mutated TTR proteins serves as the fundamental cornerstone for delivering precise medical care to individuals affected by ATTR. Laboratory assessments indicated a brain natriuretic peptide of 200.12 ng/L (normal range: 0–100 ng/L) and high‐sensitivity cardiac troponin I of 0.189 μg/L (normal range: 0–0.1 μg/L). Echocardiography identified left atrial enlargement, symmetrical left ventricular hypertrophy (16 mm septal and 16 mm posterior wall), and a left ventricular ejection fraction of 56%. Cardiac‐enhanced magnetic resonance imaging revealed subendocardial late gadolinium enhancement. Tc‐99m‐PYP nuclear scintigraphy confirmed grade 3 myocardial uptake, showing an increased heart‐to‐contralateral ratio (H/CL = 2.33). Genetic testing revealed a heterozygous missense mutation in the TTR gene (c.302C>T), resulting in an alanine‐to‐valine residue change (p. Ala81Val, following the first 20 residues of signal sequence nomenclature). Biochemical analysis of this variant displayed compromised kinetic stability in both the TTRA81V:WT (wild‐type) heterozygote protein (half‐life, t1/2 = 21 h) and the TTRA81V homozygote protein (t1/2 = 17.5 h). The kinetic stability fell between that of the TTRWT (t1/2 = 42 h) and the early‐onset TTRL55P mutation (t1/2 = 4.4 h), indicating the patient's late‐onset condition. Kinetic stabilizers (Tafamidis, Diflunisal, and AG10) all exhibited the capacity to inhibit TTRA81V acid‐ and mechanical force‐induced fibril formation, albeit less effectively than with TTRWT. Chromatographic assessment of the patient's serum TTR tetramers indicated a slightly lower concentration (3.0 μM) before oral administration of Tafamidis compared with the normal range (3.6–7.2 μM). Conclusions We identified a patient with hATTR‐CM who possesses a rare TTRA81V mutation solely associated with cardiac complications. The slightly reduced kinetic stability of this mutation indicates its late‐onset nature and contributes to the gradual progression of the disease.

AbstractBackground The effectiveness of nirmatrelvir–ritonavir has mainly been shown in non-hospitalized patients with mild-to-moderate coronavirus disease 2019 (COVID-19). The real-world effectiveness of nirmatrelvir-ritonavir urgently needs to be determined using representative in-hospital patients with COVID-19 during the Omicron wave of the pandemic.Methods We performed a multicentre, retrospective study in five Chinese PLA General Hospital medical centers in Beijing, China. Patients hospitalized with COVID-19 from 10 December 2022 to 20 February 2023 were eligible for inclusion. A 1:1 propensity score matching was performed between the nirmatrelvir-ritonavir group and the control group.Results 1010 recipients of nirmatrelvir-ritonavir and 1010 matched controls were finally analyzed after matching. Compared with matched controls, the nirmatrelvir-ritonavir group had a lower incidence rate of all-cause death (4.6/1000 vs. 6.3/1000 person-days, p = 0.013) and a higher incidence rate of clinical improvement (47.6/1000 vs. 45.8/1000 person-days, p = 0.012). Nirmatrelvir-ritonavir was associated with a 22% lower all-cause mortality and a 14% higher incidence of clinical improvement. Initiation of nirmatrelvir-ritonavir within 5 days after symptom onset was associated with a 50% lower mortality and a 26% higher clinical improvement rate. By contrast, no significant associations were identified among patients receiving nirmatrelvir-ritonavir treatment more than 5 days after symptom onset. Nirmatrelvir-ritonavir was also associated with a 50% increase in survival days and a 12% decrease in days to clinical improvement.Conclusion Among hospitalized patients with COVID-19 during the Omicron wave in Beijing, China, the early initiation of nirmatrelvir-ritonavir was associated with clinical benefits of lowering mortality and improving clinical recovery.

IntroductionThyroid-associated ophthalmopathy (TAO) is an autoimmune-driven orbital inflammatory disease. Despite research efforts, its exact pathogenesis remains unclear. This study aimed to characterize the intestinal flora and metabolic changes in patients with TAO to identify the flora and metabolites associated with disease development.MethodsThirty patients with TAO and 29 healthy controls were included in the study. The intestinal flora and metabolites were analyzed using high-throughput sequencing of the 16S rRNA gene and non-targeted metabolomics technology, respectively. Fresh fecal samples were collected from both populations for analysis.ResultsReduced gut richness and diversity were observed in patients with TAO. Compared to healthy controls, significant differences in relative abundance were observed in patients with TAO at the order level Clostridiales, family level Staphylococcaceae, genus level Staphylococcus, Fournierella, Eubacterium siraeum, CAG-56, Ruminococcus gnavus, Intestinibacter, Actinomyces, and Erysipelotrichaceae UCG-003 (logFC>1 and P

Abstract Patients with locally advanced head and neck squamous cell carcinoma (LA‐HNSCC) have poor survival outcomes. The real‐world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)‐based chemoradiotherapy in patients with LA‐HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3‐year overall survival (OS) rate. Log‐rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow‐up time was 54.2 (95% confidence interval [CI]: 52.7–55.9) months. The study group was associated with improved OS (hazard ratio [HR] = 0.75, 95% CI: 0.57–0.99, p = 0.038) and progression‐free survival (PFS) (HR = 0.74, 95% CI: 0.58–0.96, p = 0.021). Subgroup analysis revealed that aged 50–60 year, IV, N2, radiotherapy dose ≥ 60 Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab‐related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA‐HNSCC patients in an IMRT era.

BackgroundSpinal muscular atrophy (SMA) is a genetic progressive neuromuscular disease. Nusinersen is the first disease modifying drug approved to treat patients with SMA. Our study aimed to evaluate the efficacy of nusinersen treatment on motor function in children with SMA.MethodsA retrospective analysis was conducted on the data of 52 genetically confirmed SMA patients from November 2020 to September 2023. Motor function was assessed based on standardized scales from baseline to 14 months of follow-up.ResultsOf patients in this study, the majority had SMA type 2 (40/52, 76.9%), 5 (9.6%) and 7 (13.5%) patients had SMA types 1 and 3, respectively. The median disease duration was 11 months (range 0–52), and the median age at initiation of treatment was 44.5 months (range 5–192). Motor function of all the patients with SMA improved from baseline to 14 months of follow-up. Mean increases of 4.6-point (p = 0.173), 4.7-point (p = 0.021) and 2.7-point (p = 0.013) were observed from baseline to 14 months of follow-up for the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores, the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM), respectively. Increased disease duration and age of treatment initiation were negatively correlated with the changes in HFMSE scores (r = −0.567, p = 0.043; r = −0.771 and p = 0.002, respectively). Similar results were observed for the RULM scores (r = −0.714, p = 0.014; r = −0.638 and p = 0.035, respectively).ConclusionOur study suggested that 14 months of treatment with nusinersen was effective and improved the motor function of children with SMA types 1, 2, or 3. In addition, disease duration and age at treatment initiation were negatively correlated with treatment outcome in the patients.

IntroductionObservational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation.MethodsFor Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments.ResultsOur results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34–4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32–3.43]), benign neoplasm of the larynx (2.01 [1.36–2.96]), melanoma (1.74 [1.17–2.59]), follicular lymphoma (1.50 [1.06–2.11]), autoimmune thyroiditis (2.47 [1.49–4.08]), and autoimmune hyperthyroidism (1.93 [1.17–3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland.ConclusionCasting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported.

Abstract Plant movements for survival are nontrivial. Antheridia in the moss Physcomitrium patens (P. patens) use motion to eject sperm in the presence of water. However, the biological and mechanical mechanisms that actuate the process are unknown. Here, the burst of the antheridium of P. patens, triggered by water, results from elastic instability and is determined by an asymmetric change in cell geometry. The tension generated in jacket cell walls of antheridium arises from turgor pressure, and is further promoted when the inner walls of apex burst in hydration, causing water and cellular contents of apex quickly influx into sperm chamber. The outer walls of the jacket cells are strengthened by NAC transcription factor VNS4 and serve as key morphomechanical innovations to store hydrostatic energy in a confined space in P. patens. However, the antheridium in liverwort Marchantia polymorpha (M. polymorpha) adopts a different strategy for sperm release; like jacket cell outer walls of P. patens, the cells surrounding the antheridium of M. polymorpha appear to play a similar role in the storage of energy. Collectively, the work shows that plants have evolved different ingenious devices for sperm discharge and that morphological innovations can differ.

Purpose: – This research conducted a thorough literature review to analyze current research on Employee Green Behavior (EGB) and its contexts. It identified key areas of emphasis in EGB and provided a precise roadmap for future research. Design/methodology/approach: The research on employee green behavior will be visually represented using bibliometric analysis. Additionally, we provided a comprehensive overview of the correlation between relevant theories and determinants of employee green behavior. We also offered specific suggestions for future research to deepen consumer researchers' understanding of this concept. Findings: A bibliometric analysis was conducted on 275 journal articles regarding employee green behavior sourced from the Web of Science database spanning 2012 to 2023. The study revealed an increasing focus on employee green behavior research across diverse fields such as management, economics, psychology, sociology, and law. China, the United States, and Italy emerged as the top three countries both in publication volume and literature centrality. The academic literature primarily centers on investigating antecedent variables of green employee behavior, broadly categorized into corporate social responsibility, organizational support, green human resource management, transformational and ethical leadership, organizational commitment, job satisfaction, responsible leadership, intentions, values, organizational identification, and organizational climate. To comprehensively analyze prior studies, content analysis was performed, outlining and scrutinizing four empirical areas including antecedents, mediators, moderators, and outcomes of employee green behavior. While research on antecedents and influencing mechanisms of green loyalty was prevalent among the influencing variables, boundary conditions such as moderators received relatively less attention. Originality/value: This comprehensive literature review offers a clear understanding of the conceptual content, organization, and assessment of employee green behavior. Furthermore, it includes a bibliometric analysis of 275 papers on employee green behavior published between 2012 and 2023 in the Web of Science database. The text analysis reveals insights into the theoretical foundation, antecedent and outcome variables, and processes of employee green behavior, providing valuable guidance for future research.

Organoids are three-dimensional structures derived from primary tissue or tumors that closely mimic the architecture, histology, and function of the parental tissue. In recent years, patient-derived organoids (PDOs) have emerged as powerful tools for modeling tumor heterogeneity, drug screening, and personalized medicine. Although most cancer organoids are derived from primary tumors, the ability of organoids from metastatic cancer to serve as a model for studying tumor biology and predicting the therapeutic response is an area of active investigation. Recent studies have shown that organoids derived from metastatic sites can provide valuable insights into tumor biology and may be used to validate predictive models of the drug response. In this comprehensive review, we discuss the feasibility of culturing organoids from multiple metastatic cancers and evaluate their potential for advancing basic cancer research, drug development, and personalized therapy. We also explore the limitations and challenges associated with using metastasis organoids for cancer research. Overall, this review provides a comprehensive overview of the current state and future prospects of metastatic cancer-derived organoids.

Abstract Aims We aimed to explore the associations between urine albumin-to-creatinine ratio (uACR) and cardia-cerebrovascular disease (CVD) in Chinese population with type 2 diabetes(T2D). Methods We included 8975 participants with T2D but free of prevalent CVD (including myocardial infarction, ischemic and hemorrhagic stroke) at baseline from Kailuan study who were assessed with uACR between 2014 and 2016. The participants were divided into three groups based on their baseline uACR: normal (

Abstract The biomechanical characteristics of runs in firefighters with different rescue tasks are unclear. This study aimed to explore the biomechanical characteristics of firefighters running in different rescue tasks and provide theoretical and practical references for firefighter training and occupational injury prevention. Eighteen professional healthy male firefighters were randomly selected as participants and tested running on different rescue tasks: wearing firefighting protective clothing (FPC), FPC+carrying a gas can (20 kg, FPC+ C), and FPC+carrying a mannequin (60 kg, FPC+M). Eight Qualisys infrared cameras and an AMTI 3D force measurement platform were used for the participant's acquisition of lower limb kinematic/kinetic data. The results showed that gait velocity and stride length of the FPC+GC and FPC+ M rescue tasks were significantly decreased compared to the FPC rescue task, while the support time was significantly increased. Compared to the FPC rescue task, the FPC+GC rescue task showed significant decreases in vertical ground reaction force (vGRF), minimum ankle dorsiflexion angle, and the maximum ankle plantarflexion power. In contrast, the FPC+M rescue task demonstrated significant increases in ankle range of motion, maximum hip extension angle, minimum knee flexion angle, maximum ankle dorsiflexion angle, maximum hip extension moment, maximum knee flexion moment, maximum hip flexion power, and hip and knee stiffness while exhibiting significant decreases in minimum ankle dorsiflexion angle. Compared to the FPC+ GC rescue task, the FPC+M rescue task exhibited significant increases in the maximum hip extension angle, minimum knee flexion angle, maximum ankle dorsiflexion angle, maximum hip flexion moment, maximum hip extension moment, maximum knee flexion moment, maximum ankle plantarflexion moment, maximum hip flexion power, maximum ankle dorsiflexion power, hip stiffness, and vGRF. Conversely, it showed significant decreases in the maximum knee flexion power. In conclusion, compared to the FPC rescue task, the FPC+GC and FPC+M rescue tasks altered the firefighter's gait performance, as evidenced by decreased gait velocity and stride length and increased support time. FPC+M rescue task would increase firefighter's risk of hip and knee injuries. Therefore, we suggest firefighters increase their strength training of the trunk, hip, and knee joint muscles as part of their daily training programs under large weight load status (60 kg and above) to reduce injury risk during rescue tasks.

Abstract Background and aim Two oral antivirals (Nirmatrelvir- ritonavir and Azvudine) are widely used in China practice during the Omicron wave of the pandemic. However, little evidence regarding the real-world effectiveness of these two oral antivirals in in-hospital patients. We aimed to evaluate the clinical effectiveness of nirmatrelvir-ritonavir versus azvudine among adult hospitalized patients with COVID-19. Methods This retrospective cohort study used data from three Chinese PLA General Hospital medical centres. Hospitalized patients with COVID-19 treated with azvudine or nirmatrelvir-ritonavir from Dec 10, 2022, to February 20, 2023, and did not require invasive ventilation support on admission were eligible for inclusion. Results After exclusions and propensity-score matching, the final analysis included 486 azvudine recipients and 486 nirmatrelvir-ritonavir recipients. By 28 days of initiation of the antivirus treatment, the crude incidence rate of all-cause death was similar in both types of antivirus treatment (nirmatrelvir-ritonavir group 2.8 events 1000 person-days [95% CI, 2.1–3.6] vs azvudine group 3.4 events/1000 person-days [95% CI, 2.6–4.3], P = 0.38). Landmark analysis showed that all-cause death was lower in the nirmatrelvir-ritonavir (3.5%) group than the azvudine (6.8%, P = 0.029) within the initial 10-day admission period, while no significant difference was observed for results between 10 and 28 days follow-up. There was no significant difference between the nirmatrelvir-ritonavir group and the azvudine group in cumulative incidence of the composite disease progression event (8.6% with nirmatrelvir-ritonavir vs. 10.1% with azvudine, HR, 1.22; 95% CI 0.80–1.86, P = 0.43). Conclusion Among patients hospitalized with COVID-19 during the omicron wave in Beijing, similar in-hospital clinical outcomes on 28 days were observed between patients receiving nirmatrelvir-ritonavir and azvudine. However, it is worth noticing that nirmatrelvir-ritonavir appears to hold an advantage over azvudine in reducing early mortality. Further randomized controlled trials are needed to verify the efficacy of those two antivirus medications especially in early treatment.

Abstract Background Cellular states of different immune cells can affect the activity of the whole immune microenvironment. Methods Here, leveraging reference profiles of microenvironment cell states that were constructed based on single-cell RNA-seq data of melanoma, we dissected the composition of microenvironment cell states across 463 skin cutaneous melanoma (SKCM) bulk samples through CIBERSORT-based deconvolution of gene expression profiles and revealed high heterogeneity of their distribution. Correspondence analysis on the estimated cellular fractions of melanoma bulk samples was performed to identify immune phenotypes. Based on the publicly available clinical survival and therapy data, we analyzed the relationship between immune phenotypes and clinical outcomes of melanoma. Results By analysis of the relationships among those cell states, we further identified three distinct tumor microenvironment immune phenotypes: “immune hot/active”, “immune cold-suppressive” and “immune cold-exhausted”. They were characterized by markedly different patterns of cell states: most notably the CD8 T Cytotoxic state, CD8 T Mixed state, B non-regulatory state and cancer-associated fibroblasts (CAFs), depicting distinct types of antitumor immune response (or immune activity). These phenotypes had prognostic significance for progression-free survival and implications in response to immune therapy in an independent cohort of anti-PD1 treated melanoma patients. Conclusions The proposed strategy of leveraging single-cell data to dissect the composition of microenvironment cell states in individual bulk tumors can also extend to other cancer types, and our results highlight the importance of microenvironment cell states for the understanding of tumor immunity.

Alarm flood due to abnormality propagation is the most difficult alarm overloading problem in nuclear power plants (NPPs). Root-cause analysis is suggested to help operators in understand emergency events and plant status. Multilevel Flow Modeling (MFM) has been extensively applied in alarm management by virtue of the capability of explaining causal dependencies among alarms. However, there has never been a technique that can identify the actual root cause for complex alarm situations. This paper presents an automated root-cause analysis system based on MFM. The causal reasoning algorithm is first applied to identify several possible root causes that can lead to massive alarms. A novel root-cause ranking algorithm can subsequently be used to isolate the most likely faults from the other root-cause candidates. The proposed method is validated on a pressurized water reactor (PWR) simulator at HAMMLAB. The results show that the actual root cause is accurately identified for every tested operating scenario. The automation of root-cause identification and ranking affords the opportunity of real-time alarm analysis. It is believed that the study can further improve the situation awareness of operators in the alarm flooding situation.

With increasing public environmental awareness, green activities in retail and distribution processes have become crucial tools for retailers to boost demand and enhance competitiveness. This study develops an analytical model to study the green investment choices of two differentiated retailers dealing with a common green manufacturer. It also explores the impacts of these investment choices on the manufacturer's operational decisions, channel efficiency, consumer welfare, and the environment. We derive three main results. First, the powerful retailer always favors green investments, whereas the less powerful (inferior) retailer may either prefer or avoid green investments. The fiercer the inter-retailer competition, the lower the willingness of the inferior retailer to introduce green investments. Second, although all supply chain parties may disagree on their preferences for retailers' green investments, a bilateral green investment (i.e., both retailers make green investments) can reach an incentive alignment for all firms if the differentiation between retailers is low enough and the competition between them is not substantially fierce. Moreover, a bilateral green investment improves consumer welfare and channel efficiency because of the great demand expansion and double marginalization reduction. Third, the retailers' green investments can motivate the manufacturer to produce greener products, but they do not necessarily benefit the environment. We show that the supply chain's economic sustainability aligns with its environmental sustainability only if the environmental improvement efficiency of green investments is substantially high. We further examine the impact of retailers with differentiated green investment abilities and the manufacturer's green investment efficiency to verify the robustness of the main results.

Abstract Background The advancement of single-cell sequencing has progressed our ability to solve biological questions. Cell type annotation is of vital importance to this process, allowing for the analysis and interpretation of enormous single-cell datasets. At present, however, manual cell annotation which is the predominant approach remains limited by both speed and the requirement of expert knowledge. Methods To address these challenges, we constructed a hierarchically organized marker map through manually curating over 26,000 cell marker entries from about 7000 publications. We then developed WISE, a weighted and integrated gene set enrichment method, to integrate the prevalence of canonical markers and ordered differentially expressed genes of specific cell types in the marker map. Benchmarking analysis suggested that our method outperformed state-of-the-art methods. Results By integrating the marker map and WISE, we developed a user-friendly and convenient web server, ACT ( http://xteam.xbio.top/ACT/ or http://biocc.hrbmu.edu.cn/ACT/ ), which only takes a simple list of upregulated genes as input and provides interactive hierarchy maps, together with well-designed charts and statistical information, to accelerate the assignment of cell identities and made the results comparable to expert manual annotation. Besides, a pan-tissue marker map was constructed to assist in cell assignments in less-studied tissues. Applying ACT to three case studies showed that all cell clusters were quickly and accurately annotated, and multi-level and more refined cell types were identified. Conclusions We developed a knowledge-based resource and a corresponding method, together with an intuitive graphical web interface, for cell type annotation. We believe that ACT, emerging as a powerful tool for cell type annotation, would be widely used in single-cell research and considerably accelerate the process of cell type identification.

It is recently suggested that air-formed film plays an important role in controlling corrosion resistance of Mg-Li alloys. However, the structure of the air-formed film and its effect on corrosion resistance of Mg-Li alloys has not been fully understood. Firstly, the air-formed films formed on α and β phases in a dual-phase LZ91 Mg-Li alloy after exposure to laboratory air for up to 48 h have been examined by SEM under the assistance of ultramicrotomy. Then, the effect of the air-formed film on surface potential and, consequently, corrosion/oxidation behavior of the alloy has been investigated. Finally, in order to exclude the influence from α phase, the structure of the air-formed film on β phase and its effect on corrosion/oxidation behavior of Mg-Li alloys have been studied based on a single-phase LA141 Mg-Li alloy. The results show that the air-formed film is thin and negligible on α phase but thick on β phase after prolonged exposure to laboratory air. The thick air-formed film on β phase has a multilayer structure with an inner layer consisting of MgO/Mg(OH)2 and outer layer consisting of Li2CO3, which greatly elevates the surface potential of β phase in air. Both LZ91 and LA141 Mg-Li alloys firstly undergo uniform corrosion and then filiform corrosion when immersed in NaCl solution and the pre-existed air-formed film on β-Li phase can retard the occurrence of filiform corrosion in the alloys.

Abstract Aims/Introduction The hemoglobin glycation index (HGI) represent the disparity between actual glycated hemoglobin measurements and predicted HbA1c. It serves as a proxy for the degree of non‐enzymatic glycation of hemoglobin, which has been found to be positively correlated with diabetic comorbidities. In this study, we investigated the relationship between HGI and non‐alcoholic fatty liver disease (NAFLD), along with other relevant biological markers in patients with diabetes. Materials and Methods This cross‐sectional study consisted of 3,191 adults diagnosed with type 2 diabetes mellitus. We calculated the predicted glycated hemoglobin levels based on fasting blood glucose levels. Multivariate binary logistic regression analysis was conducted to examine the correlation between the HGI and NAFLD. Hepatic steatosis was diagnosed using ultrasonography. Results Among all participants, 1,784 (55.91%) were diagnosed with NAFLD. Participants with confirmed NAFLD showed elevated body mass index, diastolic blood pressure, liver enzyme, total cholesterol, triglyceride, low‐density lipoprotein and uric acid levels compared with those without NAFLD. In the unadjusted model, participants in the last tertile of HGI were 1.40‐fold more likely to develop NAFLD than those in the first tertile (95% confidence interval 1.18–1.66; P

Burkholderia is the second largest source of natural product bacteria after Actinomyces and can produce many secondary metabolites including pyrrolnitrin (PRN). Natural products of microbial origin are usually found in trace amounts, so in metabolic engineering, promoter engineering is often used to regulate gene expression to increase yield. In this study, an endogenous strong promoter was identified based on RNA-seq to overexpress biosynthetic genes to increase the production of PRN. By analyzing the transcriptomic data of the antagonistic bacterium Burkholderia sp. JP2-270 in three different development periods, we screened 50 endogenous promoters with high transcriptional activity, nine of which were verified by an obvious fluorescent signal via fluorescence observation. Then, combined with RT-qPCR analysis, Php, the promoter of a hypothetical protein, was found to be significantly expressed in all three periods. In order to increase the suitability of endogenous promoters, the promoter Php was shortened at different lengths, and the results show that a sequence length of 173 bp was necessary for its activity. Moreover, this promoter was used to overexpress the PRN biosynthesis genes (prnA, prnB, prnC and prnD) in JP2-270, resulting in a successful increase in gene expression levels by 40–80 times. Only the overexpression of the prnB gene successfully increased PRN production to 1.46 times that of the wild type. Overall, the endogenous strong promoters screened in this study can improve gene expression and increase the production of secondary metabolites in JP2-270 and other strains.

MicroRNAs (miRNAs) are increasingly being considered essential diagnostic biomarkers and therapeutic targets for multiple diseases. In recent years, researchers have emphasized the need to develop probes that can harness extracellular miRNAs as input signals for disease diagnostics. In this study, we introduce a novel miRNA-responsive biosensor (miR-RBS) designed to achieve highly sensitive and specific detection of miRNAs, with a particular focus on targeted organ-specific visualization. The miR-RBS employs a Y-structured triple-stranded DNA probe (Y-TSDP) that exhibits a fluorescence-quenched state under normal physiological conditions. The probe switches to an activated state with fluorescence signals in the presence of high miRNA concentrations, enabling rapid and accurate disease reporting. Moreover, the miR-RBS probe had a modular design, with a fluorescence-labeled strand equipped with a functional module that facilitates specific binding to organs that express high levels of the target receptors. This allowed the customization of miRNA detection and cell targeting using aptameric anchors. In a drug-induced liver injury model, the results demonstrate that the miR-RBS probe effectively visualized miR-122 levels, suggesting it has good potential for disease diagnosis and organ-specific imaging. Together, this innovative biosensor provides a versatile tool for the early detection and monitoring of diseases through miRNA-based biomarkers.

With global urbanization accelerating, high-rise buildings have become a common feature in the urban landscape, especially in coastal cities, where they encounter unique wind-load challenges. This study aims to quantify the structural response and occupant comfort of a high-rise residential building under wind-induced accelerations by integrating wind tunnel testing with finite element analysis (FEA). The research focuses on critical response parameters, including displacement, acceleration, and stress, to evaluate the building’s performance. Wind tunnel tests provided detailed wind pressure distribution data across the building’s surface, while multi-degree-of-freedom and finite element models facilitated precise numerical simulations. The findings highlight a significant directional and temporal variability in wind-load responses, with the most pronounced effects observed at a wind-direction angle of 105° relative to the building’s front-facing axis (0°). The study confirms that the combined application of wind tunnel tests and FEA offers a comprehensive approach to understanding wind-induced responses, essential for the scientifically accurate and effective design of high-rise structures.

To study the mixed fermentation technology of blueberry and corn peptide by Lacticaseibacillus rhamnosus ZYN-0417 and Lactiplantibacillus plantarum ZYN-0221 and its effect on fermentation quality, fermentation conditions were optimized using a single-factor test and a Plackett–Burman design combined with a Box–Behnken response surface methodology, with blueberry juice and corn peptide as raw materials and L. rhamnosus ZYN-0417 and Lp. plantarum ZYN-0221 as the starter. The results showed that the optimum fermentation conditions were as follows: the volume ratio of ZYN-0417 and ZYN-0221 was 1:1, the amount of blueberry juice was 20%, the amount of corn peptide was 22%, the amount of glucose was 2%, the amount of inoculation was 5%, the fermentation time was 40 h, and the fermentation temperature was 37 °C. Under optimum conditions, the viable count of lactic acid bacteria in fermented blueberry and corn peptide was 16.28 log CFU/mL, the pH value was 4.86, the total acid content was 14.00 g/L, the total sugar content was 39.98 g/100 g, the protein content was 48.34 g/100 g, the scavenging ability of the DPPH, ABTS+ and ·OH− radicals increased by 10.14%, 10.98% and 25.02%, respectively, the chelating ability of Fe2+ increased by 14.92%, the content of total phenol increased by 1.43 mg/L, the content of total flavonoids increased by 0.38 mg/L, the activity of superoxide dismutase increased by 122.10 U/mL, and the activation rate of alcohol dehydrogenase increased by 5.74%. The results showed that mixed lactic acid bacteria could be used as a starter of blueberry and corn peptide and effectively improve the nutritional value of the product.

Carbon-based perovskite solar cells (C-PSCs) are promising candidates for large-scale photovoltaic applications due to their theoretical low cost and high stability. However, the fabrication of high-performance C-PSCs with large-area electrodes remains challenging. In this work, we propose a novel playdough-like graphite putty as top electrode in the perovskite devices. This electrode with soft nature can form good contact with the hole-transporting layer and the conductive substrate at room temperature by a simple pressing technique, which facilitates the fabrication of both small-area devices and perovskite solar modules. In this preliminary research, the corresponding small devices and modules can achieve efficiencies of 20.29% (∼0.15 ​cm2) and 16.01% (∼10 ​cm2), respectively. Moreover, we analyze the limitations of the optical and electrical properties of this playdough-like graphite electrode on the device performance, suggesting a direction for further improvement of C-PSCs in the future.