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Yaning Gao, Liang Chen, Zhengjun Wen, Huiying Jiang, Jing Feng Respiratory and Critical Care Medicine Department, Beijing Jingmei Group General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Liang Chen, Email huxike000111@sohu.comPurpose: Our aim was to determine the risk factors for multidrug resistance in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP).Methods: The information of 196 patients with Klebsiella pneumoniae infection was collected. The patients were subsequently assigned to the carbapenem-resistant, multidrug-resistant, and non-multidrug-resistant groups. The risk factors for multidrug resistance in CRKP patients were assessed via least absolute shrinkage and selection operator and logistic regression analyses. Moreover, a nomogram was constructed dependent on the identified risk factors, and calibration and decision curves were plotted to detect its accuracy.Results: Length of stay (LOS) [odds ratio (OR) and 95% confidence interval (CI): 4.558 (1.157– 17.961), P = 0.030], intensive care unit (ICU) stay within 30 days [OR and 95% CI: 12.643 (3.780– 42.293), P < 0.001], Glasgow Coma Scale (GCS) score [OR and 95% CI: 13.569 (2.738– 67.236), P = 0.001], fungal infection [OR and 95% CI: 6.398 (1.969– 20.785), P = 0.002], and cardiovascular disease (CVD) [OR and 95% CI: 3.871 (1.293– 11.592), P = 0.016] were identified as risk factors for multidrug resistance in CRKP patients. The concordance index (C-index) of the constructed nomogram was 0.950 (95% CI: 0.945– 0.955). Moreover, decision curve analysis elucidated the nomogram utilization across a wide range of probability thresholds, ranging from 1% to 100%. Finally, internal validation using random data validated the robustness of the predictive model, yielding a C-index of 0.937.Conclusion: The LOS, ICU stay within 30 days, GCS score, fungal infection, and CVD were recognized as risk factors for multidrug resistance in CRKP patients. The constructed nomogram could accurately predict multidrug-resistant CRKP infections in patients.Plain Language Summary: The LOS, ICU stay within 30 days, GCS, fungal infection, and CVD were identified as risk factors for multidrug resistance in CRKP patients.The nomogram constructed in this study had high predictive accuracy.This study provides a reference for the formulation of personalized prevention and therapy strategies.Keywords: Klebsiella pneumoniae, multidrug resistance, carbapenem, prediction model, risk factors

Fang Xu,&ast; Peng Shu,&ast; Chenchen Li, Shanshan Huo, Zhuping Wen&ast; Nephrology Department, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Xu; Peng Shu, Nephrology Department, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No.26 Shengli Street, Jiang’ an District, Wuhan, Hubei Province, People’s Republic of China, Tel +8615802716692, Email 453328433@qq.com; 312855784@qq.comObjective: This study aimed to assess the effectiveness of an electronic cannulation atlas in preventing and treating complications of arteriovenous fistula.Methods: The observation group, consisting of 92 dialysis patients from July to December 2021, was managed with an electronic cannulation atlas. After 6 months, the incidence of complications such as stenosis, hematoma, thrombus, aneurysm, and cannulation failure was compared between the groups. Nurse satisfaction with the electronic cannulation atlas system was also assessed through a questionnaire.Results: The observation group had lower incidence rates of arteriovenous fistula stenosis, thrombus, aneurysm, and failure rate of cannulation compared to the control group, with statistically significant differences (p< 0.05). The incidence rates of hematoa were similar in both groups, showing no significant difference (p> 0.05). After 3 months of management, the incidence of arteriovenous fistula complications in the observation group was significantly lower than in the control group (p< 0.05). Additionally, utilizing the electronic cannulation atlas system was found to increase nurses’ job satisfaction.Conclusion: The use of electronic cannulation atlas for the treatment of patients’ arteriovenous fistula could effectively reduce the incidence of complications of patients’ arteriovenous fistula, reduce the failure rate of cannulation, reduce the workload of nurses, and improve the job satisfaction of nurses.Keywords: arteriovenous fistula, informatization, cannulation atlas, management of hemodialysis patients, complications

Zhongwei Wen, Yiqiang Chen, Tangjuan Liu, Jiahui Han, Yuting Jiang, Ke Zhang Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Yiqiang Chen, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Email chenyiq0708@163.comIntroduction: Respiratory infections are a major global health concern, with Klebsiella pneumoniae standing out due to its evolving antibiotic resistance. This study compares the resistance profiles of hypervirulent Klebsiella pneumoniae (hvKP) and classical Klebsiella pneumoniae (cKP), aiming to shed light on their clinical implications.Methods: We analyzed 86 cases, comprising 42 hvKP and 44 cKP strains, using comprehensive antimicrobial susceptibility testing and clinical data evaluation to assess antibiotic tolerance and resistance mechanisms.Results: Our findings reveal distinct resistance patterns between hvKP and cKP, highlighting the role of chromosomal mutations and plasmid-mediated gene transfer in conferring antibiotic resistance. Notably, hvKP strains exhibited unique resistance trends, including the production of extended-spectrum β-lactamases (ESBLs) and carbapenemases, differing from those of cKP.Discussion: This research underscores the importance of continuous surveillance and the development of targeted therapies against antibiotic-resistant Klebsiella pneumoniae. It emphasizes the critical need for judicious antibiotic use and novel therapeutic approaches to combat respiratory infections caused by these increasingly resistant pathogens.Keywords: Klebsiella pneumoniae, antibiotic resistance, hypervirulent Klebsiella pneumoniae, hvKP, classical Klebsiella pneumoniae, cKP, public health

Jiameng Gao,1,2,&ast; Zhiyuan Zhang,1,2,&ast; Jing Yu,1,2,&ast; Nan Zhang,1,2 Yu Fu,1,2 Xuemei Jiang,1,2 Zheyu Xia,3 Qingqing Zhang,1,2 Zongmei Wen1,2 1Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Lung Transplantation, Shanghai, People’s Republic of China; 3School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongmei Wen; Qingqing Zhang, Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Tel +86 13761635280 ; +86 13764542055, Email wzm1103@126.com; elfe666@163.comPurpose: Ischemia reperfusion injury (IRI) unavoidably occurs during lung transplantation, further contributing to primary graft dysfunction (PGD). Neutrophils are the end effectors of IRI and activated neutrophils release neutrophil extracellular traps (NETs) to further amplify damage. Nevertheless, potential contributions of NETs in IRI remain incompletely understood. This study aimed to explore NET-related gene biomarkers in IRI during lung transplantation.Methods: Differential expression analysis was applied to identify differentially expressed genes (DEGs) for IRI during lung transplantation based on matrix data (GSE145989, 127003) downloaded from GEO database. The CIBERSORT and weighted gene co-expression network analysis (WGCNA) algorithms were utilized to identify key modules associated with neutrophil infiltration. Moreover, the least absolute shrinkage and selection operator regression and random forest were applied to identify potential NET-associated hub genes. Subsequently, the screened hub genes underwent further validation of an external dataset (GSE18995) and nomogram model. Based on clinical peripheral blood samples, immunofluorescence staining and dsDNA quantification were used to assess NET formation, and ELISA was applied to validate the expression of hub genes.Results: Thirty-eight genes resulted from the intersection between 586 DEGs and 75 brown module genes, primarily enriched in leukocyte migration and NETs formation. Subsequently, four candidate hub genes (FCAR, MMP9, PADI4, and S100A12) were screened out via machine learning algorithms. Validation using an external dataset and nomogram model achieved better predictive value. Substantial NETs formation was demonstrated in IRI, with more pronounced NETs observed in patients with PGD ≥ 2. PADI4, S100A12, and MMP9 were all confirmed to be up-regulated after reperfusion through ELISA, with higher levels of S100A12 in PGD ≥ 2 patients compared with non-PGD patients.Conclusion: We identified three potential NET-related biomarkers for IRI that provide new insights into early detection and potential therapeutic targets of IRI and PGD after lung transplantation.Keywords: ischemia reperfusion injury, neutrophil extracellular traps, lung transplantation, primary graft dysfunction, WGCNA, machine learning

The 3D Gaussian Splatting technique has significantly advanced the construction of radiance fields from multi‐view images, enabling real‐time rendering. While point‐based rasterization effectively reduces computational demands for rendering, it often struggles to accurately reconstruct the geometry of the target object, especially under strong lighting conditions. Strong lighting can cause significant color variations on the object's surface when viewed from different directions, complicating the reconstruction process. To address this challenge, we introduce an approach that combines octree‐based implicit surface representations with Gaussian Splatting. Initially, it reconstructs a signed distance field (SDF) and a radiance field through volume rendering, encoding them in a low‐resolution octree. This initial SDF represents the coarse geometry of the target object. Subsequently, it introduces 3D Gaussians as additional degrees of freedom, which are guided by the initial SDF. In the third stage, the optimized Gaussians enhance the accuracy of the SDF, enabling the recovery of finer geometric details compared to the initial SDF. Finally, the refined SDF is used to further optimize the 3D Gaussians via splatting, eliminating those that contribute little to the visual appearance. Experimental results show that our method, which leverages the distribution of 3D Gaussians with SDFs, reconstructs more accurate geometry, particularly in images with specular highlights caused by strong lighting. The source code can be downloaded from https://github.com/LaoChui999/GS-Octree. [ABSTRACT FROM AUTHOR]

Clusters of galaxies are merging during the formation of large-scale structures in the Universe. Based on optical survey data, we identify a large sample of pre-mergers of galaxy clusters and merging subclusters in rich clusters. We find 39 382 partners within a velocity difference of 1500 km s |$^{-1}$| and a projected separation of 5  |$r_{500}$| around 33 126 main clusters, where |$r_{500}$| is the radius of the main cluster. Based on the galaxy distribution inside rich clusters with more than 30 member galaxy candidates, we identify subclusters by modelling the smoothed optical distribution with a two-component profile, and a coupling factor is obtained for merging subclusters in 7845 clusters. In addition, we find 3446 post-collision mergers according to the deviations of brightest cluster galaxies from other member galaxies, most of which have been partially validated by using the Chandra and XMM–Newton X-ray images. Two new bullet-like clusters have been identified by using the optical and X-ray images. The large samples of merging clusters of galaxies presented here are important databases for studying the hierarchical structure formation, cluster evolution, and the physics of intergalactic medium. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Triple-negative breast cancer (TNBC) is a heterogeneous disease with aggressive behavior and poor prognosis. Here, we used gene expression profiling to define new subtypes of TNBC, which may improve prevention and treatment through personalized medicine. MATERIALS AND METHODS: Gene expression profiles from the public datasets GSE76250, GSE61724, GSE61723, and GES76275 were subjected to co-expression analysis to identify differentially expressed genes (DEGs) between TNBC and non-TNBC tissues. Consistency clustering was used to define TNBC subtypes, whose correlation with gene modules was analyzed. Enrichment analysis was used to identify module genes' biological functions and pathways. Single-sample gene set enrichment analysis was used to assess immune cell infiltration in the different TNBC subtypes, and the ChAMP package was used to examine methylation sites in TNBC. RESULTS: A total of 4,958 DEGs in TNBC were identified, which showed the same expression differences across all datasets as in the dataset GSE76250 and clustered into 9 co-expression modules. TNBC samples clustered into two subtypes based on nine hub genes from the modules. Class I showed the most significant correlation with module 1, whose genes were related mainly to interleukin-1 response, while class II showed the most significant correlation with module 6, whose genes were related mainly to the transforming growth factor-β pathway. Class I was significantly enriched in cell cycle and DNA replication, and tumors of this subtype showed lower immune cell infiltration than class II tumors. Tumor infiltration by Th2 cells correlated positively with the expression of MCM10 and negatively with the expression of PREX2. A greater methylation of CIDEC, DLC1, EDNRB, EGR2 and SRPK1 correlated with better prognosis. CONCLUSIONS: Class I TNBC, for which a useful biomarker is MCM10, may be associated with a worse prognosis than class II TNBC, for which PREX2 may serve as a biomarker. [ABSTRACT FROM AUTHOR]

Abstract The frigid and droughty climate of Xinjiang in China has given rise to unique indigenous sheep breeds with robust adaptability and resistance. To investigate the genetic mechanism of adaptability of Xinjiang sheep to the local extreme environment, we conducted population genetic structure analyses for three native Xinjiang sheep breeds: Altay sheep (ALT), Bashbay Sheep (BSBC), and Duolang sheep (DLC), as well as two foreign sheep breeds: Suffolk and Dorset, using the Ovine Infinium HD SNP BeadChip(680 K). Our findings revealed distinct genetic and evolutionary histories between Xinjiang and foreign sheep breeds. Principal Component Analysis (PCA) and phylogenetic tree effectively differentiate these five sheep breeds based on their geographical origins, and the domestication level of Xinjiang sheep is comparatively lower than that of foreign sheep breeds. Furthermore, by utilizing three selective signature methods, namely Fixation Index (Fst), Cross Population Extended Haplotype Homozygosity Test (XP-EHH), and Nucleotide Diversity (π), we have successfully identified 22 potential candidate genes. Among these genes, there are TBXT, PDGFD, and VEGFA, which are closely related to tail type and lipid metabolism; VIL1, SLC11A1, and ZBTB46, which are associated with immune function; and candidate genes such as BNC1, HDAC1, and BMP5, which impact sheep reproductive traits. This study establishes a foundation for conserving and utilizing local sheep germplasm resources in Xinjiang and provides molecular insights into the genetic mechanisms governing sheep adaptation to extreme cold and arid environments.

Abstract Photon upconversion through lanthanide-doped nanoparticles is of great significance for various applications. However, the current development of upconversion nanoparticles is hindered by the low quantum efficiency and long radiative lifetimes of lanthanide ions, restricting their applications in time-dependent nanophotonics. Herein, we report ultrafast upconversion superfluorescence with a lifetime of sub-2.5 ns in lanthanide-doped nanoparticles at room temperature. Upon excitation with an 800-nm fs-pulsed laser, we achieve a large number (N = 912) of correlated dipoles in Nd3+-concentrated nanoparticles, resulting in collective coherent emission with two orders of magnitude amplification in intensity and more than three orders of magnitude improvement in the radiative decay rate. Furthermore, we demonstrate that the control of excitation power and emitting sample length enables the lifetime manipulation of upconversion emission in a wide range from μs to sub-ns, accompanied by the typical superfluorescence signature of Burnham-Chiao ringing. These findings may benefit applications in many advanced technologies such as quantum counting and high-speed super-resolution bioimaging.

Abstract Background For patients with advanced non‐small cell lung cancer (NSCLC) who have received frontline immunochemotherapy, subsequent treatment options are limited. As the first dual programmed cell death‐1 (PD‐1)/cytotoxic T lymphocyte‐associated antigen‐4 bispecific antibody approved globally, cadonilimab demonstrated potential antitumor activity in advanced NSCLC patients resistant to anti‐PD‐1/PD‐L1 antibodies. Methods We retrospectively collected efficacy and safety data from advanced NSCLC patients treated with cadonilimab‐based regimens in later therapy lines. Results A total of 41 advanced NSCLC patients refractory to anti‐PD‐1/PD‐L1 therapy were enrolled. More than half of the patients received cadonilimab‐based regimen as a fourth or later line of treatment. At the data cutoff date, treatment efficacy could be evaluated in 23 patients. One patient (4.3%) achieved partial response, eight patients (34.8%) experienced stable disease, and 14 patients (60.9%) progressed. The objective response rate and disease control rate were 4.3% and 39.1%, respectively. The median progression‐free survival for all evaluated patients was 108.0 days. Due to the short follow‐up period, the median overall survival has not yet been reached. Treatment‐related adverse events (TRAEs) and immune‐related AEs occurred in 63.4% and 22% patients, respectively. The most common TRAEs included gamma‐glutamyl transferase elevation (17.1%), coughing (14.6%), and fatigue (12.2%). Five patients (12.2%) experienced grade ≥3 TRAEs. Conclusions In this heavily pretreated cohort of advanced NSCLC patients, cadonilimab‐based regimens showed moderate antitumor efficacy with a generally tolerable and manageable safety profile. However, more evidence is needed to support the administration of cadonilimab in NSCLC patients refractory to previous anti‐PD‐1/PD‐L1 therapy.

Abstract Grazing is a significant anthropogenic disturbance to grasslands, impacting their function and composition, and affecting carbon budgets and greenhouse gas emissions. However, accurate evaluations of grazing impacts are limited by the absence of long-term high-resolution grazing intensity data (i.e., the number of livestock per unit area). This study utilized census livestock data and a satellite-based vegetation index to develop the first Long-term High-resolution Grazing Intensity (LHGI) dataset of grassland in seven pastoral provinces in western China from 1980 to 2022. The LHGI dataset effectively captured spatial variations in grazing intensity, with validation at 73 sites showing a correlation coefficient (R2) of 0.78. The county-level validation showed an averaged R2 values of 0.73 ± 0.03 from 1980 to 2022. This dataset serves as a vital resource for estimating grassland carbon cycling and livestock system CH4 emissions, as well as contributing to grassland management.

Abstract The obese heart undergoes metabolic remodeling and exhibits impaired calcium (Ca2+) homeostasis, which are two critical assaults leading to cardiac dysfunction. The molecular mechanisms underlying these alterations in obese heart are not well understood. Here, we show that the Rab-GTPase activating protein AS160 is a lipid-responsive regulator of Ca2+ homeostasis through governing lysophosphatidylinositol metabolism and signaling. Palmitic acid/high fat diet inhibits AS160 activity through phosphorylation by NEK6, which consequently activates its downstream target Rab8a. Inactivation of AS160 in cardiomyocytes elevates cytosolic Ca2+ that subsequently impairs cardiac contractility. Mechanistically, Rab8a downstream of AS160 interacts with DDHD1 to increase lysophosphatidylinositol metabolism and signaling that leads to Ca2+ release from sarcoplasmic reticulum. Inactivation of NEK6 prevents inhibition of AS160 by palmitic acid/high fat diet, and alleviates cardiac dysfunction in high fat diet-fed mice. Together, our findings reveal a regulatory mechanism governing metabolic remodeling and Ca2+ homeostasis in obese heart, and have therapeutic implications to combat obesity cardiomyopathy.

Abstract Flaviviruses strategically utilize the endoplasmic reticulum (ER) in their replication cycles. However, the role of ER autophagy (ER-phagy) in viral replication process remains poorly understood. Here, we reveal that prolonged Zika virus (ZIKV) infection results from the degradation of ER-phagy receptor FAM134B, facilitated by viral NS2A protein. Mechanistically, ER-localized NS2A undergoes K48-linked polyubiquitination at lysine (K) 56 by E3 ligase AMFR. Ubiquitinated NS2A binds to FAM134B and AMFR orchestrates the degradation of NS2A-FAM134B complexes. AMFR-catalyzed NS2A ubiquitination not only targets FAM134B degradation but also hinders the FAM134B-AMFR axis. Notably, a recombinant ZIKV mutant (ZIKV-NS2AK56R), lacking ubiquitination and ER-phagy inhibition, exhibits attenuation in ZIKV-induced microcephalic phenotypes in human brain organoids and replicates less efficiently, resulting in weakened pathogenesis in mouse models. In this work, our mechanistic insights propose that flaviviruses manipulate ER-phagy to modulate ER turnover, driving viral infection. Furthermore, AMFR-mediated flavivirus NS2A ubiquitination emerges as a potential determinant of viral pathogenecity.

Abstract Viral pneumonia is characterized by inflammation in the lungs triggered by respiratory viruses. Dayuan Yin (DYY), a traditional Chinese medicine formula known for treating infectious diseases, is hypothesized to offer therapeutic benefits in treating viral pneumonia, although its specific molecular impacts remain understudied. This study aimed to evaluate the therapeutic effects of DYY in mitigating HCoV-229E virus-induced pneumonia in mice. This study employed an HCoV-229E virus-infected mouse model to investigate the therapeutic potential and underlying molecular mechanisms of DYY on virus-induced pneumonia. The respiratory function and organ indices post-treatment were assessed. Lung tissue and tracheal lesions were evaluated via immunohistochemistry. Spleen immune cell composition was analyzed using flow cytometry. Inflammatory cytokines and viral loads were quantified using hypersensitive multiplex electrochemiluminescence method and PCR analysis, respectively. The expression levels of MAS1, Ras, Raf1, MEK1/2, and ERK1/2 in lung tissues were determined through western blot analysis. DYY significantly improved respiratory function, and reduced organ pathology in infected mice. It effectively decreased viral loads and inflammatory cytokines such as IL-6, IL-1β, and TNF-α in lung tissues. Enhancements in immune response were evidenced by increased CD4/CD8 ratios in the spleen. DYY also notably upregulated MAS1 protein levels and suppressed the activation of the Ras/Raf1/MEK/ERK signaling pathway. DYY enhanced respiratory function and exerted significant antiviral and immunomodulatory effects in mice infected with the HCoV-229E virus, primarily by modulating MAS1 expression and inhibiting the Ras/Raf1/MEK/ERK pathway. Graphical Abstract

The adiabatic shear band is a common dynamic failure mechanism in metal materials at high strain rates. In this work, a new approach was proposed to improve mechanical properties and inhibit the formation and propagation of the adiabatic shear band in the pure Mo single crystal. The microstructure evolution of the pure Mo and Mo-Nb single crystals subjected to the dynamic load was investigated by EBSD and TEM. At a strain rate of 2500 s−1, the developed adiabatic shear band was totally distributed in the pure Mo single crystal, and the slip is the main deformation mechanism. A thinner adiabatic shear band was distributed in the Mo-3Nb single crystal accompanied by a few bands of deformation twins and then disappeared in the Mo-6Nb single crystal, replaced by the {112} deformation twinning. At high strain rates, the dynamic deformation mechanism of the Mo single crystal is sensitive to the Nb element, which attributes to the reduction of the generalized stacking fault energy.

This study examines the hot deformation behavior of Mo-14Re alloy at various true strains (15%, 35%, 65%) and strain rates (0.01 s−1, 10 s−1) at a temperature of 1400K. The findings indicate that dynamic recovery (DRV) and dynamic recrystallization (DRX) occur concomitantly as strain increases at a low strain rate of 0.01 s−1, with DRV being the predominant softening mechanism. At a strain of 65%, DRX emerges as the primary softening process. Conversely, under high strain rates of 10 s−1, DRX is inhibited, and the Mo-14Re alloy experiences work hardening due to an increase in dislocation density. Microscopic analysis shows that the high-density dislocations facilitate the continued nucleation and growth of recrystallized grains at low strain rates. At high strain rates, tangled dislocations hinder dislocation motion and recrystallization. Regarding texture evolution, stronger {100}//CD and weaker {111}//CD fiber texture is observed at low strain rates of 0.01 s−1, while stronger {111}//CD and weaker {100}//CD fiber texture forms at high strain rates of 10 s−1, with enhanced texture intensity. Mechanistic analysis confirms the activation of the {110}, {112}, and {123} dislocation slip systems at elevated temperatures, with the {123} system being the most dominant.

Abstract Over the past three decades, there has been increasing interest in miniaturized percutaneous nephrolithotomy (mPCNL) techniques featuring smaller tracts as they offer potential solutions to mitigate complications associated with standard PCNL (sPCNL). However, despite this growing acceptance and recognition of its benefits, unresolved controversies and acknowledged limitations continue to impede widespread adoption due to a lack of consensus on optimal perioperative management strategies and procedural tips and tricks. In response to these challenges, an international panel comprising experts from the International Alliance of Urolithiasis (IAU) took on the task of compiling an expert consensus document on mPCNL procedures aimed at providing urologists with a comprehensive clinical framework for practice. This endeavor involved conducting a systematic literature review to identify research gaps (RGs), which formed the foundation for developing a structured questionnaire survey. Subsequently, a two-round modified Delphi survey was implemented, culminating in a group meeting to generate final evidence-based comments. All 64 experts completed the second-round survey, resulting in a response rate of 100.0%. Fifty-eight key questions were raised focusing on mPCNLs within 4 main domains, including general information (13 questions), preoperative work-up (13 questions), procedural tips and tricks (19 questions), and postoperative evaluation and follow-up (13 questions). Additionally, 9 questions evaluated the experts’ experience with PCNLs. Consensus was reached on 30 questions after the second-round survey, while professional statements for the remaining 28 key questions were provided after discussion in an online panel meeting. mPCNL, characterized by a tract smaller than 18 Fr and an innovative lithotripsy technique, has firmly established itself as a viable and effective approach for managing upper urinary tract stones in both adults and pediatrics. It offers several advantages over sPCNL including reduced bleeding, fewer requirements for nephrostomy tubes, decreased pain, and shorter hospital stays. The series of detailed techniques presented here serve as a comprehensive guide for urologists, aiming to improve their procedural understanding and optimize patient outcomes.

Abstract Chlorophyll a (Chl-a) is a key indicator of marine ecosystems, and certain hydro-meteorological parameters (HMPs) are highly correlated with its fluctuations. Here, relevant and accessible HMPs were used as inputs, combined with machine learning (ML) algorithms for estimating 3D Chl-a in the South China Sea (SCS). With the inputs of temperature, salinity, depth, wind speed, wind direction, sea surface pressure, and relative humidity, the LightGBM-based model performed well, achieving high R2 values of 0.985 and 0.789 in validation and testing sets, respectively. Based on a large number of in situ measurements, this model enables the estimation of the 3D distribution of summer Chl-a in the SCS over the past fifteen years using a 3D hydrographic dataset combined with surface meteorological parameters. The results show that the 3D distribution of the model estimated Chl-a is characterized similarly to the previous studies and can capture the effect of hydro-meteorological conditions on Chl-a distribution. The environmental variables affecting Chl-a were considered more comprehensively in this study, and the methodological framework has the potential to be applied to the low-cost monitoring of the remaining water quality parameters.

Abstract Background The family Lauraceae is subdivided into six main lineages: Caryodaphnopsideae, Cassytheae, Cryptocaryeae, Hypodaphnideae, Laureae, and Neocinnamomeae. However, phylogenetic relationships among these lineages have been debatable due to incongruence between trees constructed using nuclear ribosomal DNA (nrDNA) sequences and chloroplast (cp) genomes. As with cp DNA, the mitochondrial (mt) DNA of most flowering plants is maternally inherited, so the phylogenetic relationships recovered with mt genomes are expected to be consistent with that from cp genomes, rather than nrDNA sequences. Results The mitogenome of Machilus yunnanensis, with a length of 735,392 bp, has a very different genome size and gene linear order from previously published magnoliid mitogenomes. Phylogenomic reconstructions based on 41 mt genes from 92 Lauraceae mitogenomes resulted in highly supported relationships: sisterhood of the Laureae and a group containing Neocinnamomeae and Caryodaphnopsideae, with Cassytheae being the next sister group, followed by Cryptocaryeae. However, we found significant incongruence among the mitochondrial, chloroplast, and nuclear phylogenies, especially for the species within the Caryodaphnopsideae and Neocinnamomeae lineages. Time-calibrated phylogenetic analyses showed that the split between Caryodaphnopsideae and Neocinnamomeae dated to the later Eocene, around 38.5 Ma, Laureae originated in the Late Cretaceous, around 84.9 Ma, Cassytheae originated in the mid-Cretaceous around 102 Ma, and Cryptocaryeae originated in the Early Cretaceous around 116 Ma. From the Late Cretaceous to the Paleocene, net diversification rates significantly increased across extant clades of major lineages, and both speciation rates and net diversification rates continued steady growth towards the present. Conclusions The topology obtained here for the first time shows that mt genes can be used to support relationships among lineages of Lauraceae. Our results highlight that both Caryodaphnopsideae and Neocinnamomeae lineages are younger than previously thought, likely first diversifying in the Eocene, and species in the other extant lineages of Lauraceae dates in a long-time span from the Early Cretaceous to the Eocene, and the climate of a period of about 90 million years was relatively warm, while the extant species of Lauraceae then continuously diversified with global cooling from the Eocene to the present day.

Intracellular delivery of biologicals such as peptides, proteins, and nucleic acids presents a great opportunity for innovative therapeutics. However, the endosome entrapment remains a major bottleneck in the intracellular delivery of biomacromolecules, largely limiting their therapeutic potential. Here, we converted a cell-penetrating peptide (CPP), low molecular weight protamine (LMWP), to endosomal escape peptides (EEPs) by masking LMWP with a pH-responsive counter-ionic peptide. The resulting masked CPPs (mLMWP and mLMWP2) effectively promoted the escape of peptide/protein cargoes from endosomes into the cytoplasm. Consequential lysosome repair and lysophagy were initiated upon the endolysosomal leakage. Minimal reactive oxygen species (ROS) elevation or cell death was observed. Based on mLMWP2, we constructed an intracellular protein delivery system containing an antibody as a targeting module, mLMWP2 as an endosomal escape module, and the desired protein cargo. With the HER2-targeting delivery system, we efficiently translocated cyclization recombination enzyme (Cre) and BH3-interacting domain death agonist (BID) into the cytosol of HER2+ cells to exert their biological activity. Thereby, the modular delivery system shows its potential as a promising tool for scientific studies and therapeutic applications.

Abstract Background With the increasing prevalence of chronic diseases, the demand for medical services from chronic disease patients has become diversified and personalized. The advantages and role of traditional Chinese medicine in the prevention and treatment of chronic diseases gradually emerging. The preferences and willingness to pay for traditional Chinese medicine services (TCMS) among patients with chronic diseases, as well as any disparities between urban and rural patients, have not been examined in past studies. Objective This study aimed to investigate the preferences of chronic disease patients for TCMS, explore the value/importance that patients place on different treatment attributes, and evaluate whether there are urban-rural differences in their preferences and willingness to pay for TCMS. Methods A total of 317 patients from Jiangsu Province, China participated in a discrete choice experiment that elicited the preferences for TCMS. The choice questions were constructed by six attributes: out-of-pocket (OOP) cost, institution, medical provider, treatment method, treatment duration, treatment efficacy. Mixed logit models were used to estimate the stated preference and marginal willingness to pay for each attribute. Results The choice preferences of chronic disease patients for TCMS in this study were influenced by the four attributes: institution, treatment method, and treatment efficacy, and OOP cost. Improvements in treatment efficacy were the most concerning, followed by being treated in traditional Chinese medicine (TCM) hospital. Patients were willing to pay more to get better treatment outcomes. Compared with primary care institutions, patients were willing to pay more for treatment in TCM hospitals. The preferences for economic attribute (OOP cost) varied between urban and rural areas, and rural patients tended to favor scenarios that imposed a lower economic burden on them. Conclusion The chronic disease patients’ preferences for TCMS were determined mainly by treatment efficacy but also by institution, treatment method and OOP cost. The urban-rural difference in preference identified in this study highlights that effective policy interventions should consider the characteristics of patients’ demand in different regions.

Abstract Bract coloration is one of the key ornamental traits in Bougainvillea, yet research has predominantly focused on phenotypic color traits and pigment composition, with limited understanding of the molecular mechanisms underlying color formation. This gap hinders the improvement and innovation in bract coloration. To elucidate the regulatory mechanisms of bract coloration in Bougainvillea and to enhance the utilization of its germplasm resources, this study employed the Illumina Novaseq 6000 sequencing platform to conduct transcriptomic sequencing on 21 samples of bracts exhibiting seven distinct phenotypes. Comparative analysis against Nr, Pfam, EggNOG, GO, and KEGG databases annotated 90,279 unigenes. The highest annotation rates were achieved with the Nr (40.13%), GO (30.44%), and EggNOG (25.64%) databases. Among the species annotated, Beta vulgaris (20.08%) and Chenopodium quinoa (14.58%) shared the highest homology with Bougainvillea bract transcriptomes. WGCNA analysis identified 12 positively correlated tissue-specific modules, of which 2 are related to bract color formation. By comparing transcriptome data and genes within these specific modules against the KEGG database, a total of 321 unigenes associated with bract color formation in Bougainvillea were discovered. Among these, 220 unigenes are involved in anthocyanin synthesis, 43 unigenes are involved in betalain synthesis, 23 unigenes are annotated as Chlorophyll a-b binding protein genes, and 35 unigenes participate in carotenoid synthesis. Quantitative real-time PCR (qRT-PCR) validation of 16 differentially expressed genes (DEGs) including PAL2, CHS1, ANS, BZ1, 6GT, CDOPA5GT, ANR, CHS2, and DOPA, revealed significant expression differences among magenta, yellow, white, and cherry-colored bracts, suggesting their potential as candidate genes for bract color development. This study not only enriches the transcriptomic data of Bougainvillea but also identifies genes associated with bract coloration, providing a valuable theoretical basis for future gene cloning, genetic engineering, and breeding efforts in Bougainvillea.

Abstract Background Digital health literacy (DHL) is pivotal for individuals to access trustworthy health information and make informed decisions, closely intertwined with health behaviors and psychological resilience—these factors collectively shape an individual’s approach to health management. Despite extensive research on digital health literacy in broader populations, the specific dynamics of digital health literacy in relation to health behaviors and psychological resilience among undergraduate nursing students in China remain understudied, highlighting a gap that this research endeavors to address. This study aims to assess the levels of digital health literacy among undergraduate nursing students in China, and to explore its association with health lifestyles and psychological resilience, which are considered influential factors. Methods Employing a descriptive cross-sectional research design, eligible Chinese nursing undergraduates were surveyed from June to October 2023. This study recruited a total of 418 undergraduate nursing students. After excluding 11 students on leave, 407 students participated in questionnaire completion and submission. The College Students’ Digital Health Literacy Scale, Healthy Lifestyle Assessment Scale and The Psychological Resilience Scale were used in this study. Results The mean scores for digital health literacy, health lifestyles, and psychological resilience were 74.78 ± 8.44, 127.14 ± 11.22, and 79.21 ± 11.02, respectively. Pearson correlation analysis results indicated that the correlations between digital health literacy and both health lifestyles (r = 0.707, P

Based on the daily precipitation data of 2, 424 stations and conventional weather chart data in mainland China in 2021, a statistical analysis of the main heavy rain weather processes from April to October of that year was conducted. The main influencing systems and precipitation situations were outlined, and a comparative analysis of the number of heavy rain days and major heavy rain events from 2008 to 2021 from April to October was performed. The results show that from April to October 2021, China experienced a total of 199 heavy rain days and 32 major heavy rain events. The number of heavy rain days was 10 days more than the average for the previous 13 years (2008-2020), while the number of major heavy rain events remained the same as the average for the previous 13 years. Among them, there were 7 occurrences in July, 6 in May and August each, 5 in June, 4 in September, and 3 in October, with 1 occurrence in April. Among the 32 major heavy rain events, 5 were caused by the landing or influence of tropical cyclones. The northern heavy rain from July 18th to 22nd, including the "7.20" extreme heavy rain in Zhengzhou, was the most widely affected and economically damaging major heavy rain event, with Zhengzhou in Henan Province recording the country's largest daily precipitation of 552.5 mm on July 20th of that year. The maximum accumulated rainfall for a single event in the year reached 820 mm, also occurring in Zhengzhou, Henan Province (July 18th to 22nd) and was caused by the joint influence of a trough, shear line, and warm and humid airflow.

Abstract Background The prognostic significance of obstructive sleep apnea (OSA) in patients with unstable angina (UA) based on remnant cholesterol (RC) or triglyceride (TG) levels remains unclear. This study aims to evaluate the effects of the interaction between RC, TG, and OSA on cardiovascular outcomes in UA patients. Methods In this prospective cohort study, OSA was diagnosed when apnea-hypopnea index of ≥ 15 events/h. Patients with high RC (HRC, n = 370) or high TG (HTG, n = 362) included RC or TG in the highest tertile, and those in the middle and lowest tertiles were defined as normal RC (NRC, n = 736) or normal TG (NTG, n = 744). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction, ischemia stroke, ischemia-driven revascularization, or hospitalization for UA. Results A total of 1,106 eligible UA patients were enrolled, among which 560 (50.6%) had OSA. RC and TG levels were increased in OSA patients, but there was no difference in the prevalence of OSA between the NRC and HRC or NTG and HTG groups. During a median follow-up of 1.9 (1.1, 3.0) years, OSA was associated with an increased risk of MACCE occurrence compared to non-OSA in UA patients with HRC (adjusted HR 2.06; 95% CI 1.20–3.51, P = 0.008), but not in those with NRC (adjusted HR 1.21; 95% CI 0.84–1.75, P = 0.297). The incremental risk in HRC was attributable to higher rates of hospitalization for UA and ischemia-driven revascularization. Results for HTG and NTG were similar. Conclusion OSA was associated with a worse prognosis in UA patients with HRC or HTG, emphasizing the necessity of identifying OSA presence in this population. Trial registration Clinicaltrials.gov; No: NCT03362385.

Abstract Recent years have witnessed an increasing number of manipulated online reviews in e-commerce platforms. Previous research has provided substantial evidence that vendor manipulation of online reviews has a significant negative impact on the stakeholders involved in the e-commerce business. Many platforms take various governance measures to filter manipulated reviews. Nevertheless, the effectiveness of these measures still remains unknown to a large extent. To bridge this research gap, this paper investigates the effect of differentiated platform governance, including defined as interventions to counterattack manipulation intensity, manipulation duration, and perceived quality manipulated, on the probability of future review manipulation. We develop a game theoretical model that incorporates the strategic interactions between the platform and vendors, which yield several testable hypotheses. We then conduct an empirical analysis of platform governance and review manipulation by using the review manipulation data collected from Amazon.com. Results of the analytical model and empirical analysis show that platform governance that targets manipulation intensity and manipulation duration can both effectively mitigate review manipulation probability. On the contrary, platform governance to counterattack manipulating perceived product quality exhibits an inverted U-shape relationship with review manipulation probability. This study provides novel insights into how to better mitigate online review manipulation for e-commerce platforms.

Abstract Background This study aimed to screen southern and southwestern Chinese individuals using expanded carrier screening (ECS), which explores the carrier status of recessively inherited diseases in southern and southwestern China, evaluates the clinical effectiveness of ECS application, and helps recognize high-risk fetuses that may have genetic disorders early in pregnancy, to provide better reproductive guidance. Methods ECS for 220 diseases based on next-generation sequencing was performed on 3024 southern and southwestern Chinese individuals (1512 couples). Carrier status was analyzed; genes and loci with high frequencies of variants and on high-risk couples (ARCs) were focused to evaluate the clinical utility of our ECS technology and provide them precise fertility guidance. Results In total, Pathogenic/likely pathogenic(P/LP) variants were found in 1885 individuals, so the carrier frequency was 62.3%, and 23.2% of the individuals were carriers of multiple diseases. furthermore, 2837 variants were detected, and the average number of P/LP variants carried per subject was 0.938. Additionally, 128 ARCs carried P/LP variants of the same gene, and the theoretical incidence rate in their offspring was as high as 2.12%. Conclusion This study validated the application of our ECS technique for carrier screening in southern China, identifying carrier status and providing accurate carrier frequencies for hundreds of genetic diseases.

Abstract Background Exposure to air pollution contributes to cardiovascular disease-related deaths and morbidity, including stroke. However, few studies have examined the global stroke burden linked to air pollution. This study aimed to evaluate the global stroke morbidity and mortality associated with air pollution from 1990 to 2021. Method With the Global Burden of Disease Study (GBD) 2021, the numbers, and age-standardized rates (ASRs) of deaths and disability-adjusted life years (DALYs) for air pollution-related stroke were reported globally. Further subgroup analyses were conducted by age, sex, region and country, and stroke subtypes. A linear regression model explored global temporal trends and a cluster analysis examined temporal trends across GBD regions. To predict trends until 2040, the age-period-cohort (APC) model and the Bayesian age-period-cohort (BAPC) model were applied. Results In 2021, there were 1,989,686 (95% uncertainty interval [95% UI], 1,530,479-2,493,238) deaths and 44,962,167 (95% UI, 35,020,339 − 55,467,024) DALYs due to air pollution-related stroke. The ASRs increased with age, peaking generally over 85 years. Males, the Central African region, and Guinea-Bissau showed higher stroke burdens Intracerebral hemorrhage was the most lethal subtype, with an ASR of 11.69 (95% UI 8.94–14.69) for deaths and 276.93 (95% UI 212.21-344.36) for DALYs. From 1990 to 2021, the crude number of deaths and DALYs increased by 13.4% and 6.3%, respectively, for the global stroke burden but showed a declining trend when age-standardized. Most GBD regions in Asia and Africa experienced an increasing stroke burden linked to air pollution, while Europe and America showed a decreasing trend. Predictions indicated a gradual reduction in ASRs, with higher rates in males from 2020 to 2040. Conclusions The global stroke burden associated with air pollution remained significant despite a decreasing trend until 2021. Although future predictions suggested a reduction, the crude counts for stroke burden remained substantial, with significant regional disparities. This warranted the implementation of public health policies and ongoing efforts.

Abstract Background This study aimed to analyze the associations of cardiometabolic index (CMI) with diabetic statuses and insulin resistance (IR) using data from the National Health and Nutrition Examination Survey (NHANES) and examined the potential mediating role of inflammation in these correlations. Methods This study enrolled 9477 participants across four NHANES cycles from 2011 to 2018. The primary outcomes of the study included the risk of having prediabetes, diabetes and the level of the homeostasis model assessment of IR (HOMA-IR). Other outcomes including the levels of fasting blood glucose (FBG), hemoglobin A1c (HbA1c), oral glucose tolerance test (OGTT) results, fasting insulin, the risk of oral hypoglycemic medicine use, insulin use, and retinopathy were also collected and analyzed. Logistic regression model, subgroup analysis, restricted cubic spine (RCS), and Pearson correlation coefficients were conducted to assess the associations of CMI with diabetic statuses and IR. The mediating role of inflammation was evaluated to investigate the potential mechanism of the associations between CMI and diabetic statuses. Results Among included participants, the CMI levels in normal participants, prediabetes and diabetes in this study were 0.48, 0.73 and 1.07. After multivariable adjustment, CMI was positively associated with the risk of prediabetes (OR = 1.49, 95% CI = 1.24–1.79), diabetes (OR = 2.14, 95% CI = 1.82–2.50) and the level of HOMA-IR (β = 2.57, 95% CI = 2.14–3.01). Besides, an increased CMI was correlated with higher levels of FBG, HBA1c, OGTT results and fasting insulin as well as the greater risk of oral hypoglycemic medicine use and insulin use. The RCS showed an inverted L-shaped association of CMI with prediabetes and diabetes (P for non-linearity

Abstract Bcakground Soil respiration (Rs), as the second largest CO2 emissions of terrestrial ecosystems, is sensitive to disturbance and consequent environmental changes. Mowing is strategically implemented as an management approach and has the potential to influence carbon cycling in meadow steppes. However, it remains unclear how and why Rs and its heterotrophic (Rh) and autotrophic (Ra) components respond to consecutive mowing and associated ecological consequences. Here, we conducted a field mowing experiment in a meadow steppe in 2018 and monitored Rs, Rh, and Ra from 2019 to 2022. Results We observed a significant reduction in Rs by 4.8% across four years, primarily attributed to a decrease in Rh. This decline in Rs intensified over time, indicating an accumulative effect of mowing. In addition, mowing induced an generally increasing Ra/Rs ratio over the experimental years with a simultaneous increase in the ratio of belowground to aboveground biomass (BGB/AGB). Furthermore, structural equation modeling results revealed that the decline in Rs was largely ascribed to reduced microbial biomass carbon (MBC) under mowing, while the increased Ra/Rs was primarily explained by the enhanced BGB/AGB. Partial regression analysis suggested that the biotic factor of microbial biomass dominated changes in soil respiration induced by mowing rather than abiotic soil temperature. Conclusions Our findings showed that consecutive mowing decreased Rs and raised Ra/Rs in meadow steppe by decreasing plant biomass and altering the proportion of biomass allocation. This observed decline in Rs would help to reduce CO2 concentration in atmosphere as well as alleviate global warming. However, considering the concurrent lower microbial biomass, the potential positive impacts of mowing on climate and ecosystem function should be reevaluated in future grassland management practices.

The mechanical properties and insulation damage of stator end windings in permanent magnet synchronous generator (PMSG) are investigated by theoretical analysis, finite element analysis (FEA) and experiment verification. First, a theoretical model of the winding electromagnetic force (EF) and vibration response before and after eccentricity faults are established. Then, the stress/strain distribution of the end windings under different working conditions is analyzed. Finally, the insulation damage behavior of end windings with initial cracks is studied and characterized using the stress intensity factor (SIF). The results indicate that the winding EF and vibration responses vary under different faults. The stress/strain at the joint of the winding is the largest, and the insulation layer has the maximum stress/strain under the same section. Additionally, the SIF amplitude of the crack at the winding joint is the largest. And the SIF amplitude of the crack will increase with the increase of fault degree/crack depth/crack length. The contribution of this paper lies in the comprehensive analysis of the winding EF distribution, vibration response, stress and strain, and insulation damage before and after eccentricity. This analysis can provide valuable reference for the health monitoring of PMSG eccentricity faults and the prevention of winding insulation damage.

Static air-gap eccentricity (SAGE) is a common fault in generators. Current researches primarily focus on the parallel SAGE types, while the inclined static air-gap eccentricity (ISAGE) has been rarely investigated. This paper proposes an improved air-gap eccentricity model and presents a study on the electromagnetic-mechanical properties in synchronous generators under typical ISAGE running conditions. Such electromagnetic-mechanical properties include not only the magnetic flux density (MFD) variations, but also the mechanical responses of the electromagnetic torque (EMT) and rotor unbalanced magnetic pulls (UMP). The typical ISAGE factors include: 1) a varied rotor inclined angle θ, and 2) different values of axial inclined distance z (indicates the offset combination case of the two rotor ends). This work is based on the MFD analysis calculation. Theoretical analysis, finite element analysis, and experimental study are carried out, respectively, by taking a 5 kVA two-pole prototype generator as the study object. It is shown that the electromagnetic-mechanical properties of the generator will change when the inclined eccentricity occurs. The EMT, and the rotor UMP as well as the vibrations will increase as the rotor inclined θ and z increase. Specifically, the 2nd harmonic has the most significant variation.

Abstract Autosomal dominant Fanconi syndrome due to a GATM variant (GATM‐FS), causes accumulation of misfolded arginine‐glycine amidinotransferase (AGAT) in proximal renal tubules leading to cellular injury. GATM‐FS presents during childhood and progresses to end‐stage kidney disease (ESKD) in adults. We study creatine metabolism in two individuals of unrelated families with a known GATM variant and the effect of creatine supplementation in kidney organoids. Plasma and urine metabolites were measured by mass spectrometry. Brain creatine was assessed by magnetic resonance spectroscopy (MRS). Guanidinoacetate (GAA) synthesis by the AGAT mutant was measured in patient‐derived immortalized lymphocytes using stable isotopes of arginine and glycine. The effect of creatine on GATM expression was assessed in human kidney cells and organoids. Several family members from two unrelated families were diagnosed with Fanconi syndrome and had the c.1022C>T (p. P341L) variant in GATM. Two affected individuals in both families had moderately reduced plasma GAA levels. In comparison to wild‐type cells, GAA synthesis by patient‐derived GATMP341L+/− lymphoblastoid cell lines (LCL) was reduced, but not absent as in GATM cells from a patient with creatine deficiency syndrome. In vitro studies on human kidney organoids revealed reduced AGAT expression after treatment with creatine. Finally, we showed in one patient that creatine supplementation (5 g daily) substantially increased plasma creatine levels. We report low plasma and urine GAA in patients with autosomal dominant GATM‐FS and show that creatine downregulates AGAT in human kidney cells.