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Background: The triglyceride glucose (TyG) index, as a reliable marker of insulin resistance, is associated with the incidence and poor prognosis of various cardiovascular diseases. However, the relationship between the TyG index and clinical outcomes in patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve replacement (TAVR) remains unclear. Methods: This study consecutively enrolled 1569 patients with AS underwent TAVR at West China Hospital of Sichuan University between April 2014 and August 2023. The outcomes of interest included all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE). Multivariate adjusted Cox regression and restricted cubic splines (RCS) regression analyses were used to assess the associations between the TyG index and the clinical outcomes. The incremental prognostic value of the TyG index was further assessed by the time-dependent Harrell's C-index, integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). Results: During a median follow-up of 1.09 years, there were 146, 70, and 196 patients experienced all-cause death, cardiovascular death, and MACE, respectively. After fully adjusting for confounders, a per-unit increase of TyG index was associated with a 441% (adjusted HR: 5.41, 95% CI: 4.01–7.32), 385% (adjusted HR: 4.85, 95% CI: 3.16–7.43), and 347% (adjusted HR: 4.47, 95% CI: 3.42–5.85) higher risk of all-cause mortality, cardiovascular mortality and MACE, respectively. The RCS regression analyses revealed a linear association between TyG index and endpoints (all P for non-linearity > 0.05) with 8.40 as the optimal binary cutoff point. Furthermore, adding TyG index to the basic risk model provided a significant incremental value in predicting poor prognosis (Time-dependent Harrell's C-index increased for all the endpoints; All-cause mortality, IDI: 0.11, P < 0.001; NRI: 0.32, P < 0.001; Cardiovascular mortality, IDI: 0.043, P < 0.001; NRI: 0.37, P < 0.001; MACE, IDI: 0.092, P < 0.001; NRI: 0.32, P < 0.001). Conclusions: In patients with severe AS receiving TAVR, there was a positive linear relationship between TyG index and poor prognosis, with 8.4 as the optimal bivariate cutoff value. Our findings suggest TyG index holds potential value for risk stratification and guiding therapeutic decisions in patients after TAVR. [ABSTRACT FROM AUTHOR]

Background: Pediatric patients undergoing liver transplantation are particularly susceptible to complications arising from intraoperative fluid management strategies. Conventional liberal fluid administration has been challenged due to its association with increased perioperative morbidity. This study aimed to assess the impact of intraoperative high-volume fluid therapy on pediatric patients who are undergoing living donor liver transplantation (LDLT). Methods: Conducted at the Children's Hospital of Chongqing Medical University from March 2018 to April 2021, this retrospective study involved 90 pediatric patients divided into high-volume and non-high-volume fluid administration groups based on the 80th percentile of fluid administered. We collected the perioperative parameters and postoperative information of two groups. Multivariable logistic regression was utilized to assess the association between estimated blood loss (EBL) and high-volume FA. Kaplan-Meier survival analysis was used to compare patient survival after pediatric LDLT. Results: Patients in the high-volume FA group received a higher EBL and longer length of stay than that in the non-high-volume FA group. Multivariate logistic regression analysis indicated that hours of maintenance fluids and fresh frozen plasma were significantly associated risk factors for the occurrence of EBL during pediatric LDLT. In addition, survival analysis showed no significant differences in one-year mortality between the groups. Conclusions: High-volume fluid administration during LDLT is linked with poorer intraoperative and postoperative outcomes among pediatric patients. These findings underscore the need for more conservative fluid management strategies in pediatric liver transplantations to enhance recovery and reduce complications. [ABSTRACT FROM AUTHOR]

By generalizing a criterion of Mufa Chen for Markov jump processes, we establish the necessary and sufficient conditions for the extinction, explosion and coming down from infinity of a continuous-state nonlinear Neveu's branching process. [ABSTRACT FROM AUTHOR]

Feature selection is a common data preprocessing technique that aims to construct better models by selecting the most predictive features. Existing particle swarm optimization-based feature selection algorithms encounter two challenges when dealing with high-dimensional problems: easy to fall into local optimum and high computational cost. Therefore, this paper proposes an evolutionary dual-task feature selection method based on probability-based initialization particle swarm optimization (PPSO-EDT), which aims to find optimal solutions by transferring knowledge between two related tasks. Firstly, a probability-based initialization strategy is designed to accelerate population convergence by fully utilizing the correlation between labels and features. Secondly, a task generation strategy based on feature correlation was designed, which constructs the main task and auxiliary task by selecting feature subsets with highly correlated values and feature subsets without redundancy, respectively. Finally, an multi-task transfer mechanism is used to transfer knowledge and find optimal solutions. The results on 12 high-dimensional datasets indicate that the proposed method achieves high classification performance with a small feature subset in a relatively short amount of time. [ABSTRACT FROM AUTHOR]

Lettuce is one of the most widely cultivated and consumed dicotyledonous vegetables globally. Despite the availability of its reference genome sequence, lettuce gene annotation remains incomplete, impeding comprehensive research and the broad application of genomic resources. Long-read RNA isoform sequencing (Iso-Seq) offers substantial advantages for analyzing RNA alternative splicing and aiding gene annotation, yet it faces throughput limitations. We present the HIT-ISOseq method tailored for bulk sample analysis, significantly enhancing RNA sequencing throughput on the PacBio platform by concatenating cDNA. Here we show, HIT-ISOseq generates 3-4 cDNA molecules per CCS read in lettuce, yielding 15.7 million long reads per PacBio Sequel II SMRT Cell 8 M. We validate its effectiveness in analyzing six lettuce tissue samples, including roots, stems, and leaves, revealing tissue-specific gene expression patterns and RNA isoforms. Leveraging diverse tissue long-read RNA sequencing, we refine the transcript annotation of the lettuce reference genome, expanding its GO and KEGG annotation repertoire. Collectively, this study serves as a foundational reference for genome annotation and the analysis of multi-sample isoform expression, utilizing high-throughput long-read transcriptome sequencing. A study demonstrates that an enhanced long-read RNA sequencing method significantly improves lettuce genome annotation, broadening its GO and KEGG annotations, and effectively identifies tissue-specific gene expression and RNA isoforms. [ABSTRACT FROM AUTHOR]

Background: To investigate the effects of acupuncture on post-stroke limb spasm model rats and the underlying mechanism. Methods: A total of 50 Sprague-Dawley rats were randomly divided into three groups, Control group (10), Model group (20) and Zhishen Tiaoxing (ZSTX) acupuncture group (20). Middle cerebral artery occlusion was conducted in SD rats to establish post-stroke limb spasm rats, which were treated with ZSTX acupuncture. Behavioral assays were determined by the Narrow ally test, the limb muscle tension was detected by the BL-420S test system, and infarct volume was assessed after the cerebral infarction by 2, 3, 5-triphenyltetrazolium chloride staining. Heterogeneous neurotransmitter Y -aminobutyric acid (GABA) and its receptors GABAA and GABAB in the cerebral cortex of the infarct area were determined by immunofluorescence assay. The release of Trkb and K-Cl cotransporter isoform 2 was detected by an immunofluorescence double labeling study. Western Blot was utilized to measure the expression of BDNF and Trkb. Results: The results showed that the behavioral assays in post-stroke limb spasm rats were significantly improved by the treatment of ZSTX acupuncture. 14 days of ZSTX acupuncture can effectively inhibit muscle tone and decrease Infarct volume, which was measured with BL-420S biological function experiment system and triphenyltetrazolium chloride. Meanwhile, the results of Double-Label Immunofluorescence Assays showed that ZSTX acupuncture improved the expression of GABA, GABAA, GABAB, BDNF, and K-Cl cotransporter isoform 2. Double-Label Immunofluorescence Assays and WB results showed that 14 days ZSTX acupuncture declined the expression of Trkb. Conclusions: Our results suggest that 14 days of ZSTX acupuncture can significantly improve post-stroke limb spasm. Meanwhile, the pathogenesis of post-stroke limb spasm and the efficacy of ZSTX acupuncture involve metabolic pathways of neurotransmitters, and electro-acupuncture can treat post-stroke limb spasm by regulating BDNF/Trkb-KCC2 signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: To summarize the clinical characteristics and prognosis of febrile infection-related epilepsy syndrome with claustrum lesions (FIRES-C). Method: Clinical data of FIRES-C patients were collected retrospectively. The study reviewed and analyzed their clinical manifestations, treatment strategies, and prognosis. Result: Twenty patients were enrolled, including 13 females and 7 males, with a median onset age of 20.5 years. All patients developed seizures after fever, with a median interval of 5 days. Brain MRI showed symmetric lesions in the claustrum in all patients. The median interval from seizure onset to abnormal MRI signals detection was 12.5 days. All patients had negative results for comprehensive tests of neurotropic viruses and antineuronal autoantibodies. Seventy percent of cases had been previously empirically diagnosed with autoimmune encephalitis or viral encephalitis before. All patients received anti-seizure medicine. Eleven patients (55%) received antiviral therapy. All patients received immunotherapy, including glucocorticoids (100%), intravenous immunoglobulin (IVIg) (65%), plasma exchange (PLEX) (10%), tocilizumab (10%), rituximab (5%), and cyclophosphamide (5%). Sixty percent of patients received long-term immunotherapy (≥ 3 months). The median follow-up was 11.5 months;60% of patients were diagnosed with refractory epilepsy. Conclusion: Bilateral claustrum lesion on MRI is a distinctive neuroimage feature for FIRES, which may serve as an indication for the initial clinical assessments. FIRES-C should be classified as a type of inflammatory encephalopathy characterized by a monophasic nature. Some FIRES-C patients respond to immunotherapy and antiseizure treatments but most experience refractory epilepsy as a long-term outcome. [ABSTRACT FROM AUTHOR]

We reported a chiral oxamide‐phosphine ligand (COAP−Ph)‐Pd‐catalyzed asymmetric [3+2] cycloaddition reaction between vinyl cyclopropane compounds derived from 1,3‐indanedione and 2‐vinylcyclopropane‐1,1‐dicarboxylates with cyclic sulfonyl 1‐azadienes. The corresponding reactions provided a series of enantiomerically active spiro cyclopentane‐indandione and cyclopentane structures bearing three consecutive stereogenic centers in good yields with good diastereo‐ and enantioselectivity. The COAP−Pd complex serves not only to promote generation of chiral π‐allyl‐palladium intermediates and induce the asymmetry of the reaction, but also depress the background reaction. [ABSTRACT FROM AUTHOR]

Food is the top priority for the people, and safety is the top priority for food. The quality and safety of food are related to the national economy and people's livelihood. With the development of Chinese economy and the improvement of people's quality of life, the scale of the food industry has also grown year by year, and the society and consumers have more stringent requirements on the quality of food production and its own safety. However, food quality and safety incidents occur frequently, making food quality and safety management an important task for improving people's livelihoods. Machine learning has been widely applied in the field of food quality and safety, with strong self-learning ability, good non-linear fitting ability, and fast modeling. Among them, neural network models and supervised learning methods can accurately and quickly detect and control the quality of food in the production process. This article focuses on the research progress of machine learning in the field of food quality and safety, and discusses it in three directions: Food quality inspection, food process traceability, and food safety warning. In order to clarify the focus, advantages and disadvantages, and future development direction of machine learning algorithms in food regulation, and provide theoretical support and technical guidance for the intelligent development of ensuring food quality and safety. [ABSTRACT FROM AUTHOR]

This study investigates the ablation resistance of C/C–SiC composites using the ground simulation internal flow‐field supersonic oxygen‐rich ablation test technology. The microstructure evolution and ablation mechanism of the composites in a supersonic oxygen‐rich environment were explored by examining the macroscopic and microscopic ablation morphologies of the composites before and after the test. The results demonstrate that C/C–SiC composites exhibit excellent ablation resistance, with mass and linear ablation rates of.46 × 10−2 g/s and.42 × 10−2 mm/s, respectively, after 120 s of ablation in a low gas temperature and high oxygen‐rich ablation thermal environment. As the gas temperature increases, the mass and linear ablation rates of C/C–SiC composites gradually increase, even though the oxygen enrichment within the gas components decreases. When the gas temperature reaches 2178–2491 K, the mass and linear ablation rates increase to 1.31 × 10−2 g/s and.84 × 10−2 mm/s, respectively. Furthermore, at high temperatures above 2650 K, the mass and linear ablation rates of the composites exhibit a geometric multiple increase, reaching 4.73 × 10−2 g/s and 1.89 × 10−2 mm/s, respectively. These findings indicate that the ablation resistance of C/C–SiC composites in the supersonic oxygen‐rich ablation environment is more sensitive to gas temperature than oxygen enrichment. The main factors contributing to the increased ablation rate of C/C–SiC composites in the supersonic oxygen‐rich ablation process include the formation of a glass SiO2 oxide film, transition to molten SiO2, erosion of molten SiO2, and high‐temperature sublimation of the SiC matrix. [ABSTRACT FROM AUTHOR]

Objective To analyze the clinical characteristics of anti-neuronal antibody positive paraneoplastic neurological syndrome related to immune checkpoint inhibitors (ICI-PNS). Methods and Results A total of 5 patients with anti-neuronal antibody positive ICI-PNS in Peking Union Medical College Hospital from January 2012 to March 2024 were included. Tumor types included small cell lung cancer (2 cases), malignant melanoma (one case), Hodgkin lymphoma (one case) and cervical cancer (one case). Immune checkpoint inhibitors (ICIs) included programmed death 1 (PD-1) inhibitors (3 cases), programmed cell death ligand 1 (PD-L1) inhibitors (one case) and bispecific PD-1/cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors (one case). All 5 patients presented with high-risk neurologic phenotypes of paraneoplastic neurological syndrome (PNS), of which 4 presented with limbic encephalitis and one presented with rapidly progressive cerebellar syndrome. Anti-neuronal antibodies detected in serum and/or cerebrospinal fluid of patients included anti-Hu, γ-aminobutyric acid receptor type B (GABABR), sex-determining region of Y chromosome-related high mobility group box 1 (SOX1), metabotropic glutamate receptor 5 (mGluR5) and Yo antibodies. Neurological syndromes occurred within 2 weeks after receiving ICIs in 4 patients. The modified Rankin Score (mRS) of 4 patients was 3 at peak of illness, and one patient was 5 at peak of illness. The Common Terminology Criteria for Adverse Events (CTCAE) was grade 3 in all 5 patients. After withdrawal of ICIs and treatment with glucocorticoids and intravenous immunoglobulin (IVIg), the neurological symptoms of the patients were improved. Conclusions High/intermediate-risk anti-neuronal antibodies are diagnostic markers of ICI-PNS. Evaluation of ICI-PNS clinical phenotypes and CTCAE grading are important for immunotherapy. Discontinuation of ICIs, administration of glucocorticoids and IVIg can improve the prognosis of patients. [ABSTRACT FROM AUTHOR]

This study aimed to identify factors that affect physicians' generic prescribing behavior based on the theory of planned behaviors (TPB). Methods: Data were collected by both electronic and paper-based surveys from 1297 Chinese physicians, and 1047 surveys were retained. The structural equation model (SEM) was employed to investigate the relationship between four behavioral constructs, namely, attitudes, subjective norms, perceived control of behaviors, and intentions. Results: About 50% of Chinese physicians had a positive attitude towards generic drugs that had passed the "Consistency Evaluation of Quality and Efficacy of Generic Drugs" (high-quality generic drugs), but their knowledge of generic drugs was relatively inadequate. The path coefficients for the effect of attitudes, subjective norms, and perceived behavioral control on behavioral intention were 0.285, 0.366, and 0.322 respectively. The path coefficients for the effect of behavioral intention and perceived behavioral control on prescribing behavior were 0.009 and 0.410 respectively. Conclusion: Physicians' attitudes, subjective norms, and perceived behavioral control were significant positive correlation predictors of behavioral intention. Subjective norms and perceived behavior control had a greater impact than attitude on physicians' prescribing intention. However, the generic prescribing behavior is not under the volitional control of Chinese physicians. Physicians' prescribing practice is likely affected by perceived strong control over prescribing generic drugs. [ABSTRACT FROM AUTHOR]

Emotional disorders, such as anxiety and depression, represent a major societal problem; however, the underlying neurological mechanism remains unknown. The ventral lateral septum (LSv) is implicated in regulating processes related to mood and motivation. In this study, we found that LSv GABAergic neurons were significantly activated in mice experiencing chronic social defeat stress (CSDS) after exposure to a social stressor. We then controlled LSv GABAergic neuron activity using a chemogenetic approach. The results showed that although manipulation of LSv GABAergic neurons had little effect on anxietylike behavioral performances, the activation of LSv GABAergic neurons during CSDS worsened social anxiety during a social interaction (SI) test. Moreover, LSv GABAergic neurons showed strong projections to the paraventricular nucleus (PVN) of the hypothalamus, which is a central hub for stress reactions. Remarkably, while activation of GABAergic LSv-PVN projections induced social anxiety under basal conditions, activation of this pathway during CSDS alleviated social anxiety during the SI test. On the other hand, the chemogenetic manipulation of LSv GABAergic neurons or LSvGABA-PVN projections had no significant effect on despair-like behavioral performance in the tail suspension test. Overall, LS GABAergic neurons, particularly the LSv GABAergic-PVN circuit, has a regulatory role in pathological anxiety and is thus a potential therapeutic target for the treatment of emotional disorders. [ABSTRACT FROM AUTHOR]

Summary: Zingiber (Zingiberaceae: Zingibereae) is an economically important but taxonomically difficult genus, with names frequently misapplied. Here, we thoroughly review all names corresponding to the currently recognised 54 species from China including their synonyms, and clarify the status of their types. Lectotypes are designated for 40 names (including one second‐step), neotypes for 3 names, and epitypes for 3 names. Additional and often uncited isotypes have been discovered for numerous names, and such additional records are here provided. Tupistra bambusifolia var. rubromaculosa, Z. simaoense, Z. confine and Z. larsenii are newly treated as synonyms of Z. atrorubens, Z. densissimum, Z. officinale and Z. recurvatum respectively. A new combination, Z. bambusifolium, is proposed, based on Tupistra bambusifolia. This study will form the nomenclatural basis of an ongoing taxonomic revision of the genus in China, and phylogenetic study of the genus. [ABSTRACT FROM AUTHOR]

The fungal plasma membrane H+-ATPase (Pma1) pumps protons out of the cell to maintain the transmembrane electrochemical gradient and membrane potential. As an essential P-type ATPase uniquely found in fungi and plants, Pma1 is an attractive antifungal drug target. Two recent Cryo-EM studies on Pma1 have revealed its hexameric architecture, autoinhibitory and activation mechanisms, and proton transport mechanism. These structures provide new perspectives for the development of antifungal drugs targeting Pma1. In this article, we review the history of Pma1 structure determination, the latest structural insights into Pma1, and drug discoveries targeting Pma1. [ABSTRACT FROM AUTHOR]

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 < 0.001]. In the rhythm control subgroup, E/e′ [odds ratio (OR) 0.878 (95% CI 0.792–0.974), P = 0.014], left ventricular end‐diastolic diameter [OR 0.874 (95% CI 0.777–0.983), P = 0.024], and CHA2DS2‐VASc score (congestive HF, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischaemic attack, vascular disease, age 65–74 years, and sex category) [OR 0.647 (95% CI 0.438–0.955), P = 0.028] were identified as three independent predictors of LVEF trajectory improvement. Conclusions: Rhythm control is associated with improved LVEF trajectory and clinical outcomes and may thus be considered the optimal therapeutic strategy for patients with both HF and AF. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate the factors influencing relapse and prognosis in patients with primary autoimmune cerebellar ataxia (PACA), an area previously not well understood. Methods: This prospective cohort study included patients who satisfied the modified diagnostic criteria of PACA. A modified Rankin scale score ≤ 2 at the last follow-up was defined as a favorable prognosis. Cox and Logistic regression were utilized to identify relapsing and prognostic factors, respectively. Results: A total of 68 patients were included and 35.3% were male. The median onset age was 42.9 years (IQR 22.1–54.0). Neuronal autoantibodies were detected in 33 (50.8%) patients. Of the 65 patients who received first-line immunotherapy, 55 (84.6%) were responsive and 10 (15.4%) were not. Responsiveness to first-line immunotherapy emerged as an independent factor for favorable prognosis (HR 16.762; 95% CI 2.877–97.655; p = 0.002), as did the absence of peripheral neuropathy/radiculopathy (HR 14.286; 95% CI 2.41–83.333; p = 0.003). Relapses occurred in 19 (27.9%) patients. Onset age ≤ 43 years (HR 5.245; 95% CI 1.499–18.35; p = 0.009), presence of peripheral neuropathy/radiculopathy (HR 4.280; 95% CI 1.622–11.298; p = 0.003) and elevated cerebrospinal fluid (CSF) protein concentration (HR 3.443; 95% CI 1.083–10.951; p = 0.036) were statistically significant relapsing factors. Conclusion: This study identified younger onset age, presence of peripheral neuropathy/radiculopathy and elevated CSF protein concentration as relapsing factors, and absence of peripheral neuropathy/radiculopathy and responsiveness to first-line immunotherapy as independent factors for favorable prognosis in PACA patients. These findings may guide individualized treatment strategies and potentially improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background and Aims: The clinical effects of multivessel interventions in patients with unstable angina/non‐ST‐segment elevation myocardial infarction (UA/NSTEMI), multivessel disease (MVD) and chronic kidney disease (CKD) remain uncertain. This study aimed to investigate the safety and effectiveness of intervention in non‐culprit lession(s) among this cohort. Methods: We consecutively included patients diagnosed with UA/NSTEMI, MVD and CKD between January 2008 and December 2018 at our centre. After successful percutaneous coronary intervention (PCI), we compared 48‐month overall mortality between those undergoing multivessel PCI (MV‐PCI) through a single‐procedure or staged‐procedure approach and culprit vessel‐only PCI (CV‐PCI) after 1:1 propensity score matching. We conducted stratified analyses and tests for interaction to investigate the modifying effects of critical covariates. Additionally, we recorded the incidence of contrast‐induced nephropathy (CIN) to assess the perioperative safety of the two treatment strategies. Results: Of the 749 eligible patients, 271 pairs were successfully matched. Those undergoing MV‐PCI had reduced all‐cause mortality (hazard ratio (HR): 0.67, 95% confidence interval (CI): 0.48–0.67). Subgroup analysis showed that those with advanced CKD (estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2) could not benefit from MV‐PCI (P = 0.250), and the survival advantage also tended to diminish in diabetes (Pinteraction < 0.01; HR = 0.95, 95% CI = 0.65–1.45). Although the staged‐procedure approach (N = 157) failed to bring additional survival benefits compared to single‐procedure MV‐PCI (N = 290) (P = 0.460), it showed a tendency to decrease the death risk. CIN risks in MV‐PCI and CV‐PCI groups were not significantly different (risk ratio = 1.60, 95% CI = 0.94–2.73). Conclusion: Among patients with UA/NSTEMI and non‐diabetic CKD and an eGFR > 30 mL/min/1.73 m2, MV‐PCI was associated with a reduced risk of long‐term death but did not increase the incidence of CIN during the management of MVD compared to CV‐PCI. And staged procedures might be a preferable option over single‐procedure MV‐PCI. [ABSTRACT FROM AUTHOR]

As the malignancy with the highest global incidence, breast cancer represents a significant threat to women's health. Recent advances have shed light on the importance of mitochondrial function in cancer, particularly in metabolic reprogramming within tumors. Recognizing this, we developed a novel risk signature based on mitochondrial-related genes to improve prognosis prediction and risk stratification in breast cancer patients. In this study, transcriptome data and clinical features of breast cancer samples were extracted from two sources: the TCGA, serving as the training set, and the METABRIC, used as the independent validation set. We developed the signature using LASSO-Cox regression and assessed its prognostic efficacy via ROC curves. Furthermore, the signature was integrated with clinical features to create a Nomogram model, whose accuracy was validated through clinical calibration curves and decision curve analysis. To further elucidate prognostic variations between high and low-risk groups, we conducted functional enrichment and immune infiltration analyses. Additionally, the study encompassed a comparison of mutation landscapes and drug sensitivity, providing a comprehensive understanding of the differing characteristics in these groups. Conclusively, we established a risk signature comprising 8 mitochondrial-related genes—ACSL1, ALDH2, MTHFD2, MRPL13, TP53AIP1, SLC1A1, ME3, and BCL2A1. This signature was identified as an independent risk predictor for breast cancer patient survival, exhibiting a significant high hazard ratio (HR = 3.028, 95%CI 2.038–4.499, P < 0.001). Patients in the low-risk group showed a more favorable prognosis, with enhanced immune infiltration, distinct mutation landscapes, and greater sensitivity to anti-tumor drugs. In contrast, the high-risk group exhibited an adverse trend in these aspects. This risk signature represents a novel and effective prognostic indicator, suggesting valuable insights for patient stratification in breast cancer. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the repeatability of cartilage volume and thickness values at 1.5 T MRI using a fully automatic cartilage segmentation method and reproducibility of the method between 1.5 T and 3 T data. Methods: The study included 20 knee joints from 10 healthy subjects with each subject having undergone double-knee MRI. All knees were scanned at 1.5 T and 3 T MR scanners using a three-dimensional (3D) high-resolution dual-echo in steady state (DESS) sequence. Cartilage volume and thickness of 21 subregions were quantified using a fully automatic cartilage segmentation research application (MR Chondral Health, version 3.0, Siemens Healthcare, Erlangen, Germany). The volume and thickness values derived from fully automatically computed segmentation masks were analyzed for the scan–rescan data from the same volunteers. The accuracy of the automatic segmentation of the cartilage in 1.5 T images was evaluated by the dice similarity coefficient (DSC) and Hausdorff distance (HD) using the manually corrected segmentation as a reference. The volume and thickness values calculated from 1.5 T and 3 T were also compared. Results: No statistically significant differences were found for cartilage thickness or volume across all subregions between the scan–rescanned data at 1.5 T (P > 0.05). The mean DSC between the fully automatic and manually corrected knee cartilage segmentation contours at 1.5 T was 0.9946. The average value of HD was 2.41 mm. Overall, there was no statistically significant difference in the cartilage volume or thickness in most-subregions between the two field strengths (P > 0.05) except for the medial region of femur and tibia. Bland–Altman plot and intraclass correlation coefficient (ICC) showed high consistency between results obtained based on same and different scanning sequences. Conclusion: The cartilage segmentation software had high repeatability for DESS images obtained from the same device. In addition, the overall reproducibility of the images obtained from equipment of two different field strengths was satisfactory. [ABSTRACT FROM AUTHOR]

The present study investigated whether physical cleansing can reduce the mindset effect in problem-solving in two experiments. Both experiments followed the same procedure. In the first stage, participants formed a mindset through the Luchins' water-jar task (Experiment 1) or the idiom maze task (Experiment 2). The second stage is cleansing manipulation. In Experiment 1, participants were asked to clean their hands with wipes (cleansing condition) or examine the packaging of the wipes (no-cleansing condition). In Experiment 2, participants were asked to watch a washing-hands video (cleansing condition) or watch an examining-pen video (no-cleansing condition). At last, all participants completed the mindset effect test problems. The results showed that the participants in the cleansing condition were less affected by the mindset than those in the no-cleansing condition, indicating that physical cleansing reduced the mindset effect. Our results provide new evidence for the clean-slate effects and support the hypothesis that physical cleansing is an embodied process of psychological separation. [ABSTRACT FROM AUTHOR]

Aiming at the problem that it is difficult to quickly realize digital modeling due to the large number of parts of the full-pitch stacked winding of large-scale hydroelectric generators and the complex connection logic between the wire bars, this paper proposes a modeling method of full-pitch stacked winding of generators driven by connection logic. Firstly, based on 3D modeling software and the 3D visualization application engine platform, an interactive virtual component model library is constructed. Then, according to the electrical principle of the full-pitch stacked winding, the connection logic is converted into a two-dimensional sequence with clear relationship, so that the winding can be quickly visualized in the virtual scene. Finally, the logic driving model that can be quickly understood by the computer, auxiliary applications such as generator stator winding structure cognition and fault repair is designed. This method shortens the time to construct the 3D model of stator winding, and at the same time, the combination of clear hierarchical equipment tree and 3D visualization model and human-computer interaction interface helps operation and maintenance personnel quickly understand the complex structure of winding and its assembly relationship. [ABSTRACT FROM AUTHOR]

The task of scene text recognition involves processing information from two modalities: images and text, thereby requiring models to have the ability to extract features from images and model sequences simultaneously. Although linguistic knowledge greatly aids scene text recognition tasks, the extensive use of language models in sequence modeling and model prediction stages in recent years has made model architectures increasingly complex and inefficient. In this paper, we propose LCSTR, a pure convolutional visual model that can complete text recognition without the need for attention mechanisms or language models. This approach applies large kernels to text recognition tasks for the first time, extracting word-level text information through large text-aware blocks, capturing long-range dependencies between characters, and using small text-aware blocks to obtain local features within characters. Experiments show that this model strikes a good trade-off between accuracy and speed, achieving notable results on seven public benchmarks, validating the generalizability and effectiveness of this method. Furthermore, owing to the absence of a language module, this model demonstrates remarkable accuracy even in limited sample scenarios, and the lightweight and low computational overhead features make it suitable for engineering applications. [ABSTRACT FROM AUTHOR]

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Thladiantha nudiflora Hemsl. ex F.B.Forbes & Hemsl. 1887 (Cucurbitaceae) has been widely known as a traditional medicine plant. In this study, we sequenced, assembled, and annotated the complete chloroplast genome of T. nudiflora. The chloroplast genome of T. nudiflora is 156,824 base pair (bp) in length, containing a large single-copy region of 86,566 bp and a small single-copy region of 18,070 bp, separated by a pair of inverted repeats of 26,094 bp. The chloroplast genome contains 132 genes, including 87 protein-coding, 37 transfer RNA, and eight ribosomal RNA genes. Phylogenetic analysis of the chloroplast genome revealed that species of the genus Thladiantha were clustered together in the phylogenetic trees. This study will not only shed light on T. nudiflora's evolutionary position but also provide valuable chloroplast genomic information for future studies into the origins and diversification of the genus Thladiantha and the Cucurbitaceae family. [ABSTRACT FROM AUTHOR]

Two new phenolic glycosides (1 and 2), one known analogue (3), along with a new diterpene glucoside (4) were obtained from ethanolic extract of the stems of Eurya chinensis R. Br. The structures of these isolated compounds were identified by extensive analysis of HRESIMS and NMR spectroscopic data. The cytotoxicities of these compounds were evaluated on MCF-7, A549, HepG2, CaCo2 and 5-8 F cell lines by MTT method, but no obvious activities were observed. [ABSTRACT FROM AUTHOR]

Currently, social media is full of rumors. To stop rumors from spreading further, rumor detection has received increasing attention. Recent rumor detection methods treat all propagation paths and all nodes on the paths as equally important, resulting in models that fail to extract the key features. In addition, most methods ignore user features, leading to limitations in the performance improvement of rumor detection. To address these problems, we propose a Dual-Attention Network model on propagation Tree structures named DAN-Tree, where a node-and-path dual-attention mechanism is designed to organically fuse deep structure and semantic information on the propagation structures of rumors, and path oversampling and structural embedding are employed to enhance the learning of deep structures. Finally, we deeply integrate user profiles into the propagation trees in DAN-Tree, thus proposing the DAN-Tree++ model to further improve performance. Empirical studies on four rumor datasets have shown that DAN-Tree outperforms the state-of-the-art rumor detection models learning on propagation structures, and the results on two datasets with user information validate the superior performance of DAN-Tree++ over other models using both user profiles and propagation structures. What's more, DAN-Tree, especially DAN-Tree++, has achieved the best performance on early detection tasks. [ABSTRACT FROM AUTHOR]

Background: The use of suboptimal controls in randomized trials of new cancer drugs can produce potentially unreliable clinical efficacy results over the current standard of care and expose patients to substandard therapy. We aim to investigate the proportion of randomized trials of investigational cancer drugs that used a suboptimal control arm and the number of trial participants at risk of exposure to suboptimal treatments in China. The association between the use of a suboptimal control and concluding statistical significance on the primary endpoint was also examined. Methods and findings: This observational study included randomized controlled trials (RCTs) of cancer drugs that were authorized by specific Chinese institutional review boards between 2016 and 2021, supporting investigational new drug applications of these drugs in China. The proportion of trials that used a suboptimal control arm and the total number of trial participants at risk of exposure to suboptimal treatments were calculated. In a randomized trial for a specific condition, a comparator was deemed suboptimal if it was not recommended by clinical guidelines published in priori or if there existed a regimen with a higher level of recommendation for the indication. The final sample included 453 Phase II/III and Phase III randomized oncology trials. Overall, 60 trials (13.2%) adopted a suboptimal control arm. Among them, 58.3% (35/60) used comparators that were not recommended by a prior guideline for the indication. The cumulative number of trial participants at risk of exposure to suboptimal treatments totaled 18,610 by the end of 2021, contributing 15.1% to the total number of enrollees of all sampled RCTs in this study. After adjusting for the year of ethical approval, region of participant recruitment, line of therapy, and cancer site, second-line therapies (adjusted odds ratio [aOR] = 2.7, 95%CI [1.2, 5.9]), adjuvant therapies (aOR = 8.9, 95% CI [3.4, 23.1]), maintenance therapies (aOR = 5.2, 95% CI [1.6, 17.0]), and trials recruiting participants in China only (aOR = 4.1, 95% CI [2.1, 8.0]) were more likely to adopt a suboptimal control. For the 105 trials with publicly available results, no statistically significant difference was observed between the use of a suboptimal control and concluding positive on the primary endpoint (100.0% [12/12] versus 83.9% [78/93], p = 0.208). The main limitation of this study is its reliance on clinical guidelines that could vary across cancer types and time in assessing the quality of the control groups. Conclusions: In this study, over one-eighth of randomized trials of cancer drugs registered to apply for regulatory approval in China used a suboptimal comparator. Our results highlight the necessity to refine the design of randomized trials to generate optimal clinical evidence for new cancer therapies. In this observational study, Yichen Zhang and colleagues explore how comparator arms are used in randomized oncology trials registered in China. Author summary: Why was this study done?: ■ Using inappropriate controls in randomized trials of new cancer drugs can expose patients to harm and produce potentially unreliable results of clinical efficacy. ■ In November 2021, China's Center for Drug Evaluation issued the Guidance on Clinical Value-Oriented Oncology Drug Research and Development. It stated that an active control arm should be selected with consideration of whether it reflects the optimal treatment in current clinical practices. ■ Previous descriptive analysis showed that oncology trials are expanding in China; however, no literature evaluated the quality of their control arms. What did the researchers do and find?: ■ This observational study reports the annual trend and proportion of 453 Phase II/III and Phase III randomized oncology trials registered in China between 2016 and 2021 that adopted a suboptimal control arm. We also calculated the cumulative number of trial participants at risk of exposure to suboptimal treatments. ■ We observed a fluctuating yet overall upward trend in the number of trials and participants that used a suboptimal comparator during our observation period. Overall, 60 trials adopted a suboptimal control arm and the cumulative number of trial participants at risk of exposure to suboptimal treatments totaled 18,610 by the end of 2021. ■ Trials with a suboptimal control reported higher but statistically non-significant proportions of positive results than those using an optimal control. What do these findings mean?: ■ Trial sponsors, ethical review boards, and oncologists should make collaborative efforts to protect patients from unnecessary harm and drugs with uncertain clinical benefits over the existing standard of care. ■ Regulatory agencies should be cautious when reviewing investigational new drug applications whose supporting trial used a suboptimal control and when making subsequent market authorization decisions. ■ A limitation of this study is the reliance on clinical guidelines that could vary across cancer types and time in assessing the quality of the control groups. Hence, though oncologists and clinical pharmacists were consulted when assessing the sample trials, our results may have inherent subjectivity. [ABSTRACT FROM AUTHOR]

The aim of this study is to analyze the clinical characteristics and outcomes of Chinese patients with progressive multifocal leukoencephalopathy (PML) who were treated with programmed cell death protein 1 (PD1) blockade therapies. We retrospectively analyzed patients who were admitted to our hospital between October 1, 2020, and October 1, 2022, diagnosed with PML and treated with PD1 blockade therapies. Four patients with PML who were treated with PD1 blockade therapies were identified. All patients were male, and their ages ranged from 19 to 54 years old. One patient (Case 2) exhibited mild pleocytosis, while three patients (Cases 2–4) had markedly reduced T lymphocyte cell counts prior to treatment. The time interval between symptom onset and treatment initiation ranged from six to 54 weeks. All patients received pembrolizumab treatment, with a total of two to four doses administered. Three patients who responded to pembrolizumab treatment showed clinical improvement starting around 8 weeks after the initiation of therapy. Although one patient did not show clinical improvement, they ultimately survived until the last follow-up. None of the patients in this study exhibited immune-related adverse events or immune reconstitution inflammatory syndrome. PD1 blockade appears to be a promising novel therapeutic option for PML; additional prospective studies are necessary to confirm its efficacy. [ABSTRACT FROM AUTHOR]

Social hierarchy greatly influences behavior and health. Both human and animal studies have signaled the medial prefrontal cortex (mPFC) as specifically related to social hierarchy. Dopamine D1 receptors (D1Rs) and D2 receptors (D2Rs) are abundantly expressed in the mPFC, modulating its functions. However, it is unclear how DR-expressing neurons in the mPFC regulate social hierarchy. Here, using a confrontation tube test, we found that most adult C57BL/6J male mice could establish a linear social rank after 1 week of cohabitation. Lower rank individuals showed social anxiety together with decreased serum testosterone levels. D2R expression was significantly downregulated in the dorsal part of mPFC (dmPFC) in lower rank individuals, whereas D1R expression showed no significant difference among the rank groups in the whole mPFC. Virus knockdown of D2Rs in the dmPFC led to mice being particularly prone to lose the contests in the confrontation tube test. Finally, simultaneous D2R activation in the subordinates and D2R inhibition in the dominants in a pair switched their dominant–subordinate relationship. The above results indicate that D2Rs in the dmPFC play an important role in social dominance. Our findings provide novel insights into the divergent functions of prefrontal D1Rs and D2Rs in social dominance, which may contribute to ameliorating social dysfunctions along with abnormal social hierarchy. [ABSTRACT FROM AUTHOR]

Background: 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (18F-FDG PET) could help evaluate metabolic abnormalities by semi-quantitative measurement to identify autoimmune encephalitis (AE). Few studies have been conducted to analyze the prognostic factors of AE. The study aimed to explore the values of diagnosis and treatment evaluation by 18F-FDG PET and preliminarily discussed the potential value in predicting the prognosis of AE patients. Methods: AE patients underwent 18F-FDG PET/CT and magnetic resonance imaging (MRI). There were two steps to analyse 18F-FDG PET imaging data. The first step was visual assessment. The second step was to analyse 18F-FDG PET parameters using Scenium software (Siemens Molecular Imaging Ltd). The mean standardized uptake value (SUVmean) and maximum standardized uptake value (SUVmax) of brain relative regional metabolism (BRRM) were quantified in the case and control groups according to the anatomical automatic labeling (AAL) partition. The main statistical method was the Kruskal–Wallis test. Finally, the simple linear regression method was used to analyse the relationships between 18F-FDG PET parameters and the modified Rankin Scale (mRS) scores before and after treatment. Results: The results on 18F-FDG PET showed that visual assessment abnormalities were in the mesial temporal lobe (MTL) (70.8%), (mainly infringing on the hippocampus and amygdala), basal ganglia (62.5%), frontal lobes (37.5%), occipital lobes (29.2%), and parietal lobes (12.5%). The positive rate of abnormalities on 18F-FDG PET was more sensitive than that on MRI (95.5% vs 32.2%, p = 0.001). The number of lesions on PET was positively correlated with the mRS scores before and after treatment, and the correlation before treatment was more significant. Before treatment, the SUVmean of the left occipital lobe was the most remarkable (SUVmean, R2 = 0.082, p > 0.05) factor associated with the mRS score, and the correlation was negative. With regard to prognosis, the SUVmax of the MTL was the most notable (R2 = 0.1471, p > 0.05) factor associated with the mRS score after treatment, and the correlation was positive. Conclusions: 18F-FDG PET could be more sensitive and informative than MRI in the early phases of AE. The common pattern of AE was high MTL metabolism on 18F-FDG PET, which was associated with hypometabolism of the occipital lobe, and the number of lesions on PET before treatment may be significant factors in assessing disease severity. The SUVmax of MTL hypermetabolism may serve as a prognostic biomarker in AE. [ABSTRACT FROM AUTHOR]

Heat stress can cause testicular damage and affect male fertility. Tanshinone IIA (TSA) is a monomer substance derived from plants, with antioxidant and anti-apoptotic effects. Whether it can repair testicular damage caused by heat stress is unclear. This study aims to construct a mouse testicular heat stress injury model and intervene with TSA. Various methods such as histopathology, high-throughput sequencing, bioinformatics analysis, and molecular biology were used to investigate whether TSA can alleviate heat stress-induced testicular injury and its mechanism. Results showed that heat stress significantly reduced the diameter of the mouse seminiferous tubules, increased cell apoptosis in the testicular tissue, and significantly decreased testosterone levels. After TSA intervention, testicular morphology and cell apoptosis improved significantly, and testosterone secretion function was restored. High-throughput transcriptome sequencing found that key differentially expressed genes between the HS group and the control and TSA groups clustered in the apoptosis and TGFβ signaling pathways. Using western blot technology, we found that the HS group upregulated TGFβ1/Smad2/Smad3 pathway protein expression, causing cell apoptosis, testicular tissue organic lesions, and affecting testicular secretion function. Through TSA intervention, we found that it can inhibit TGFβ1/Smad2/Smad3 pathway protein expression, thereby restoring testicular damage caused by heat stress. This study confirms that TSA can effectively restore testicular damage caused by heat stress in mice, possibly by inhibiting the TGFβ1/Smad2/Smad3 pathway to suppress apoptosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of hepatocyte growth factor and its receptor c-Met (HGF/ c-Met) signaling pathway in early follicular development in mice via detecting the expression of HGF/c-Met in early mouse ovarian tissue and then analyze the biological process of HGF/c-Met signaling pathway and its possible involvement in intracellular signaling pathways by using bioinformatics for the purpose of further studying the molecular mechanism of the signaling pathway in the early follicle development. Methods. Thirty-five female Kunming mice and 15 male ones were fed in 15 cages with the female-to-male ratio of 2,1. The ovaries of mice at 3, 7, 14 and 21 days after birth were collected. Immunohistochemical staining and Western blotting were applied to detect the expression levels of HGF and c-Met protein in the ovarian tissues. Quantitative Real-time PCR,q-PCR, was used to detect the expression levels of HGF and C-Met mRNA in the early ovarian tissues of mice. Results, HGF and c-Met proteins were expressed in the ovarian tissues of the mice at 3, 7, 14 and 21 days, presenting an increasing trend with the increase of age by day,P < 0.05,. The mRNA levels of HGF and c-Met also showed the same trend,P < 0.05,. Bioinformatics analysis revealed that the HGF/c-Met signaling pathway involved in a variety of biological processes and signaling pathways such as PI3K/AKT. Conclusions,HGF/c-Met signaling pathway is involved in early follicular development in mice. It may regulate primal follicular initiation and follicular develop, ment through intracellular signaling pathway PI3K/AKT. [ABSTRACT FROM AUTHOR]

Groundwater storage (GWS) in confined aquifer systems is often influenced by climate variability and anthropogenic activities, and it is vital to quantify their contributions for the purpose of groundwater management and surface water allocation plans. In this study, we characterize the spatiotemporal evolution of the GWS in confined aquifer systems across Hengshui, North China Plain, and investigate its relationships with changing climate conditions and human activities through the integration of InSAR-derived surface displacements with hydraulic head observations and precipitation data, during 2004–2010 and 2016–2020. Our results indicate that the GWS in confined aquifer systems decreased markedly by 4.59 ± 0.35 km3 with an accelerating trend during the study period. The GWS variations show a strong correlation with precipitation during irrigation periods (March to July), and hence, the climate and anthropogenic-driven GWS variations can be separated from each other with a linear model. We find that the GWS depletion caused by climate variability and anthropogenic activities were −0.31 ± 0.10 km3 and −4.28 ± 0.40 km3, respectively, during the study period. The mean contribution of anthropogenic activities to the GWS variations was −71.9%, implying that the GWS variations in confined aquifer systems were primarily anthropogenic driven. It is also found that the well observations alone poorly characterize the spatiotemporal evolution of the GWS due to their limited spatial density, and the integrated InSAR/well approach appears to be promising for overcoming this challenge. [ABSTRACT FROM AUTHOR]

In recent years, people's quality of life has increased, and the requirements for fruits have also become higher; blueberries are particularly popular because of their rich nutrients. In the blueberry industry chain, sensory evaluation is an important link in determining the quality of blueberries. Therefore, to make a more objective scientific evaluation of blueberry quality and reduce the influence of human factors, on the basis of traditional sensory evaluation methods, machine learning is introduced to establish a support vector regression prediction model optimized by the particle swarm algorithm. Ten physical and chemical flavor indices of blueberries (such as catalase, flavonoids, and soluble solids) were used as input data, and sensory evaluation scores were used as output data. Three different predictive models were applied and compared: a particle swarm optimization support vector machine, a convolutional neural network, and a long short-term memory network model. To ensure reliability, the experiments with each of the three models were repeated 20 times, and the mean of each index was calculated. The experimental results showed that the root mean square error and mean absolute error of the particle swarm optimization support vector machine were 0.45 and 0.40, respectively; these values were lower than those of the convolutional neural network (0.96 and 0.78, respectively) and the long short-term memory network (1.22 and 0.97, respectively). Hence, these results highlighted the superiority of the proposed model when sample data are limited. [ABSTRACT FROM AUTHOR]

The Tibetan Plateau and its surroundings have recently experienced several catastrophic glacier-related disasters. It is of great scientific and practical significance to establish ground-based early warning systems (EWSs) to understand the processes and mechanisms of glacial disasters and warn against potential threats to downstream settlements and infrastructure. However, there are few sophisticated EWSs on the Tibetan Plateau. With the support of the Second Tibetan Plateau Scientific Expedition and Research Program (STPSER), an EWS was developed and implemented in the Sedongpu Valley, southeastern Tibetan Plateau, where repeated river blockages have occurred due to ice/rock collapse debris flow. The EWS collected datasets of optical/thermal videos/photos, geophone waveforms, water levels, and meteorological variables in this sparsely populated zone. It has successfully warned against three ice-rock collapse–debris flow–river blockage chain events, and seven small-scale ice-rock collapse–debris flow events. Meanwhile, it was found that the low-cost geophone can effectively indicate the occurrence and magnitude of ice/rock collapses by local thresholds, and water level observation is an efficient way to warn of river blockages. Our observations showed that there were no immediate meteorological triggers for the ice-rock collapses and associated debris flows. Several factors, such as the volume and location of the collapses and the percentage of ice content involved, influence the velocities of debris flows and the magnitude of river blockages. There are still two possible glaciers in the study area that are at risk of ice collapse. It is worth monitoring their dynamic changes using high-resolution satellite data and the ground-based EWS to safeguard the surrounding hydrological projects and infrastructure in this transboundary region. [ABSTRACT FROM AUTHOR]

Chitin is one of the most abundant natural biopolymers and serves as a critical structural component of extracellular matrices, including fungal cell walls and insect exoskeletons. As a linear polymer of β-(1,4)-linked N-acetylglucosamine, chitin is synthesized by chitin synthases, which are recognized as targets for antifungal and anti-insect drugs. In this study, we determine seven different cryo-electron microscopy structures of a Saccharomyces cerevisiae chitin synthase in the absence and presence of glycosyl donor, acceptor, product, or peptidyl nucleoside inhibitors. Combined with functional analyses, these structures show how the donor and acceptor substrates bind in the active site, how substrate hydrolysis drives self-priming, how a chitin-conducting transmembrane channel opens, and how peptidyl nucleoside inhibitors inhibit chitin synthase. Our work provides a structural basis for understanding the function and inhibition of chitin synthase. Chitin, the second most abundant natural polysaccharide in nature, is synthesized by chitin synthases, which are recognized as targets for antifungal and anti-insect drugs. Here the authors determine cryo-EM structures of the chitin synthase, which reveal its activation, catalytic and inhibitory mechanisms [ABSTRACT FROM AUTHOR]

According to estimates by the Food and Agriculture Organization of the United Nations (FAO), about a third of all food produced for human consumption in the world is lost or wasted—approximately 1.3 billion tons. Among this, the amount lost during the storage stage is about 15–20% for vegetables and 10–15% for fruits. It is 5–10% for vegetables and fruits during the distribution stage, resulting in a large amount of resource waste and economic losses. At the same time, the global population affected by hunger has reached 828 million, exceeding one-tenth of the total global population. The improvement of the cold chain system will effectively reduce the amount of waste and loss of food during the storage and transportation stages. Firstly, this paper summarizes the concept and development status of traditional preservation technology; environmental parameter sensor components related to fruit and vegetable spoilage in the intelligent cold chain system; the data transmission and processing technology of the intelligent cold chain system, including wireless network communication technology (WI-FI) and cellular mobile communication; short-range communication technology, and the low-power, wide-area network (LPWAN). The smart cold chain system is regulated and optimized through the Internet of Things, blockchain, and digital twin technology to achieve the sustainable development of smart agriculture. The deep integration of artificial intelligence and traditional preservation technology provides new ideas and solutions for the problem of food waste in the world. However, the lack of general standards and the high cost of the intelligent cold chain system are obstacles to the development of the intelligent cold chain system. Governments and researchers at all levels should strive to highly integrate cold chain systems with artificial intelligence technology, establish relevant regulations and standards for cold chain technology, and actively promote development toward intelligence, standardization, and technology. [ABSTRACT FROM AUTHOR]

Derived from the D‐luciferin regeneration pathway in firefly body, the click condensation reaction between 2‐cyanobenzothiazole (CBT) and D‐cysteine (Cys) (CBT‐Cys click reaction) possesses unique advantages, including superior biocompatibility, high second order reaction rate, and metal‐free mild conditions, emerging as a powerful bioorthogonal tool for a variety of chemical biological applications. Moreover, owing to its programmable controllability (e.g., pH, reduction, or enzyme), CBT‐Cys click reaction is exploited to fabricate stimuli‐activatable imaging probes with self‐assembling behaviors in physiological context. At stimuli‐rich pathological lesions of interest, these probes undergo CBT‐Cys click reaction to form cyclic dimers/oligomers or linear polymers, and further self‐assemble into nanostructures. The in situ formed nanostructures promote the selective accumulation and retention of imaging agent cargos at pathological lesions, thus enabling precise and enhanced in vivo imaging of diseases (especially tumors). To address the significance and recent breakthroughs of smart CBT‐Cys probes for enhanced optical imaging of tumors/other diseases, we herein propose this mini‐review, in which advances (particularly in recent 5 years) and potential challenges (or chances) in this field are emphasized. [ABSTRACT FROM AUTHOR]

The Songnen Plain of Northeast China is one of the three largest soda saline–alkaline regions in the world. To better understand soil alkalinization in this important agricultural region of China, it is vital to explore the driving factors of soil alkalinity. Combined with prior research on the Wuyu'er–Shuangyang River Basin, this study examined the driving factors of soil alkalinity using the Geodetector method. First, the analysis results of the risk detector, the factor detector, and the ecological detector revealed the primary driving factors of soil alkalinity in the study area. Next, the analysis results of the interaction detector determined how combinations of driving factors impacted soil alkalinity in the study area. In general, the natural driving factors of altitude and spring temperature, especially altitude, played a key role in soil alkalinization. These results indicated that the closed terrain and warming trends were the main causes of soil alkalinization in the study area. In addition, there were significant enhance-nonlinear and enhance-bivariate relationships among the driving factors, which indicated that combined driving factors contributed more to soil alkalinization than individual driving factors. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is a chronic inflammatory disease of arteries fueled by lipids. It is a major cause of cardiovascular morbidity and mortality. Mesenchymal stem cells have been used for the treatment of atherosclerotic lesions. Adipose-derived stem cells (ADSCs) have been shown to regulate the activation state of macrophages and exhibit anti-inflammatory capabilities. However, the effect of allogeneic ADSCs in the treatment of AS have not been investigated. In this study, the early treatment effect and preliminary mechanism analysis of allogeneic rabbit ADSCs intravenous transplantation were investigated in a high-fat diet rabbit model. The polarization mechanism of rabbit ADSCs on the macrophage was further analyzed in vitro. Compared with the model group, blood lipid levels declined, the plaque area, oxidized low-density lipoprotein (ox-LDL) uptake, scavenger receptor A1 and cluster of differentiation (CD) 36 levels were all significantly reduced, and the accumulation of inflammatory M1 macrophages, apoptosis, interleukin (IL)-6 and tumor necrosis factor (TNF)-α expression were decreased. The endothelial cells (CD31), M2 macrophages, IL-10 and the transforming growth factor (TGF)-β levels increased. In vitro, ADSCs can promote the M1 macrophage phenotypic switch toward the M2 macrophage through their secreted exosomes, and the main mechanism includes increasing arginase 1 expression and IL-10 secretion, declining inducible nitric oxide synthase (iNOS) expression and TNF-α secretion, and activating the STAT6 pathway. Therefore, allogeneic rabbit ADSC transplantation can transmigrate to the aortic atherosclerotic plaques and show a good effect in lowering blood lipids and alleviating atherosclerotic plaque in the early stage of AS by inhibiting ox-LDL uptake, inflammatory response, and endothelial damage. [ABSTRACT FROM AUTHOR]

The tyrosine kinase inhibitor (TKI) Sunitinib is one the therapies approved for advanced renal cell carcinoma. Here, we undertake proteogenomic profiling of 115 tumors from patients with clear cell renal cell carcinoma (ccRCC) undergoing Sunitinib treatment and reveal the molecular basis of differential clinical outcomes with TKI therapy. We find that chromosome 7q gain-induced mTOR signaling activation is associated with poor therapeutic outcomes with Sunitinib treatment, whereas the aristolochic acid signature and VHL mutation synergistically caused enhanced glycolysis is correlated with better prognosis. The proteomic and phosphoproteomic analysis further highlights the responsibility of mTOR signaling for non-response to Sunitinib. Immune landscape characterization reveals diverse tumor microenvironment subsets in ccRCC. Finally, we construct a multi-omics classifier that can detect responder and non-responder patients (receiver operating characteristic–area under the curve, 0.98). Our study highlights associations between ccRCC molecular characteristics and the response to TKI, which can facilitate future improvement of therapeutic responses. Many clear cell renal cell carcinoma (ccRCC) patients do not respond or develop resistance to tyrosine kinase inhibitors, such as Sunitinib. Here, the authors perform a proteogenomics analysis of Chinese ccRCC patients treated with Sunitinib and develop a multi-omics classifier to distinguish responders from non-responders. [ABSTRACT FROM AUTHOR]

Azide-alkyne cycloaddition reaction is a very common organic reaction to synthesize nitrogen-containing heterocycles. Once catalyzed by Cu(I) or Ru(II), it turns out to be a click reaction and thus is widely applied in chemical biology for labeling. However, besides their poor regioselectivity towards this reaction, these metal ions are not biologically friendly. Hence, it is an urgent need to develop a metal-free azide–alkyne cycloaddition reaction for biomedical applications. In this work, we found that, in the absence of metal ions, supramolecular self-assembly in an aqueous solution could realize this reaction with excellent regioselectivity. Nap-Phe-Phe-Lys(azido)-OH firstly self-assembled into nanofibers. Then, Nap-Phe-Phe-Gly(alkynyl)-OH at equivalent concentration approached to react with the assembly to yield the cycloaddition product Nap-Phe-Phe-Lys(triazole)-Gly-Phe-Phe-Nap to form nanoribbons. Due to space confinement effect, the product was obtained with excellent regioselectivity. Employing the excellent properties of supramolecular self-assembly, we are applying this strategy to realize more reactions without metal ion catalysis. Metal-free versions of azide–alkyne cycloadditions could find widespread applications in biomedical contexts. Here, the authors report an assembly-driven, regioselective azide–alkyne cycloaddition. [ABSTRACT FROM AUTHOR]

Vascular network labeling in transparent tissues provides more complete information on blood vessels. To achieve a fast and efficient method for vascular network labeling in transparent tissues, we compared various vascular labeling methods under different tissue clearing protocols. FITC‐Dextran labeling and CUBIC cleaning treatment were found to be the best options for vascular network labeling in cleared mouse tissues. Satisfactory labeling of vascular networks in various organs can be achieved by selecting FITC‐Dextran with different molecular weights and different administration methods. [ABSTRACT FROM AUTHOR]

Introduction: Accumulating evidence indicates that abnormalities in the composition of gastrointestinal (GI) microbiota play a vital role in stress-related disorders. Both human beings and animals perceive stressful events differently, i.e., resilience or susceptibility. However, the role of GI microbiota in stress resilience/susceptibility and the underlying mechanisms remain largely unknown. Methods and Results: Sixty male C57BL/6J mice were exposed to 10-day chronic social defeat stress (CSDS), and 28 were found to be resilient to CSDS. We next analyzed microbiota compositions in the cecum using 16S rDNA gene sequencing, which revealed a significant increase in the relative abundance of Lactobacillus at the genus level in the resilient mice. In subsequent experiments, we found that oral administration of a strain of Lactobacillus (Lactobacillus murinus) for 2 weeks attenuated the increased levels of stress-induced corticosterone and anxiety-like behavior in stress-susceptible mice. The mRNA expression of tryptophan hydroxylase 2 (a rate-limiting enzyme in serotonin [5-HT] synthesis) was also significantly increased in the dorsal raphe nucleus (DR) of stress-susceptible mice. Conclusions:Lactobacillus contributes to stress resilience, and the DR 5-HT system may play an important role during this process. The above results suggest that certain organisms in the GI tract may play an essential role in stress response and be useful in the prevention and treatment of some stress-related psychiatric disorders, such as depression. [ABSTRACT FROM AUTHOR]