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The compound 2,4,6-trichlorophenol poses significant risks to both the aquatic environment and human health. Its inherent persistence and stability present challenges in achieving complete purification, thus warranting its inclusion as a priority pollutant. The present study reports the development of an amphiphilic small-molecule compound that self-assembles into nanovesicles exhibiting remarkable adsorption and photodegradation capabilities. Through the synergistic effects of hydrogen bonding, van der Waals forces, π-π interactions, and electrostatic interactions, these vesicles efficiently adsorb 2,4,6-trichlorophenol from aqueous solutions within 1 min while demonstrating exceptional environmental stability and broad applicability. Upon self-assembly into vesicles, not only are more adsorption sites exposed, but charge separation and migration within the vesicles are also facilitated. Through the synergistic effects of adsorption and photodegradation, complete removal of 2,4,6-trichlorophenol in aqueous solution can be achieved within 8 h while exhibiting excellent recycling capability. This approach offers a viable strategy for designing and synthesizing pure organic photodegradable materials.

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INTRODUCTION: c-Jun N-terminal kinase (JNK) regulates various biological processes through the phosphorylation cascade and is closely associated with numerous diseases, including inflammation, cardiovascular diseases, and neurological disorders. Therefore, JNKs have emerged as potential targets for disease treatment. AREAS COVERED: This review compiles the patents and literatures concerning JNK inhibitors through retrieving relevant information from the SciFinder, Google Patents databases, and PubMed from 2015 to the present. It summarizes the structure-activity relationship (SAR) and biological activity profiles of JNK inhibitors, offering valuable perspectives on their potential therapeutic applications. EXPERT OPINION: The JNK kinase serves as a novel target for the treatment of neurodegenerative disorders, pulmonary fibrosis, and other illnesses. A variety of small-molecule inhibitors targeting JNKs have demonstrated promising therapeutic potential in preclinical studies, which act upon JNK kinases via distinct mechanisms, encompassing traditional ATP competitive inhibition, covalent inhibition, and bidentate inhibition. Among them, several JNK inhibitors from PregLem SA, Celegene SA, and Xigen SA have accomplished the early stage of clinical trials, and their results will guide the development and indications of future JNK inhibitors.

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An unexpected, divergent and efficient approach toward furanoid-bridged fullerene dimers C120O and C120O2 was established under different solvent-free ball-milling conditions by simply using pristine C60 as the starting material, water as the oxygen source and FeCl3 as the mediator. The structures of C120O and C120O2 were unambiguously established by single-crystal X-ray crystallography. A plausible reaction mechanism is proposed on the basis of control experiments. Furthermore, C120O2 has been applied in organic solar cells as the third component and exhibits good performance.

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c-Jun N-terminal kinases (JNKs) including JNK1/2/3 are key members of mitogen-activated protein kinase family. Wherein JNK3 is specifically expressed in brain and emerges as therapeutic target, especially for neurodegenerative diseases. However, developing JNK3 selective inhibitors as chemical probes to investigate its therapeutic potential in diseases remains challenging. Here, we adopted the covalent strategy for identifying JNK3-selective covalent inhibitorJC16I, with high inhibitory activity against JNK3. Despite targeting a conserved cysteine the vicinity of ATP pocket in JNK family, JC16I exerted a greater than 160-fold selectivity for JNK3 over JNK1/2. Importantly, even at low concentration, JC16I showed enhanced and long-lasting inhibition against cellular JNK3. In addition, its alkyne-containing probe JC-P1 could label JNK3 in SH-SY5Y cell lysate and living cells, with goodproteome-wide selectivity. Furthermore, JC16I selectively suppressed the abnormal activation of JNK3 signaling and sufficiently exhibited neuroprotective effect in Parkinson's diseases (PD) models. Overall, our findings highlight the potential of developing isoform-selective and cell-active JNK3 inhibitors by covalent drug design strategy targeting a conserved cysteine. This work not only provides a valuable chemical probe for JNK3-targeted investigations in vitro and in vivo but also opens new avenues for the treatment of PD.

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Straw return has important impacts on black soil protection, food security, and environmental protection. One year of straw return (S1) reduces rice yield and increases greenhouse gas (GHG) emissions. However, the effects of successive years of straw return on rice yield, soil nutrients, and GHG emissions in the northeast rice region are still unclear. Therefore, we conducted four successive years of straw return (S4) in a positional experiment to investigate the effects of different years of straw return on rice yield, soil nutrients, and GHG emissions in the northeast rice region. The experimental treatments included the following: no straw return (S0), a year of straw return (S1), two successive years of straw return (S2), three successive years of straw return (S3), and four successive years of straw return (S4). Compared with S1, the rice yields of S2, S3, and S4 increased by 10.89%, 15.46%, and 16.98%, respectively. But only S4 increased by 4.64% compared to S0, while other treatments were lower than S0. S4 increased panicles per m2 and spikelets per panicle by 9.34% and 8.93%, respectively, compared to S1. Panicles per m2 decreased by 8.06% at S4 compared to S0, while spikelets per panicle increased by 13.23%. Compared with S0, the soil organic carbon, total nitrogen, NH4+-N, NO3--N, available phosphorus, and available potassium of S4 increased by 11.68%, 10.15%, 24.62%, 21.38%, 12.33%, and 13.35%, respectively. Successive years of rice straw return decreased GHG intensity (GHGI). Compared with S1, the GHGI of S4, S3, and S2 decreased by 16.2%, 11.84%, and 9.36%, respectively. Thus, S4 increased rice yield and soil nutrients, reducing GHGI.

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BACKGROUND: The blood-cerebrospinal fluid barrier (BCSFB) comprises the choroid plexus epithelia. It is important for brain development, maintenance, function, and especially for maintaining immune homeostasis in the cerebrospinal fluid (CSF). Although previous studies have shown that the peripheral immune function of the body is impaired upon exposure to microgravity, no studies have reported changes in immune cells and cytokines in the CSF that reflect neuroimmune status. The purpose of this study is to investigate the alterations in cerebrospinal fluid (CSF) immune homeostasis induced by microgravity and its mechanisms. This research is expected to provide basic data for brain protection of astronauts during spaceflight. METHODS: The proportions of immune cells in the CSF and peripheral blood (PB) of SMG rats were analyzed using flow cytometry. Immune function was evaluated by measuring cytokine concentrations using the Luminex method. The histomorphology and ultrastructure of the choroid plexus epithelia were determined. The concentrations of intercellular junction proteins in choroid plexus epithelial cells, including vascular endothelial-cadherin (VE-cadherin), zonula occludens 1 (ZO-1), Claudin-1 and occludin, were detected using western blotting and immunofluorescence staining to characterize BCSFB injury. RESULTS: We found that SMG caused significant changes in the proportion of CD4 and CD8 T cells in the CSF and a significant increase in the levels of cytokines (GRO/KC, IL-18, MCP-1, and RANTES). In the PB, there was a significant decrease in the proportion of T cells and NKT cells and a significant increase in cytokine levels (GRO/KC, IL-18, MCP-1, and TNF-α). Additionally, we observed that the trends in immune markers in the PB and CSF were synchronized within specific SMG durations, suggesting that longer SMG periods (≥21 days) have a more pronounced impact on immune markers. Furthermore, 21d-SMG resulted in ultrastructural disruption and downregulated expression of intercellular junction proteins in rat choroid plexus epithelial cells. CONCLUSIONS: We found that SMG disrupts the BCSFB and affects the CSF immune homeostasis. This study provides new insights into the health protection of astronauts during spaceflight.

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Barrera Hematoencefálica , Plexo Coroideo , Citocinas , Homeostasis , Simulación de Ingravidez , Animales , Homeostasis/fisiología , Ratas , Plexo Coroideo/inmunología , Plexo Coroideo/metabolismo , Masculino , Citocinas/metabolismo , Citocinas/líquido cefalorraquídeo , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/inmunología , Líquido Cefalorraquídeo/inmunología , Líquido Cefalorraquídeo/metabolismo , Ratas Sprague-Dawley , Células Epiteliales/metabolismo , Células Epiteliales/inmunología

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BACKGROUND: In-cell NMR is a valuable technique for investigating protein structure and function in cellular environments. However, challenges arise due to highly crowded cellular environment, where nonspecific interactions between the target protein and other cellular components can lead to signals broadening or disappearance in NMR spectra. RESULTS: We implemented chemical reduction methylation to selectively modify lysine residues on protein surfaces aiming to weaken charge interactions and recover obscured NMR signals. This method was tested on six proteins varying in molecular size and lysine content. While methylation did not disrupt the protein's native conformation, it successful restored some previously obscured in-cell NMR signals, particularly for proteins with high isoelectric points that decreased post-methylation. SIGNIFICANCE: This study affirms lysine methylation as a feasible approach to enhance the sensitivity of in-cell NMR spectra for protein studies. By mitigating signal loss due to nonspecific interactions, this method expands the utility of in-cell NMR for investigating proteins in their natural cellular environment, potentially leading to more accurate structural and functional insights.

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Lisina , Resonancia Magnética Nuclear Biomolecular , Lisina/química , Lisina/análisis , Metilación , Proteínas/química , Proteínas/análisis , Humanos

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BACKGROUND: Our study delves into postpartum depression (PPD) extending observation up to six months postpartum, addressing the gap in long-term follow-ups and uncover critical intervention points. METHOD: Through a continuous three-wave cohort study involving 3174 of 10,730 invited postpartum women, we utilized machine learning to predict PPD risk, incorporating self-reported surveys and health records from October 2021 to Jan 2023. RESULTS: PPD prevalence slightly decreased from 30.9 % to 29.1 % over six months. The Random Forest model emerged as the most effective, identifying key predictors of PPD at different stages. The top three factors at first month were newborn's birth weight, maternal weight before delivery and before pregnancy. The EPDS scores of last time, newborn's birth weight and maternal weight before pregnancy and before delivery were main predictors for EPDS scores at third and sixth months postpartum. LIMITATION: The study faces limitations such as potential selection bias due to the convenience sampling method and the reliance on self-reported measures, which may introduce reporting bias. Furthermore, the high attrition rate could affect the representativeness of the sample and the generalizability of the findings. CONCLUSION: There is a slight decrease in PPD rates over six months, yet the prevalence remains high. This underscores the need for early and ongoing mental health support for new mothers. Our study highlights the efficacy of machine learning in enhancing PPD risk assessment and tailoring intervention strategies, paving the way for more personalized healthcare approaches in postpartum care.

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Depresión Posparto , Aprendizaje Automático , Humanos , Depresión Posparto/epidemiología , Depresión Posparto/diagnóstico , Femenino , Adulto , China/epidemiología , Estudios de Seguimiento , Embarazo , Factores de Riesgo , Prevalencia , Estudios de Cohortes , Adulto Joven , Pueblos del Este de Asia

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Overweight/obesity among adolescents in Shandong Province, China, has been rising, posing significant public health challenge. Comprehensive investigation is needed to develop effective interventions. Following the Strengthening the Reporting of Observational Studies in Epidemiology guidelines, a stratified random cluster sampling approach was used from September to October 2023 across 17 cities in Shandong Province. The study included 165 middle schools, surveying 99,638 students aged 12 ∼ 15. After applying exclusion criteria, 97,356 students (97.71% effective rate) completed anthropometric measurements and questionnaires. Overweight/obesity were assessed based on national and international standards. Univariable chi-square test and multivariable logistic regression were used to analyze factors influencing overweight/obesity. In 2023, the overweight/obesity rate among 12 ∼ 15-year-olds in Shandong was 19.75%. Significant factors included sex, age, residence, family income, parental weight status and activity, mother's gestational diabetes history, birth weight, physical activity, sleep, screen time, homework, and diet. Girls, older adolescents, and those with physically active parents or who themselves engaged in over 1.5 h of daily physical activity had lower odds of being overweight/obese. Adequate sleep and frequent consumption of vegetable and fruit were also protective. Higher odds were associated with urban residence, high family income, overweight/obese parents, maternal gestational diabetes, high birth weight, excessive screen time, extensive homework, and frequent fast food consumption. Overweight/obesity in Shandong adolescents is influenced by multiple determinants. Holistic interventions addressing genetic, behavioral, and environmental factors are essential for promoting healthier lifestyles and reducing the prevalence in this demographic.

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Fast-charging, non-aqueous lithium-based batteries are desired for practical applications. In this regard, LiMn2O4 is considered an appealing positive electrode active material because of its favourable ionic diffusivity due to the presence of three-dimensional Li-ion diffusion channels. However, LiMn2O4 exhibits inadequate rate capabilities and rapid structural degradation at high currents. To circumvent these issues, here we introduce quintuple low-valence cations to increase the entropy of LiMn2O4. As a result, the entropy-increased LiMn2O4-based material, i.e., LiMn1.9Cu0.02Mg0.02Fe0.02Zn0.02Ni0.02O4, when tested in non-aqueous lithium metal coin cell configuration, enable 1000 cell cycles at 1.48 A g-1 (corresponding to a cell charging time of 4 minutes) and 25°C with a discharge capacity retention of about 80%. We demonstrate that the increased entropy in LiMn2O4 leads to an increase in the disordering of dopant cations and a contracted local structure, where the enlarged LiO4 space and enhanced Mn-O covalency improve the Li-ion transport and stabilize the diffusion channels. We also prove that stress caused by cycling at a high cell state of charge is relieved through elastic deformation via a solid-solution transition, thus avoiding structural degradation upon prolonged cycling.

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Analysis of bacterial carbohydrate-active enzymes (CAZymes) contributes significantly to comprehending the response exhibited by coral symbionts to the external environment. This study explored the impact of bleaching on the bacteria and their CAZymes in coral Favites sp. through metagenomic sequencing. Notably, principal coordinates analysis (PCoA) unveiles substantial difference in bacterial communities between bleached and unbleached corals. Proteobacteria, Actinobacteria, Acidobacteria, Bacteroidota, and Chloroflexi, exhibit noteworthy alterations during coral bleaching. CAZymes profiles in bleached coral disclosed a significant increase in Glycosyltransferases (GTs) abundance, suggesting an intensified biosynthesis of polysaccharides. Conversely, there is a marked reduction in other CAZymes abundance in bleached coral. Proteobacteria, Bacteroidota, Chlorobi, and Planctomycetota exhibit greater contributions to CAZymes in bleached corals, with Rhodobacterales, Cytophagales, Burkholderiales, Caulobacterales, and Hyphomicrobiales being the main contributors. While Acidobacteria, Actinobacteria, and Chloroflexi demonstrate higher contributions to CAZymes in unbleached corals. The changes in bacteria and their CAZymes reflect the ecological adaptability of coral holobionts when facing environmental stress. The alterations in CAZymes composition caused by bleaching events may have profound impacts on coral nutrient absorption and ecosystem stability. Therefore, understanding the dynamic changes in CAZymes is crucial for assessing the health and recovery potential of coral ecosystems.

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Antozoos , Bacterias , Animales , Antozoos/microbiología , Bacterias/genética , Bacterias/enzimología , Simbiosis , Microbiota

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BACKGROUND: Venous thromboembolism is the leading cause of death in cancer patients, second only to tumor progression. The Khorana score is recommended by clinical guidelines for identifying ambulatory cancer patients at high risk of venous thromboembolism during chemotherapy. However, its predictive performance is debated among cancer patients. OBJECTIVES: To map the applicability of the Khorana score in cancer patients and to assess its predictive performance across various cancer types, providing guidance for clinicians and nurses to use it more appropriately. DESIGN: Systematic review and meta-analysis. METHODS: A comprehensive literature search of the electronic database was first conducted on August 30, 2023, and updated on May 20, 2024. Studies examining the Khorana score's predictive performance (including but not limited to the areas under the curve, C-index, and calibration plot) in cancer patients were included. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was applied to evaluate the methodological quality of the included studies. Data synthesis was achieved via random-effects meta-analysis using the R studio software. The subgroup analysis was performed according to the study design, clinical setting, cancer type, anti-cancer treatment stage, and country. RESULTS: The review incorporated 67 studies, including 58 observational studies and nine randomized controlled trials. All included studies assessed the Khorana score's discrimination, with the C-index ranging from 0.40 to 0.84. The pooled C-index for randomized controlled trials was 0.61 (95 % CI 0.51-0.70), while observational studies showed a pooled C-index of 0.59 (95 % CI 0.57-0.60). Subgroup analyses revealed the pooled C-index for lung cancer, lymphoma, gastrointestinal cancer, and mixed cancer patients as 0.60 (95 % CI 0.53-0.67), 0.56 (95 % CI 0.51-0.61), 0.59 (95 % CI 0.39-0.76), and 0.60 (95 % CI 0.58-0.61), respectively. Inpatient and outpatient settings had the pooled C-index of 0.60 (95 % CI 0.58-0.63) and 0.58 (95 % CI 0.55-0.61), respectively. Calibration was assessed in only four studies. All included studies were identified to have a high risk of bias according to PROBAST. CONCLUSION: The Khorana score has been widely validated in various types of cancer patients; however, it exhibited poor capability (pooled C-index<0.7) in accurately discriminating VTE risk among most types of cancer patients either in inpatient or outpatient settings. The Khorana score should be used with caution, and high-quality studies are needed to further validate its predictive performance. REGISTRATION: The protocol for this study is registered with PROSPERO (registration number: CRD42023470320).

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Neoplasias , Tromboembolia Venosa , Humanos , Neoplasias/complicaciones , Tromboembolia Venosa/etiología , Medición de Riesgo/métodos

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Pulmonary arterial hypertension (PAH) is an obstructive vasculopathy that, if not promptly treated, culminates in right heart failure. Therefore, pre-clinical studies are needed to support and optimize therapeutic approaches of PAH. Here, we explore a prospective function of sevoflurane in experimental PAH through regulating TRAF6. Monocrotaline (MCT)-induced PAH rats were subjected to sevoflurane inhalation and intratracheal instillation of lentivirus overexpressing TRAF6. Platelet-derived growth factor (PDGF)-treated pulmonary artery smooth muscle cells (PASMCs) were exposed to sevoflurane and genetically manipulated for TRAF6 overexpression. It was found that MCT and PDGF challenge upregulated the levels of TRAF6 in rat lung tissues and PASMCs, but sevoflurane treatment led to reduced TRAF6 expression. Sevoflurane inhalation in MCT-induced rats resulted in alleviative pulmonary vascular remodeling, mitigated right ventricular dysfunction and hypertrophy, improved mitochondrial function and dynamics, and inactivation of NF-κB pathway. In vitro studies confirmed that exposure to sevoflurane repressed PDGF-induced proliferation, migration, and phenotype switching of PASMCs, and suppressed mitochondrial dysfunction and NF-κB activation in PDGF-stimulated PASMCs. The beneficial impact of sevoflurane on pathological changes of lung and cell phenotype of PASMCs were reversed by overexpression of TRAF6. In summary, our study suggested the protective properties of sevoflurane in targeting PAH by downregulating TRAF6 expression, providing a novel avenue for the management of PAH.

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Regulación hacia Abajo , Miocitos del Músculo Liso , Hipertensión Arterial Pulmonar , Arteria Pulmonar , Ratas Sprague-Dawley , Sevoflurano , Factor 6 Asociado a Receptor de TNF , Animales , Sevoflurano/farmacología , Sevoflurano/toxicidad , Regulación hacia Abajo/efectos de los fármacos , Ratas , Masculino , Factor 6 Asociado a Receptor de TNF/metabolismo , Factor 6 Asociado a Receptor de TNF/genética , Hipertensión Arterial Pulmonar/inducido químicamente , Hipertensión Arterial Pulmonar/metabolismo , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Hipertensión Arterial Pulmonar/patología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/patología , Arteria Pulmonar/metabolismo , Monocrotalina/toxicidad , FN-kappa B/metabolismo , Proliferación Celular/efectos de los fármacos , Remodelación Vascular/efectos de los fármacos , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Células Cultivadas

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Hepatocyte growth factor (HGF) and its receptor, c-Met, play important roles in the occurrence, development, and treatment of gastric cancer (GC). This review explored the function of the HGF/c-Met signaling pathway in GC and its potential targeted therapeutic mechanisms. As one of the most common malignant tumors worldwide, GC has a complex pathogenesis and limited therapeutic options. Therefore, a thorough understanding of the molecular mechanism of GC is very important for the development of new therapeutic methods. The HGF/c-Met signaling pathway plays an important role in the proliferation, migration, and invasion of GC cells and has become a new therapeutic target. This review summarizes the current research progress on the role of HGF/c-Met in GC and discusses targeted therapeutic strategies targeting this signaling pathway, providing new ideas and directions for the treatment of GC.

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Meningitis caused by Moraxella osloensis is rare and easily misdiagnosed clinically. Here, we report the first case of meningitis caused by M. osloensis in China by taking advantage of the metagenomic next-generation sequencing technology in cerebrospinal fluid for pathogen screening. In addition, we extend the neurological signs, clinical symptoms, diagnostic methods, and treatment of this rare disease.

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Meningitis Bacterianas , Moraxella , Infecciones por Moraxellaceae , Humanos , Moraxella/aislamiento & purificación , Moraxella/genética , Infecciones por Moraxellaceae/diagnóstico , Infecciones por Moraxellaceae/tratamiento farmacológico , Infecciones por Moraxellaceae/microbiología , Infecciones por Moraxellaceae/complicaciones , Meningitis Bacterianas/diagnóstico , Meningitis Bacterianas/microbiología , Meningitis Bacterianas/tratamiento farmacológico , Masculino , Femenino

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PURPOSE: To evaluate the application effects of The-Optimal-Lymph-Flow IT System in Chinese patients at high risk of developing breast cancer-related lymphedema. METHODS: A total of 104 breast cancer patients were randomly assigned to either the control group or the intervention group. The intervention group was provided with the The-Optimal-Lymph-Flow program, while the control group received the usual care. Trial outcomes including symptom experience, quality of life, and limb volume were evaluated at baseline, and at end of the 1- and 3-month trials. RESULTS: After controlling for covariates, the incidence of eight symptoms was significantly higher in the control group than in the intervention group. There were significant differences in the changes in the severity of symptoms and arm volume between the two groups from baseline to 3 months after the intervention. CONCLUSIONS: The application of TOLF in patients at high risk of developing lymphedema following breast cancer treatment significantly improved the lymphedema-related symptoms experienced in the early stage after surgery. Trial registration ChiCTR1800016713.

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Person Re-identification (Re-ID) aims to match person images across non-overlapping cameras. The existing approaches formulate this task as fine-grained representation learning with deep neural networks, which involves extracting image features using a deep convolutional network, followed by mapping the features into a discriminative space through another smaller network, in order to make full use of all possible cues. However, recent Re-ID methods that strive to capture every cue and make the space more discriminative have resulted in longer features, ranging from 1024 to 14336, leading to higher time (distance computation) and space (feature storage) complexities. There are two potential solutions: reduction-after-training methods (such as Principal Component Analysis and Linear Discriminant Analysis) and reduction-during-training methods (such as 1 × 1 Convolution). The former utilizes a statistical approach aiming for a global optimum but lacking end-to-end optimization of large data and deep neural networks. The latter lacks theoretical guarantees and may be vulnerable to training noise such as dataset noise or initialization seed. To address these limitations, we propose a method called Euclidean-Distance-Preserving Feature Reduction (EDPFR) that combines the strengths of both reduction-after-training and reduction-during-training methods. EDPFR first formulates the feature reduction process as a matrix decomposition and derives a condition to preserve the Euclidean distance between features, thus ensuring accuracy in theory. Furthermore, the method integrates the matrix decomposition process into a deep neural network to enable end-to-end optimization and batch training, while maintaining the theoretical guarantee. The result of the EDPFR is a reduction of the feature dimensions from fa and fb to fa' and fb', while preserving their Euclidean distance, i.e.L2(fa,fb)=L2(fa',fb'). In addition to its Euclidean-Distance-Preserving capability, EDPFR also features a novel feature-level distillation loss. One of the main challenges in knowledge distillation is dimension mismatch. While previous distillation losses, usually project the mismatched features to matched class-level, spatial-level, or similarity-level spaces, this can result in a loss of information and decrease the flexibility and efficiency of distillation. Our proposed feature-level distillation leverages the benefits of the Euclidean-Distance-Preserving property and performs distillation directly in the feature space, resulting in a more flexible and efficient approach. Extensive on three Re-ID datasets, Market-1501, DukeMTMC-reID and MSMT demonstrate the effectiveness of our proposed Euclidean-Distance-Preserving Feature Reduction.

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Aim: To build a ferroptosis-related prognostic model for patients with colon adenocarcinoma (COAD). Methods: COAD expression profiles from The Cancer Genome Atlas were used as the training set and GSE39582 from Gene Expression Omnibus as the validation set. Differentially expressed ferroptosis-related genes between patients with COAD and normal controls were screened, followed by tumor subtype exploration based on ferroptosis-related gene expression levels. A ferroptosis score (FS) model was constructed using least absolute shrinkage and selection operator penalized Cox analysis. Based on FS, patients were subgrouped into high- and low-risk subgroups and overall survival was predicted. The potential prognostic value of the FS model and the clinical characteristics were investigated using receiver operating characteristic curves. Results: Twenty-four differentially expressed ferroptosis-related genes were identified, four of which (CYBB, PRNP, ACSL4, and ACSL6) were included in the prognostic signature. Moreover, age, pathological T stage, and tumor recurrence were independent prognostic factors for COAD. The FS model combined with three independent prognostic factors showed the best prognostic value (The Cancer Genome Atlas: area under the curve = 0.897; GSE39582: area under the curve = 0.858). Conclusion: The novel prognostic model for patients with COAD constructed by pairing the FS model with three important independent prognostic factors showed promising clinical predictive value.

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Background: As one of the serious complications of sepsis in children, sepsis-associated encephalopathy (SAE) is associated with significantly poor prognosis and increased mortality. However, predictors of outcomes for pediatric SAE patients have yet to be identified. The aim of this study was to develop nomograms to predict the 14-day and 90-day mortality of children with SAE, providing early warning to take effective measures to improve prognosis and reduce mortality. Methods: In this multicenter, retrospective study, we screened 291 patients with SAE admitted to the PICU between January 2017 and September 2022 in Shandong Province. A least absolute shrinkage and selector operation (LASSO) method was used to identify the optimal prognostic factors predicting the outcomes in pediatric patients with SAE. Then, multivariable logistic regression analysis was performed based on these variables, and two nomograms were built for visualization. We used the area under the curve (AUC), calibration curves and decision curves to test the accuracy and discrimination of the nomograms in predicting outcomes. Results: There were 129 patients with SAE in the training cohort, and there were 103 and 59 patients in the two independent validation cohorts, respectively. Vasopressor use, procalcitonin (PCT), lactate and pediatric critical illness score (PCIS) were independent predictive factors for 14-day mortality, and vasopressor use, PCT, lactate, PCIS and albumin were independent predictive factors for 90-day mortality. Based on the variables, we generated two nomograms for the early identification of 14-day mortality (AUC 0.853, 95% CI 0.787-0.919, sensitivity 72.4%, specificity 84.5%) and 90-day mortality (AUC 0.857, 95% CI 0.792-0.923, sensitivity 72.3%, specificity 90.6%), respectively. The calibration plots for nomograms showed excellent agreement of mortality probabilities between the observed and predicted values in both training and validation cohorts. Decision curve analyses (DCA) indicated that nomograms conferred high clinical net benefit. Conclusion: The nomograms in this study revealed optimal prognostic factors for the mortality of pediatric patients with SAE, and individualized quantitative risk evaluation by the models would be practical for treatment management.

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Serine protease 50 (PRSS50/TSP50) is highly expressed in spermatocytes. Our study investigated its role in testicular development and spermatogenesis. Initially, PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes. To further explore this, we generated PRSS50 knockout ( Prss50 -/- ) mice ( Mus musculus), which exhibited abnormal spermatid nuclear compression and reduced male fertility. Furthermore, dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50 -/- mice, accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells. Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and elevated levels of MAP kinase phosphatase 3 (MKP3), a specific ERK antagonist, potentially accounting for testicular dysplasia in adolescent Prss50 -/- mice. Taken together, these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis, with the MKP3/ERK signaling pathway playing a significant role in this process.

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Sistema de Señalización de MAP Quinasas , Meiosis , Ratones Noqueados , Espermatozoides , Animales , Masculino , Ratones , Meiosis/fisiología , Espermatozoides/fisiología , Espermatogénesis/fisiología , Fosfatasa 6 de Especificidad Dual/genética , Fosfatasa 6 de Especificidad Dual/metabolismo , Testículo/metabolismo , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo