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Background: The growing population of elderly neurocritically ill patients highlights the need for effective prognosis prediction tools. This study aims to develop and validate machine learning (ML) models for predicting 28-day mortality in intensive care units (ICUs)., Methods: Data were extracted from the Medical Information Mart for Intensive Care IV(MIMIC-IV) database, focusing on elderly neurocritical ill patients with ICU stays ≥ 24 h. The cohort was split into 70 % for training and 30 % for internal validation. We analyzed 58 variables, including demographics, vital signs, medications, lab results, comorbidities, and medical scores, using Lasso regression to identify predictors of 28-day mortality. Seven ML algorithms were evaluated, and the best model was validated with data from Guizhou Medical University Affiliated Hospital. A log-rank test was used to assess survival differences in Kaplan-Meier curves. Shapley Additive Explanations (SHAP) were used to interpret the best model, while subgroup analysis identified variations in model performance across different populations., Results: The study included 1,773 elderly neurocritically ill patients, with a 28-day mortality rate of 28.6 %. The Light Gradient Boosting Machine (LightGBM) outperformed other models, achieving an area under the curve (AUC) of 0.896 in internal validation and 0.812 in external validation. Kaplan-Meier analysis showed that higher LightGBM prediction scores correlated with lower survival probabilities. Key predictors identified through SHAP analysis included partial pressure of arterial carbon dioxide (PaCO 2 ), Acute physiology and chronic health evaluation II (APACHE II), white blood cell count, age, and lactate. The LightGBM model demonstrated consistent performance across various subgroups., Conclusions: The LightGBM model effectively predicts 28-day mortality risk in elderly neurocritically ill patients, aiding clinicians in management and resource allocation. Its reliable performance across diverse subgroups underscores its clinical utility., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

The utilization of catalysts in lithium--sulfur batteries has proven to be an efficacious avenue for enhancing the kinetics of polysulfide conversion. Specially, the size and electronic structure of catalysts play a pivotal role in harnessing the active sites and intrinsic catalysis activity. Outstanding MoSe 2 and NbSe 2 are were selected from 16 universal transition metal selenides based on the proposed binary descriptor. Then, an alloying strategy is was devised to prepare Mo 0.25 Nb 0.75 Se 2 flakelets for further improvement of the intrinsic catalysis. The integration of density functional theory calculations and electrochemical analysis demonstrates that alloying Mo with Nb can regulate the surface energy and indexes of band match and lattice mismatch, thereby enabling Mo 0.25 Nb 0.75 Se 2 to possess a small size, suitable adsorption energy and low reaction energy barrier. This optimization enhances the catalysis of sulfur reduction/evolution reaction and the reversible deposition/stripping of lithium. Consequently, an assembled Ah-level pouch cell is realized with dramatic cycle stability. With the electrolyte/sulfur ratio of 2.36 μL mg S -1 , the cell can deliver a high energy density of up to 505.4 Wh kg total -1 . This work pioneers a universal strategy for sculpting the geometric configurations and electronic structures of catalysts, to achieve enhanced catalytic activity and precise interpretation of structure-activity relationships., (© 2024 Wiley-VCH GmbH.)

Knee pain, affecting an estimated 654 million people worldwide, so blood flow restriction training (BFRT) is catching the spotlight as an effective intervention. Evidence continues to demonstrate the effectiveness of BFRT in managing knee pain. However, the mechanism by which BFRT alleviates knee pain remains unclear, thereby limiting its application in clinical pain management. This study aims to elucidate the underlying mechanisms of BFRT to better understand its efficacy in treating knee pain. This review will discuss the influence of muscle hypertrophy, endogenous opioid system, endocannabinoids, inflammation regulation, and conditional pain regulation on BFRT treatment of knee pain. Current studies on BFRT have limitations, such as small sample sizes, relatively low-quality evidence, and lack of mechanistic studies. Therefore, further research on BFRT is needed, particularly high-quality and large-sized randomized controlled trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Xie, Jiang, Yuan, Luo, Song and Hu.)

Background: Diagnosing and managing follicular thyroid neoplasms (FTNs) remains a significant challenge, as the malignancy risk cannot be determined until after diagnostic surgery., Objective: We aimed to use interpretable machine learning to predict the malignancy risk of FTNs preoperatively in a real-world setting., Methods: We conducted a retrospective cohort study at the Peking University Third Hospital in Beijing, China. Patients with postoperative pathological diagnoses of follicular thyroid adenoma (FTA) or follicular thyroid carcinoma (FTC) were included, excluding those without preoperative thyroid ultrasonography. We used 22 predictors involving demographic characteristics, thyroid sonography, and hormones to train 5 machine learning models: logistic regression, least absolute shrinkage and selection operator regression, random forest, extreme gradient boosting, and support vector machine. The optimal model was selected based on discrimination, calibration, interpretability, and parsimony. To address the highly imbalanced data (FTA:FTC ratio>5:1), model discrimination was assessed using both the area under the receiver operating characteristic curve and the area under the precision-recall curve (AUPRC). To interpret the model, we used Shapley Additive Explanations values and partial dependence and individual conditional expectation plots. Additionally, a systematic review was performed to synthesize existing evidence and validate the discrimination ability of the previously developed Thyroid Imaging Reporting and Data System for Follicular Neoplasm scoring criteria to differentiate between benign and malignant FTNs using our data., Results: The cohort included 1539 patients (mean age 47.98, SD 14.15 years; female: n=1126, 73.16%) with 1672 FTN tumors (FTA: n=1414; FTC: n=258; FTA:FTC ratio=5.5). The random forest model emerged as optimal, identifying mean thyroid-stimulating hormone (TSH) score, mean tumor diameter, mean TSH, TSH instability, and TSH measurement levels as the top 5 predictors in discriminating FTA from FTC, with the area under the receiver operating characteristic curve of 0.79 (95% CI 0.77-0.81) and AUPRC of 0.40 (95% CI 0.37-0.44). Malignancy risk increased nonlinearly with larger tumor diameters and higher TSH instability but decreased nonlinearly with higher mean TSH scores or mean TSH levels. FTCs with small sizes (mean diameter 2.88, SD 1.38 cm) were more likely to be misclassified as FTAs compared to larger ones (mean diameter 3.71, SD 1.36 cm). The systematic review of the 7 included studies revealed that (1) the FTA:FTC ratio varied from 0.6 to 4.0, lower than the natural distribution of 5.0; (2) no studies assessed prediction performance using AUPRC in unbalanced datasets; and (3) external validations of Thyroid Imaging Reporting and Data System for Follicular Neoplasm scoring criteria underperformed relative to the original study., Conclusions: Tumor size and TSH measurements were important in screening FTN malignancy risk preoperatively, but accurately predicting the risk of small-sized FTNs remains challenging. Future research should address the limitations posed by the extreme imbalance in FTA and FTC distributions in real-world data., (© Rui Shan, Xin Li, Jing Chen, Zheng Chen, Yuan-Jia Cheng, Bo Han, Run-Ze Hu, Jiu-Ping Huang, Gui-Lan Kong, Hui Liu, Fang Mei, Shi-Bing Song, Bang-Kai Sun, Hui Tian, Yang Wang, Wu-Cai Xiao, Xiang-Yun Yao, Jing-Ming Ye, Bo Yu, Chun-Hui Yuan, Fan Zhang, Zheng Liu. Originally published in JMIR Cancer (https://cancer.jmir.org).)

Background: Previous studies have shown inconsistent findings regarding the association of alcohol consumption with sarcopenia. Therefore, this study comprehensively investigated the association of alcohol consumption with sarcopenia in a nationally representative sample of US adults., Methods: This population-based study included adults aged 18 years and older from the National Health and Nutrition Examination Survey (NHANES) III. Alcohol exposure was defined as daily alcohol intake, alcohol drinking history, number of drinking days per week, and frequency of binge drinking days per month. Weighted logistic regressions were used to determine associations., Results: Four cohorts were selected from the NHANES III: cohort 1 ( n  = 7,592), cohort 2 ( n  = 12,060), cohort 3 ( n  = 7,608), and cohort 4 ( n  = 7,649), corresponding to alcohol exposure categories of daily alcohol intake, drinking history, number of drinking days per week, and frequency of binge drinking days per month. In the full model, the risk of sarcopenia was significantly associated with mild (odds ratio [OR]: 1.65; 95% confidence interval [CI]: 1.08-2.51), moderate (OR: 2.04; 95% CI: 1.12-3.71), and heavy drinkers (OR: 2.42; 95% CI: 1.17-4.97) compared to nondrinkers. There was an association between the development of sarcopenia and current drinkers (OR: 1.69; 95% CI: 1.12-2.56) but not former drinkers (OR: 1.21; 95% CI: 0.88-1.66). Compared to nondrinkers, an increased risk of developing sarcopenia was observed in participants who consumed alcohol 2 days (OR: 2.36; 95% CI: 1.40-3.99) or > 2 days (OR: 1.84; 95% CI: 1.10-3.07) per week, and those who engaged in binge drinking for ≤1 day per month (OR: 1.68; 95% CI: 1.09-2.60) or > 1 day per month (OR: 2.10; 95% CI: 1.10-4.01). Sensitivity analyses based on different definitions of sarcopenia yielded similar results. Stratified analyses revealed that these associations were present in females but not males., Conclusion: Alcohol intake was associated with an increased risk of sarcopenia in all individuals, with this association being primarily observed in females rather than males., Competing Interests: FJ was a speaker of Gilead Sciences, MSD, and Ascletis. He was also a consulting or advisory board in Gilead Sciences and MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Yang, Ran, Yeo, Wen, Tuo, Li, Yuan, Dai, Wang, Ji and Tantai.)

Background: The flexible and navigable suction ureteral access sheath (FANS-UAS) is regarded as a complement to flexible ureteroscopy in retrograde intrarenal surgery. Management of lower pole stones (LPS) is challenging due to the difficulty of anatomical access to the inferior renal calyx., Case Description: The novel FANS-UAS (11/13.5 Fr; 40/50 cm length; 7 cm navigable tip length; 180° angulation) from Well Lead Medical (Guangzhou, China) has been commercially-available in July 2024 and first-used in The University of Hong Kong-Shenzhen Hospital. This case series included five candidates (three males; mean age 37.8±15.1 years) with LPS (max. diameter 7-10.5 mm) undergoing FANS-UAS with flexible ureteroscopic lithotripsy. Success rate of FANS-UAS catheterization was 80% as a male patient displayed poor ureter elasticity intraoperatively and the operation had to be completed with a 10/12 Fr tip-flexible UAS and stone basket. LPS, including those with an infundibulopelvic angle <30°, could be easily navigated and removed with insignificant to no residual stones remaining. No stone basket was used. Grade I and II ureteric injuries occurred in two separate patients that were resolved upon four weeks of ureteral stenting. No significant intra- and post-operative complication was observed. The mean total operative duration was 66.5±22.6 minutes. Computed tomography scans were conducted at day one post-operation. Among the cases with successful FANS-UAS insertion, the absolute and relative stone free rate, defined as complete absence and absence of residual fragments <2 mm, was 75% and 100%, respectively. All patients remained stone-free at one-month follow-up with no adverse events., Conclusions: Early outcomes of the novel 11/13.5 Fr FANS-UAS applied successfully on four patients demonstrate its feasibility, safety, and efficiency in removing LPS. However, improvements in design may be necessitated in the future. For the meantime, prolonged follow-up and larger patient samples are necessitated to further elucidate its outcomes and prognosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-388/coif). The authors have no conflicts of interest to declare., (Copyright © 2025 AME Publishing Company. All rights reserved.)

A photopromoted Pd-catalyzed Heck reaction of gem-difluorocyclopropyl bromides (DFCBs) with styrenes to deliver vinyl gem-difluorinated cyclopropanes (VDFCs) under mild conditions has been developed. The reaction demonstrates good functional group compatibility while providing high E/Z ratio of the products. Furthermore, the desired VDFCs can be easily transformed into fluorinated cyclic/acyclic architectures, which may broaden its applications in organic synthesis., (© 2024 Wiley-VCH GmbH.)

Hepatic fibroblasts comprise groups of stromal cells in the liver that are phenotypically distinct from hepatic stellate cells. However, their physiology is poorly understood. By single-cell RNA sequencing, we identified Cd34 and Dpt as hepatic fibroblast-specific genes. Cd34-CreER labeled periportal-venous and periductal fibroblasts, but few pericentral-venous fibroblasts. Cd34+ fibroblasts generated ∼25% of myofibroblasts in periportal fibrosis and ∼40% of cancer-associated fibroblasts (CAFs) in intrahepatic cholangiocarcinoma (ICC). Myofibroblast formation by Cd34+ fibroblasts required Tgfbr2. Depletion of Cd34+ fibroblasts increased the frequency of the ductal epithelial cells under homeostasis and accelerated the progression of ICC. Dpt-CreER labeled periportal- and pericentral-venous fibroblasts, but much less periductal fibroblasts. Dpt+ cells generated ∼15% of myofibroblasts in periportal fibrosis, but few myofibroblasts in pericentral fibrosis or CAFs in ICC. Thus, an orthogonal combination of Cd34-CreER and Dpt-CreER dissected the fates of periductal, periportal-venous, and pericentral-venous fibroblasts. Both periductal and periportal-venous fibroblasts contribute to liver fibrosis. Periductal fibroblasts also contribute to ductal homeostasis and ICC progression., (© 2025 Wang et al.)

Background: Autoimmune phenomena can be used in some patients with nonalcoholic fatty liver disease (NAFLD) in the clinic, but these patients are not autoimmune hepatitis patients., Aim: To determine whether autoimmunity is present in patients with NAFLD, this study was performed., Methods: A total of 104 patients with NAFLD diagnosed by liver biopsy at Tianjin Second People's Hospital between 2019 and 2023 were enrolled. The patients were divided into three groups according to their biopsy results: The NAFL ( n = 36), nonalcoholic steatohepatitis ( n = 51), and liver cirrhosis groups ( n = 17)., Results: The differences in IgA, an immune marker, among the three groups of patients were statistically significant ( P = 0.025). In all NAFLD patients, antinuclear antibody and anti-smooth muscle antibody were the most common autoantibodies. The antinuclear antibody detection rate was the highest at 48.1%. The cirrhosis group had the highest autoantibody positivity rate (64.7%). Portal enlargement is also common in NAFLD patients. The rates of positivity for portal lymphoplasmacytic infiltration, small bile duct hyperplasia and interfacial hepatitis were highest in the cirrhosis group; the differences between the cirrhosis group and the other two groups were significant ( P < 0.05). Hepatocellular rosettes were identified only in the cirrhosis group (11.8%)., Conclusion: Autoimmune phenomena occur in NAFLD patients, especially in patients with NAFLD-related cirrhosis, in whom this phenomenon may be more pronounced., Competing Interests: Conflict-of-interest statement: Yu-Jin Zhu and Yan Zhang has received research funding from Tianjin Second People's Hospital., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Inspired by the recently reported novel two-dimensional material B 3 C 2 P 3 , we performed one-dimensional shearing along the zigzag direction to obtain four B 3 C 2 P 3 nanoribbons with various edge atom combinations. An asymmetric hydrogen passivation scheme was employed to modulate the electronic properties and successfully open the band gap, especially the 2H-1H passivation with dihydrogenation and monohydrogenation at the top and bottom edges, respectively, achieving bipolar magnetic semiconductors with edge P-atoms contributing to the main magnetism. Furthermore, three crucial spin-polarized transmission spectra yielded a significant spin-dependent Seebeck effect (SDSE), displaying superior thermoelectric conversion capabilities by generating pure spin currents. Our work shows that this asymmetric H-passivation effectively enables the enhancement of the spin caloritronic transport properties of the B 3 C 2 P 3 , which is of great significance for the exploitation of novel materials and their applications in spintronics.

NMN is a precursor in the biosynthesis of NAD + , a molecule that plays a crucial role within cells. Supplementation with NMN can elevate NAD + levels in the blood, improving symptoms of diabetes, neurodegenerative diseases, and cancer, as well as providing anti-aging benefits. Escherichia coli was engineered to heterologously express nicotinamide phosphoribosyltransferase (Nampt), enabling the recombinant E. coli to synthesize NAD derivatives from nicotinamide. The 3D structure of Nadv complexed with NAM and NMN was determined to explore the molecular mechanism by which Nadv catalyzes NMN synthesis. NAM binds at two sites: one at the catalytic site and one at the allosteric binding site, while NMN binds exclusively at the catalytic site. In both structural models, a loop between β15 and β16 is missing, likely due to its high flexibility, leading to diffuse electron density. Compared with other resolved Nampt structures, an additional 12-amino-acid loop was identified after α-helix 12 near the catalytic site. This study lays the groundwork for the engineering of Nadv, facilitating its efficient application in biological synthesis of NMN., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To systematically evaluate the impact of aspirin on the pulmonary inflammatory response in animal models of acute lung injury/acute respiratory distress syndrome (ALI/ARDS)., Methods: Experimental research on aspirin therapy or prevention of ALI/ARDS in animal models were searched in PubMed, Web of Science, Cochrane library, Embase, China biology medicine, CNKI, Wanfang, VIP. The search time limit was from the establishment of the database to July 17, 2023. The control group established the ALI/ARDS model without any pharmacological intervention. The intervention group was given aspirin or aspirin-derived compounds or polymeric-aspirin (Poly-A) at different time points before and after the preparation of the model, of which there was no restriction on the dosage form, dosage, mode of administration, or number of doses. The primary outcome indicators included bronchoalveolar lavage fluid (BALF) or lung tissue myeloperoxidase (MPO) activity, interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and the counts of neutrophils in BALF. Two researchers screened the literature and extracted information based on inclusion and exclusion criteria. Literature quality was assessed by the bias risk assessment tool SYRCLE. RevMan 5.3 software was used for data synthesis and statistical analysis., Results: A total of 17 papers were eventually included, involving a total of 449 animal models, all of which were murine. One paper was at high risk of bias and the rest 16 papers were at moderate risk of bias. Meta-analysis showed that compared with the control group, the neutrophil count in BALF [standardized mean difference (SMD) = -5.06, 95% confidence interval (95%CI) was -7.00 to -3.12, P < 0.000 01], the myeloperoxidase (MPO) activity in BALF or lung tissue (SMD = -3.45, 95%CI was -4.43 to -2.47, P < 0.000 01), the TNF-α level in BALF or lung tissue (SMD = -2.78, 95%CI was -3.58 to -1.98, P < 0.000 01), and the IL-1β level in BALF or lung tissue (SMD = -3.12, 95%CI was -4.56 to -1.69, P < 0.000 1) were significantly decreased in the ALI/ARDS model of the intervention group., Conclusions: Aspirin reduces the level of lung inflammation in animal models of ALI/ARDS. However, there are problems of poor quality and significant heterogeneity of the included studies, which still need our further validation.

Monocomponent catalysts exhibit the limited catalytic conversion of polysulfides due to their intrinsic electronic structure, but their catalytic activity can be improved by introducing heteroatoms to regulate its electronic structure. However, the rational selection principles of doping elements remain unclear. Here, we are guided by theoretical calculations to select the suitable doping elements based on the balanced relationship between the adsorption strength of lithium polysulfides (LiPSs) and catalytic activity of lithium sulfide. We apply the screening method to develop a new catalyst of phosphorus doped RuSe 2 , manifesting the further enhanced conductivity compared with original RuSe 2 , facilitating charge transfer and further modulating the d-band center of RuSe 2 , thereby augmenting its effectiveness in interacting with LiPSs. Consequently, the assembled cell exhibits an areal capacity of 7.7 mAh cm -2 , even under high sulfur loading of 8.0 mg cm -2 and a lean electrolyte condition (5.0 μL mg -1 ). This rational screening strategy offers a robust solution for the design of advanced catalysts in the field of lithium-sulfur batteries and potentially other domains as well., (© 2024 Wiley-VCH GmbH.)

Morphological studies of the proboscis can provide valuable insights into the evolutionary adaptations of Lepidoptera. However, such research is relatively limited for Pieridae, a family that is significant both ecologically and economically. In this study, scanning electron microscopy (SEM) was employed to investigate the proboscis and associated sensilla of adult C. erate , with an emphasis on ultrastructural details and potential sex-specific differences. The proboscis in both sexes exhibits a similar structure, consisting of two elongated maxillary galeae connected by dorsal and ventral legulae. It is divided into three distinct zones based on morphological changes in the dorsal legulae. The outer surface of the proboscis is characterized by spike-like microbumps on transverse ridges, while the inner surface (food canal) is smooth throughout all three zones, with regularly spaced transverse grooves. Three types of sensilla comprising five subtypes were identified: sensilla chaetica (sc), sensilla basiconica (sb1, sb2, and sb3), and sensilla styloconica (ss). The functional implications of these morphological features are also discussed briefly.

The economical and efficient removal of nickel nitrate from industrial wastewater remains a challenge. Herein, we developed an innovative electrochemical membrane filtration system that used a periodic polarity reversal process to adjust the acid-base environment near membrane interface for the recovery of nickel (II) and ammonia. The Ru based electrocatalytic layer could boost the selective reduction of nitrate to ammonia by generating atomic hydrogen, resulting in the precipitation of Ni 2+ by the increasing pH at the membrane interface. Then, the precipitation of Ni(OH) 2 could be effectively stripped and collected under the periodic polarity reversal process. In-situ interfacial measurements demonstrated that the polarity reversal process enabled a reversible transformation between strongly acidic (pH < 2) and alkaline (pH > 13) environments within a 200 µm range at the membrane interface. In continuous flow operation treating real industrial wastewater containing 96.7 mg-N L -1 nitrate and 135.0 mg L -1 Ni 2+ , the system demonstrated the capability to achieve 92.5 ± 2.6 % nitrate removal (with a recovery efficiency of 15.1 ± 1.9 g-NH 3 kWh -1 ) and 99.7 ± 0.1 % Ni²⁺ removal (with a recovery efficiency of 24.9 ± 2.4 g-Ni kWh -1 ). Additionally, the specific treatment cost was approximately $0.17 m -3 , attributed to the recovery of Ni(OH)₂ and ammonia. Furthermore, this system could deliver a significant economic benefit ($1.64 per m 3 ) for treating a high concentration real wastewater (331.5 mg-N L -1 nitrate and 1496.3 mg L -1 Ni 2+ ), outperforming traditional alkali precipitation and biological nitrification/denitrification processes. Overall, our study presents an economical and sustainable method for recovering valuable chemicals from wastewater containing heavy metals and inorganic nitrogen, potentially advancing cost-effective water treatment technologies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Tumor-derived exosomes (TDEs) play crucial roles in intercellular communication. Hypoxia in the tumor microenvironment enhances secretion of TDEs and accelerates tumor metastasis. Jiedu recipe (JR), a traditional Chinese medicinal formula, has demonstrated efficacy in preventing the metastasis of hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unknown., Methods: Animal experiments were performed to investigate the metastasis-preventing effects of JR. Bioinformatics analysis and in vitro assays were conducted to explore the potential targets and active components of JR. TDEs were assessed using nanoparticle tracking analysis (NTA) and Western blotting (WB). Exosomes derived from normoxic or hypoxic HCC cells (H-TDEs) were collected to establish premetastatic mouse models. JR was intragastrically administered to evaluate its metastasis-preventive effects. WB and lysosomal staining were performed to investigate the effects of JR on lysosomal function and autophagy. Bioinformatics analysis, WB, NTA, and immunofluorescence staining were used to identify the active components and potential targets of JR., Results: JR effectively inhibited subcutaneous-tumor-promoted lung premetastatic niche development and tumor metastasis. It inhibited the release of exosomes from tumor cells under hypoxic condition. JR treatment promoted both lysosomal acidification and suppressed secretory autophagy, which were dysregulated in hypoxic tumor cells. Quercetin was identified as the active component in JR, and the epidermal growth factor receptor (EGFR) was identified as a potential target. Quercetin inhibited EGFR phosphorylation and promoted the nuclear translocation of transcription factor EB (TFEB). Hypoxia-impaired lysosomal function was restored, and secretory autophagy was alleviated by quercetin treatment., Conclusion: JR suppressed HCC metastasis by inhibiting hypoxia-stimulated exosome release, restoring lysosomal function, and suppressing secretory autophagy. Quercetin acted as a key component of JR and regulated TDE release through EGFR-TFEB signaling. Our study provides a potential strategy for retarding tumor metastasis by targeting H-TDE secretion. Please cite this article as: Jia WT, Xiang S, Zhang JB, Yuan JY, Wang YQ, Liang SF, Lin WF, Zhai XF, Shang Y, Ling CQ, Cheng BB. Jiedu recipe, a compound Chinese herbal medicine, suppresses hepatocellular carcinoma metastasis by inhibiting the release of tumor-derived exosomes in a hypoxic microenvironment through the EGFR-TFEB signaling pathway. J Integr Med. 2024; 22(6): 697-709., (Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

Low concentrations or limited residence times in tumor tissues, making celastrol (Cel) difficult to exert significant therapeutic effects. Thus, we developed Zein/hyaluronic acid core-shell nanoparticles (Cel/Zein@HA NPs) for active targeted delivery of Cel via CD44 receptor over-expression on cancer cells, which may strengthen the therapeutic efficacy of Cel and improve delivery targeting. Cel-loaded Zein nanoparticles (core), are elegantly enveloped by a hydrophilic HA coating that forms the shell, resulting in significantly improved encapsulation efficiency and ensured good stability. The cellular uptake of Cel/Zein@HA NPs in HepG2 cells was 1.57-fold higher than nontargeting Cel/Zein NPs. Near-infrared fluorescence imaging confirmed the accumulation of Cel/Zein@HA NPs in H22 liver cancer tumors in mice, resulting in effective antitumor effects and good biosafety. Besides, in vitro and in vivo experiments showed that compared with Cel/Zein NPs, Cel/Zein@HA NPs had more efficient inhibitory effect on tumor proliferation and lower systemic toxicity. Further studies revealed that Cel/Zein@HA NPs induced apoptosis in hepatocellular carcinoma cells by modulating Bax and Bcl-2 expression, while also inhibiting tumor angiogenesis by decreasing CD31 and VEGF levels. Overall, this study presents a promising strategy for enhancing targeted liver cancer therapy through the utilization of biopolymer nanoparticle-based nano-pharmaceuticals that facilitate CD44-mediated cellular uptake., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Oblique lateral interbody fusion (OLIF) is becoming widely used in patients with single-segment spinal tuberculosis (STB). The learning curve and complications associated with OLIF for the treatment of STB are still unknown. This study aims to figure out the learning curve and associated complications experience of OLIF for the treatment of STB., Methods: Between September 2018 and August 2023, 61 STB patients underwent OLIF plus percutaneous pedicle screw fixation (PPSF) were consecutively included in this research. Cumulative sum analysis (CUSUM) was applied to establish the learning curve of OLIF and determine the cut-off case number. All cases were divided into learning and experienced groups based on the cut-off case number. Clinical characteristics and relating surgical complications were compared and analyzed between the two groups., Results: The best-fitting curve was quadratic. The fitting equation was CUSUM (min) = 95.83 + 34.16x - 0.611 x  2 (x means operation case). The cut-off operation case number was 27 cases. The presence of significant differences particularly in the duration of operation, operative blood loss, overall incidence, and severity of postoperative complications was noteworthy between the two groups., Conclusion: A total of 27 cases is the minimum number to master OLIF combined with PPSF for the treatment of patients with single-segment STB. When surgeons master this operation, the operative time, operative blood loss, overall incidence, and severity of postoperative complications will improve., (© 2024. The Author(s).)

Mitochondria play an important role in pressure overload-induced cardiac hypertrophy. The present study aimed to investigate the role of mitochondrial transient receptor potential vanilloid 3 (TRPV3) in myocardial hypertrophy. A 0.7 mm diameter U-shaped silver clip was used to clamp the abdominal aorta of Sprague Dawley (SD) rats and establish an animal model of abdominal aortic constriction (AAC). Rat H9C2 myocardial cells were treated with angiotensin II (Ang II) to establish a hypertrophic myocardial cell model, and TRPV3 expression was knocked down using TRPV3 small interfering RNA (siRNA). JC-1 probe was used to detect mitochondrial membrane potential (MMP). DHE probe was used to detect ROS generation. Enzyme activities of mitochondrial respiratory chain complex I and III and ATP production were detected by assay kits. Immunofluorescence staining was used to detect TRPV3 expression in H9C2 cells. Western blot was used to detect the protein expression levels of β-myosin heavy chain (β-MHC), mitochondrial TRPV3 and mitochondrial NOX4. The results showed that, in the rat AAC model heart tissue and H9C2 cells treated with Ang II, the protein expression levels of β-MHC, mitochondrial TRPV3 and mitochondrial NOX4 were up-regulated, MMP was decreased, ROS generation was increased, mitochondrial respiratory chain complex I and III enzyme activities were decreased, and ATP production was reduced. After knocking down mitochondrial TRPV3 in H9C2 cells, the protein expression levels of β-MHC and mitochondrial NOX4 were down-regulated, MMP was increased, ROS generation was decreased, mitochondrial respiratory chain complex I and III enzyme activities were increased, and ATP production was increased. These results suggest that mitochondrial TRPV3 in cardiomyocytes exacerbates mitochondrial dysfunction by up-regulating NOX4, thereby participating in the process of pressure overload-induced myocardial hypertrophy.

Purpose: To compare clinical outcomes of transjugular intrahepatic portosystemic shunt (TIPS) created with the single covered-uncovered stent (Viatorr TIPS Endoprosthesis) versus covered stent (Fluency) versus a combination of covered and uncovered stent., Materials and Methods: From May 2016 and July 2019, a total of 180 liver cirrhosis patients with recurrent variceal bleeding underwent TIPS creation with single covered-uncovered stent (n = 63) or covered stent (n = 41) or a covered and uncovered stent combination (n = 76). Shunt dysfunction, rebleeding, overt hepatic encephalopathy and mortality was estimated using the Kaplan-Meier method and compared with the log-rank test., Results: The difference of baseline characteristics among these three groups were not significant. The included patients had a median age of 51 years (IQR 43-61), and 101 (56.1%) were men. The 1-year and 2-year shunt dysfunction rates were 1.6% and 3.2% in the single covered-uncovered stent group, 7.3% and 7.3% in the covered stent group and 5.3% and 6.6% in the combination group, respectively. There was no significant difference among groups [Hazard Ratio (HR) (95%CI): 1 vs 2.29 (0.38 - 13.72) vs 2.10 (0.41 - 10.83); P = 0.913]. No significant differences in the incidence of all-cause rebleeding were observed between the groups at 1 year (Viatorr vs Fluency vs combination: 11.1% vs 17.1% vs 10.5%) as well as 2 years (15.9% vs 17.1% vs 11.8%), with the HR (95%CI) being 1 vs 1.27 (0.5-3.21) vs 0.74 (0.30-1.82); P = 0.475). The 1-year and 2-year incidence of overt hepatic encephalopathy were 30.2% and 30.2% in the single covered-uncovered stent group, 22.0% and 22.0% in the covered stent group and 25.0% and 25.0% in the combination group, respectively. However, there was no significant difference among these three groups (P = 0.402). In addition, there was no significant difference in the 1-year and 2-year mortality (6.3% and 7.9% vs. 4.9% and 9.8% vs. 6.6% and 9.2%, P = 0.606)., Conclusion: No significant difference was observed among different stent groups. Fluency covered stent and the generic bare stent/Fluency covered stent was not an unreasonable alternative to the Viatorr stent for TIPS creation., (© 2024. The Author(s).)

Our previous study showed that pyridoxine 5'-phosphate oxidase (PNPO) is a tissue biomarker of ovarian cancer (OC) and has a prognostic implication but detailed mechanisms remain unclear. The current study focused on PNPO-regulated lysosome/autophagy-mediated cellular processes and the potential role of PNPO in chemoresistance. We found that PNPO was overexpressed in OC cells and was a prognostic factor in OC patients. PNPO significantly promoted cell proliferation via the regulation of cyclin B1 and phosphorylated CDK1 and shortened the G2M phase in a cell cycle. Overexpressed PNPO enhanced the biogenesis and perinuclear distribution of lysosomes, promoting the degradation of autophagosomes and boosting the autophagic flux. Further, an autolysosome marker LAMP2 was upregulated in OC cells. Silencing LAMP2 suppressed cell growth and induced cell apoptosis. LAMP2-siRNA blocked PNPO action in OC cells, indicating that the function of PNPO on cellular processes was mediated by LAMP2. These data suggest the existence of the PNPO-LAMP2 axis. Moreover, silencing PNPO suppressed xenographic tumor formation. Chloroquine counteracted the promotion effect of PNPO on autophagic flux and inhibited OC cell survival, facilitating the inhibitory effect of PNPO-shRNA on tumor growth in vivo. Finally, PNPO was overexpressed in paclitaxel-resistant OC cells. PNPO-siRNA enhanced paclitaxel sensitivity in vitro and in vivo. In conclusion, PNPO has a regulatory effect on lysosomal biogenesis that in turn promotes autophagic flux, leading to OC cell proliferation, and tumor formation, and is a paclitaxel-resistant factor. These data imply a potential application by targeting PNPO to suppress tumor growth and reverse PTX resistance in OC., (© 2024. The Author(s).)

Aims: Patients with heart valvular regurgitation is increasing; early screening of potential patients developing heart failure (HF) is crucial., Methods: From 1 November 2019 to 31 October 2023, a total of 509 patients with heart valvular regurgitation hospitalized in the Department of Cardiovascular Disease of the First Affiliated Hospital of Guangzhou University of Traditional Medicine were enrolled. Three hundred fifty-six cases were selected as the training set for modelling, and 153 cases were selected as the validation set for the internal validation of the model., Results: A predictive model of heart failure with the following nine risk factors was developed: atrial fibrillation (AF), pulmonary infection (PI), coronary artery disease (CAD), creatinine (CREA), low-density lipoprotein cholesterol (LDL-C), d-dimer (DDi), left ventricular end-diastolic diameter (LVEDd), mitral regurgitation (MR) and aortic regurgitation (AR). The model was evaluated by the C-index [the training set: area under curve (AUC) 0.937, 95% confidence interval (CI) 0.911-0.963; the validation set: AUC 0.928, 95% CI 0.890-0.967]. Hosmer-Lemeshow test (the training set: χ 2 10.908, P = 0.207; the validation set: χ 2 4.896, P = 0.769) revealed that both the training and validation sets performed well in terms of model differentiation and calibration. Decision curve analysis showed that both the training and validation sets have higher net benefits, indicating that the model has good utility. Ten-fold cross-validation showed that the training set has high similarities with the validation set, which means that the model has good stability., Conclusions: The occurrence of heart failure in patients with valvular regurgitation has a significant correlation with AF, PI, CAD, CREA, LDL-C, DDi, LVEDd, MR and AR. Based on these risk factors, a prediction model for heart failure was developed and validated, which showed good differentiation and utility, high accuracy and stability, providing a method for predicting heart failure., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: To identify the cognitive load of different turning tasks in simulated flight, a flight experiment was designed based on real "preliminary screening" training modules for pilots., Methods: Heart Rate Variability (HRV) and flight data were collected during the experiments using a flight simulator and a heart rate sensor bracelet. The turning behaviors in flight were classified into climbing turns, descending turns, and level flight turns. A recognition model for the cognitive load associated with these turning behaviors was developed using machine learning and deep learning algorithms., Results: pnni&#95;20, range&#95;nni, rmssd, sdsd, nni&#95;20, sd1, triangular&#95;index indicators are negatively correlated with different turning load. The LSTM-Attention model excelled in recognizing turning tasks with varying cognitive load, achieving an F1 score of 0.9491., Conclusion: Specific HRV characteristics can be used to analyze cognitive load in different turn-ing tasks, and the LSTM-Attention model can provide references for future studies on the selection characteristics of pilot cognitive load, and offer guidance for pilot training, thus having significant implications for pilot training and flight safety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Yu, Wu, Cao, Zhou and Yuan.)

Background: Cervical cancer is the most prevalent malignant tumor in women. This study aims to detect collagen type V α1 chain (COL5A1) expression and its clinical relevance in the prognosis of patients with cervical cancer., Methods: Cervical cancer tissues and their paired adjacent normal tissues were prepared for tissue microarray. The expression of COL5A1 protein and the scores of the expression were evaluated by immunohistochemistry (IHC) staining. The prognostic value of COL5A1 was analyzed by R software version 4.2.1 with "survival, survminer, ggplot2" packages and Gene Expression Profiling Interactive Analysis (GEPIA). The cBioPortal database was utilized for the analysis of COL5A1 gene mutations., Results: COL5A1 protein was overexpressed in human cervical cancer tissues compared to their paired adjacent normal tissues detected by IHC ( P  < 0.001). High expression of COL5A1 tends to be in elderly patients with cervical cancer. Survival analyses of clinical data of patients with cervical cancer showed that a high level of COL5A1 expression was significantly correlated with shorter overall survival ( P  = 0.031) and disease-free survival ( P  = 0.042) of patients. Further analyses of The Cancer Genome Atlas-Cervical Squamous Cell Carcinoma and the GEPIA survival datasets confirmed the association of high COL5A1 expression with poor overall survival of patients ( P  = 0.040 and P  = 0.018, respectively). The analysis of genomic alterations of COL5A1 using the cBioPortal tool revealed that the COL5A1 gene was altered in 4% of cervical cancer patients and COL5A1 corresponding protein alterations with post-translational modifications were hydroxylation., Conclusion: COL5A1 is a tissue biomarker correlated with the poor prognosis of patients with cervical cancer, which may lead to a new clinical application., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

As a medicinal and edible homologous Chinese herb, Polygonatum sibiricum has been used as a primary ingredient in various functional and medicinal products. Damage to the intestinal mucosal barrier can lead to or worsen conditions such as type 2 diabetes and Alzheimer's disease. Traditional Chinese medicine and its bioactive components can help prevent and manage these conditions by restoring the integrity of the intestinal mucosal barrier. This review delves into the mode of action of P. sibiricum polysaccharide in disease prevention and management through the restoration of the intestinal barrier. Polysaccharide from P. sibiricum effectively treats conditions by repairing the intestinal mucosal barrier, offering insights for treating complex diseases and supporting the application of P. sibiricum in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ren, Sun, Liao, Wang, Liu, Duan, Sun, Li and Yuan.)

Background: Biliary tract cancers (BTCs) are a heterogeneous group of tumors with high malignancy, poor prognosis, and limited treatment options., Aim: To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs., Methods: This open-label, non-randomized, double-center, phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University. Eligible patients were administered nab-paclitaxel (150 mg/m 2 , day 1) and capecitabine (2000 mg/m 2 , twice daily, days 1-7) in 14-day cycles until experiencing intolerable toxicity or disease progression. The primary outcome was the objective response rate (ORR). The secondary outcomes included the disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and safety., Results: A total of 44 patients successfully completed the trial, with a median age of 64.00 years (interquartile range, 35.00-76.00), and 26 (59.09%) were females. Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage. Among the remaining 43 patients undergoing at least one imaging assessment, the ORR was 23.26% [95% confidence interval (CI): 11.80%-38.60%], and the DCR was 69.77% (95%CI: 53.90%-82.80%). The median OS was 14.1 months (95%CI: 8.3-19.9), and the median PFS was 4.4 months (95%CI: 2.5-6.3). A total of 41 patients (93.18%) experienced at least one adverse event (AE), with 10 patients (22.73%) encountering grade ≥ 3 AEs, and the most frequent AEs of any grade were alopecia (79.50%), leukopenia (54.55%), neutropenia (52.27%), and liver dysfunction (40.91%), and no treatment-related deaths were documented., Conclusion: Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

In recent years, most studies on the gut microbiome have primarily focused on feces samples, leaving the microbial communities in the intestinal mucosa relatively unexplored. To address this gap, our study employed shotgun metagenomics to analyze the microbial compositions in normal rectal mucosa and matched feces from 20 patients with colonic polyps. Our findings revealed a pronounced distinction of the microbial communities between these two sample sets. Compared with feces, the mucosal microbiome contains fewer genera, with Burkholderia being the most discriminating genus between feces and mucosa, highlighting its significant influence on the mucosa. Furthermore, based on the microbial classification and KEGG Orthology (KO) annotation results, we explored the association between rectal mucosal microbiota and factors such as age, gender, BMI, and polyp risk level. Notably, we identified novel biomarkers for these phenotypes, such as Clostridium ramosum and Enterobacter cloacae in age. The mucosal microbiota showed an enrichment of KO pathways related to sugar transport and short chain fatty acid metabolism. Our comprehensive approach not only bridges the knowledge gap regarding the microbial community in the rectal mucosa but also underscores the complexity and specificity of microbial interactions within the human gut, particularly in the Chinese population., Importance: This study presents a system-level map of the differences between feces and rectal mucosal microbial communities in samples with colorectal cancer risk. It reveals the unique microecological characteristics of rectal mucosa and its potential influence on health. Additionally, it provides novel insights into the role of the gut microbiome in the pathogenesis of colorectal cancer and paves the way for the development of new prevention and treatment strategies., Competing Interests: The authors declare no conflict of interest.

Cerebral ischemia-reperfusion injury (CIRI) is the second leading cause of death worldwide, posing a huge risk to human life and health. Therefore, investigating the pathogenesis underlying CIRI and developing effective treatments are essential. Ferroptosis is an iron-dependent mode of cell death, which is caused by disorders in iron metabolism and lipid peroxidation. Previous studies demonstrated that ferroptosis is also a form of autophagic cell death, and nuclear receptor coactivator 4(NCOA4) mediated ferritinophagy was found to regulate ferroptosis by interfering with iron metabolism. Ferritinophagy and ferroptosis are important pathogenic mechanisms in CIRI. This review mainly summarizes the link and regulation between ferritinophagy and ferroptosis and further discusses their mechanisms in CIRI. In addition, the potential treatment methods targeting ferritinophagy and ferroptosis for CIRI are presented, providing new ideas for the prevention and treatment of clinical CIRI in the future., (© 2024. The Author(s).)

The human endometrial decidualization is a transformative event in the pregnant uterus that involves the differentiation of stromal cells into decidual cells. While crucial to the establishment of a successful pregnancy, the metabolic characteristics of decidual cells in vivo remain largely unexplored. Here, we integrated the single-cell RNA sequencing (scRNA-seq) datasets on the endometrium of the menstrual cycle and the maternal-fetal interface in the first trimester to comprehensively decrypt the metabolic characteristics of stromal fibroblast cells. Our results revealed that the differentiation of stromal cells into decidual cells is accompanied by increased amino acid and sphingolipid metabolism. Furthermore, metabolic heterogeneity exists in decidual cells with differentiation maturity disparities. Decidual cells with high metabolism exhibit higher cellular activity and show a strong propensity for signaling. In addition, significant metabolic reprogramming in amino acids and lipids also occurs during the transition from non-pregnancy to pregnancy in the uteri of pigs, cattle, and mice. Our analysis provides comprehensive insights into the dynamic landscape of stromal fibroblast cell metabolism, contributing to our understanding of the metabolism at the molecular dynamics underlying the decidualization process in the human endometrium., (© 2024. The Author(s).)

An ambient-light-promoted stereospecific olefinic C(sp 2 )-S bond construction of thioacids and 1,1-diarylethenes has been demonstrated, affording various ( Z )-vinyl thioesters in 51-85% yields under solvent- and catalyst-free conditions. Mechanistic studies indicated that the formation of thioacid-olefin complexes is responsible for generating a carbonyl thiyl radical and dioxygen in the air participates in the reaction and functions as a traceless reagent. Moreover, synthetic applications have been demonstrated by the gram scale synthesis and aggregation-induced emission property of representative compound 3i .

Massively parallel sequencing allows for integrated genotyping of different types of forensic markers, which reduces DNA consumption, simplifies experimental processes, and provides additional sequence-based genetic information. The STRseqTyper122 kit genotypes 63 autosomal STRs, 16 X-STRs, 42 Y-STRs, and the Amelogenin locus. Amplicon sizes of 117 loci were below 300 bp. In this study, MiSeq FGx sequencing metrics for STRseqTyper122 were presented. The genotyping accuracy of this kit was examined by comparing to certified genotypes of NIST standard reference materials and results from five capillary electrophoresis-based kits. The sensitivity of STRseqTyper122 reached 125 pg, and > 80% of the loci were correctly called with 62.5 pg and 31.25 pg input genomic DNA. Repeatability, species specificity, and tolerance for DNA degradation and PCR inhibitors of this kit were also evaluated. STRseqTyper122 demonstrated reliable performance with routine case-work samples and provided a powerful tool for forensic applications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The sequencing electroreduction-electrooxidation process has emerged as a promising approach for the degradation of the chloronitrobenzenes (CNBs) due to its elimination of electro-withdrawing groups in the reduction process, facilitating further removal in the subsequent oxidation process. Herein, we developed a cathode consisting of atom Pd on a Ti plate, which enabled the electro-generation of atomic hydrogen (H*) and the efficient electrocatalytic activation of H 2 O 2 to hydroxyl radical (•OH). Cyclic voltammetry (CV) curves and electron spin resonance (ESR) spectra verified the existence of H* and •OH. The electroreduction-electrooxidation system achieved 94.7% of 20 mg L -1 2,4-DCNB removal with a relatively low H 2 O 2 addition (5 mM). Moreover, the inhibition rate of Photobacterium phosphoreum in the effluent decreased from 95% to 52% after the sequencing electroreduction-electrooxidation processes. It was further revealed that the H* dominated the electroreduction process and triggered the electrooxidation process. Our work sheds light on the effective removal of electron-withdrawing groups substituted aromatic contaminants from water and wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Yuan Jia, Xi Chen, Xueye Wang, Yun Guo, Renhui Ren, Chengxin Niu, Yang Li reports financial support was provided by National Key Research and Development Program of China. Xueye Wang reports financial support was provided by National Key Research and Development Program of China. Yang Li reports financial support was provided by China Postdoctoral Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: There have been few studies on the role of autophagy in pancreatic neuroendocrine tumours (PNETs). SQSTM1/p62 (also called Sequestosome 1) is a potential autophagy regulator, and its biological roles and clinical significance in PNETs remain poorly understood., Purpose: The purpose of this study was to evaluate the clinical significance of SQSTM1/p62 in human PNET specimens and to evaluate its potential value as a therapeutic target by studying its biological function in PNET cell lines., Methods: SQSTM1/p62 protein expression was assessed in 106 PNET patient specimens by immunohistochemistry, and the relationship between SQSTM1/p62 protein expression and the clinicopathological features of PNETs in patients was analysed. The proliferation, invasion and apoptosis of SQSTM1/p62-knockdown QGP-1 and INS-1 cells were assessed by the MTT assay, a Transwell assay and flow cytometry. Cell autophagy was assessed by western blotting and mCherry-GFP-LC3B., Results: The protein expression of SQSTM1/p62 in PNET patient specimens was significantly correlated with tumour recurrence (p = 0.005) and worse prognosis (log rank p = 0.020). Downregulation of the SQSTM1/p62 gene inhibited tumour cell proliferation and migration and induced PNET cell death. Downregulation of SQSTM1/p62 activated autophagy in PNET cell lines but blocked autophagic flow. Knockdown of the SQSTM1/p62 gene inhibited mTOR phosphorylation., Conclusion: The SQSTM1/P62 protein could be an independent prognostic marker for PNET patients. Downregulating SQSTM1/P62 can inhibit PNET progression, inhibit mTOR phosphorylation and block autophagic flow., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This study was conducted to investigate the incidence of deep venous thrombosis (DVT), outcomes and its characteristics in patients with chronic heart failure (CHF) in a retrospective setting., Outcomes: Patients died of cardiac shock or acute exacerbation of heart failure (HF), admitted to intensive care unit (ICU) due to acute exacerbation of HF, patients decided to withdraw treatment and return home due to acute exacerbation of HF., Methods: From January 2015 to June 2022, we admitted 359 patients diagnosed with CHF, and lower limb ultrasonography was performed for the examination of DVT after admission. The incidence of DVT was recorded and patients with known risk factors of VTE were identified and excluded after incidence of DVT was calculated. Patients' clinical data were then collected., Results: The occurrence of DVT was 10.0% (36/359), as calf intramuscular vein thrombosis was the main constitution (n  =  28, 75%). DVT patients with other factors (carcinoma, surgery, stroke, previous history of DVT) constituted a considerable part (33.3%, 12/36). Age, history of Diabetes Mellitus (DM), levels of DDi (D-Dimer), levels of alanine transferase (ALT) and left ventricular end-diastolic diameter (LVEDd) were independent predictors or risk factors of DVT in CHF patients, while chronic kidney disease (CKD) stage 1-4, white blood cell (WBC) and direct oral anticoagulant (DOAC) were protective factors. Incidence of DVT was correlated with a poor outcome of CHF patients (Pearson Chi-Square test, Value 19.612, P  <  0.001)., Conclusions: In this retrospective study, incidence of DVT was found to be relatively high among hospitalized CHF patients, while patients with DVT was associated with a poor prognosis., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background: Inflammatory processes could potentially impact both mood and suicide risk, however, the relationship between cytokines and suicidal ideation remains unclear. This study aimed to investigate the association between plasma levels of cytokines and suicidal ideation in population with major depressive disorders (MDD)., Methods: A cross-sectional study was performed to assess the peripheral plasma levels of interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α) in 88 Chinese Han first-episode drug-naïve MDD patients. Suicidal ideation in the past week were identified using the Beck Scale for Suicide Ideation-Chinese Version (BSI-CV). The Hamilton Depression Rating Scale-17 (HAMD-17), the Hamilton Anxiety Rating Scale-14 (HAMA-14) and the Childhood Trauma Questionnaire (CTQ) was used to assess depression, anxiety and childhood trauma. Multivariable logistic regression models were used to estimate the association between cytokines and suicidal ideation. Interaction and stratified analyses were conducted according to age, sex, marital status, education, smoking status, BMI and physical activity., Results: Among the 88 participants, 42 individuals (47.7%) reported suicidal ideation within the past week. In the fully adjusted model, a statistically significant trend was observed in the association between IL-2 level and suicidal ideation (OR: 1.40, 95% CI: 1.00-1.97). The stratified analysis showed a statistically significant association between IL-6 level and suicidal ideation among younger people (OR: 1.17, 95% CI: 1.01-1.36) and a significant positive association between IL-8 (OR: 1.59, 95% CI: 1.03-2.44) and IL-10 (OR: 2.51, 95% CI: 1.27-4.96) levels and suicide ideation among higher educated populations., Limitations: The cross-sectional design, residual confounding effects and small sample size CONCLUSION: Our findings indicate a significant positive association between plasma IL-2 level and suicidal ideation in MDD patients. IL-2 has the potential to be a biomarker of suicidal ideation in patients with depression., Competing Interests: Declaration of Competing Interest All the authors declared that there is no conflict of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Kawasaki disease is a pediatric acute systemic vasculitis that specifically involves the coronary arteries. Timely initiation of immunoglobulin plus aspirin is necessary for diminishing the incidence of coronary artery abnormalities (CAAs). The optimal dose of aspirin, however, remains controversial. The trial aims to evaluate if low-dose aspirin is noninferior to moderate-dose in reducing the risk of CAAs during the initial treatment of Kawasaki disease., Methods: This is a multi-center, prospective, randomized, open-label, blinded endpoint, noninferiority trial to be conducted in China. The planned study duration is from 2023 to 2026. Data will be analyzed according to intention-to-treat principles. Participants are children and adolescents under the age of 18 with Kawasaki disease, recruited from the inpatient units. A sample size of 1,346 participants will provide 80% power with a one-sided significance level of 0.025. Qualifying children will be randomized (1:1) to receive either intravenous immunoglobulin (2 g/kg) plus oral moderate-dose aspirin (30-50 mg·kg -1 ·d -1 ) until the patient is afebrile for at least 48 hours, or immunoglobulin plus low-dose aspirin (3-5 mg·kg -1 ·d -1 ) as initial treatment. The primary outcome will be the occurrence of CAAs at 8 weeks after immunoglobulin infusion. Independent blinded pediatric cardiologists will assess the primary endpoint using echocardiography., Conclusions: There is a shortage of consensus on the dose of aspirin therapy for Kawasaki disease due to the lack of evidence. The results of our randomized trial will provide more concrete evidence for the efficacy and adverse events of low- or moderate-dose aspirin in the acute phase of Kawasaki disease., Trial Registration: www.chictr.org.cn: ChiCTR2300072686., Competing Interests: Conflict of interest The authors have indicated they have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The urban thermal environment is an important indicator for evaluating the ecological environment of a city. It directly affects the health of residents and the sustainable development of the urban economy. However, there is currently a lack of analysis on the impact pathways of the thermal environment considering both natural and human factors. Based on the MODIS MYD11A2 land surface temperature data, meteorological data, and human activity data of Xi'an metropolitan area in 2020, ArcGIS spatial geostatistical analysis was used to study the temporal and spatial distribution pattern of the thermal environment in different seasons, and redundancy analysis was utilized to select the main factors affecting the thermal environment. Then, structural equation modeling was used to quantify the direct and indirect effects of the dominant factors on the urban thermal environment. The results showed that:① The surface temperature in the Xi'an urban area showed a spatial pattern of higher temperatures in the north and lower temperatures in the south, with a decrease in temperature from the city center to the surrounding areas. The most severe heat environment pollution occurred in the summer. ② The redundancy analysis (RDA) results indicated that the main factors that affected the thermal environment were air temperature, impermeable surfaces, vegetation, and precipitation. ③ The results of the structural equation modeling (SEM) indicated that meteorological, surface, and anthropogenic factors affected the urban thermal environment mainly through direct pathways, which were much more important than all indirect pathways. Factors such as temperature, impervious surfaces, and point of interest density had a significant positive effect on the thermal environment (0.10 and 0.33). On the other hand, factors such as water bodies, precipitation, and vegetation had a significant negative effect on the thermal environment (-0.29 and -0.25). Human activities had a greater direct impact on nocturnal surface temperatures than surface and meteorological factors. Increasing economic efficiency is beneficial for mitigating the urban heat island effect. The results of the study can provide a reference for studying local climate change in urban heat islands and for the construction of green and ecologically livable urban environments.

We herein first report the homodimerization and tandem diamination of diazo compounds with primary amines catalyzed by the iron(II) phthalocyanine (PcFe(II)), which can construct one C-C bond and two C-N bonds within 20 min in one-pot. Compared to the traditional metal-catalyzed N-H insertion reaction between amines with diazo reagents, the developed reaction almost does not generate the N-H insertion product, but the homodimerization/tandem diamination product. The proposed mechanism studies indicate that primary amines play a crucial role in the homocoupling of diazo compounds via dimerization of iron(III)-acetonitrile radical generated from the reaction between diazoacetonitrile with PcFe(II) coordinated by bis(amines); the β-hydride elimination is involved, and then, the attack of primary amines toward the carbon atoms on the formed C-C bond is followed. Moreover, this novel reaction can be used to effectively prepare substituted 2,3-diaminosuccinonitriles with high yields and even up to >99:1 d.r., encouragingly these products contain both 1,2-diamines and succinonitrile motifs, which are two classes of important organic compounds with significant applications in many yields. This reaction is also suitable for the gram-scale preparation of 2,3-bis(phenylamino)succinonitrile ( 2a ) with a yield of 84%. Therefore, the developed reaction represents a new type of transformation.

Reactive chlorine species (RCS) are inevitably generated in electrochemical oxidation process for treating high-salinity industrial wastewater, thereby resulting in the competition with coexisting hydroxyl radicals (•OH) for oxidizing recalcitrant organic compounds. Due to the low redox potentials compared to •OH, the role of RCS has been often overlooked. In this work, we developed an electroactive membrane filtration (EMF) system that had a high removal efficiency (99.1 ± 0.5 %) for tetrabromobisphenol S (TBBPS) at low energy consumption (1.45 kWh m -3 ). Electron spin resonance spectroscopy and molecular probing tests indicated the predominance of Cl 2 •- , of which steady-state concentration (2.2 ×10 -10 M) was extremely higher than those of ClO• (6.7 ×10 -13 M), •OH (0.95 ×10 -13 M), and Cl• (2.39 ×10 -15 M). The density functional theory (DFT) and intermediate product analysis highlighted that Cl 2 •- radicals had a higher electrophilic attack efficacy than •OH radicals for inducing changes in the electron density of the carbon atoms around phenolic hydroxyl groups, thus leading to the generation of transition state intermediates and accelerating the degradation of TBBPS. Our work demonstrates the vital role of Cl 2 •- radicals for pollutant degradation, highlighting the potential of this technology for cost-effective removal of recalcitrant organic compounds from water and wastewater., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The cerebellum is a key structure involved in balance and motor control, and has become a new stimulation target in brain regulation technology. Interference theta-burst simulation (iTBS) is a novel simulation mode of repetitive transcranial magnetic simulation. However, the impact of cerebellar iTBS on balance function and gait in stroke patients is still unknown., Aim: The aim of this study was to determine whether cerebellar iTBS can improve function, particularly balance and gait, in patients with post-stroke hemiplegia., Design: This study is a randomized, double-blind, sham controlled clinical trial., Setting: The study was carried out at the Department of Rehabilitation Medicine in a general hospital., Population: Patients with stroke with first unilateral lesions were enrolled in the study., Methods: Thirty-six patients were randomly assigned to the cerebellar iTBS group or sham stimulation group. The cerebellar iTBS or pseudo stimulation site is the ipsilateral cerebellum on the paralyzed side, which is completed just before daily physical therapy. The study was conducted five times a week for two consecutive weeks. All patients were assessed before the intervention (T0) and at the end of 2 weeks of treatment (T1), respectively. The primary outcome was the Berg Balance Scale (BBS), while secondary outcome measures included the Fugl Meyer Lower Limb Assessment Scale (FMA-LE), timed up and go (TUG), Barthel Index (BI), and gait analysis., Results: After 2 weeks of intervention, the BBS, FMA-LE, TUG, and BI score in both the iTBS group and the sham group were significantly improved compared to the baseline (all P<0.05). Also, there was a significant gait parameter improvement including the cadence, stride length, velocity, step length compared to the baseline (P<0.05) in the iTBS group, but only significant improvement in cadence was identified in the sham group (P<0.05). Intergroup comparison showed that the BBS (P<0.001), FMA-LE (P<0.001), and BI (P=0.002) in the iTBS group were significantly higher than those in the sham group, and the TUG in the iTBS was significantly lower than that in the sham group (P=0.002). In addition, there were significant differences in cadence (P=0.029), strip length (P=0.046), gain velocity (P=0.002), and step length of affected lower limb (P=0.024) between the iTBS group and the sham iTBS group., Conclusions: Physical therapy is able to improve the functional recovery in hemiplegic patients after stroke, but the cerebellar iTBS can facilitate and accelerate the recovery, particularly the balance function and gait. Cerebellar iTBS could be an efficient and facilitative treatment for patients with stroke., Clinical Rehabilitation Impact: Cerebellar iTBS provides a convenient and efficient treatment modality for functional recovery of patients with stroke, especially balance function and gait.

Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut-brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Cui et al.)

Triterpenoid saponins, synthesized via the mevalonic acid (MVA) pathway in the cytoplasm, provide protection against pathogens and pests in plants and health benefits for humans. However, the mechanisms by which triterpenoid saponins are transported between cellular compartments remain uncharacterized. Here, we characterize a tonoplast localized multidrug and toxic compound extrusion transporter, GmMATE100 (encoded by Glyma.18G143700 ), from soybean ( Glycine max L.). GmMATE100 is co-expressed with soyasaponin biosynthetic genes, and its expression was induced by MeJA treatment, which also led to soyasaponin accumulation in soybean roots. GmMATE100 efficiently transports multiple type-B soyasaponins as well as type-A soyasaponins with low affinity from the cytosol to the vacuole in a yeast system. The GmMATE100 loss-of-function mutant showed a significant decrease in type-A and type-B soyasaponin contents in soybean roots. This study not only characterized the first soybean triterpenoid saponin transporter but also provided new knowledge for the rational engineering of soyasaponin content and composition in soybean plants to modulate their levels within crop environments.

Allergic asthma is a chronic non-communicable disease characterized by lung tissue inflammation. Current treatments can alleviate the clinical symptoms to some extent, but there is still no cure. Recently, the transplantation of mesenchymal stem cells (MSCs) has emerged as a potential approach for treating allergic asthma. Gingival-derived mesenchymal stem cells (GMSCs), a type of MSC recently studied, have shown significant therapeutic effects in various experimental models of autoimmune diseases. However, their application in allergic diseases has yet to be fully elucidated. In this study, using an OVA-induced allergic asthma model, we demonstrated that GMSCs decrease CD11b + CD11c + proinflammatory dendritic cells (DCs), reduce Th2 cells differentiation, and thus effectively diminish eosinophils infiltration. We also identified that the core functional factor, hepatocyte growth factor (HGF) secreted by GMSCs, mediated its effects in relieving airway inflammation. Taken together, our findings indicate GMSCs as a potential therapy for allergic asthma and other related diseases., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Mesenchymal stem cells (MSCs) have demonstrated potent immunomodulatory properties that have shown promise in the treatment of autoimmune diseases, including rheumatoid arthritis (RA). However, the inherent heterogeneity of MSCs triggered conflicting therapeutic outcomes, raising safety concerns and limiting their clinical application. This study aimed to investigate the potential of extracellular vesicles derived from human gingival mesenchymal stem cells (GMSC-EVs) as a therapeutic strategy for RA. Through in vivo experiments using an experimental RA model, our results demonstrate that GMSC-EVs selectively homed to inflamed joints and recovered Treg and Th17 cell balance, resulting in the reduction of arthritis progression. Our investigations also uncovered miR-148a-3p as a critical contributor to the Treg/Th17 balance modulation via IKKB/NF-κB signaling orchestrated by GMSC-EVs, which was subsequently validated in a model of human xenograft versus host disease (xGvHD). Furthermore, we successfully developed a humanized animal model by utilizing synovial fibroblasts obtained from patients with RA (RASFs). We found that GMSC-EVs impeded the invasiveness of RASFs and minimized cartilage destruction, indicating their potential therapeutic efficacy in the context of patients with RA. Overall, the unique characteristics - including reduced immunogenicity, simplified administration, and inherent ability to target inflamed tissues - position GMSC-EVs as a viable alternative for RA and other autoimmune diseases.

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: This study aims to establish a prognostic nomogram for patients who underwent transarterial chemoembolization (TACE) for recurrent hepatocellular carcinoma (HCC) after hepatectomy., Patients and Methods: Patients who underwent TACE for recurrent early- and middle-stage HCC after hepatectomy between 2009.01 and 2015.12 were included. Enrolled patients were randomly divided into training (n=345) and validation (n=173) cohorts according to a computer-generated randomized number. Independent factors for overall survival (OS) were determined and included in the nomogram based on the univariate and multivariate analyses of the training group. The nomogram was validated and compared to other prognostic models. Discriminative ability and predictive accuracy were determined using the Harrell C index (C-index), area under the receiver operating characteristic curve (AUROC), and calibration curve., Results: The final nomogram was established based on four parameters including resection-to-TACE time interval, recurrent tumor diameter, recurrent tumor number, and AFP level. The C-indexes of the nomogram for predicting OS were 0.67 (95% CI 0.63-0.70) and 0.71 (95% CI 0.68-0.74) in the training and validation cohort respectively. The AUROCs for predicting the 1-year, 2-year and 3-year OS based on the nomogram were also superior to those of the other models. The calibration curve for 3-year survival showed a high congruence between the predicted and actual survival probabilities. According to the scores calculated by the nomogram, patients were stratified into three subgroups: high-risk (scoring ≥53 points), middle-risk (scoring ≥26 and <53 points), and low-risk (scoring <26 points) subgroups with a median OS of 10.1 (95% CI 0.63-0.70), 20.3 (95% CI 17.5-22.5) and 47.0 (95% CI 34.2-59.8) months, respectively., Conclusion: The proposed nomogram served as a new tool to predict individual survival in patients who underwent TACE for recurrent HCC after hepatectomy, with favorable performance and discrimination. For high-risk patients, treatment should be optimized beyond TACE alone based on the nomogram., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Xie et al.)