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Background & Aims: Hepatic ischemia-reperfusion injury (HIRI) often occurs in liver surgery, such as partial hepatectomy and liver transplantation, in which myeloid macrophage-mediated inflammation plays a critical role. Cell division cycle 42 (Cdc42) regulates cell migration, cytoskeleton rearrangement, and cell polarity. In this study, we explore the role of myeloid Cdc42 in HIRI. Methods: Mouse HIRI models were established with 1-hour ischemia followed by 12-hour reperfusion in myeloid Cdc42 knockout (Cdc42mye) and Cdc42flox mice. Myeloid-derived macrophages were traced with RosamTmG fluorescent reporter under LyzCre-mediated excision. The experiments for serum or hepatic enzymic activities, histologic and immunologic analysis, gene expressions, flow cytometry analysis, and cytokine antibody array were performed. Results: Myeloid deletion of Cdc42 significantly alleviated hepatic damages with the reduction of hepatic necrosis and inflammation, and reserved hepatic functions following HIRI in mice. Myeloid Cdc42 deficiency suppressed the infiltration of myeloid macrophages, reduced the secretion of proinflammatory cytokines, restrained M1 polarization, and promoted M2 polarization of myeloid macrophages in livers. In addition, inactivation of Cdc42 promoted M2 polarization via suppressing the phosphorylation of STAT1 and promoting phosphorylation of STAT3 and STAT6 in myeloid macrophages. Furthermore, pretreatment with Cdc42 inhibitor, ML141, also protected mice from hepatic ischemia-reperfusion injury. Conclusions: Inhibition or deletion of myeloid Cdc42 protects liver from HIRI via restraining the infiltration of myeloid macrophages, suppressing proinflammatory response, and promoting M2 polarization in macrophages.

Recently, the use of unmanned aerial vehicle (UAV) imagery for object detection in forest fire detection has gained significant attention and has shown remarkable performance. However, most existing object detection models have neglected the exploration of relationships between positive sample features, which is crucial for learning more representative and color-robust features. In addition, small objects in UAV images poses challenges in capturing sufficient object information and hinders accurate object detection. To address these issues, we propose FCLGYOLO that aims to constrain positive sample features and enrich the object information in the feature maps. Specifically, a feature invariance and covariance constraint structure proposed to maintain feature invariance among positive samples and remove internal correlations. Furthermore, a local guided global module proposed to enrich object positioning and semantic information in the feature map, which leverages local features that focus on spatial information to facilitate the learning of global features that focus on frequency information. It is interesting to show that FCLGYOLO performs well even in the presence of heavy smoke or tree occlusions. Compared with multiple state-of-the-art object detection models on a forest fire dataset, experimental results demonstrate the superiority of FCLGYOLO.

Abstract Background Alzheimer’s disease (AD) is one of the most burdening diseases of the century with no disease-modifying treatment at this time. Nonhuman primates (NHPs) share genetic, anatomical, and physiological similarities with humans, making them ideal model animals for investigating the pathogenesis of AD and potential therapies. However, the use of NHPs in AD research has been hindered by the paucity of AD monkey models due to their long generation time, ethical considerations, and technical challenges in genetically modifying monkeys. Methods Here, we developed an AD-like NHP model by overexpressing human tau in the bilateral hippocampi of adult rhesus macaque monkeys. We evaluated the pathological features of these monkeys with immunostaining, Nissl staining, cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), positron emission tomography (PET), and behavioural tests. Results We demonstrated that after hippocampal overexpression of tau protein, these monkeys displayed multiple pathological features of AD, including 3-repeat (3R)/4-repeat (4R) tau accumulation, tau hyperphosphorylation, tau propagation, neuronal loss, hippocampal atrophy, neuroinflammation, Aβ clearance deficits, blood vessel damage, and cognitive decline. More interestingly, the accumulation of both 3R and 4R tau is specific to NHPs but not found in adult rodents. Conclusions This work establishes a tau-induced AD-like NHP model with many key pathological and behavioural features of AD. In addition, our model may potentially become one of the AD NHP models adopted by researchers worldwide since it can be generated within 2 ~ 3 months through a single injection of AAVs into the monkey brains. Hence, our model NHPs may facilitate mechanistic studies and therapeutic treatments for AD.

Abstract Background Minority stress from racism and heterosexism may uniquely interact to impact the mental health of racialized sexual minorities. We examined variations in anxiety and depressive symptoms by reported by ethno-racial identity among gay, bisexual, and other men who have sex with men (gbMSM) in Vancouver, Canada. Methods We recruited gbMSM aged ≥ 16 years from February 2012 to February 2015 using respondent-driven sampling (RDS). Participants completed computer assisted self-interviews (CASI) at enrollment and every 6 months until February 2017. We examined factors associated with moderate/severe anxiety and depression scores (> 10) on the Hospital Anxiety and Depression Scale (HADS) and differences in key explanatory variables including sociodemographic, psychosocial, and substance use factors. We used multivariable mixed effects models to assess whether moderate/severe scores were associated with ethno-racial identity across all visits. Results After RDS-adjustment, of 774 participants, 79.9% of participants identified as gay. 68.6% identified as white, 9.2% as Asian, 9.8% as Indigenous, 7.3% as Latin American, and 5.1% as other ethno-racial identities. Participants contributed a median of 6 follow-up visits (Q1-Q3: 4–7). In the multivariable analysis, Asian participants had decreased odds of moderate/severe anxiety scores compared to white participants (aOR = 0.39; 95% CI: 0.18–0.86), and Latin American participants had decreased odds of moderate/severe depression scores compared to both white (aOR = 0.17; 95% CI: 0.08–0.36) and Asian (aOR = 0.07; 95% CI: 0.02–0.20) participants. Conclusion Asian and Latino gbMSM reported decreased mental health symptoms compared to white participants. Asian and Latino gbMSM in Vancouver appear to manage multiple minority stressors without adversely affecting their mental health.

Abstract Budorcas taxicolor bedfordi is a rare animal uniquely distributed in the Qinling Mountains (China). Human disturbance and habitat fragmentation have directly affected the survival of B. t. bedfordi. It is urgent to clarify the genetic diversity and genetic structure of the B. t. bedfordi population and implement effective conservation measures. In this study, 20 new polymorphic microsatellite loci were isolated by Illumina sequencing. The genetic diversity and population structure of 124 B. t. bedfordi individuals from three populations (Niubeliang population, Zhouzhi population, and Foping population) were analysed according to these 20 microsatellite loci. Our results indicated that B. t. bedfordi had a low level of genetic variability and that there was inbreeding in the three populations. The population genetic structure analyses showed that the Niubeliang population had a trend of differentiation from other populations. National roads can affect population dispersal, while ecological corridors can promote population gene exchange. None of the three B. t. bedfordi populations experienced bottleneck effects. For conservation management plans, the Zhouzhi population and Foping population should be considered one management unit, and the Niubeliang population should be considered another management unit. We suggest building an ecological corridor to keep the habitat connected and formulating tourism management measures to reduce the influence of human disturbance on B. t. bedfordi.

Abstract Developing atomically synergistic bifunctional catalysts relies on the creation of colocalized active atoms to facilitate distinct elementary steps in catalytic cycles. Herein, we show that the atomically-synergistic binuclear-site catalyst (ABC) consisting of $${{{{{\rm{Zn}}}}}}^{\delta+}$$ Zn δ + -O-Cr6+ on zeolite SSZ-13 displays unique catalytic properties for iso-stoichiometric co-conversion of ethane and CO2. Ethylene selectivity and utilization of converted CO2 can reach 100 % and 99.0% under 500 °C at ethane conversion of 9.6%, respectively. In-situ/ex-situ spectroscopic studies and DFT calculations reveal atomic synergies between acidic Zn and redox Cr sites. $${{{{{\rm{Zn}}}}}}^{\delta+}$$ Zn δ + ( $$0 \, < \, \delta \, < \, 2$$ 0 < δ < 2 ) sites facilitate β-C-H bond cleavage in ethane and the formation of Zn-H δ- hydride, thereby the enhanced basicity promotes CO2 adsorption/activation and prevents ethane C-C bond scission. The redox Cr site accelerates CO2 dissociation by replenishing lattice oxygen and facilitates H2O formation/desorption. This study presents the advantages of the ABC concept, paving the way for the rational design of novel advanced catalysts.

Abstract Background A deterioration in the meat quality of broilers has attracted much more attention in recent years. L-malic acid (MA) is evidenced to decrease meat drip loss in broilers, but the underlying molecular mechanisms are still unclear. It’s also not sure whether the outputs obtained under experimental conditions can be obtained in a commercial condition. Here, we investigated the effects and mechanisms of dietary MA supplementation on chicken meat drip loss at large-scale rearing. Results Results showed that the growth performance and drip loss were improved by MA supplementation. Meat metabolome revealed that L-2-aminoadipic acid, β-aminoisobutyric acid, eicosapentaenoic acid, and nicotinamide, as well as amino acid metabolism pathways connected to the improvements of meat quality by MA addition. The transcriptome analysis further indicated that the effect of MA on drip loss was also related to the proper immune response, evidenced by the enhanced B cell receptor signaling pathway, NF-κB signaling pathway, TNF signaling pathway, and IL-17 signaling pathway. Conclusions We provided evidence that MA decreased chicken meat drip loss under commercial conditions. Metabolome and transcriptome revealed a comprehensive understanding of the underlying mechanisms. Together, MA could be used as a promising dietary supplement for enhancing the water-holding capacity of chicken meat.

Abstract Chemoresistance poses a significant impediment to effective treatments for non-small-cell lung cancer (NSCLC). P21-activated kinase 4 (PAK4) has been implicated in NSCLC progression by invasion and migration. However, the involvement of PAK4 in cisplatin resistance is not clear. Here, we presented a comprehensive investigation into the involvement of PAK4 in cisplatin resistance within NSCLC. Our study revealed enhanced PAK4 expression in both cisplatin-resistant NSCLC tumors and cell lines. Notably, PAK4 silencing led to a remarkable enhancement in the chemosensitivity of cisplatin-resistant NSCLC cells. Cisplatin evoked endoplasmic reticulum stress in NSCLC. Furthermore, inhibition of PAK4 demonstrated the potential to sensitize resistant tumor cells through modulating endoplasmic reticulum stress. Mechanistically, we unveiled that the suppression of the MEK1-GRP78 signaling pathway results in the sensitization of NSCLC cells to cisplatin after PAK4 knockdown. Our findings establish PAK4 as a promising therapeutic target for addressing chemoresistance in NSCLC, potentially opening new avenues for enhancing treatment efficacy and patient outcomes.

Abstract Background In public health emergencies, nurses are vulnerable to adverse reactions, especially job burnout. It is critical to identify nurses at risk of burnout early and implement interventions as early as possible. Methods A cross-sectional survey of the hospitals in Xiangyang City was conducted in January, 2023 using stratified cluster sampling. Anonymized data were collected from 1584 working nurses. The Impact of Events Scale-Revised (IES-R) and the Chinese version of the Maslach Burnout Inventory-General Survey (MBI-GS) were used to evaluate the post-traumatic stress disorder (PTSD) and burnout of nurses in public health emergencies. Logistic regression analysis was established to screen for risk factors of burnout, and a nomogram was developed to predict the risk of burnout. A calibration curve and the area under the receiver operating characteristic (ROC) curve were used to validate the nomogram internally. Results This study showed that only 3.7% of nurses were completely free of PTSD during a public health emergency. We found that PTSD varied by age, marital status, procreation status, length of service, employee status, and whether working in the ICU. The nurses aged 30 ~ 40 years old, single, married without children, non-regular employees, worked for less than three years or worked in the ICU had higher levels of PTSD. Regarding the prevalence of burnout, 27.4%, 48.5%, and 18.6% of nurses had a high level of emotional exhaustion (EE), depersonalization (DP), and diminished personal accomplishment (PA), respectively. There, 31.1% of nurses had more than two types of job burnout. The number of night shifts, the type of hospital, marital status, and the severity of PTSD were all associated with higher rates of exhaustion among nurses. As a graphical representation of the model, a nomogram was created and demonstrated excellent calibration and discrimination in both sets (AUC = 0.787). Conclusions This study confirmed the PTSD and burnout are common problems for in-service nurses during public health emergencies and screened out the high-risk groups of job burnout. It is necessary to pay more attention nurses who are single and working in general hospitals with many night shifts, especially nurses with severe PTSD. Hospitals can set up nurses’ personal health records to give timely warnings to nurses with health problems, and carry out support interventions to relieve occupational stress.

Abstract Introduction Sepsis is a global public health burden. Deep vein thrombosis (DVT) is the third most common cause of death from cardiovascular disease after heart attacks and strokes. We designed this experiment to investigate the factors influencing DVT formation in patients with sepsis. Methods In this survey, 918 septic patients admitted to Peking Union Medical College Hospital, who underwent DVT screening were enrolled. The data were collected from June 8, 2013 to October 12, 2022. The differences between septic patients with and without DVT were studied from following aspects: basic information, comorbidities, inflammatory cytokines, albumin, source of infection, sequential organ failure assessment (SOFA) score, coagulation and prognosis. Main results In this study, the prevalence of DVT in patients with sepsis was 0.23. Elderly patients with sepsis were prone to DVT (p value

Abstract Background Minimally invasive direct coronary artery bypass (MIDCAB) surgery offers an effective option for coronary artery disease (CAD) patients with the avoidance of median sternotomy and fast postoperative recovery. However, MIDCAB is still associated with significant postoperative pain which may lead to delayed recovery. The erector spinae plane block (ESPB) is a superficial fascial plane block. There have not been randomized controlled trials evaluating the effects of ESPB on analgesia and patient recovery following MIDCAB surgery. We therefore designed a double-blind prospective randomized placebo-controlled trial, aiming to prove the hypothesis that ESPB reduces postoperative pain scores in patients undergoing MIDCAB surgery. Methods The study protocol has been reviewed and approved by the Ethical Review Committee of Peking University People’s Hospital. Sixty adult patients of either sex scheduled for MIDCAB surgery under general anesthesia (GA) will be included. Patients will be randomly allocated to receive either a preoperative single-shot ESPB with 30 mL of ropivacaine 0.5% (ESPB group) or normal saline 0.9% (control group). The primary outcomes are the difference between the two groups in numeric rating scale (NRS) scores at rest at different time points (6, 12, 18, 24, 48 h) after surgery. The secondary outcomes include NRS scores on deep inspiration within 48 h, postoperative hydromorphone consumption, and quality of patient recovery at 24 h and 48 h, using the Quality of Recovery-15 (QoR-15) scale. The other outcomes include intraoperative fentanyl requirements, the need for additional postoperative rescue analgesics, time to tracheal extubation and chest tube removal after surgery, incidence of postoperative nausea and vomiting (PONV) and postoperative cognitive dysfunction (POCD), intensive care unit (ICU) length of stay (LOS), hospital discharge time, and 30-day mortality. Adverse events will be also evaluated. Discussion This is a novel randomized controlled study evaluating a preoperative ultrasound-guided single-shot unilateral ESPB on analgesia and quality of patient recovery in MIDCAB surgery. The results of this study will characterize the degree of acute postoperative pain and clinical outcomes following MIDCAB. Our study may help optimizing analgesia regimen selection and improving patient comfort in this specific population. Trial registration The study was prospectively registered with the Chinese Clinical Trial Registry (trial identifier: ChiCTR2100052810). Date of registration: November 5, 2021.

Abstract Background The liver ranks as the sixth most prevalent site of primary cancer in humans, and it frequently experiences metastases from cancers originating in other organs. To facilitate the development of effective treatments and improve survival rates, it is crucial to comprehend the intricate and diverse transcriptome landscape of primary and metastatic liver cancers. Methods We conducted long-read isoform sequencing and short-read RNA sequencing using a cohort of 95 patients with primary and secondary liver cancer who underwent hepatic resection. We compared the transcriptome landscapes of primary and metastatic liver cancers and systematically investigated hepatocellular carcinoma (HCC), paired primary tumours and liver metastases, and matched nontumour liver tissues. Results We elucidated the full-length isoform-level transcriptome of primary and metastatic liver cancers in humans. Our analysis revealed isoform-level diversity in HCC and identified transcriptome variations associated with liver metastatis. Specific RNA transcripts and isoform switching events with clinical implications were profound in liver cancer. Moreover, we defined metastasis-specific transcripts that may serve as predictors of risk of metastasis. Additionally, we observed abnormalities in adjacent paracancerous liver tissues and characterized the immunological and metabolic alterations occurring in the liver. Conclusions Our findings underscore the power of full-length transcriptome profiling in providing novel biological insights into the molecular mechanisms underlying tumourigenesis. These insights will further contribute to improving treatment strategies for primary and metastatic liver cancers.

Introduction: The present study aimed to investigate whether and how normobaric intermittent hypoxic training (IHT) or remote ischemic preconditioning (RIPC) plus normoxic training (RNT) has a synergistic protective effect on lipid metabolism and vascular function compared with normoxic training (NT) in overweight or obese adults. Methods: A total of 37 overweight or obese adults (36.03 ± 10.48 years) were randomly assigned to 3 groups: NT group (exercise intervention in normoxia), IHT group (exercise intervention in normobaric hypoxic chamber), and RNT group (exercise intervention in normoxia + RIPC twice daily). All participants carried out the same 1-h exercise intervention for a total of 4 weeks, 5 days per week. Physical fitness parameters were evaluated at pre- and postexercise intervention. Results: After training, all three groups had a significantly decreased body mass index (p < 0.05). The IHT group had reduced body fat percentage, visceral fat mass (p < 0.05), blood pressure (p < 0.01), left ankle-brachial index (ABI), maximal heart rate (HRmax) (p < 0.05), expression of peroxisome proliferator-activated receptor-γ (PPARγ) (p < 0.01) and increased expression of SIRT1 (p < 0.05), VEGF (p < 0.01). The RNT group had lowered waist-to-hip ratio, visceral fat mass, blood pressure (p < 0.05), and HRmax (p < 0.01). Conclusion: IHT could effectively reduce visceral fat mass and improve vascular elasticity in overweight or obese individuals than pure NT with the activation of SIRT1-related pathways. And RNT also produced similar benefits on body composition and vascular function, which were weaker than those of IHT but stronger than NT. Given the convenience and economy of RNT, both intermittent hypoxic and ischemic training have the potential to be successful health promotion strategies for the overweight/obese population.

Introduction: Liver fibrosis is a life-threatening pathological anomaly which usually evolves into advanced liver cirrhosis and hepatocellular carcinoma although limited therapeutic option is readily available. FUN14 domain containing 1 (FUNDC1) is a mitophagy receptor with little information in liver fibrosis. Objective: This study was designed to examine the role for FUNDC1 in carbon tetrachloride (CCl4)-induced liver injury. Methods: GEO database analysis and subsequent validation of biological processes including western blot, immunofluorescence, and co-immunoprecipitation were applied to clarify the regulatory role of FUNDC1 on mitophagy and ferroptosis. Results: Our data revealed elevated FUNDC1 levels in liver tissues of patients with liver fibrotic injury and CCl4-challenged mice. FUNDC1 deletion protected against CCl4-induced hepatic anomalies in mice. Moreover, FUNDC1 deletion ameliorated CCl4-induced ferroptosis in vivo and in vitro. Mechanically, FUNDC1 interacted with glutathione peroxidase (GPx4), a selenoenzyme to neutralize lipid hydroperoxides and ferroptosis, via its 96–133 amino acid domain to facilitate GPx4 recruitment into mitochondria from cytoplasm. GPx4 entered mitochondria through mitochondrial protein import system-the translocase of outer membrane/translocase of inner membrane (TOM/TIM) complex, prior to degradation of GPx4 mainly through mitophagy along with ROS-induced damaged mitochondria, resulting in hepatocyte ferroptosis. Conclusion: Taken together, our data favored that FUNDC1 promoted hepatocyte injury through GPx4 binding to facilitate its mitochondrial translocation through TOM/TIM complex, where GPx4 was degraded by mitophagy to trigger ferroptosis. Targeting FUNDC1 may be a promising therapeutic approach for liver fibrosis.

Abstract Pressure sensors play a vital role in aerospace, automotive, medical, and consumer electronics. Although microelectromechanical system (MEMS)-based pressure sensors have been widely used for decades, new trends in pressure sensors, including higher sensitivity, higher accuracy, better multifunctionality, smaller chip size, and smaller package size, have recently emerged. The demand for performance upgradation has led to breakthroughs in sensor materials, design, fabrication, and packaging methods, which have emerged frequently in recent decades. This paper reviews common new trends in MEMS pressure sensors, including minute differential pressure sensors (MDPSs), resonant pressure sensors (RPSs), integrated pressure sensors, miniaturized pressure chips, and leadless pressure sensors. To realize an extremely sensitive MDPS with broad application potential, including in medical ventilators and fire residual pressure monitors, the “beam-membrane-island” sensor design exhibits the best performance of 66 μV/V/kPa with a natural frequency of 11.3 kHz. In high-accuracy applications, silicon and quartz RPS are analyzed, and both materials show ±0.01%FS accuracy with respect to varying temperature coefficient of frequency (TCF) control methods. To improve MEMS sensor integration, different integrated “pressure + x” sensor designs and fabrication methods are compared. In this realm, the intercoupling effect still requires further investigation. Typical fabrication methods for microsized pressure sensor chips are also reviewed. To date, the chip thickness size can be controlled to be

Abstract Certain intestinal microbiota alterations appear to positively correlate with tumorigenesis of CAC due to the disruption of the balance between the host and microorganisms. It is proven that blocking MyD88 signaling can prevent colitis-associated colorectal cancer (CAC) development in mice. We are aim to reveal the role of MyD88 signaling of maintaining colonic microbiota homeostasis for preventing CAC development. We here analyzed the landscape of gut microbiome in the mice model of AOM/DSS-induced CAC with MyD88 inhibitor treatment. PCoA revealed significant reduction in Lactobacillus load and increase in Escherichia load in the mucosal microbial composition of mice with CAC, compared with normal controls (NCs). Inhibitor-treatment led to almost undetectable Proteobacteria (Escherichia) and the retention of the dominance of Firmicutes and Bacteroidota (Muribaculaceae) in the mucosa. RNA sequencing analysis identified genes were up-regulated (Hp, SAA3 and IL-1F9) and down-regulated (CYP3A44, SLC30A10, GPNMB and OTC) in Inhibitor-treated mice (vs. CAC). Meanwhile, Inhibitor-treated mice had higher percentage of MUC2-positive area in colon sections (vs. CAC, which was less than NCs) by IF staining and decreased Escherichia in the mucus layer (vs. CAC) by FISH. And intestinal microbiota from mice with MyD88 inhibitor treatment could lessen the outcome of CAC by fecal microbiota transplantation. The development of CAC was involved in the increasing and ectopic Escherichia in the decreasing colonic mucus layer. MyD88 signaling blockade may maintain the host-microbiota homeostasis by up-regulating MUC2 production, increasing probiotics and their protective effects, and inhibiting the reproduction of Escherichia.

Abstract To evaluate the feasibility of cryoballoon (CB) ablation of atrial fibrillation (AF) under the guidance of a new three-dimensional (3D) mapping system KODEX-EPD. 40 patients scheduled for CB ablation of AF in the first affiliated Hospital of Xinjiang Medical University from August 2021 to July 2022 were randomly divided into two groups: KODEX-EPD 3D mapping system guidance group (KODEX group, n = 20) and conventional two-dimensional perspective group (standard group, n = 20). The ablation time, operation time, fluoroscopy time, fluoroscopy dose, contrast agent dosage and follow-up data were compared between the two groups. Besides, the feasibility and accuracy of the dielectric sensing system in evaluating pulmonary vein (PV) occlusion in patients with AF during CB ablation were verified. All pulmonary veins were being isolated. The ablation time (36.40 ± 6.72 min vs 35.15 ± 6.29 min, P > 0.05) and the operation time (64.20 ± 11.82 min vs 66.00 ± 13.18 min, P > 0.05) were not statistically different in the two groups. The standard group has longer fluoroscopy time, dose and contrast medium dosage. There were significant differences in fluoroscopy time (532.30 ± 72.83 s vs 676.25 ± 269.33 s, P 0.05) or the operation time (69.00 ± 5.00 min vs 62.60 ± 13.10 min, P > 0.05); however, compared to the first 5 patients, fluoroscopy time (587.40 ± 38.34 s vs 513.93 ± 73.02 s, P 0.05). Using the KODEX-EPD system, the CB ablation procedure can correctly evaluate the PV occlusion, and significantly reduce fluoroscopy exposure and contrast medium without significantly increasing the operation time.

The goal of "deep participation in global ocean governance" is clearly proposed in the outline of the 14th Five-Year Plan, which is of great significance for China to build maritime power. This paper introduced the concept of global ocean governance based on governance theory, compared the development history of global ocean governance, constructed a SWOT-PEST matrix to analyze the advantages and disadvantages, opportunities and challenges of China's participation in global ocean governance, and proposed strategic choices and practical paths for China's deep participation in global ocean governance based on the analysis results. The results showed that global ocean governance had gone through three development stages including ocean controling and competition, development and rule building, and deep adjustment and evolution. China's participation in global ocean governance was roughly divided into four stages including passive participation, active participation, full participation and deep participation, and China's influence and voice in global ocean governance was gradually increasing. The internal advantages of China's participation in global ocean governance outweighed its disadvantages, and the external threats outweighed its opportunities, and the strategic choice of path should be transitioned from the current stage of diversified strategy to the future growth strategy. The practical path for China's participation in global ocean governance included promoting the concept of ocean governance, enhancing the capacity of ocean governance, improving the regulation of global ocean governance and building an ocean cooperation platform.

Background: Complete lymph node dissection (CLND) for patients with melanoma remains controversial. This meta-analysis aimed to compare the prognoses and complications between the CLND and control groups (patients who receive adjuvant treatment or observation only) in patients with sentinel lymph node (SLN)-positive melanoma. Methods: The PubMed, Embase, Cochrane, and Web of Science databases were searched for cohort studies and randomized clinical trials (RCTs) conducted between 1964 and 2022, and the quality of the studies was assessed using the Cochrane risk-of-bias tool and Newcastle-Ottawa Scale. Hazard ratios (HR) or risk ratios (RR) with 95% confidence intervals (CIs) were calculated for each outcome. Heterogeneity and sensitivity tests were also conducted, and publication bias tests were performed when the pooled number of studies was >10. Results: Fifteen studies, including 11 cohort studies and 4 RCTs, were enrolled and assessed for quality. Analysis of overall survival showed no significant difference between the CLND and control groups (HR=1.02, 95% CI: 0.69–1.51, P=0.922). Similarly, recurrence-free survival (HR=0.84, 95% CI: 0.6–1.16, P=0.287), disease-free survival (HR=1.06, 95% CI: 0.65–1.72, P=0.82), and disease-specific survival (HR=0.84, 95% CI: 0.59–1.21, P=0.355) showed no difference between the two groups. CLND did not reduce the risk of recurrence (RR=0.98, 95% CI: 0.8–1.2, P=0.851). Conclusion: Remarkably, patients who underwent CLND were more likely to have complications such as flap necrosis and lymphedema than the controls. CLND does not improve patient prognosis and may increase the incidence of complications.

Due to its immune evasion capability, the SARS-CoV-2 Omicron variant was declared a variant of concern by the World Health Organization. The spread of Omicron in Changchun (i.e., the capital of Jilin province in northeast of China) during the spring of 2022 was successfully curbed under the strategy of a dynamic Zero-COVID policy. To evaluate the impact of immune evasion on vaccination and other measures, and to understand how the dynamic Zero-COVID measure stopped the epidemics in Changchun, we establish a compartmental model over different stages and parameterized the model with actual reported data. The model simulation firstly shows a reasonably good fit between our model prediction and the data. Second, we estimate the testing rate in the early stage of the outbreak to reveal the real infection size. Third, numerical simulations show that the coverage of vaccine immunization in Changchun and the regular nucleic acid testing could not stop the epidemic, while the 'non-pharmaceutical' intervention measures utilized in the dynamic Zero-COVID policy could play significant roles in the containment of Omicron. Based on the parameterized model, numerical analysis demonstrates that if one wants to achieve epidemic control by fully utilizing the effect of 'dynamic Zero-COVID' measures, therefore social activities are restricted to the minimum level, and then the economic development may come to a halt. The insight analysis in this work could provide reference for infectious disease prevention and control measures in the future.

Molecular dynamics method was used to establish composite wall/inorganic nanopores of three pore sizes, three shale oil systems, five CO2-cosolvent systems, and pure CO2 system. The process of CO2-cosolvent displacement of crude oil in shale nanopores and carbon storage was simulated and the influencing factors of displacement and storage were analyzed. It is shown that the attraction of the quartz wall to shale oil increases with the degree of hydroxylation. The higher the degree of quartz hydroxylation, the more difficult it is to extract the polar components of shale oil. Nanopore size also has a great impact on shale oil displacement efficiency. The larger the pore size, the higher the shale oil displacement efficiency. The closer the cosolvent molecules are to the polarity of the shale oil, the higher the mutual solubility of CO2 and shale oil. The more the non-polar components of shale oil, the lower the mutual solubility of CO2 and shale oil with highly polar cosolvent. Ethyl acetate is more effective in stripping relatively high polar shale oil, while dimethyl ether is more effective in stripping relatively low polar shale oil. Kerogen is highly adsorptive, especially to CO2. The CO2 inside the kerogen is not easy to diffuse and leak, thus allowing for a stable carbon storage. The highest CO2 storage rate is observed when dimethyl ether is used as a cosolvent, and the best storage stability is observed when ethyl acetate is used as a cosolvent.

Abstract Background Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes. Methods The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed between 2000 and 2012 are included in this study. A comprehensive retrospective analysis was performed on the clinicopathological features, treatment approaches, and outcomes of these cases. The establishment of novel prognostic models was based on in-depth examination of baseline parameters, and subsequent validation in an independent cohort of MCL cases. Results In front-line strategies, the use of hematopoietic stem cell transplantation was the most significant parameter affecting outcomes, for both overall survival (OS, p

Abstract Background Social support has previously been found to be associated with improved health outcomes of individuals managing chronic illnesses, including amongst people living with HIV (PLWH). For women and people who use injection drugs who continue to experience treatment disparities in comparison to other PLWH, social support may have potential in facilitating better treatment engagement and retention. In this analysis, we examined determinants of social support as measured by the Medical Outcomes Study – Social Support Survey (MOS-SSS) scale, and quantified the relationship between MOS-SSS and HIV treatment interruptions (TIs) among PLWH in British Columbia, Canada. Methods Between January 2016 and September 2018, we used purposive sampling to enroll PLWH, 19 years of age or older living in British Columbia into the STOP HIV/AIDS Program Evaluation study. Participants completed a baseline survey at enrolment which included the MOS-SSS scale, where higher MOS-SSS scores indicated greater social support. Multivariable linear regression modeled the association between key explanatory variables and MOS-SSS scores, whereas multivariable logistic regression modeled the association between MOS-SSS scores and experiencing TIs while controlling for confounders. Results Among 644 PLWH, we found that having a history of injection drug use more than 12 months ago but not within the last 12 months, self-identifying as Indigenous, and sexual activity in the last 12 months were positively associated with MOS-SSS, while being single, divorced, or dating (vs. married), experiences of lifetime violence, and diagnosis of a mental health disorder were inversely associated. In a separate multivariable model adjusted for gender, ethnicity, recent homelessness, sexual activity in the last 12 months, and recent injection drug use, we found that higher MOS-SSS scores, indicating more social support, were associated with a lower likelihood of HIV treatment interruptions (adjusted odds ratio: 0.90 per 10-unit increase, 95% confidence interval: 0.83, 0.99). Conclusions Social support may be an important protective factor in ensuring HIV treatment continuity among PLWH. Future research should examine effective means to build social support among communities that have potential to promote increased treatment engagement.

AbstractMutations in the gene encoding the transient receptor potential vanilloid member 4 (TRPV4), a Ca2+ permeable nonselective cation channel, cause TRPV4‐related disorders. TRPV4 is widely expressed in the brain; however, the pathogenesis underlying TRPV4‐mediated Ca2+ deregulation in neurodevelopment remains unresolved and an effective therapeutic strategy remains to be established. These issues were addressed by isolating mutant dental pulp stem cells from a tooth donated by a child diagnosed with metatropic dysplasia with neurodevelopmental comorbidities caused by a gain‐of‐function TRPV4 mutation, c.1855C > T (p.L619F). The mutation was repaired using CRISPR/Cas9 to generate corrected isogenic stem cells. These stem cells were differentiated into dopaminergic neurons and the pharmacological effects of folic acid were examined. In mutant neurons, constitutively elevated cytosolic Ca2+ augmented AKT‐mediated α‐synuclein (α‐syn) induction, resulting in mitochondrial Ca2+ accumulation and dysfunction. The TRPV4 antagonist, AKT inhibitor, or α‐syn knockdown, normalizes the mitochondrial Ca2+ levels in mutant neurons, suggesting the importance of mutant TRPV4/Ca2+/AKT‐induced α‐syn in mitochondrial Ca2+ accumulation. Folic acid was effective in normalizing mitochondrial Ca2+ levels via the transcriptional repression of α‐syn and improving mitochondrial reactive oxygen species levels, adenosine triphosphate synthesis, and neurite outgrowth of mutant neurons. This study provides new insights into the neuropathological mechanisms underlying TRPV4‐related disorders and related therapeutic strategies.

Abstract Background About 15–60% of individuals with ankle sprains may develop functional ankle instability (FAI), which is characterised by ankle pain, decreased muscle strength, limited range of motion, and impaired balance, causing a decline in social activity and quality of life. However, the relationship between those characters is still unclear. This study aimed to investigate whether a relationship existed between ankle pain, active range of motion (AROM), strength and balance and if ankle pain, AROM and strength can predict balance in individuals with FAI. Methods Seventy-seven subjects (46 males; 31 females) with unilateral FAI participated in this study. Ankle pain was measured by the visual analogue scale (VAS), ankle AROM was measured using a universal goniometer, ankle strength was measured using a handheld dynamometer, the static balance was measured by the Time in Balance Test (TBT) and the dynamic balance was measured by the modified Star Excursion Balance Test (mSEBT). Pearson product-moment correlations were used to determine the correlations between ankle pain, AROM, strength and balance. Multiple linear regressions were used to investigate if ankle pain, AROM and strength can predict balance in individuals with FAI. Results VAS and AROM-plantarflexion predicted 25.6% of the TBT (f2 = 0.344, P

Abstract Acral melanoma (AM) is a rare subtype of melanoma characterized by a high incidence of lymph node (LN) metastasis, a critical factor in tumor dissemination and therapeutic decision-making. Here, we employ single-cell and spatial transcriptomic analyses to investigate the dynamic evolution of early AM dissemination. Our findings reveal substantial inter- and intra-tumor heterogeneity in AM, alongside a highly immunosuppressive tumor microenvironment and complex intercellular communication networks, particularly in patients with LN metastasis. Notably, we identify a strong association between MYC + Melanoma (MYC +MEL) and FGFBP2 +NKT cells with LN metastasis. Furthermore, we demonstrate that LN metastasis requires a metabolic shift towards fatty acid oxidation (FAO) induced by MITF in MYC +MEL cells. Etomoxir, a clinically approved FAO inhibitor, can effectively suppress MITF-mediated LN metastasis. This comprehensive dataset enhances our understanding of LN metastasis in AM, and provides insights into the potential therapeutic targeting for the management of early AM dissemination.

Abstract Background Right ventricle failure (RVF) is a progressive heart disease that has yet to be fully understood at the molecular level. Elevated M-type pyruvate kinase 2 (PKM2) tetramerization alleviates heart failure, but detailed molecular mechanisms remain unclear. Objective We observed changes in PKM2 tetramerization levels during the progression of right heart failure and in vitro cardiomyocyte hypertrophy and explored the causal relationship between altered PKM2 tetramerization and the imbalance of redox homeostasis in cardiomyocytes, as well as its underlying mechanisms. Ultimately, our goal was to propose rational intervention strategies for the treatment of RVF. Method We established RVF in Sprague Dawley (SD) rats by intraperitoneal injection of monocrotaline (MCT). The pulmonary artery pressure and right heart function of rats were assessed using transthoracic echocardiography combined with right heart catheterization. TEPP-46 was used both in vivo and in vitro to promote PKM2 tetramerization. Results We observed that oxidative stress and mitochondrial disorganization were associated with increased apoptosis in the right ventricular tissue of RVF rats. Quantitative proteomics revealed that PKM2 was upregulated during RVF and negatively correlated with the cardiac function. Facilitating PKM2 tetramerization promoted mitochondrial network formation and alleviated oxidative stress and apoptosis during cardiomyocyte hypertrophy. Moreover, enhancing PKM2 tetramer formation improved cardiac mitochondrial morphology, mitigated oxidative stress and alleviated heart failure. Conclusion Disruption of PKM2 tetramerization contributed to RVF by inducing mitochondrial fragmentation, accumulating ROS, and finally promoted the progression of cardiomyocyte apoptosis. Facilitating PKM2 tetramerization holds potential as a promising therapeutic approach for RVF.

Understanding urban sprawl and its drivers is crucial for sustainable urban development. Most studies on Chinese urbanization have focused on coastal areas, paying little attention to urban centers in western China. This study examines urban expansion based on the Google Earth Engine (GEE), remotely sensed image, urban expansion model, and analysis of buffer and quadrant location in the Geographic Information System (GIS). Additionally, driving forces of urban expansion are examined based on the principle component analysis (PCA). Results indicate that urban land area increased more than 5.60 times, reaching 124,723 ha, an increase of over 400 % during 1990–2020. The urban expansion rate and intensity significantly increased and exhibited spatio-temporal heterogeneity. We identified that urban spatial expansion patterns changed from patch filling to patch border expansion, and urban expansion direction was mainly in the southern, northeastern, southwestern, and northwestern regions, extending along the traffic corridor, ring road, and adjacent cities. We suggest that economic development, population, and urbanization have become the driving factors of urban expansion. The GEE provides a new geographic processing algorithm based on massive image datasets, facilitating remote sensing processing. The results revealed that Chengdu is following trends witnessed in coastal cities of China; however, the significance of various drivers of urban expansion in these cities differs from that of the eastern cities. This study will help formulate policies for better urban land management and sustainable land development.

With the development of the aquaculture industry for high efficiency, energy saving, and environmentally friendly methods, recirculating aquaculture has attracted increasing attention from researchers and practitioners. A recirculating aquaculture system (RAS) consists primarily of an aquaculture module and a water purification module. In the aquaculture module, nitrogen in the feed could be released into the water phase through various routes (i.e., the feedstuff residue and aquaculture animal excretion), whose species can be transformed by microbes. Free ammonia and nitrite have acute toxic effects on aquaculture animals, rendering the efficient removal of ammonia and nitrite essential for the RAS. Compared with physical and chemical methods, biological treatment methods based on microbial nitrification can convert ammonia and nitrite into less toxic nitrate with the advantages of good treatment performance, low operation cost, and little secondary contamination, and have been widely utilized in the purification of multiple wastewaters (e.g., municipal wastewater, industrial wastewater, agricultural wastewater, and ammonia-contaminated groundwater). For the treatment of recirculating water with low and fluctuating nitrogen loads, a biofilm process based on the attached growth of microbes is more suitable than an activated sludge process based on the suspended growth of microbes. To date, a variety of biofilm processes have been developed, among which the fixed-bed biofilm reactor (FBBR) and moving-bed biofilm reactor (MBBR) have been widely investigated for the control of ammonia and nitrite in aquaculture wastewater. However, the relevant studies were mostly conducted in laboratory- and pilot-scale RASs. Thus, there is still a lack of comparative investigations of FBBR and MBBR, which are simultaneously operated in a full-scale RAS.Therefore, a parallel FBBR and MBBR were joined to a full-scale RAS for Macculochella peeli. The FBBR and MBBR were simultaneously and continuously operated for 35 d to investigate variations in their water quality and microbial community structures. The results indicate that the FBBR and MBBR had similar variations in ammonia, nitrite, nitrate, and pH in the effluents. Over the entire operational period, the dissolved inorganic nitrogen (DIN) concentrations gradually increased; the ammonia and nitrite concentrations and their proportions in DIN first increased and then decreased stepwise; and the nitrate concentrations increased gradually, while the variation in the nitrate proportions in DIN was opposite to that of ammonia and nitrite. Both the FBBR and MBBR could transform ammonia and nitrite to nitrate, which resulted in nitrate accumulation and a pH decrease in aquaculture water. During the operation period, the nitrification capacity gradually matured, and ammonia oxidation could occur prior to nitrite oxidation. At 35 d, the concentrations of ammonia, nitrite and nitrate were 0.32 (0.29), 0.27 (0.22) and 29.75 (29.76) mg/L with their proportions in DIN of 1.05% (0.96%), 0.90% (0.72%) and 98.05% (98.32%) in FBBR (MBBR) effluent; pH declined from7.62 (7.59) to 7.25 (7.22) in FBBR (MBBR) effluent.The number of operational taxonomic units (OTU) obtained from the FBBR and MBBR samples were 2, 088 and 1, 852, respectively, and 1, 174 OTUs were shared between FBBR and MBBR. The α indices (Chao1, ACE, Shannon, and Simpson) from the biofilm reactors indicated that FBBR possessed higher richness and diversity of the microbial community than MBBR, which could be attributed to the difference in the internal environment between FBBR and MBBR. In total, 16 phyla, 28 classes, and 149 genera were identified in the FBBR samples, which were slightly fewer than those from the MBBR samples (i.e., 19 phyla, 31 classes, and 155 genera). However, the relative abundance of microbes demonstrated that FBBR and MBBR had similar predominant microbes: Proteobacteria (69.42% in FBBR and 86.92% in MBBR) at the phylum level, γ-Proteobacteria (40.71% in FBBR and 64.36% in MBBR) and α-Proteobacteria (26.58% in FBBR and 21.74% in MBBR) at the class level, and Acinetobacter (27.50% in FBBR and 53.29% in MBBR) at the genus level. Nitrosomonas and Nitrospira constituted the nitrifiers in both FBBR and MBBR, but the relative abundance of nitrifiers was higher in FBBR. Furthermore, the relative abundance of Nitrospira was far higher than that of Nitrosomonas, indicating that complete ammonia oxidation bacteria might exist in FBBR and MBBR. In addition, Vibrio was not found in FBBR and MBBR, but Bdellovibrio was observed. The results of this study can provide technical support for the selection of biological purification technology for RAS, and thus improve the green development of the aquaculture industry.Future studies will focus on: Investigating the effects of water quality conditions and operational parameters on the water treatment performance of FBBR and MBBR; Determining the species of complete ammonia oxidation bacteria and their relative abundances on the filler surface in FBBR and MBBR; Effectively eliminating nitrate in the aquaculture water by introducing microbial denitrification process after FBBR and MBBR to control the total nitrogen in RAS; Establishing a flexible and feasible strategy for controlling the pH in recirculating water by exploring the solid-phase buffers that could serve as the slow-release sources of alkalinity in the biofilm reactor.

AbstractContext 5-Fluorouracil (5-FU)-injured stromal cells may cause chronic bone marrow suppression; however, the underlying mechanism remains unclear. Angelica sinensis polysaccharide (ASP), the main biologically active ingredient of the Chinese herb, Angelica sinensis (Oliv.) Diels (Apiaceae), may enrich the blood and promote antioxidation.Objective This study investigated the protective antioxidative effects of ASP on perivascular mesenchymal progenitors (PMPs) and their interactions with hematopoietic cells.Materials and methods PMPs were dissociated from C57BL/6 mouse femur and tibia and were subsequently divided into the control, ASP (0.1 g/L), 5-FU (0.025 g/L), and 5-FU + ASP (pre-treatment with 0.1 g/L ASP for 6 h, together with 0.025 g/L 5-FU) then cultured for 48 h. Hematopoietic cells were co-cultured on these feeder layers for 24 h. Cell proliferation, senescence, apoptosis, and oxidative indices were detected, along with stromal osteogenic and adipogenic differentiation potentials. Intercellular and intracellular signaling was analyzed by real-time quantitative reverse transcription polymerase chain reaction and Western blotting.Results ASP ameliorated the reactive oxygen species production/scavenge balance in PMPs; improved osteogenic differentiation; increased SCF, CXCL12, VLA-4/VCAM-1, ICAM-1/LFA1, and TPO/MPL, Ang-1/Tie-2 gene expression. Further, the ASP-treated feeder layer alleviated hematopoietic cells senescence (from 21.9 ± 1.47 to 12.1 ± 1.13); decreased P53, P21, p-GSK-3β, β-catenin and cyclin-D1 protein expression, and increased glycogen synthase kinase (GSK)-3β protein expression in co-cultured hematopoietic cells.Discussion and conclusions ASP delayed oxidative stress-induced premature senescence of 5-FU-treated feeder co-cultured hematopoietic cells via down-regulation of overactivated Wnt/β-catenin signaling. These findings provide a new strategy for alleviating myelosuppressive stress.

Nitrogen fertilizer levels significantly affect crop growth and development, necessitating precision management. Most studies focus on nitrogen nutrient estimation using vegetation indices and textural features, overlooking the diagnostic potential of color features. Hence, we investigated cotton nitrogen nutrition status using unmanned aerial vehicle (UAV) image features and the nitrogen nutrient index (NNI). Random frog algorithm - and random forest-screened image feature sets significantly correlated with the NNI, which were substituted into four machine learning algorithms for NNI estimation modeling. The composite scores (F) of optimal image feature sets were calculated using the coefficient of variation method for comprehensive cotton nitrogen nutrient diagnosis. Validation of the model for determining the critical nitrogen concentration in cotton yielded a coefficient of determination R2 = 0.89, root mean square error RMSE = 0.50 g (100 g)-1, and mean absolute error MAE = 0.44, demonstrating improved performance. Additionally, our novel NNI estimation model constructed based on the optimal image feature sets exhibited R2c = 0.97, RMSEc = 0.02, MAEc = 0.02, R2v = 0.85, RMSEv = 0.05, and MAEv = 0.04. Polynomial fitting of the composite index with NNI indicated that the model was reliable and yielded the following diagnostic criterion: 0.48 < F2 < 0.67 indicated nitrogen overapplication, whereas F2 < 0.48 or F2 > 0.67 indicated nitrogen deficiency. This study demonstrates the superior effectiveness of using UAV RGB image feature sets for NNI estimation and the quick, accurate diagnosis of cotton nitrogen levels, which will help guide nitrogen fertilizer application.

The velocity contribution and velocity gradient contribution to the transport of the heat flux defined by Fourier's law, q, are numerically investigated in this paper to investigate the reason induced the unique characteristics of Nusselt number in twisted and straight square tubes for periodically fully developed laminar flow. The reason of local Nusselt number in straight square tube at some regions is larger than that in twisted square tube are reported. It is found that the summation of velocity and its gradient contributions determines local Nusselt number under UWT. Both velocity and velocity gradient contributions are not uniformly distributed in the cross section in straight and twisted tubes. Velocity and its gradient both promote the transport of the local heat flux components along the normal direction of the wall surface which have larger values in straight square tube at some regions and result local Nusselt number has larger values. The summation contributions of velocity and its gradient are much larger in twisted square tube, especially in the region close to the wall surface. Thus the averaged heat flux components have much larger value and averaged Nusselt number in twisted square tube is larger than that in straight square tube.

Introduction: Hepatocellular carcinoma (HCC) has been a highly common and pathological disease worldwide, while current therapeutic regimens have limitations. Chebulae Fructus, a common herbal medicine in Asia, has been documented to exert potential therapeutic effects on HCC in ancient medicine clinical practice. However, the molecular mechanism underlying its inhibitory effects on HCC requires further investigation.Methods: In this study, the anti-HCC effect of the aqueous extract of Chebulae Fructus (CFE) on human HCC and its underlying mechanism were evaluated. Assays including CCK8, EdU staining, crystal violet staining, cell clone formation, flow cytometry, wound healing, and transwell were used in vitro. The cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models were used in vivo. Transcriptomics analysis, qRT-PCR, ELISA, IHC staining, and Western blotting were employed to determine the mechanism of action of CFE.Results: The results demonstrate that CFE effectively suppressed the proliferation and activity of HepG2 and PLC/PRF/5 HCC cells. CFE also induced apoptosis, and suppressed the migration and invasion abilities of these cells. Furthermore, CFE exhibited inhibitory effects on tumor growth in both H22 and PLC/PRF/5 mouse models, as well as in an HCC PDX model which is derived from patient tumor samples. Moreover, it was identified that CFE treatment specifically suppressed the Apelin/APJ system in HCC cells and tumor tissues. To investigate the role of the Apelin/APJ system in mediating the effects of CFE treatment, an APJ overexpressed cell model is established. Interestingly, it was found that the overexpression of APJ significantly diminished the inhibitory effects of CFE on HCC in vitro.Discussion: Collectively, this study provides compelling evidence that CFE exerts significant anti-HCC effects in cell and animal models. Moreover, our findings suggest that the Apelin/APJ system may play a vital role in the therapeutic effects of CFE against HCC.

Abstract South China Karst faces the challenge of balancing ecological conservation and regional development, a task made more intricate by the geological limitations of carbonate formations. Large‐scale conservation and restoration initiatives have mitigated rocky desertification and positioned South China Karst as a global hotspot for vegetation regrowth over the past two decades. However, challenges stemming from geological constraints and oversights in recognizing the synergies within social‐ecological systems remain. Here, we propose a social‐ecological framework that integrates the extended timescale of both historical and recent human impacts with the corresponding processes of forest evolution. The framework elucidates the enduring and continuous progression of “forest‐deforestation‐reforestation,” offering applicability for optimizing ecological space across diverse social‐ecological contexts. Moreover, it serves to enhance the sustainability of reforestation efforts when faced with geological constraints.

Abstract Understanding historical soil moisture (SM) variations and their relationship with temperature in high‐latitude humid regions is essential for predicting hot droughts under widespread warming. This paper presents the first‐ever annual‐resolution summer surface SM reconstruction (1736–2006 CE) in Sweden, located in northern Europe (NE). The reconstruction utilizes the paleoclimate proxy, tree‐ring δ18O, which exhibits a strong correlation with reanalysis SM data during 1948–2007 CE (r = −0.67, p

ObjectiveThis study aimed to assess the impact of gestational diabetes mellitus (GDM) on fetal heart structure and function using a technique called fetal heart quantification (Fetal HQ), with a focus on mitochondrial dynamics, which employs advanced imaging technology for comprehensive analysis.MethodsA total of 180 fetuses with normal heart structures, aged 24–40 weeks of gestation, were examined. A 2–3 s cine loop in the standard four-chamber oblique view was captured and analyzed using the speckle-tracking technique with Fetal HQ. Various echocardiographic parameters were evaluated, including four-chamber view (4CV), global spherical index (GSI), global longitudinal strain (GLS), 24-segment spherical index (SI), ventricular fractional area change (FAC), cardiac output (CO), and stroke volume (SV). These parameters were compared between the GDM group and the control group during two gestational periods: 24+0 to 28+0 weeks and 28+1 to 40+1 weeks. Statistical analysis was performed using independent samples t-tests and Mann-Whitney U tests to identify significant differences.ResultsTwenty fetuses from mothers with GDM and 40 from the control group were recruited at 24+0 to 28+0 weeks. At 28+1 to 40+1 weeks, 40 fetuses from mothers with GDM and 80 from the control group were recruited. The fetal left ventricular global longitudinal function was similar between the GDM and control groups. However, compared to the controls, right ventricular function in the GDM group was lower only at 28+1 to 40+1 weeks. In the GDM group, the global spherical index (GSI) was lower than in the control group at 28+1 to 40+1 weeks (1.175 vs. 1.22; p = 0.001). There were significant decreases in ventricular FAC (38.74% vs. 42.83%; p < 0.0001) and 4CV GLS for the right ventricle (−22.27% vs. −26.31%; p = 0.005) at 28+1 to 40+1 weeks.ConclusionOur findings suggest that GDM is associated with decreased right ventricular function in the fetal heart, particularly during the later stages of pregnancy (28+1 to 40+1 weeks), compared to fetuses from healthy pregnancies. The Fetal HQ technique represents a valuable tool for evaluating the structure and function of fetal hearts affected by GDM during the advanced stages of pregnancy.

Abstract The equivalence of absorption rates and extents between generic drugs and their reference formulations is crucial for ensuring therapeutic comparability. Bioequivalence (BE) studies are widely utilized and play a pivotal role in substantiating the approval and promotional efforts for generic drugs. Virtual BE simulation is a valuable tool for mitigating risks and guiding clinical BE studies, thereby minimizing redundant in vivo BE assessments. Herein, we successfully developed a physiologically based absorption model for virtual BE simulations, which precisely predicts the BE of the apixaban test and reference formulations. The modeling results confirm that the test and reference formulations were bioequivalent under both fasted and fed conditions, consistent with clinical studies. This highlights the efficacy of physiologically based absorption modeling as a powerful tool for formulation screening and can be adopted as a methodological and risk assessment strategy to detect potential clinical BE risks.

BackgroundIn recent epochs, the field of critical medicine has experienced significant advancements due to the integration of artificial intelligence (AI). Specifically, AI robots have evolved from theoretical concepts to being actively implemented in clinical trials and applications. The intensive care unit (ICU), known for its reliance on a vast amount of medical information, presents a promising avenue for the deployment of robotic AI, anticipated to bring substantial improvements to patient care. ObjectiveThis review aims to comprehensively summarize the current state of AI robots in the field of critical care by searching for previous studies, developments, and applications of AI robots related to ICU wards. In addition, it seeks to address the ethical challenges arising from their use, including concerns related to safety, patient privacy, responsibility delineation, and cost-benefit analysis. MethodsFollowing the scoping review framework proposed by Arksey and O’Malley and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a scoping review to delineate the breadth of research in this field of AI robots in ICU and reported the findings. The literature search was carried out on May 1, 2023, across 3 databases: PubMed, Embase, and the IEEE Xplore Digital Library. Eligible publications were initially screened based on their titles and abstracts. Publications that passed the preliminary screening underwent a comprehensive review. Various research characteristics were extracted, summarized, and analyzed from the final publications. ResultsOf the 5908 publications screened, 77 (1.3%) underwent a full review. These studies collectively spanned 21 ICU robotics projects, encompassing their system development and testing, clinical trials, and approval processes. Upon an expert-reviewed classification framework, these were categorized into 5 main types: therapeutic assistance robots, nursing assistance robots, rehabilitation assistance robots, telepresence robots, and logistics and disinfection robots. Most of these are already widely deployed and commercialized in ICUs, although a select few remain under testing. All robotic systems and tools are engineered to deliver more personalized, convenient, and intelligent medical services to patients in the ICU, concurrently aiming to reduce the substantial workload on ICU medical staff and promote therapeutic and care procedures. This review further explored the prevailing challenges, particularly focusing on ethical and safety concerns, proposing viable solutions or methodologies, and illustrating the prospective capabilities and potential of AI-driven robotic technologies in the ICU environment. Ultimately, we foresee a pivotal role for robots in a future scenario of a fully automated continuum from admission to discharge within the ICU. ConclusionsThis review highlights the potential of AI robots to transform ICU care by improving patient treatment, support, and rehabilitation processes. However, it also recognizes the ethical complexities and operational challenges that come with their implementation, offering possible solutions for future development and optimization.

Abstract Owing to the highly parallel network structure of the biological neural network and its triggered processing mode, tactile sensory neurons can realize the perception of external signals and the functions of perception, memory, and data processing by adjusting the synaptic weight. In this paper, a piezoresistive pressure sensor is combined with a memristor to design an artificial tactile sensory neuron. The polyurethane sponge sensor has excellent sensitivity and can convert physical stimuli into electrical signals, and the chitosan‐based memristor has stable bipolar resistive switching characteristics, allowing further information to be memorized and processed. The neuron can respond to tactile stimuli of different degrees, durations, and frequencies; realize potentiation/depression modulation, paired‐pulse facilitation, and spike‐timing‐dependent plasticity; exhibit spike‐rate‐dependent plasticity; and store and erase tactile information through memistor state switching, which has great application potential in biological sensing systems.

BackgroundToxoplasmosis affects a quarter of the world's population. Toxoplasma gondii (T.gondii) is an intracellular parasitic protozoa. Macrophages are necessary for proliferation and spread of T.gondii by regulating immunity and metabolism. Family with sequence similarity 96A (Fam96a; formally named Ciao2a) is an evolutionarily conserved protein that is highly expressed in macrophages, but whether it play a role in control of T. gondii infection is unknown.Methodology/principal findingsIn this study, we utilized myeloid cell-specific knockout mice to test its role in anti-T. gondii immunity. The results showed that myeloid cell-specific deletion of Fam96a led to exacerbate both acute and chronic toxoplasmosis after exposure to T. gondii. This was related to a defectively reprogrammed polarization in Fam96a-deficient macrophages inhibited the induction of immune effector molecules, including iNOS, by suppressing interferon/STAT1 signaling. Fam96a regulated macrophage polarization process was in part dependent on its ability to fine-tuning intracellular iron (Fe) homeostasis in response to inflammatory stimuli. In addition, Fam96a regulated the mitochondrial oxidative phosphorylation or related events that involved in control of T. gondii.Conclusions/significanceAll these findings suggest that Fam96a ablation in macrophages disrupts iron homeostasis and inhibits immune effector molecules, which may aggravate both acute and chronic toxoplasmosis. It highlights that Fam96a may autonomously act as a critical gatekeeper of T. gondii control in macrophages.

Sepsis is a clinical syndrome caused by uncontrollable immune dysregulation triggered by pathogen infection, characterized by high incidence, mortality rates, and disease burden. Current treatments primarily focus on symptomatic relief, lacking specific therapeutic interventions. The core mechanism of sepsis is believed to be an imbalance in the host’s immune response, characterized by early excessive inflammation followed by late immune suppression, triggered by pathogen invasion. This suggests that we can develop immunotherapeutic treatment strategies by targeting and modulating the components and immunological functions of the host’s innate and adaptive immune systems. Therefore, this paper reviews the mechanisms of immune dysregulation in sepsis and, based on this foundation, discusses the current state of immunotherapy applications in sepsis animal models and clinical trials.

The main component of O-glycoproteins, mucin, is known to play important roles in physiological conditions and oncogenic processes, particularly correlated with poor prognosis in different carcinomas. Diffuse-type gastric cancer (DGC) has long been associated with genomic stability and unfavorable clinical outcomes. To investigate further, we obtained clinical information and the RNA-seq data of the TCGA-STAD cohort. Through the use of unsupervised clustering methods and GSEA, we identified two distinct clusters, characterized by higher and lower expression of MUC2 and MUC20, denoted as cluster 1 and cluster 2, respectively. Subsequently, employing CIBERSORT, it was determined that cluster 2 exhibited a higher tumor mutation burden (TMB) and a greater abundance of CD8+ T cells and activated CD4+ memory T cells, in addition to immune checkpoints (ICPs). On the other hand, cluster 1 showed a lower TIDE score estimation, indicating a higher probability of tumor immune escape. Furthermore, overexpression of MUC15 and MUC20 was confirmed through qPCR and Western blotting, and their specific roles in mediating the epithelial-mesenchymal transition (EMT) process of GC cells (SNU484 and Hs746t) were validated via CCK-8 assay and wound healing assay in vitro. These findings highlight the potential prognostic value of MUC20 and offer insights into the prospects of immunotherapy for DGC by targeting MUC20.

Abstract The Tibetan Plateau (TP) is an area highly sensitive to climate change and is warming faster than the global average. The TP temperature change has a significant impact on the local ecological environment and the downstream weather and climate. The TP will undoubtedly warm in the future, but the warming extent is uncertain. Using the Coupled Model Inter‐comparison Project Phase 6 multi‐model ensemble, we found that models simulating smaller TP temperature increases in recent decades tend to project weaker warming in the future. This relationship is driven by the simulation of snowmelt response to greenhouse gas increases, as snow‐related albedo feedback dominates the TP temperature changes in both historical and future periods. Based on a two‐step emergent constraint approach, the rectified TP warming magnitude increases by about 0.3°C compared to the unconstrained result under both the medium and high emission scenarios, and the inter‐model uncertainty is reduced by about 60%.

Surgical sutures are necessary for the rotator cuff (RC) repair to reconnect the torn and degenerating cuff tendon to its footprint. Early‐stage immunomodulation, angiogenesis, and the progressive mechanobiological response encourage complex healing processes involving micro‐nano dimensional reconstruction, including tendon‐bone interface integration and tendon remodeling. However, commercially available sutures with mismatched micrometer‐scale diameters resulted in mechanobiological and biological deficiencies, severely impeding RC regeneration. We developed a bionic functional surgical suture (SS) with helical and hierarchical micro‐nano structures using nano‐ and micro‐Poly (DL‐lactide‐co‐glycolide) (PLGA) yarns (ny), which was subsequently crosslinked in situ with a temporary chemotactic (TC) layer of physiological fibrin networks (TC‐nySS). The TC‐nySS has both mechanobiological and biological advantages: 1) biomimetic helical and hierarchical micro‐nano structures showed progressive degradation behavior, inducing the incremental mechanobiological response of the repaired tissues; 2) outer TC layer of biochemical modification by fibrin networks supplied dual‐functions of angiogenesis and immunomodulation at the early stage, subsequently resulting in timely vascularization and inflammatory regressions due to superior degradation behavior of the constructs. Consequently, TC‐nySS with structural and biochemical designs that elicit process‐matching mechanobiological and biological responses tailored to the RC regeneration successfully achieved the complex healing processes, including superior tendon‐bone interface integration and tendon remodelling.

Background: Potential effect of greenspace exposure on human microbiota have been explored by a number of observational and interventional studies, but the results remained mixed. We comprehensively synthesized these studies by performing a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methods: Comprehensive literature searches in three international databases (PubMed, Embase, and Web of Science) and three Chinese databases (China National Knowledge Infrastructure, Wanfang, and China Biology Medicine disc) were conducted from inception to November 1, 2023. Observational and interventional studies that evaluated associations between greenspace exposure and human microbiota at different anatomical sites were included. Studies were assessed using the National Toxicology Program’s office of Health Assessment and Translation risk of bias tool and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation framework. Two authors independently performed study selection, data extraction, and risk of bias assessment, and evidence grading. Study results were synthesized descriptively. Results: Twenty studies, including 11 observational studies and 9 interventional studies, were finally included into the systematic review. The microbiota of the included studies was from gut (n = 13), skin (n = 10), oral cavity (n = 5), nasal cavity (n = 5) and eyes (n = 1). The majority of studies reported the associations of greenspace exposure with increased diversity (e.g., richness and Shannon index) and/or altered overall composition of human gut (n = 12) and skin microbiota (n = 8), with increases in the relative abundance of probiotics (e.g., Ruminococcaceae) and decreases in the relative abundance of pathogens (e.g., Streptococcus and Escherichia/Shigella). Due to limited number of studies, evidence concerning greenspace and oral, nasal, and ocular microbiota were still inconclusive. Conclusion: The current evidence suggests that greenspace exposure may diversify gut and skin microbiota and alter their composition to healthier profiles. These findings would be helpful in uncovering the potential mechanisms underlying greenspace and human health and in promoting a healthier profile of human microbiota.

Summary: The quantum denoising technology efficiently removes noise from images; however, the existing algorithms are only effective for additive noise and cannot remove multiplicative noise, such as speckle noise in synthetic aperture radar (SAR) images. In this paper, based on the grayscale morphology method, a quantum SAR image denoising algorithm is proposed, which performs morphological operations on all pixels simultaneously to remove the noise in the SAR image. In addition, we design a feasible quantum adder to perform cyclic shift operations. Then, quantum circuits for dilation and erosion are designed, and the complete quantum circuit is then constructed. For a 2n×2n quantum SAR image with q grayscale levels, the complexity of our algorithm is O (n+q). Compared with classical algorithms, it achieves exponential improvement and also has polynomial-level improvements than existing quantum algorithms. Finally, the feasibility of our algorithm is validated on IBM Q.

Summary: Background: Ultra-processed foods (UPFs) are emerging as a risk factor for colorectal cancer (CRC), yet how post-diagnostic UPF intake may impact CRC prognosis remains unexplored. Methods: Data collected from food frequency questionnaires were used to estimate intakes of total UPFs and UPF subgroups (serving/d) at least 6 months but less than 4 years post-diagnosis among 2498 patients diagnosed with stages I–III CRC within the Nurses’ Health Study and Health Professionals Follow-up Study during 1980–2016. Hazard ratios (HR) and 95% confidence intervals (CIs) of all-cause, CRC- and cardiovascular disease (CVD)-specific mortality in association with UPF consumption were estimated using an inverse probability weighted multivariable Cox proportional hazards regression model, adjusted for confounders. Findings: The mean (SD) age of patients at diagnosis was 68.5 (9.4) years. A total of 1661 deaths were documented, including 321 from CRC and 335 from CVD. Compared to those in the lowest quintile (median = 3.6 servings/d), patients in the highest quintile (median = 10 servings/d) of post-diagnostic UPF intake had higher CVD mortality (HR = 1.65, 95% CI = 1.13–2.40) but not CRC or all-cause mortality. Among UPF subgroups, higher consumption of fats/condiments/sauces was associated with a higher risk of CVD-specific mortality (highest vs. lowest quintile of intake, HR = 1.96, 95% CI = 1.41–2.73), and higher intake of ice cream/sherbet was associated with an increased risk of CRC-specific mortality (highest vs. lowest quintile, HR = 1.86, 95% CI: 1.33–2.61). No statistically significant association was found between UPF subgroups and overall mortality. Interpretation: Higher post-diagnostic intake of total UPFs and fats/condiments/sauces in CRC survivors is associated with higher CVD mortality, and higher ice cream/sherbet intake is linked to higher CRC mortality. Funding: US National Institutes of Health and the American Cancer Society.

In the course of our research on utilizing edible flower resources to promote health, five ellagitannins (1–5) were isolated from pomegranate (Punica granatum L.) flower by bioassay-guided fractionation. Among them, mallotusinin (1) and tercatain (2) were first isolated from pomegranate flower, and punicatannin D (4) was an unprecedented compound. Compounds 1–3 exhibited significant xanthine oxidase (XO) inhibitory activity compared with allopurinol, and a potent inhibition on α-glucosidase that was superior to acarbose was observed for compounds 1–4. The XO inhibitory activity is positively correlated with the amount of galloyl moiety (3 > 2 > 1). Presenting tetrahydroxydibenzofuranoyl substituent or increasing the number of galloyl group enhanced the inhibition capacity of α-glucosidase (1 > 3 > 2). The inhibitory mechanism was further clarified in terms of kinetic studies and molecular docking. This study revealed that the ellagitannins present in pomegranate flower might be promising functional food ingredients with anti-hyperuricemia and anti-hyperglycemia properties.

Background: Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer. Methods: Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs). Results: Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18–1.27) in men, and 1.26 (1.22–1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10–2.51) for men and 1.94 (1.78–2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = –1.01 in men, p