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Abstract Rosacea is a chronic inflammatory skin disease that typically affects the central facial area. Its main clinical symptoms include paroxysmal flushing, telangiectasia, and non-temporary erythema. Cell-free adipose tissue extracts (ATEs) are liquid components extracted from human adipose tissue that contain large amounts of growth factors. Despite the scar-reducing, anti-aging, and wound-healing effects of ATEs, the efficacy of ATEs in rosacea remains unknown. Therefore, the anti-rosacea effects of ATEs were investigated in human cathelicidin peptide (LL-37) induced rosacea mice and capsaicin (CAP)-stimulated HaCaT keratinocytes. In vitro, ATEs significantly reduced TRPV1 expression, intracellular calcium ions influx and the release of inflammatory factors (such as KLK5, IL-6, IL-8 and TNF-α) after intervening in CAP-stimulated cells. The in vivo results revealed that ATEs alleviated rosacea symptoms, such as erythema score, erythema area, transepidermal water loss, abnormal epidermal thickness, mast cell infiltration and telangiectasia upon downregulating TRPV1 and CD31 expression. Moreover, the up-regulated TRPV1 protein expression was also recovered by ATEs administration in vivo and in vitro. Meanwhile, ATEs demonstrated good biocompatibility. In summary, ATEs could be a potential therapeutic agent for rosacea by regulating inflammation and alleviating telangiectasia.

Abstract Background Child dental anxiety is a prevalent issue in the field of pediatric dentistry. At present, several non-pharmacological interventions are employed to mitigate anxiety during dental treatments for children. The objective of this study is to assess the effectiveness of diverse non-pharmacological interventions in reducing dental anxiety, as well as enhancing heart rate during pediatric dental treatments. To achieve this, we conducted a systematic review and a network meta-analysis (NMA) to compare the efficacy of various outcome indicators. Methods A thorough search was conducted in the databases of PubMed, Embase, Web of Science, Cochrane Library, Scopus, APA PsycInfo, CINAHL, and AMED to identify all eligible randomized controlled trials (RCTs) from the beginning of the databases up to August 1, 2024. The quality assessment was carried out using the Cochrane Collaboration’s bias risk tool. The two outcome measures under consideration were dental anxiety and heart rate. Network graphs, league tables and SUCRA were constructed using R 4.2.3 software and Stata 16 software. This study is registered in PROSPERO under the registration number CRD42023467610. Results The study examined 12 different non-pharmacological approaches, drawing from a pool of 61 research studies involving 6,113 participants aged 4 to 16 years. The results of the network meta-analysis revealed that music (SUCRAs: 93.60%) proved to be the most effective measure in mitigating dental anxiety, followed by aromatherapy (SUCRAs: 78.58%) and game (SUCRAs: 70.99%). Moreover, hypnosis (SUCRAs: 98.80%), music (SUCRAs: 79.58%), and relaxation (SUCRAs: 72.41%) were identified as the top three interventions for decreasing heart rate. Conclusion In this NMA, when contemplating dental anxiety outcomes, music is recommended as a priority. For heart rate outcomes, hypnosis may be a preferred measure. However, owing to the limited number of articles, the conclusion of this study still requires additional confirmation or correction through more high-quality primary studies in the future.

This paper investigates the attitude tracking control problem for the cruise mode of a dual-system convertible unmanned aerial vehicle (UAV) in the presence of parameter uncertainties, unmodeled uncertainties and wind disturbances. First, a fixed-time disturbance observer (FXDO) based on the bi-limit homogeneity theory is designed to estimate the lumped disturbance of the convertible UAV model. Then, a fixed-time integral sliding mode control (FXISMC) is combined with the FXDO to achieve strong robustness and chattering reduction. Bi-limit homogeneity theory and Lyapunov theory are applied to provide detailed proof of the fixed-time stability. Finally, numerical simulation experimental results verify the robustness of the proposed algorithm to model parameter uncertainties and wind disturbances. In addition, the proposed algorithm is deployed in a open-source UAV autopilot and its effectiveness is further demonstrated by hardware-in-the-loop experimental results.

Abstract Pressure ulcers (PU) are caused by persistent long-term pressure, which compromises the integrity of the epidermis, dermis, and subcutaneous adipose tissue layer by layer, making it difficult to heal. Platelet products such as platelet lysate (PL) can promote tissue regeneration by secreting numerous growth factors based on clinical studies on skin wound healing. However, the components of PL are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel that has lately emerged as a promising material for tissue engineering and regenerative medicine. The PL liquid was extracted, flow cytometrically detected for CD41a markers, and evenly dispersed in the GelMA hydrogel to produce a surplus growth factor hydrogel system (PL@GM). The microstructure of the hydrogel system was observed under a scanning electron microscope, and its sustained release efficiency and biological safety were tested in vitro. Cell viability and migration of human dermal fibroblasts, and tube formation assays of human umbilical vein endothelial cells were applied to evaluate the ability of PL to promote wound healing and regeneration in vitro. Real-time polymerase chain reaction (PCR) and western blot analyses were performed to elucidate the skin regeneration mechanism of PL. We verified PL’s therapeutic effectiveness and histological analysis on the PU model. PL promoted cell viability, migration, wound healing and angiogenesis in vitro. Real-time PCR and western blot indicated PL suppressed inflammation and promoted collagen I synthesis by activating STAT3. PL@GM hydrogel system demonstrated optimal biocompatibility and favorable effects on essential cells for wound healing. PL@GM also significantly stimulated PU healing, skin regeneration, and the formation of subcutaneous collagen and blood vessels. PL@GM could accelerate PU healing by promoting fibroblasts to migrate and secrete collagen and endothelial cells to vascularize. PL@GM promises to be an effective and convenient treatment modality for PU, like chronic wound treatment.

Abstract Episyrphus balteatus can provide dual ecosystem services including pest control and pollination, which the larvae are excellent predators of aphid pest whereas adults are efficient pollinator. In this study, we assembled a high-quality genome of E. balteatus from northern China geographical population at the chromosome level by using Illumina, PacBio long reads, and Hi-C technologies. The 467.42 Mb genome was obtained from 723 contigs, with a contig N50 of 9.16 Mb and Scaffold N50 of 118.85 Mb, and 90.25% (431.75 Mb) of the assembly was anchored to 4 pseudo-autosomes and one pseudo-heterosome. In total, 14,848 protein-coding genes were annotated, and 95.14% of genes were fully represented in NR, GO, KEGG databases. Besides, we also obtained the mitochondrial genome of E. balteatus of 16, 837 bp in length with 37 typical mitochondrial genes. Overall, this high-quality genome is valuable for evolutionary and genetic studies of E. balteatus and other Syrphidae hoverfly species.

Abstract Necrotizing enterocolitis (NEC) involves intestinal epithelial damage and inflammatory response and is associated with high morbidity and mortality in infants. To improve therapeutic prospects, elucidating underlying molecular mechanisms of intestinal epithelial damage during NEC is of the essence. Poly (ADP-ribose) polymerase 1 (PARP1)-dependent parthanatos is a programmed inflammatory cell death. In the present study, the presence of parthanatos-associated proteins PARP1 and poly (ADP-ribose) (PAR), along with high expression of DNA damage-associated biomarkers, 8-hydroxy-2’-deoxyguanosine (8-OHdG) and phosphorylation of histone H2AX (γH2AX), were discovered in the intestinal tissues of NEC infants. Additionally, the upregulated expression of PARP1 and PAR in NEC intestinal tissues correlated distinctly with clinical indices indicative of NEC incidence and severity. Furthermore, we demonstrated that inhibiting the expression of parthanatos-associated proteins, by either pharmacological blockage using 3-aminobenzamide (3-AB), an inhibitor of PARP1, or genetic knockout using Parp1-deficient mice, resulted in substantial improvements in both histopathological severity scores associated with intestinal injury and inflammatory reactions. Moreover, in an in vitro NEC model, reactive oxygen species (ROS)-induced DNA damage promoted the formation of PAR and nuclear translocation of apoptosis-inducing factor (AIF), thus activating PARP1-dependent parthanatos in Caco-2 cells and human intestinal organoids. Our work verifies a previously unexplored role for parthanatos in intestinal epithelial damage during NEC and suggests that inhibition of parthanatos may serve as a potential therapeutic strategy for intervention of NEC.

Abstract Background Addressing presbyopia in the aging population, particularly in non-cataractous patients, remains a challenge. This study evaluates the outcomes of refractive lens exchange (RLE) with AT LISA tri 839MP trifocal intraocular lens (IOL) implantation in a Chinese presbyopic population without cataracts. Methods The study included 164 eyes from 82 patients undergoing bilateral RLE at Peking Union Medical College Hospital. Comprehensive evaluations encompassed visual acuities, refraction, ocular aberrometry, and subjective outcomes via the VF-14 questionnaire. The focus was on postoperative visual performance, refractive outcomes, safety, objective optical quality, and patient satisfaction. Results 100%, 90.2%, and 89.0% of patients achieved binocular UDVA, UNVA, and UIVA of logMAR 0.1 or better at 6 months postoperatively. 97.6% of eyes were within ± 1.00 D of emmetropia postoperatively. Optical quality assessments showed increases in modulation transfer function and Strehl ratios (p

Approximately 50% of patients with non-small-cell lung cancer (NSCLC) are diagnosed at advanced stages and face a challenging prognosis despite the integration of targeted therapies, immunotherapy, and systemic chemotherapy into current standard care. A key factor in this context is trophoblast cell-surface antigen 2 (TROP2), which is widely expressed in NSCLC and strongly associated with poor patient outcomes. This article examines the latest developments in the application of datopotamab deruxtecan (Dato-DXd, DS-1062), a novel antibody-drug conjugate targeting TROP2, in the treatment of NSCLC. It provides a detailed assessment of Dato-DXd’s technical design, evaluates its efficacy by using recent clinical trial data, and discusses its safety profile.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusion : s: In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Abstract Background the mortality associated with severe malaria due to Plasmodiun falciparum remains high despite improvements in malaria management. Case prensentation: this case series aims to describe the efficacy and safety of the exchange transfusion combined with artesunate (ET-AS) regimen in severe P. falciparum malaria. Eight patients diagnosed with severe P. falciparum malaria were included. All patients underwent ET using the COBE Spectra system. The aimed for a post-exchange hematocrit of 30%. Half the estimated blood volume was removed and replaced using fresh frozen plasma. The regimen was well-tolerated without complications. The parasite clearance time ranged from 1 ~ 5 days. Five patients with cerebral malaria exhibited full improved consciousness within 3 days, while patient2 with hemolysis improved on day 2. Liver function improved within 1 ~ 6 days, and patient 1 and patient 6 showed improvements renal function on days 18 and 19, respectively. The length of intensive care unit stay range from 2 ~ 10 days, and all patients treated with ET-AS remained in the hospital for 3 ~ 19 days. Conclusions: these preliminary results suggest that ET-AS regimens are a safe and effective therapy for severe P. falciparum malaria and can benefit patients in clinical settings.

ObjectiveTo evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) in pulmonary cryptococcosis (PC) using bronchoalveolar lavage fluid (BALF) and lung biopsy tissue specimens.MethodsIn this retrospective study, 321 patients diagnosed with lower respiratory tract diseases who underwent mNGS using BALF and LBT samples, between January 2021 and December 2023 were included. Individuals were classified into PC and non-PC groups according to the diagnostic criteria for PC, and conventional fungal cultures were performed. A serum/BALF cryptococcal antigen (CrAg) test was performed in some patients with PC. The diagnostic efficiencies of three methods for PC (mNGS, conventional culture, and CrAg) were compared. Additionally, two mNGS methods were used in this study: original mNGS (OmNGS, testing time from January 2021 to December 2022) and modified mNGS (MmNGS, testing time from January to December 2023). The diagnostic efficiency of the two mNGS methods on PC was simultaneously compared.ResultsAmong the 321 patients, 23 (7.2%) had PC and 298 (92.8%) did not. Compared with the composite reference standard for PC diagnosis, the sensitivity, specificity, and accuracy of mNGS for PC were 78.3% (95% confidence interval [CI], 55.8%–91.7%), 98.7% (95% CI, 96.4%–99.6%), and 97.2% (95% CI, 94.7%–98.7%), respectively. The sensitivity of mNGS was similar to that of CrAg (80.0%, 12/15) (P > 0.05). The diagnostic sensitivity of both mNGS and CrAg was higher than that of conventional culture (35.0%, 7/20) (P = 0.006, P = 0.016), and the combined detection of mNGS and CrAg further improved the diagnostic sensitivity of PC (93.3%, 14/15). The area under the receiver operating characteristic curve of mNGS was superior to that of conventional culture (0.885 vs. 0.675). In addition, the diagnostic sensitivity of PC was higher than that of OmNGS (P = 0.046).ConclusionThe sensitivity of mNGS is better than that of conventional culture. The combination of mNGS and CrAg improves the testing sensitivity of Cryptococcus. MmNGS could further improve the detection of Cryptococcus. Conventional PC detection methods are indispensable and mNGS can be used as a rapid and accurate auxiliary diagnostic method for PC.

IntroductionSymbiotic bacteria play key roles in a variety of important life processes of insects such as development, reproduction and environmental adaptation, and the elucidation of symbiont population structure and dynamics is crucial for revealing the underlying regulatory mechanisms. The marmalade hoverfly (Episyrphus balteatus) is not only a remarkable aphid predator, but also a worldwide pollinator second to honeybees. However, its symbiont composition and dynamics remain unclear.MethodsHerein, we investigate the symbiotic bacterial dynamics in marmalade hoverfly throughout whole life cycle, across two sexes, and in its prey Megoura crassicauda by 16S rRNA sequencing.ResultsIn general, the dominant phyla were Proteobacteria and Firmicutes, and the dominant genera were Serratia and Wolbachia. Serratia mainly existed in the larval stage of hoverfly with the highest relative abundance of 86.24% in the 1st instar larvae. Wolbachia was found in adults and eggs with the highest relative abundance of 62.80% in eggs. Significant difference in species diversity was observed between the adults feeding on pollen and larvae feeding on M. crassicauda, in which the dominant symbiotic bacteria were Asaia and Serratia, respectively. However, between two sexes, the symbionts exhibited high similarity in species composition. In addition, our results suggested that E. balteatus obtainded Serratia mainly through horizontal transmission by feeding on prey aphids, whereas it acquired Wolbachia mainly through intergeneration vertical transmission. Taken together, our study revealed the effects of development stages, diet types and genders of E. balteatus on symbionts, and explored transmission modes of dominant bacteria Serratia and Wolbachia.DiscussionOur findings lay a foundation for further studying the roles of symbiotic bacteria in E. balteatus life cycle, which will benefit for revealing the co-adaptation mechanisms of insects and symbiotic bacteria.

Nicotinamide adenine dinucleotide (NAD+)/reduced NAD+ (NADH) and nicotinamide adenine dinucleotide phosphate (NADP+)/reduced NADP+ (NADPH) are essential metabolites involved in multiple metabolic pathways and cellular processes. NAD+ and NADH redox couple plays a vital role in catabolic redox reactions, while NADPH is crucial for cellular anabolism and antioxidant responses. Maintaining NAD(H) and NADP(H) homeostasis is crucial for normal physiological activity and is tightly regulated through various mechanisms, such as biosynthesis, consumption, recycling, and conversion between NAD(H) and NADP(H). The conversions between NAD(H) and NADP(H) are controlled by NAD kinases (NADKs) and NADP(H) phosphatases [specifically, metazoan SpoT homolog-1 (MESH1) and nocturnin (NOCT)]. NADKs facilitate the synthesis of NADP+ from NAD+, while MESH1 and NOCT convert NADP(H) into NAD(H). In this review, we summarize the physiological roles of NAD(H) and NADP(H) and discuss the regulatory mechanisms governing NAD(H) and NADP(H) homeostasis in three key aspects: the transcriptional and posttranslational regulation of NADKs, the role of MESH1 and NOCT in maintaining NAD(H) and NADP(H) homeostasis, and the influence of the circadian clock on NAD(H) and NADP(H) homeostasis. In conclusion, NADKs, MESH1, and NOCT are integral to various cellular processes, regulating NAD(H) and NADP(H) homeostasis. Dysregulation of these enzymes results in various human diseases, such as cancers and metabolic disorders. Hence, strategies aiming to restore NAD(H) and NADP(H) homeostasis hold promise as novel therapeutic approaches for these diseases.

Background/Aims: Necrotizing pancreatitis (NP) presents a more severe clinical trajectory and increased mortality compared to edematous pancreatitis. Prompt identification of NP is vital for patient prognosis. A risk prediction model for NP among Chinese patients has been developed and validated to aid in early detection. Methods: A retrospective analysis was performed on 218 patients with acute pancreatitis (AP) to examine the association of various clinical variables with NP. The least absolute shrinkage and selection operator (LASSO) regression was utilized to refine variables and select predictors. Subsequently, a multivariate logistic regression was employed to construct a predictive nomogram. The model's accuracy was validated using bootstrap resampling (n=500) and its calibration assessed via a calibration curve. The model's clinical utility was evaluated through decision curve analysis. Results: Of the 28 potential predictors analyzed in 218 AP patients, the incidence of NP was 25.2%. LASSO regression identified 14 variables, with procalcitonin, triglyceride, white blood cell count at 48 hours post-admission, calcium at 48 hours post-admission, and hematocrit at 48 hours post-admission emerging as independent risk factors for NP. The resulting nomogram accurately predicted NP risk with an area under the curve of 0.822, sensitivity of 82.8%, and specificity of 76.4%. The bootstrap-validated area under the curve remained at 0.822 (95% confidence interval, 0.737 to 0.892). This model exhibited excellent calibration and demonstrated greater predictive efficacy and clinical utility for NP than APACHE II, Ranson, and BISAP. Conclusions: We have developed a prediction nomogram of NP that is of great value in guiding clinical decision.

Abstract BackgroundCardiovascular-kidney-metabolic (CKM) health is affected by social determinants of health, especially education. CKM syndrome has not been evaluated in Chinese population, and the association of education with CKM syndrome in different sexes and its intertwined relation with lifestyles have not been explored. ObjectiveWe aimed to explore the association between educational attainment and the prevalence of CKM syndrome stages in middle-aged and older Chinese men and women as well as the potential role of health behavior based on Life’s Essential 8 construct. MethodsThis study used data from the nationwide, community-based REACTION (Risk Evaluation of Cancers in Chinese diabetic individuals: a longitudinal study). A total of 132,085 participants with complete information to determine CKM syndrome stage and education level were included. Educational attainment was assessed by the self-reported highest educational level achieved by the participants and recategorized as low (elementary school or no formal education) or high (middle school, high school, technical school/college, or above). CKM syndrome was ascertained and classified into 5 stages according to the American Heart Association presidential advisory released in 2023. ResultsAmong 132,085 participants (mean age 56.95, SD 9.19 years; n=86,675, 65.62% women) included, most had moderate-risk CKM syndrome (stages 1 and 2), and a lower proportion were at higher risk of CKM (stages 3 and 4). Along the CKM continuum, low education was associated with 34% increased odds of moderate-risk CKM syndrome for women (odds ratio 1.36, 95% CI 1.23-1.49) with a significant sex disparity, but was positively correlated with high-risk CKM for both sexes. The association between low education and high-risk CKM was more evident in women with poor health behavior but not in men, which was also interactive with and partly mediated by behavior. ConclusionsLow education was associated with adverse CKM health for both sexes but was especially detrimental to women. Such sex-specific educational disparity was closely correlated with health behavior but could not be completely attenuated by behavior modification. These findings highlight the disadvantage faced by women in CKM health ascribed to low education, underscoring the need for public health support to address this inequality.

Abstract Background Not many large‐sample investigations are available that compare the potency of the relationship of remnant cholesterol (RC) and other lipid parameters with diabetes and prediabetes. The goals of our study are to discover the relationship between RC and prediabetes, diabetes, and insulin resistance (IR) and to investigate RC, high‐density lipoprotein cholesterol (HDL‐C), non‐HDL‐C, triglycerides (TG), low‐density lipoprotein cholesterol (LDL‐C), total cholesterol (TC), TC/HDL‐C, LDL‐C/HDL‐C, and TG/HDL‐C, which are the lipid parameters that are most positively related to diabetes, prediabetes, and IR. Methods This research enrolled 36 684 subjects from China's eight provinces. We employed multiple logistic regression analysis for testing the relationship between lipid parameters and diabetes, prediabetes, and IR. Results After adjusting for potential confounders, and comparing the results with other lipid parameters, the positive relationship between RC and diabetes (odds ratio [OR] 1.417, 95% confidence interval [CI]: 1.345–1.492), prediabetes (OR 1.555, 95% CI: 1.438–1.628), and IR (OR 1.488, 95% CI: 1.404–1.577) was highest. RC was still related to diabetes, prediabetes, and IR even when TG

Abstract Background Novel diabetes phenotypes were proposed by the Europeans through cluster analysis, but Chinese community diabetes populations might exhibit different characteristics. This study aims to explore the clinical characteristics of novel diabetes subgroups under data‐driven analysis in Chinese community diabetes populations. Methods We used K‐means cluster analysis in 6369 newly diagnosed diabetic patients from eight centers of the REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study. The cluster analysis was performed based on age, body mass index, glycosylated hemoglobin, homeostatic modeled insulin resistance index, and homeostatic modeled pancreatic β‐cell functionality index. The clinical features were evaluated with the analysis of variance (ANOVA) and chi‐square test. Logistic regression analysis was done to compare chronic kidney disease and cardiovascular disease risks between subgroups. Results Overall, 2063 (32.39%), 658 (10.33%), 1769 (27.78%), and 1879 (29.50%) populations were assigned to severe obesity‐related and insulin‐resistant diabetes (SOIRD), severe insulin‐deficient diabetes (SIDD), mild age‐associated diabetes mellitus (MARD), and mild insulin‐deficient diabetes (MIDD) subgroups, respectively. Individuals in the MIDD subgroup had a low risk burden equivalent to prediabetes, but with reduced insulin secretion. Individuals in the SOIRD subgroup were obese, had insulin resistance, and a high prevalence of fatty liver, tumors, family history of diabetes, and tumors. Individuals in the SIDD subgroup had severe insulin deficiency, the poorest glycemic control, and the highest prevalence of dyslipidemia and diabetic nephropathy. Individuals in MARD subgroup were the oldest, had moderate metabolic dysregulation and the highest risk of cardiovascular disease. Conclusion The data‐driven approach to differentiating the status of new‐onset diabetes in the Chinese community was feasible. Patients in different clusters presented different characteristics and risks of complications.

Abstract Background Serotonin (5‐hydroxytryptamine) is a multifunctional bioamine serving as a neurotransmitter, peripheral hormone and mitogen in the vertebrate system. It has pleiotropic activities in central nervous system and gastrointestinal function via an orchestrated action of serotonergic elements, particularly serotonin receptor‐mediated signalling cascades. The mitogenic properties of serotonin have garnered recognition for years and have been exploited for repurposing serotonergic‐targeted drugs in cancer therapy. However, emerging conflicting findings necessitate a more comprehensive elucidation of serotonin's role in cancer pathogenesis. Main body and conclusion Here, we provide an overview of the biosynthesis, metabolism and action modes of serotonin. We summarise our current knowledge regarding the effects of the peripheral serotonergic system on tumourigenesis, with a specific emphasis on its immunomodulatory activities in human cancers. We also discuss the dual roles of serotonin in tumour pathogenesis and elucidate the potential of serotonergic drugs, some of which display favourable safety profiles and impressive efficacy in clinical trials, as a promising avenue in cancer treatment. Key points Primary synthesis and metabolic routes of peripheral 5‐hydroxytryptamine in the gastrointestinal tract. Advanced research has established a strong association between the serotonergic components and carcinogenic mechanisms. The interplay between serotonergic signalling and the immune system within the tumour microenvironment orchestrates antitumour immune responses. Serotonergic‐targeted drugs offer valuable clinical options for cancer therapy.

BackgroundVascular cognitive impairment (VCI) persistently impairs cognition and the ability to perform activities of daily living, seriously compromising patients’ quality of life. Previous studies have reported that disorders of serum iron metabolism and iron deposition in the brain can lead to inflammation, abnormal protein aggregation and degeneration, and massive neuronal apoptosis in the central nervous system, which in turn leads to a progressive decline in cognitive processes. Our previous clinical studies have found acupuncture to be a safe and effective intervention for treating VCI, but the specific mechanisms require further exploration. ObjectiveThe objective of the trial is to evaluate the clinical efficacy of Tongdu Xingshen acupuncture and to investigate whether it can improve VCI by regulating brain iron deposition and body iron metabolism. MethodsIn total, 42 patients with VCI and 21 healthy individuals will participate in this clinical trial. The 42 patients with VCI will be randomized into acupuncture and control groups, while the 21 healthy individuals will be in the healthy control group. Both the control and acupuncture groups will receive conventional medical treatment and cognitive rehabilitation training. In addition, the acupuncture group will receive electroacupuncture treatment with Tongdu Xingshen for 30 minutes each time, 6 times a week for 4 weeks. Meanwhile, the healthy control group will not receive any intervention. All 3 groups will undergo baseline assessments of brain iron deposition, serum iron metabolism, and neuropsychological tests after enrollment. The acupuncture and control groups will be evaluated again at the end of 4 weeks of treatment, as described earlier. By comparing neuropsychological test scores between groups, we will examine the efficacy of Tongdu Xingshen acupuncture in treating VCI. Additionally, we will test the correlations between neuropsychological test scores, brain iron deposition, and body iron metabolism indexes to explore the possible mechanisms of Tongdu Xingshen acupuncture in treating VCI. ResultsParticipants are currently being recruited. The first participant was enrolled in June 2023, which marked the official start of the experiment. As of the submission of the paper, there were 23 participants. The recruitment process is expected to continue until June 2025, at which point the processing and analysis of data will begin. As of May 15, 2024, up to 30 people have been enrolled in this clinical trial. ConclusionsThis study will provide data on the effects of Tongdu Xingshen acupuncture on cerebral iron deposition as well as somatic iron metabolism in patients with VCI. These results will help to prove whether Tongdu Xingshen acupuncture can improve VCI by regulating brain iron deposition and body iron metabolism, which will provide the clinical and theoretical basis for the wide application of acupuncture therapy in VCI rehabilitation. Trial RegistrationChina Clinical Registration Agency ChiCTR2300072188; https://tinyurl.com/5fcydtkv International Registered Report Identifier (IRRID)PRR1-10.2196/56484

BackgroundThe triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women.MethodsThis cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer.ResultsMultivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19–2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13–17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09–1.68), 1.27 (1.05–1.54), 1.26 (1.05–1.52), and 1.32 (1.08–1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44–3.87).ConclusionThe TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women.

Abstract This single-arm, multi-center clinical trial aimed to evaluate the safety, tolerability, DLT, recommended dose (RD), preliminary efficacy, and pharmacokinetics (PK) characteristics of lurbinectedin, a selective inhibitor of oncogenic transcription, in Chinese patients with advanced solid tumors, including relapsed SCLC. Patients with advanced solid tumors were recruited in the dose-escalation stage and received lurbinectedin in a 3 + 3 design (two cohorts: 2.5 mg/m2 and 3.2 mg/m2, IV, q3wk). The RD was expanded in the following dose-expansion stage, including relapsed SCLC patients after first-line platinum-based chemotherapy. The primary endpoints included safety profile, tolerability, DLT, RD, and preliminary efficacy profile, while the secondary endpoints included PK characteristics. In the dose-escalation stage, ten patients were included, while one patient had DLT in the 3.2 mg/m2 cohort, which was also the RD for the dose-expansion stage. At cutoff (May 31, 2022), 22 SCLC patients were treated in the ongoing dose-expansion stage, and the median follow-up was 8.1 months (range 3.0–11.7). The most common grade ≥ 3 treatment-related adverse events (TRAEs) included neutropenia (77.3%), leukopenia (63.6%), thrombocytopenia (40.9%), anemia (18.2%), and ALT increased (18.2%). The most common severe adverse events (SAEs) included neutropenia (27.3%), leukopenia (22.7%), thrombocytopenia (18.2%), and vomiting (9.1%). No treatment-related deaths occurred. The Independent Review Committee (IRC)-assessed ORR was 45.5% (95% CI 26.9–65.3). Lurbinectedin at the RD (3.2 mg/m2) showed manageable safety and acceptable tolerability in Chinese patients with advanced solid tumors, and demonstrates promising efficacy in Chinese patients with SCLC as second-line therapy. Trial registration: This study was registered with ClinicalTrials.gov NCT04638491, 20/11/2020.

Objective To investigate associations of changes in waist circumference (WC) and body mass index (BMI) with the variation of fasting blood glucose among middle aged and elderly residents with high cardiovascular risk. MethodsTotally 71 758 urban/rural permanent residents aged 35 years or older were recruited at 8 districts/counties of 3 municipalities, Jiangsu province for a baseline survey conducted during 2015 as a part of the ‘Early Screening and Comprehensive Intervention on Cardiovascular Diseases among High-Risk Populations in China’. Out of those residents surveyed, 12 369 individuals with initial records of fasting blood glucose (FBG) and at high-risk of cardiovascular diseases were followed up annually in 2017, 2018, and 2019 to observe changes in their FBG levels over time. The generalized estimating equation (GEE) was used to explore associations of the changes in WC and BMI with the variations of FBG among the participants. ResultsOf the 9 952 participants successfully followed up 3 045 (30.6%), 2 130 (21.4%), and 4 777 (48.0%) had normal WC, pre-central obesity, and obesity and 56 (0.6%), 2 669 (26.8%), 4 540 (45.6%), and 2 687 (27.0%) were assessed as having underweight, normal weight, overweight, and obesity respectively at the baseline survey. After adjusting for gender, age, education, place of residence, smoking, alcohol drinking, hypertension, diabetes mellitus, dyslipidemia, baseline WC, baseline BMI, and follow-up sequence, the results of GEE analysis revealed that compared to those with normal WC, the participants having declined WC were at a decreased risk of abnormal FBG (odds ratio [OR] = 0.911, 95% confidence interval [95%CI]: 0.867 – 0.958) but the participants having elevated WC were at an increased risk of abnormal FBG (OR = 1.070, 95%CI: 1.022 – 1.120); the results also showed that every one centimeter increase in baseline WC and one unit increase in baseline BMI were associated with 0.011 mmol/L (β = 0.027, 95%CI: 0.013 – 0.041) and 0.027 mmol/L (β = 0.027, 95%CI: 0.013 – 0.041) increase in FBG. Further subgroup analysis demonstrated that every one centimeter increase in baseline WC was associated with 0.011/0.010, 0.014/0.005, and 0.007/0.021 mmol/L increase in FBG for the participants being male/female, living in urban/rural regions, and with/without diabetes (all P < 0.001); while, every one unit increase in baseline BMI was associated with 0.030, 0.026/0.024, and 0.031 mmol/L increase in FBG for the participants being female, living in urban/rural regions, and having diabetes, respectively (all P < 0.05). ConclusionThere are positively linear associations of changes in WC and BMI with the variation of FBG among middle aged and elderly populations with high cardiovascular risk.

Abstract The carbon emissions trading system (CETS) is a helpful policy instrument for separating carbon emissions from economic expansion, and it significantly impacts energy efficiency (EE). This study uses 30 Chinese provinces from 2007 to 2020 as its research samples, and classifies energy efficiency into single-factor energy efficiency (SFE) and total-factor energy efficiency (TFE), using the difference-in-differences model to examine the effect and mechanism of the CETS on EE. As an additional tool to assess the efficacy of the CETS, the corresponding evolution of the rebound effect of energy-related carbon emissions (RECE) is also calculated. This study shows that the CETS can significantly improve EE in China's pilot provinces. The influence mechanism indicates that the effect of the CETS on EE is influenced by the level of government governance, green innovation, and industrial structure optimization. Further study finds that after the CETS was carried out, the RECE in pilot provinces was higher than that in non-pilot provinces, and 31.4% of carbon emissions reduced by EE improvement rebounded. Therefore, the CETS has yet to realize its full carbon reduction potential. The study offers specific policy proposals for the enhancement of China's CETS in light of the aforementioned findings.

As a major coal-producing area, the Shanxi section of the Yellow River Basin has been significantly affected by coal mining activities in the local ecological environment. Therefore, an in-depth study of the ecological evolution in this region holds great scientific significance and practical value. In this study, the Shanxi section of the Yellow River Basin, including its planned coal mining area, was selected as the research subject. An improved remotely sensed ecological index model (NRSEI) integrating the remotely sensed ecological index (RSEI) and net primary productivity (NPP) of vegetation was constructed utilizing the Google Earth Engine platform. The NRSEI time series data from 2003 to 2022 were calculated, and the Sen + Mann–Kendall analysis method was employed to comprehensively assess the ecological environment quality and its evolutionary trends in the study area. The findings in this paper indicate the following data: (1) The contribution of the first principal component of the NRSEI model is more than 70%, and the average correlation coefficient is higher than 0.79. The model effectively integrates the information of multiple ecological indicators and enhances the applicability of regional ecological environment evaluation. (2) Between 2003 and 2022, the ecological environment quality in the Shanxi section of the Yellow River Basin showed an overall upward trend, with the average NRSEI value experiencing phases of fluctuation, increase, decline, and stabilization. The NRSEI values in non-coal mining areas consistently remained higher than those in coal mining areas. (3) Over 60% of the areas have improved ecological conditions, especially in coal mining areas. (4) The impact of coal mining on the ecological environment is significant within a 6 km radius, while the effects gradually diminish in the 6 to 10 km range. This study not only offers a reliable methodology for evaluating ecological environment quality on a large scale and over a long time series but also holds significant guiding value for the ecological restoration and sustainable development of the Shanxi section of the Yellow River Basin and its coal mining area.

Atopic dermatitis (AD) is a common inflammatory skin disease that significantly affects patients’ quality of life. This study aimed to evaluate the therapeutic potential of cell-free fat extract (FE) in AD. In this study, the therapeutic effect of DNCB-induced AD mouse models was investigated. Dermatitis scores and transepidermal water loss (TEWL) were recorded to evaluate the severity of dermatitis. Histological analysis and cytokines measurement were conducted to assess the therapeutic effect. Additionally, the ability of FE to protect cells from ROS-induced damage and its ROS scavenging capacity both in vitro and in vivo were investigated. Furthermore, we performed Th1/2 cell differentiation with and without FE to elucidate the underlying therapeutic mechanism. FE reduced apoptosis and cell death of HaCat cells exposed to oxidative stress. Moreover, FE exhibited concentration-dependent antioxidant activity and scavenged ROS both in vitro and vivo. Treatment with FE alleviated AD symptoms in mice, as evidenced by improved TEWL, restored epidermis thickness, reduced mast cell infiltration, decreased DNA oxidative damage and lower inflammatory cytokines like IFN-γ, IL-4, and IL-13. FE also inhibited the differentiation of Th2 cells in vitro. Our findings indicate that FE regulates oxidative stress and mitigates Th2-mediated inflammation in atopic dermatitis by inhibiting Th2 cell differentiation, suggesting that FE has the potential as a future treatment option for AD.

Stem cell-based therapies exhibit considerable promise in the treatment of diabetes and its complications. Extensive research has been dedicated to elucidate the characteristics and potential applications of adipose-derived stromal/stem cells (ASCs). Three-dimensional (3D) culture, characterized by rapid advancements, holds promise for efficacious treatment of diabetes and its complications. Notably, 3D cultured ASCs manifest enhanced cellular properties and functions compared to traditional monolayer-culture. In this review, the factors influencing the biological functions of ASCs during culture are summarized. Additionally, the effects of 3D cultured techniques on cellular properties compared to two-dimensional culture is described. Furthermore, the therapeutic potential of 3D cultured ASCs in diabetes and its complications are discussed to provide insights for future research.

IntroductionAcetaldehyde dehydrogenase 2 (ALDH2) had reported as a prominent role in the development of cardiometabolic diseases among Asians. Our study aims to investigate the relationship between ALDH2 polymorphism and cardiometabolic risk factors in East Asian population.MethodWe searched databases of PubMed, Web of Science, and Embase updated to Oct 30th, 2023. We extracted data of BMI, Hypertension, SBP, DBP, T2DM, FBG, PPG, HbA1c, TG, TC, LDL-C and HDL-C.ResultIn total, 46 studies were finally included in our meta-analysis, containing, 54068 GG and, 36820 GA/AA participants. All outcomes related to blood pressure revealed significant results (hypertension OR=0.83 [0.80, 0.86]; SBP MD=-1.48 [-1.82, -1.14]; DBP MD=-1.09 [-1.58, -0.61]). FBG showed a significant difference (MD=-0.10 [-0.13, -0.07]), and the lipid resulted significantly in some outcomes (TG MD=-0.07 [-0.09, -0.04]; LDL-C MD=-0.04 [-0.05, -0.02]). As for subgroups analysis, we found that in populations without severe cardiac-cerebral vascular diseases (CCVDs), GG demonstrated a significantly higher incidence of T2DM (T2DM OR=0.88 [0.79, 0.97]), while the trend was totally opposite in population with severe CCVDs (T2DM OR=1.29 [1.00, 1.66]) with significant subgroup differences.ConclusionOur updated meta-analysis demonstrated that ALDH2 rs671 GG populations had significantly higher levels of BMI, blood pressure, FBG, TG, LDL-C and higher risk of hypertension than GA/AA populations. Besides, to the best of our knowledge, we first report GG had a higher risk of T2DM in population without severe CCVDs, and GA/AA had a higher risk of T2DM in population with severe CCVDs.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023389242.

ObjectiveThrombocytopenia is commonly associated with infectious diseases and serves as an indicator of disease severity. However, reports on its manifestation in conjunction with Klebsiella pneumoniae liver abscess (KPLA) are scarce. The present study sought to elucidate the correlation between thrombocytopenia and KPLA severity and delve into the etiological factors contributing to the incidence of thrombocytopenia.Materials and methodsA retrospective analysis of the clinical data from patients with KPLA admitted between June 2012 and June 2023 was performed. Baseline characteristics, biochemical assessments, therapeutic interventions, complications, and clinical outcomes were compared between patients with and without thrombocytopenia. To investigate the potential etiologies underlying thrombocytopenia, the association between platelet count reduction and thrombophlebitis was examined, with a particular focus on platelet consumption. Furthermore, bone marrow aspiration results were evaluated to assess platelet production anomalies.ResultsA total of 361 KPLA patients were included in the study, among whom 60 (17%) had concurrent thrombocytopenia. Those in the thrombocytopenia group exhibited significantly higher rates of thrombophlebitis (p = 0.042), extrahepatic metastatic infection (p = 0.01), septic shock (p = 0.024), admissions to the intensive care unit (p = 0.002), and in-hospital mortality (p = 0.045). Multivariate analysis revealed that thrombocytopenia (odds ratio, 2.125; 95% confidence interval, 1.114–4.056; p = 0.022) was independently associated with thrombophlebitis. Among the thrombocytopenic patients, eight underwent bone marrow aspiration, and six (75%) had impaired medullar platelet production. After treatment, 88.6% of thrombocytopenic patients (n = 47) demonstrated recovery in their platelet counts with a median recovery time of five days (interquartile range, 3–6 days).ConclusionsThrombocytopenia in patients with KPLA is indicative of increased disease severity. The underlying etiologies for thrombocytopenia may include impaired platelet production within the bone marrow and augmented peripheral platelet consumption as evidenced by the presence of thrombophlebitis.

ABSTRACTPorcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus with constantly emerging recombinant and mutant strains. Because of the high genetic diversity of PRRSV, current vaccines only provide partial protection against the infection of heterologous strains, which makes it a challenge for PRRSV prevention and control. Tubercidin is a naturally extracted compound with potential antiviral properties. However, whether tubercidin has anti-PRRSV ability is unknown. Our study found that tubercidin showed effective antiviral effects on PRRSV replication. In terms of mechanism, tubercidin suppressed PRRSV at the entry, replication, and release steps of the viral life cycle. Additionally, we demonstrated that tubercidin treatment promoted the activation of retinoic acid-inducible gene I and nuclear factor kappa-light-chain-enhancer of activated B cell signaling pathway, thus increasing the type I interferon and inflammatory cytokine expression. Furthermore, tubercidin restrained the viral non-structural protein 2 expression and viral dsRNA synthesis and ultimately inhibited PRRSV replication. Hence, our data showed that tubercidin is promising and has potential antiviral ability against PRRSV replication in vitro.IMPORTANCEPorcine reproductive and respiratory syndrome (PRRS) is one of the most important swine diseases, which causes huge economic loss worldwide. However, there is no effective therapeutic method for PRRS prevention and control. Here, we found that tubercidin, a naturally extracted adenosine analog, exhibited strong anti-porcine reproductive and respiratory syndrome virus (PRRSV) activity. Mechanically, tubercidin inhibited viral binding, replication, and release. Tubercidin suppressed PRRSV non-structural protein 2 expression, which is important for the formation of replication and transcription complex, leading to the block of viral RNA synthesis and PRRSV replication. Moreover, tubercidin could activate retinoic acid-inducible gene I/nuclear factor kappa-light-chain-enhancer of activated B cell innate immune signaling pathway and increased the expression of interferons and proinflammatory cytokines, which was the other way to inhibit PRRSV replication. Our work evaluated the potential value of tubercidin as an antiviral agent on PRRSV replication and provided a new way to prevent PRRSV replication in vitro.

Abstract Background The association between weight change during early adulthood and cardiometabolic diseases remains uncertain in Chinese population. Whether the association varies with comprehensive cardiovascular health (CVH) in midlife assessed by “Life’s Essential 8” has not been characterized. We aim to examine the associations of early adulthood weight change and midlife “Life’s Essential 8” CVH status with cardiometabolic outcomes in a Chinese cohort. Methods The study participants were from the China Cardiometabolic Disease and Cancer Cohort (4 C) Study. This analysis included 72,610 middle-aged and older participants followed for a median of 3.6 years. At baseline, the participants recalled body weight at age 20 and 40 years, and we calculated change in weight and BMI between 20 and 40 years of age. Health behaviors information in “Life’s Essential 8” was collected by questionnaire, and health factors were measured in the study center. During follow-up, we ascertained incident cardiovascular events based on medical records, and diagnosed incident diabetes according to the American Diabetes Association 2010 criteria. Results 72,610 study participants were included with a mean age of 56.0 ± 8.8 years and 29% of them were males. Weight gain of more than 10 kg between 20 and 40 years of age was associated with 22% increased risk of incident cardiovascular events (HR: 1.22; 95%CI: 1.04–1.43) and 38% increased risk of diabetes (HR: 1.38; 95%CI: 1.25–1.53) compared to stable weight. Besides, the association of weight gain more than 10 kg in early adulthood with cardiometabolic risk was even stronger in those with low CVH score in midlife (HR: 2.44; 95%CI: 2.01–2.97 for incident cardiovascular events; HR: 2.20; 95%CI: 1.90–2.55 for incident diabetes) or with few ideal cardiovascular health metrics in midlife. Conclusions Our study indicated that weight gain in early adulthood was associated with significantly increased risk of cardiometabolic diseases. And the association could be stronger in those with poor CVH profiles in midlife. These findings confirmed the significance of weight management during early adulthood and suggested that individuals who experienced substantial weight gain in early life should be encouraged to maintain good CVH status in Chinese population.

Abstract Background IOL fixation without capsular support presents challenges for surgeons. Although innovative techniques were developed to address subluxated IOLs, adjustable IOL fixation methods are seldom reported. We introduce a novel two-way adjustable double-knots intrascleral fixation combined with single sclerotomy looping technique for fixing intraocular lenses (IOL) or IOL-capsular bags. Methods A bent 30-gauge needle threaded with 8 − 0 polypropylene was introduced into the eye. A gripping forceps assisted the haptic looping. Two overhand knots were made with 8 − 0 polypropylene thread. The knots were incarcerated into a scleral tunnel made by a 30-gauge needle, with two ends of the thread left at each side of the tunnel. The IOL was adjusted to the premium position with adequate tension by pulling either end of the threads. The study included 19 eyes with aphakia, subluxated IOL-capsular bags, or subluxated crystalline lenses. The mean followed up period was 18.9 ± 7.1 months with evaluations of uncorrected visual acuity (UCVA), intraocular pressure, slit-lamp examination, and swept-source optical coherence tomography of the anterior segment. Results UCVA increased from 1.28 ± 0.74 at baseline to 0.44 ± 0.51 (logMAR) at final visit (P

Abstract Wound healing is one of the major global health concerns in diabetic patients. Overactivation of proinflammatory M1 macrophages could lead to delayed wound healing in diabetes. 4-octyl itaconate (4OI), a derivative of the metabolite itaconate, has aroused growing interest recently on account of its excellent anti-inflammatory properties. Cell membrane coating is widely regarded as a novel biomimetic strategy to deliver drugs and inherit properties derived from source cells for biomedical applications. Herein, we fused induced pluripotent stem cell-derived endothelial cell (iEC) membrane together with M1 type macrophage membrane to construct a hybrid membrane (iEC-M) camouflaged 4OI nanovesicles (4OI@iEC-M). Furthermore, bioinspired nanovesicles 4OI@iEC-M are incorporated into the injectable, multifunctional gelatin methacryloyl hydrogels for diabetic wound repair and regeneration. In our study, bioinspired nanovesicles could achieve dual-targeted deliver of 4OI into both M1 macrophages and endothelial cells, thereby promoting macrophage polarization and protecting endothelial cells. With the synergistically anti-inflammatory and immunoregulative effects, the bioinspired nanovesicles-loaded hydrogels could facilitate neovascularization and exhibit superior diabetic wound repair and regeneration. Taken together, this study might provide a novel strategy to facilitate diabetic wound healing, thereby reducing limb amputation and mortality of diabetes.

Abstract The transition from deep dormancy to seed germination is essential for the life cycle of plants, but how this process occurs in the gymnosperm Chinese yew (Taxus chinensis var mairei), the natural source of the anticancer drug paclitaxel, remains unclear. Herein, we analyse the transcriptome, proteome, spatial metabolome, and spatial lipidome of the Chinese yew and present the multi-omics profiles of dormant and germinating seeds. Our results show that abscisic acid and gibberellic acid 12 homoeostasis is closely associated with gene transcription and protein translation, and the balance between these phytohormones thereby determines if seeds remain dormant or germinate. We find that an energy supply of carbohydrates from glycolysis and the TCA cycle feed into the pentose phosphate pathway during seed germination, and energy supplied from lipids are mainly derived from the lipolysis of triacylglycerols. Using mass spectrometry imaging, we demonstrate that the spatial distribution of plant hormones and phospholipids has a remarkable influence on embryo development. We also provide an atlas of the spatial distribution of paclitaxel C in Chinese yew seeds for the first time. The data from this study enable exploration of the germination mechanism of Chinese yew seeds across several omics levels.

Abstract Fertilization can be optimized and managed during the flue-cured tobacco growing period by studying the response of soil and microbial biomass stoichiometric characteristics to fertilization. In this study, we investigated the effect of compound fertilizers combined with microbial fertilizer treatments on the stoichiometric characteristics of the rhizosphere soil and the limitations of microbial resources during the flue-cured tobacco growing period. The results indicated that soil and microbial C:N:P varied greatly with the growing period. The effect of sampling time was usually greater than that of fertilization treatment, and microbial C:N:P did not vary with the soil resource stoichiometric ratio. The microbial metabolism of the tobacco-growing soil was limited by phosphorus after extending the growing period, and phosphorus limitation gradually increased from the root extension to the maturation periods but decreased at harvest. The rhizosphere soil microbial nitrogen and phosphorus limitations were mainly affected by soil water content, soil pH, microbial biomass carbon, and the ratio of microbial biomass carbon to microbial biomass phosphorus. Applying microbial fertilizer reduced phosphorus limitation. Therefore, applying microbial fertilizer regulated the limitation of microbial resources by affecting the soil and microbial biomass C:N:P in flue-cured tobacco rhizosphere soils.

PurposeTo assess the retinal vasculature changes quantitatively using wide-field optical coherence tomography angiography (OCTA) in systemic lupus erythematosus (SLE), and explore its correlation with systemic clinical features.DesignProspective, cross-sectional, observational study.Participants and controlsPatients with SLE who presented to the Ophthalmology Department of Peking Union Medical College Hospital from November 2022 to April 2023 were collected. The subjects were divided into retinopathy and without retinopathy groups. Age and gender-matched healthy subjects were selected as controls.MethodsPatients with SLE and control subjects were imaged with 24×20 mm OCTA scans centered on the fovea and 6×6 mm OCTA scans centered on the optic disc. The sub-layers of OCTA images were stratified by the built-in software of the device and then the retinal thickness and vessel density were measured automatically. The characteristics of retinal OCTA parameters of SLE and its correlation with systemic clinical indicators of patients without retinopathy were analyzed.Main outcome measuresOCTA parameters, visual acuity, intraocular pressure, and systemic clinical indicators of patients such as disease activity index, autoimmune antibodies, and inflammatory marker levels were collected.ResultsA total of 102 SLE patients were included, 24 of which had retinopathy, and 78 had unaffected retina. Wide-field OCTA could effectively detect retinal vascular obstruction, non-perfusion area, and morphological abnormalities in patients with lupus retinopathy. SLE patients without retinopathy had significantly higher retinal superficial vessel density (SVD) in foveal (P=0.02), para-foveal temporal (P=0.01), nasal (P=0.01), peripheral foveal temporal (P=0.02), and inferior areas (P=0.02), as well as subregion temporal (P=0.01) and inferior areas (P=0.03) when compared with healthy controls (n=65 eyes from 65 participants). The area under curve (AUC) value of subregion inferior SVD combined parafoveal temporal SVD was up to 0.70. There was a significantly positive correlation between SVD and disease activity in SLE without retinopathy group. Patients with severe activity had the most significant increase in SVD.ConclusionWide-field OCTA can provide a relatively comprehensive assessment of the retinal vasculature in SLE. In the absence of pathological changes of the retina, the SVD was significantly increased and was positively correlated with the disease activity of SLE.

ObjectiveInsulin plays a central role in the regulation of energy and glucose homeostasis, and insulin resistance (IR) is widely considered as the “common soil” of a cluster of cardiometabolic disorders. Assessment of insulin sensitivity is very important in preventing and treating IR-related disease. This study aims to develop and validate machine learning (ML)-augmented algorithms for insulin sensitivity assessment in the community and primary care settings.MethodsWe analyzed the data of 9358 participants over 40 years old who participated in the population-based cohort of the Hubei center of the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals). Three non-ensemble algorithms and four ensemble algorithms were used to develop the models with 70 non-laboratory variables for the community and 87 (70 non-laboratory and 17 laboratory) variables for the primary care settings to screen the classifier of the state-of-the-art. The models with the best performance were further streamlined using top-ranked 5, 8, 10, 13, 15, and 20 features. Performances of these ML models were evaluated using the area under the receiver operating characteristic curve (AUROC), the area under the precision-recall curve (AUPR), and the Brier score. The Shapley additive explanation (SHAP) analysis was employed to evaluate the importance of features and interpret the models.ResultsThe LightGBM models developed for the community (AUROC 0.794, AUPR 0.575, Brier score 0.145) and primary care settings (AUROC 0.867, AUPR 0.705, Brier score 0.119) achieved higher performance than the models constructed by the other six algorithms. The streamlined LightGBM models for the community (AUROC 0.791, AUPR 0.563, Brier score 0.146) and primary care settings (AUROC 0.863, AUPR 0.692, Brier score 0.124) using the 20 top-ranked variables also showed excellent performance. SHAP analysis indicated that the top-ranked features included fasting plasma glucose (FPG), waist circumference (WC), body mass index (BMI), triglycerides (TG), gender, waist-to-height ratio (WHtR), the number of daughters born, resting pulse rate (RPR), etc.ConclusionThe ML models using the LightGBM algorithm are efficient to predict insulin sensitivity in the community and primary care settings accurately and might potentially become an efficient and practical tool for insulin sensitivity assessment in these settings.

The Chinese mitten crab (Eriocheir sinensis) is an important commercial species in China. E. sinensis is typically farmed in rice-crab symbiosis, as an important ecological farming model. However, E. sinensis is often exposed to a high ammonia environment due to the application of nitrogen fertilizers essential for rice growth. We investigated the molecular mechanisms in the gills of E. sinensis exposed to high ammonia at transcriptional and histological levels. We randomly assigned E. sinensis to two groups (control group, CG; ammonia stress group, AG), and gill samples were excised from the CG and AG groups for histopathological and transcriptome analyses. The histopathological evaluation revealed that ammonia stress damaged the gills of E. sinensis. The transcriptome analysis showed that some essential genes, including Xanthine dehydrogenase (XDH), Ubiquitin C-terminal hydrolase-L3 (UCHL3), O-linked N-acetylglucosamine transferase (OGT), Cathepsin B (CTSB), and Ubiquitin-conjugating enzyme E2 W (UBE2W) changed significantly during ammonia exposure. These genes are related to ammonia detoxification, the immune response, and apoptosis. This study demonstrated the molecular response mechanism of E. sinensis gills to ammonia stress at the transcriptional and histological levels. This study provides insight for further study on the molecular mechanism of ammonia stress in crustaceans and supplies technical support for rice crab symbiosis.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by abnormal cell proliferation, apoptosis repression and myeloid differentiation blockade of hematopoietic stem/progenitor cells. Developing and identifying novel therapeutic agents to reverse the pathological processes of AML are of great significance. Here in this study, we found that a fungus-derived histone deacetylase inhibitor, Apicidin, presents promising therapeutic effect on AML by inhibiting cell proliferation, facilitating apoptosis and inducing myeloid differentiation of AML cells. Mechanistic investigation revealed that QPCT is identified as a potential downstream target of Apicidin, which exhibits significantly decreased expression in AML samples compared with the normal controls and is remarkably up-regulated in AML cells upon Apicidin management. Functional study and rescue assay demonstrated that QPCT depletion further promotes cell proliferation, inhibits apoptosis and impairs myeloid differentiation of AML cells, alleviating the anti-leukemic effect of Apicidin on AML. Our findings not only provide novel therapeutic target for AML, but also lay theoretical and experimental foundation for the clinical application of Apicidin in AML patients.

Abstract Objective In this study, differentially expressed metabolites of vascular endothelial cells were examined to further understand the metabolic regulation of ischemic injury by untargeted metabolomics. Method Human umbilical vein endothelial cells (HUVECs) were selected to construct an ischemia model using oxygen–glucose deprivation (OGD) and 0, 3, 6, and 9 h of treatment. After that, cell survival levels were determined by CCK8 detection. Flow cytometry, ROS detection, JC-1 detection, and western blotting were used to measure apoptosis and oxidative stress in cells. Then, combined with UPLC Orbitrap/MS, we verified the impacted metabolism pathways by western blotting and RT‒PCR. Results CCK8 assays showed that the survival of HUVECs was decreased with OGD treatment. Flow cytometry and the expression of cleaved caspase 3 showed that the apoptosis levels of HUVECs increased following OGD treatment. The ROS and JC-1 results further suggested that oxidative stress injury was aggravated. Then, combined with the heatmap, KEGG and IPA, we found that arginine metabolism was differentially altered during different periods of OGD treatment. Furthermore, the expression of four arginine metabolism-related proteins, ASS1, ARG2, ODC1 and SAT1, was found to change during treatment. Conclusion Arginine metabolism pathway-related proteins were significantly altered by OGD treatment, which suggests that they may have a potential role in ischemic injury.

Abstract Background The association between remnant cholesterol (RC) and diabetes remains unclear because of limited study and data. This study attempted to explore the association between RC and diabetes in a large sample, multicenter general population. Methods The current study included 36 684 participants from eight provinces across China. Subjects were quartered according to the RC quartile. Logistic regression analysis was used to evaluate the association between RC and diabetes. Results After adjusting for potential confounding factors, RC was still significantly associated with diabetes (Q4: odds ratio [OR]:1.147, 95% confidence interval [CI]: 1.049–1.254, p = .003). In addition, RC and diabetes were still significantly associated when triglycerides (TG) were

To address current ecological issues and a lack of historical preservation in Beijing’s waterfront, it has become necessary to establish an urban design project that optimizes these aspects. This study focuses on “Beijing’s Waterfront Overall Urban Design,” a project that integrates government requirements with Beijing’s waterfront urban design characteristics and problems to establish an urban layer system from two dimensions: historical and ecological. It explores how the urban layer system can be applied to Beijing’s overall waterfront urban design, from investigation to evaluation, analysis, visualization, and strategy development. First, an urban layer system for Beijing’s waterfront was established from a historical perspective, based on urban setting and construction stages and space utilization, referring to the literature and field surveys. The evolution of urban layers of waterbodies, the water–city relationship, and water functions was systematically analyzed. Second, an urban layer system was established for the ecological dimension of Beijing’s waterfront based on a literature review, expert interviews, and analytic hierarchy process methods. It included four urban layers: waterbody, greening, shoreline, and ecological function. The quality of the ecological urban design of 54 waterfront reaches in Beijing was evaluated using questionnaires and field surveys. Third, a series of urban layer maps was generated using the mapping method. Finally, urban design strategies were developed based on the combined historical and ecological characteristics and problems of Beijing’s waterfront. The results of this study and the concept of an urban layer system for waterfront urban design can benefit waterfront urban design projects and future studies.

The spatial equalization of medical facilities can alleviate the wastage of medical resources and improve the efficiency of medical services. Therefore, it is necessary to carry out spatially balanced planning and assessment of medical facilities in cities. Existing studies on the balanced planning, design, and evaluation of medical facilities have been conducted from the perspective of hospital buildings in terms of spatial utilization efficiency, service satisfaction, and their physical environment on one hand, and from the perspective of regional planning of medical facilities in terms of spatial accessibility to medical facilities and the suitability of medical facilities to the social environment on the other hand. This study hopes to break down the boundaries of each perspective and effectively integrate the architecture, planning, and social well-being of medical facilities, taking spatial equilibrium as the core, in order to establish a spatial equilibrium system for medical facilities and achieve a spatial equilibrium-based assessment of the current state of medical facilities. First, the factors influencing the spatial equilibrium of hospital buildings with the support of the system and environment of hospital buildings are determined. Second, the indicators of the spatial equilibrium of hospital buildings are extracted through the consideration of influencing factors, and the indicator weights are determined by discussing the degree to which they contribute to the influence of the operation of hospital building spatial equilibrium systems, thus forming a system of equilibrium indicators for hospital buildings. Finally, a spatial equilibrium evaluation model for hospital buildings is established to assess the effects of equilibrium. The results obtained in this study provide insights into the regional planning of medical facilities and the design of hospital buildings.

PurposeThis study aims to examine scleral thickness in patients with systemic lupus erythematosus (SLE) without clinically evident scleritis and episcleritis, utilizing swept-source optical coherence tomography (SS-OCT).MethodsThis cross-sectional single center study compared scleral thickness (Nasal scleral thickness 1mm, 2mm, 3mm, 6mm from scleral spur; Temporal scleral thickness 1mm, 2mm, 3mm, 6mm from scleral spur) in 73 SLE patients without clinically evident scleritis and episcleritis and 48 healthy volunteers with SS-OCT. Further, we investigated the correlation between scleral thickness in SLE patients and various parameters including laboratory markers, disease duration, disease activity, and organ involvement.ResultsAcross all measured sites (nasal scleral thickness at distances of 1mm, 2mm, 3mm, and 6mm from the scleral spur, and temporal scleral thickness at the same distances), the scleral thickness in the SLE group was significantly greater than that in the control group (all p-values

Background Low vitamin D status has been linked to an increased risk for various inflammatory diseases. Conflicting results have been reported regarding chronic obstructive pulmonary disease (COPD). This study aims to investigate the associations of serum 25-hydroxyvitamin D (25(OH)D) concentrations with COPD risk and survival.Methods We included 403 648 participants with serum 25(OH)D measurements and free of COPD at baseline from UK Biobank. Follow-up was until 30 September 2021. Multivariable-adjusted cox regression models were applied to estimate HRs and 95% CIs for the associations of season-standardised 25(OH)D concentrations with COPD risk and survival. The restricted cubic splines were used to assess dose–response relationship. Kaplan-Meier estimation was used to create graphs of the survival curves.Results During a median follow-up of 12.3 (IQR: 11.4–13.2) years, 11 008 cases of COPD were recorded. We observed a non-linear inverse association between 25(OH)D concentrations and COPD risk. Compared with participants in the fourth quintile of 25(OH)D, those in the lowest quintile were associated with a 23% higher risk (HR, 1.23; 95% CI, 1.16 to 1.31). Stronger associations were observed for the risk in men and current smokers (Both p for interaction

The prosperity of deep learning has revolutionized many machine learning tasks (such as image recognition, natural language processing, etc.). With the widespread use of autonomous sensor networks, the Internet of Things, and crowd sourcing to monitor real-world processes, the volume, diversity, and veracity of spatial-temporal data are expanding rapidly. However, traditional methods have their limitation in coping with spatial-temporal dependencies, which either incorporate too much data from weakly connected locations or ignore the relationships between those interrelated but geographically separated regions. In this paper, a novel deep learning model (termed RF-GWN) is proposed by combining Random Forest (RF) and Graph WaveNet (GWN). In RF-GWN, a new adaptive weight matrix is formulated by combining Variable Importance Measure (VIM) of RF with the long time series feature extraction ability of GWN in order to capture potential spatial dependencies and extract long-term dependencies from the input data. Furthermore, two experiments are conducted on two real-world datasets with the purpose of predicting traffic flow and groundwater level. Baseline models are implemented by Diffusion Convolutional Recurrent Neural Network (DCRNN), Spatial-Temporal GCN (ST-GCN), and GWN to verify the effectiveness of the RF-GWN. The Root Mean Square Error (RMSE), Mean Absolute Error (MAE), and Mean Absolute Percentage Error (MAPE) are selected as performance criteria. The results show that the proposed model can better capture the spatial-temporal relationships, the prediction performance on the METR-LA dataset is slightly improved, and the index of the prediction task on the PEMS-BAY dataset is significantly improved. These improvements are extended to the groundwater dataset, which can effectively improve the prediction accuracy. Thus, the applicability and effectiveness of the proposed model RF-GWN in both traffic flow and groundwater level prediction are demonstrated.

Abstract Background The association between the Chinese Visceral Adiposity Index (CVAI) and urinary albumin to creatinine ratio (UACR) has not been illustrated. The current study aimed to investigate the association between CVAI and UACR and to compare the discriminative power of CVAI, triglyceride, body mass index (BMI), waist circumference (WC), and waist‐to‐hip ratio (WHR) with UACR in the Chinese community population. Methods This study included 34 732 participants from the REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study. Binary logistic regression analyses were performed to detect the association between CVAI, triglyceride, BMI, WC, WHR and UACR. Results Binary logistic regression analysis showed that, after adjusting for potential confounders, in women, CVAI (odds ratio [OR]:1.16, 95% confidence interval [CI]: 1.01–1.34) and triglyceride (OR: 1.18, 95% CI: 1.04–1.33) were associated with UACR, whereas BMI, WC, and WHR were not associated with UACR; in men, CVAI (OR: 1.24, 95% CI: 1.02–1.50), WC (OR: 1.21, 95% CI 1.00–1.48), and triglycerides (OR: 1.18, 95% CI 0.97–1.44) were associated with UACR, whereas BMI and WHR were not associated with UACR. Stratified analysis showed that the correlation between CVAI and UACR was stronger in the population with 5.6 ≤ fasting blood glucose (FBG)

Abstract Background Evidence regarding the impact of education on diabetes risk is scarce in developing countries. We aimed to explore the association between education and diabetes within a large population in China and to identify the possible mediators between them. Methods Information on educational level and lifestyle factors was collected through questionnaires. Diabetes was diagnosed from self‐report and biochemical measurements. A structural equation model was constructed to quantify the mediation effect of each mediator. Results Compared with their least educated counterparts, men with college education had a higher risk of diabetes (odds ratio [OR] 1.19; 95% confidence interval [CI], 1.12–1.27), while college‐educated women were less likely to have diabetes (OR 0.77; 95% CI, 0.73–0.82). Obesity was the strongest mediator in both genders (proportion of mediation: 11.6% in men and 23.9% in women), and its association with education was positive in men (β[SE] 0.0387 [0.0037]) and negative in women (β[SE] −0.0824 [0.0030]). Taken together, all behavioral factors explained 12.4% of the excess risk of diabetes in men and 33.3% in women. Conclusions In a general Chinese population, the association between education level and diabetes was positive in men but negative in women. Obesity was the major mediator underlying the education disparities of diabetes risk, with a stronger mediation effect among women.

Abstract Background Aphis gossypii Glover (Hemiptera: Aphididae), a worldwide polyphagous phloem-feeding agricultural pest, has three wing morphs (winged parthenogenetic female, gynopara, and male) in the life cycle. The exclusive males could fly from summer hosts to winter hosts, which are essential for gene exchanges of cotton aphid populations from different hosts or regions. However, the molecular mechanism of wing differentiation of male in A. gossypii remains unclear. Results Morphological observation of male A. gossypii showed that there is no distinct difference in the external morphologies of the 1st and 2nd instar nymphs. The obvious differentiation of wing buds started in the 3rd instar nymph and was visible via naked eyes in the 4th instar nymphal stage, then adult male emerged with full wings. According to morphological dynamic changes, the development of wings in males were divided into four stages: preliminary stage (the 1st instar to 2nd instar), prophase (the 3rd instar), metaphase (the 4th instar), anaphase (the 5th instar). Results of feeding behavior monitoring via EPG (electrical penetration graph) technology indicated that although the male cotton aphids had strong desire to feed (longer duration of C 55.24%, F 5.05% and Pd waves 2.56%), its feeding efficiency to summer host cotton was low (shorter E1 3.56% and E2 waves 2.63%). Dynamic transcriptome analysis of male aphid at 5 different developmental periods showed that in the 3rd instar nymph, the number of up-regulated DEGs was significant increased, and time-course gene transcriptional pattern analyses results also showed that numerous genes categorized in clusters 3, 5, and 8 had the highest expressed levels, which were consistent with morphological changes of wing buds. These results indicate that the 3rd instar nymph is the critical stage of wing bud differentiation in males. Furthermore, through pathway enrichment analysis of DEGs and WGCNA, it revealed that the neuroactive ligand-receptor interaction, Ras signaling pathway, dopaminergic synapse, circadian entrainment and the corresponding hub genes of PLK1, BUB1, SMC2, TUBG, ASPM, the kinesin family members (KIF23, KIF20, KIF18-19) and the novel subfamily of serine/threonine (Aurora kinase A and Aurora kinase B) probably played an important role in the critical stage of wing bud differentiation. Conclusion This study explored morphological changes and genes transcriptional dynamics males in cotton aphid, revealed the phenomenon of low feeding efficiency of winged males on summer host cotton, and identified key signaling pathways and potential hub genes potentially involved in wing bud differentiation of male in A. gossypii.