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In order to explore the potential application of oxygenated fuels, polyoxymethylene dimethyl ethers (PODE), as an alternative fuel for marine diesel engines, the fuel combustion performance and gas emission characteristics of pure diesel oil, diesel-blended PODE, and pure PODE were tested on a marine diesel engine under different running conditions. The experimental results indicate that oxygen consumption can be reduced by diesel-blended PODE and pure PODE. The in-cylinder pressure and exothermic curve were consistent with the trend of diesel oil. Also, the ignition delay of diesel-blended PODE and pure PODE decreased, and the diffusion rate was accelerated, which helped to improve the combustion performance of diesel engines. Diesel blended PODE and pure PODE reduced the particulate matter (PM) emissions by up to 56.9% and 86.8%, respectively, and CO emissions by up to 51.1% and 56.3%, respectively. NOx emissions were gradually decreased with engine load. CO2 emissions were slightly increased, and the effective fuel consumption was increased up to 48% and 132%, respectively. It was shown that PODE could provide comparable power in a marine diesel engine and improve the fuel combustion and gas emission of the engine as a clean alternative fuel for marine diesel engines.

Zhe-Yu Yang,1,2 Wei-Liang Chen2– 4 1Department of General Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China; 2Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China; 3Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China; 4Department of Biochemistry, National Defense Medical Center, Taiwan, Republic of ChinaCorrespondence: Wei-Liang ChenDivision of Geriatric Medicine, Department of Family Medicine, Tri-Service General Hospital, National Defense Medical Center, Number 325, Section 2, Chang-gong Road, Nei-Hu District, 114, Taipei, TaiwanTel +886-2-87923311 ext. 16567Fax +886-2-87927057Email weiliang0508@gmail.comObjective: Sarcopenic obesity is an emerging geriatric syndrome among elderly individuals. Studies revealed a complicated pathogenesis between sarcopenia and obesity. Leptin, a proinflammatory adipokine, has been implicated in the mechanism of sarcopenic obesity. This study investigated the relationship between serum leptin level and sarcopenic obesity.Methods: The study included 4063 participants aged 60 years and older from the NHANES III database. Sarcopenia was defined as a skeletal muscle index (SMI) less than one standard deviation below the young adult value. Obesity was defined as a body mass index (BMIF) over 30 kg/m2. Multivariate regression analysis was performed to examine the association between serum leptin level and sarcopenic obesity.Results: In adjusted models, serum leptin level was positively correlated with BMI (β: 1.33, p value < 0.001) and negatively correlated with SMI (β: − 0.091, p value = 0.001). A significant association between serum leptin level and sarcopenic obesity was found in multivariate analysis (β: 4.011, p value=0.014).Conclusion: Our study demonstrated that serum leptin level was related to an increased risk of sarcopenic obesity. This epidemiologic finding suggests that leptin may play a role in sarcopenic obesity.Keywords: serum leptin levels, sarcopenia, sarcopenic obesity

Jia-Yu Zhang,1,2 Jia Huang,2 Su-Ya Zhao,3 Xin Liu,4 Zhen-Cheng Xiong,5 Zhi-Ying Yang1,2 1Graduate School of Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of General Surgery, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 3Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 4Graduate School of Tianjin Medical University, Tianjin, 300041, People’s Republic of China; 5Institute of Medical Technology, Peking University Health Science Center, Beijing, 100029, People’s Republic of ChinaCorrespondence: Zhi-Ying YangDepartment of General Surgery, China-Japan Friendship Hospital, 2 Cherry Blossom East Street, Beijing, 100029, People’s Republic of ChinaEmail yangzhy@aliyun.comAim: In order to find the risk factors of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) according to the latest definition and grading system of International Study Group of Pancreatic Surgery (ISGPS) (version 2016) and propose a nomogram for predicting POPF.Methods: We conducted a retrospective analysis of 232 successive cases of PD performed at our hospital by the same operator from August 2012 to June 2020. POPF was diagnosed in accordance with the latest definition of pancreatic fistula from the ISGPS. The risk factors of POPF were analyzed by univariate and multivariate logistic regression analysis. A nomogram model to predict the risk of POPF was constructed based on significant factors.Results: There were 18 cases of POPF, accounting for 7.8% of the total. Among them, 17 cases were classified into ISGPF grade B and 1 case was classified into ISGPF grade C. In addition, 35 cases were classified into biochemical leak. Univariate and multivariate analysis showed that hypertension, non-diabetes, no history of abdominal surgery, antecolic gastrojejunostomy and soft pancreas were independent risk factors of POPF. Based on significant factors, a nomogram is plotted to predict the risk of POPF. The C-index of this nomogram to assess prediction accuracy was 0.916 (P < 0.001) indicating good prediction performance.Conclusion: Hypertension, non-diabetes, no history of abdominal surgery, antecolic gastrojejunostomy and soft pancreas were independent risk factors of POPF. Meanwhile, a nomogram for predicting POPF with good test performance and discriminatory capacity was constituted.Keywords: pancreaticoduodenectomy, pancreatic fistula, International Study Group of Pancreatic Surgery, prediction model

Jia-Yu Zhang,1 Jia Huang,2 Zhi-Ying Yang1,2 1Graduate School of Peking Union Medical College, Beijing 100029, People’s Republic of China; 2Department of General Surgery, China-Japan Friendship Hospital, Beijing 100029, People’s Republic of ChinaCorrespondence: Zhi-Ying YangDepartment of General Surgery, China-Japan Friendship Hospital, 2 Cherry Blossom East Street, Beijing 100029, People’s Republic of ChinaEmail yangzhy@aliyun.comBackground: The accessory pancreatic duct (APD) is the main drainage duct of the dorsal pancreatic bud in the embryo and varies greatly during development. An APD fistula is a rare and easily neglected complication. In this case report, the first symptom of the patient was postoperative abdominal pain and fever. He was eventually diagnosed with accessory pancreatic fistula combined with duodenal fistula. Such a case has not been reported in the literature.Case Summary: A 66-year-old man was emergently hospitalized for abdominal pain. His preliminary diagnosis was perforation of the digestive tract. He developed fever and abdominal pain after emergency subtotal gastrectomy, followed by changes in the colour of the abdominal drainage fluid. An APD fistula and duodenal stump fistula were confirmed by drainage fluid amylase analysis, contrast fistulography and percutaneous transhepatic cholangial drainage (PTCD). After PTCD, nutritional management and drug treatment, the patient recovered well.Outcome: We found and successfully cured a case of accessory pancreatic duct fistula combined with duodenal stump fistula.Keywords: gastrointestinal perforation, abdominal pain, accessory pancreatic duct fistula, duodenal stump fistula, case report

Zheng-yan Yang,1,2 Fei Wang,1,2 Keke Lu,1,2 Yue-heng Li,1,2 Zhi Zhou1,2 1Department of Preventive Dentistry, The College of Stomatology, 2Department of Preventive Dentistry, The Affiliated Hospital of Stomatology, Chongqing Medical University, Chongqing, People's Republic of China Objective: To estimate the effect of arginine-containing desensitizing toothpaste on dentin hypersensitivity (DH). Methods: Databases including China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, China Biology Medicine disc, Wangfang Data, PubMed, Web of Science, and Cochrane Trials Register were searched, and Google was used as a supplementary tool to search for information through February 2014. Randomized controlled trials (RCTs) of the treatment of DH with arginine-containing toothpaste were included. Relevant information was extracted, and a quality evaluation was performed. Meta-analyses were performed using RevMan 5.2 software. Results: Eighteen RCTs with 1,423 patients were included. The results of the meta-analyses demonstrated that at days 0 and 3; weeks 2, 4, and 8; and more than 12 weeks, arginine-containing toothpaste led to significantly improved results on the tactile sensitivity test (standardized mean difference [SMD] =1.95, 95% confidence interval [CI] [1.14, 2.76]) and the air-blast test (SMD =-1.60, 95% CI [-2.14, -1.05]) at 4 weeks and the tactile sensitivity test (SMD =2.01, 95% CI [1.41, 2.61]) and the air-blast test (SMD =-1.41, 95% CI [-1.83, -0.98]) at 8 weeks compared to toothpastes containing other desensitizing components, thus indicating a superior therapeutic effect of arginine-containing desensitizing toothpaste. However, no significant differences between arginine-containing toothpaste and toothpastes containing other desensitizing components were observed in the air-blast test at days 0 and 3 and week 2 and in the tactile sensitivity and air-blast tests at more than 12 weeks. Conclusion: The current evidence indicates that arginine-containing toothpaste is effective for DH. However, further high-quality, large-sample RCTs are needed. Keywords: arginine-containing toothpastes, dentin hypersensitivity, meta-analysis, randomized controlled trial

Zhengyan Yang, Keke Lu, Fei Wang, Yueheng Li, Zhi ZhouDepartment of Preventive Dentistry, The College of Stomatology, The Affiliated Hospital of Stomatology, Chongqing Medical University, Chongqing, People’s Republic of ChinaOn page 19, the author’s names were listed incorrectly as Yang Zhengyan, Lu Keke, Wang Fei, Li Yueheng, Zhou Zhi.The correct names are Zhengyan Yang, Keke Lu, Fei Wang, Yueheng Li, Zhi Zhou.View the original paper here.

Background: The authors conducted a systematic review and meta-analysis to examine whether patients who had metastatic colorectal cancer (mCRC) with the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G13D mutation (an amino acid substitution at position 13 in KRAS from a glycine to an aspartic acid) and received cetuximab treatment had better clinical outcomes than patients who had mCRC tumors with KRAS codon 12 mutations.Methods: Relevant studies were identified by a search of MEDLINE, EMBASE, the Chinese Biomedical Database, and Wan Fang Digital Journals from inception to October 2011. The primary clinical outcomes included the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated by using fixed-effects or random-effects models according to heterogeneity between studies.Results: Ten studies were considered eligible that included 1487 patients with mCRC. Patients who had tumors with the KRAS p.G13D mutation had a significantly higher ORR (10 studies; RR, 1.642; 95% confidence interval [CI], 1.131-2.384), longer PFS (1 study; HR, 0.54; 95% CI, 0.36-0.81), and longer OS (1 study; HR, 0.52; 95% CI, 0.33-0.80) than patients who had tumors with KRAS codon 12 mutations. Compared with patients who had KRAS wild-type tumors, patients with the p.G13D mutation had a significantly lower ORR (9 studies; RR, 0.540; 95% CI, 0.381-0.765) and nonsignificantly shorter PFS (1 study; HR, 0.99; 95% CI, 0.68-1.45) and OS (1 study; HR, 1.01; 95% CI, 0.66-1.54).Conclusions: Patients who had mCRC with the KRAS p.G13D mutation appeared to benefit more from cetuximab than patients who had tumors with KRAS codon 12 mutations. However, because of the limited sample sizes in the current meta-analysis, these results should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Objective: Behavioral interventions have been shown to ameliorate the electroencephalogram (EEG) dynamics underlying the behavioral symptoms of autism spectrum disorder (ASD), while studies have also demonstrated that mirror neuron mu rhythm-based EEG neurofeedback training improves the behavioral functioning of individuals with ASD. This study aimed to test the effects of a wearable mu rhythm neurofeedback training system based on machine learning algorithms for children with autism., Methods: A randomized, placebo-controlled study was carried out on 60 participants aged 3 to 6 years who were diagnosed with autism, at two center-based intervention sites. The neurofeedback group received active mu rhythm neurofeedback training, while the control group received a sham neurofeedback training. Other behavioral intervention programs were similar between the two groups., Results: After 60 sessions of treatment, both groups showed significant improvements in several domains including language, social and problem behavior. The neurofeedback group showed significantly greater improvements in expressive language (P=0.013) and cognitive awareness (including joint attention, P=0.003) than did the placebo-controlled group., Conclusion: Artificial intelligence-powered wearable EEG neurofeedback, as a type of brain-computer interface application, is a promising assistive technology that can provide targeted intervention for the core brain mechanisms underlying ASD symptoms., Competing Interests: Conflict of Interest Statement. The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work., (© 2024. Huazhong University of Science and Technology.)

Surface-enhanced Raman spectroscopy (SERS) is a widely used analytical technique known for its high sensitivity and broad applicability. Despite its potential, SERS faces challenges related to detection sensitivity and reproducibility. This study proposes an innovative method to enhance SERS performance by employing water microdroplets as optical lenses on localized silver nanoparticle-decorated porous silicon (LocAg-PS) substrates. The hydrophobic nature of the LocAg-PS substrate not only ensures precise positioning of the microdroplet lenses on the silver nanoparticle grafted pad (AgNP pad) but also forms a plano-convex-like microdroplet lens for the focusing of the excitation laser and the collection of scattered light. Experimental results demonstrate that using microdroplet lenses enhances the SERS signal intensity and reproducibility, providing a rapid and cost-effective solution for advanced SERS analysis.

Ethnopharmacological Relevance: According to the theory of traditional Chinese medicine, Graves' disease (GD) is called 'Ying Bing', which is a kind of goiter. Haizao Yuhu decoction, originated from the medical book of the Ming Dynasty 'Waikezhengzong', is a classic Chinese herbal formula for the treatment of 'Ying Bing' for more than 400 years. Pingkang granules, modified from the Chinese herbal formula Haizao Yuhu decoction specialized in GD, has shown effectiveness in several single-centre studies. However, high-quality clinical evidence for the management of GD using Pingkang granules remains insufficient., Aim of the Study: To obtain high-quality medical evidence for the treatment of GD with Pingkang granules through randomized controlled clinical trial., Materials and Methods: A multicentre, randomized, double-blinded, placebo-controlled clinical trial was designed. A total of 186 patients with Graves' hyperthyroidism from five medical centers were randomly assigned to receive methimazole [MMI] and Pingkang granules placebo (group A), MMI and Pingkang granules (group B), or MMI placebo and Pingkang granules (group C) in a 1:1:1 ratio for 12 weeks. The primary clinical outcomes were serum free triiodothyronine (FT 3 ) and free thyroxine (FT 4 ) levels from baseline until the end of the research. Secondary clinical outcomes included serum thyrotrophin receptor antibody (TRAb) levels at 4- and 12-weeks post-intervention, thyroid volume, peak systolic velocity of the superior thyroid artery (STA-PSV), 39-item version of Thyroid-Related Patient-Reported Outcome (ThyPRO39) scores, and safety assessment included blood routine, liver and kidney function tests from baseline to the endpoint., Results: 150 patients were included in the full analysis set for efficacy analysis, including 48, 50, and 52 in groups A, B, and C, respectively. At the endpoint, three regimens significantly reduced serum FT 3 levels (group A, p=0.0027; group B, p < 0.0001; group C, p=0.0028) and FT 4 levels (group A, p < 0.0001; group B, p < 0.0001; group C, p < 0.0001), and the combination of MMI and Pingkang granules markedly reduced serum TRAb levels (p = 0.0014). The thyroid volume in group A was significantly larger than that at baseline at week 12 (p=0.0370), and there were no statistically significant differences in the thyroid volume among groups at week 4 (p=0.7485) and 12 (p=0.1333). STA-PSV values in group B were significantly higher than those in group A at week 4 (p=0.0409). The STA-PSV levels in groups A (p < 0.0001) and C (p=0.0025) were significantly lower than those at baseline at week 4, and STA-PSV levels in all groups were significantly lower than those at baseline at week 12 (group A, p=0.0095; group B, p=0.0138; group C, p=0.0423). Pingkang granule monotherapy significantly ameliorated symptoms related to hyperthyroidism (p < 0.0001), eye (p=0.0490), tiredness (p < 0.0001), cognition (p < 0.0001), depression (p=0.0478), and susceptibility (p=0.0052). No severe adverse events were reported in either group or three regimens showed similar safety., Conclusions: Pingkang granules significantly reduced serum FT 3 , FT 4 and STA-PSV levels, improved ThyPRO39 scores, and lowered serum TRAb levels when combined with MMI in patients with Grave's hyperthyroidism., Competing Interests: Declaration of competing interest This study was supported by the Project of Clinical Center (Traditional Chinese Medicine) of Endocrinology and Metabolism Disease of Shenyang (Grant Number SKF201875), the Traditional Chinese Medicine Clinical Discipline and Specialty Capacity Construction Project of Liaoning Province (Grant Number LNZYXZK201902). All the authors declare no conflicts of interest associated with this research and the study received no financial support that could have influenced its outcomes., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Ex vivo lung perfusion (EVLP) is a critical strategy to rehabilitate marginal donor lungs, thereby increasing lung transplantation (LTx) rates. Ischemia-reperfusion (I/R) injury inevitably occurs during LTx. Exploring the common mechanisms between EVLP and I/R may unveil new treatment targets to enhance LTx outcomes., Methods: We obtained datasets from the public Gene Expression Omnibus (GEO) for EVLP (GSE127055 and GSE127057) and I/R (GSE145989) processes. We performed analysis of differentially expressed genes (DEGs) and Gene Set Enrichment Analysis (GSEA). Mitochondrial genes were sourced from the MitoCarta 3.0 database. Hub mitochondrial-related DEGs (MitoDEGs) were identified using a combination of protein-protein interaction networks and machine learning methods, which were further validated in cell and mice models of EVLP., Results: GSEA analysis of DEGs following EVLP and I/R revealed significant inhibition of mitochondrial function pathways, encompassing mitochondrial central dogma, mtRNA metabolism, OXPHOS assembly factors, metals and cofactors, and heme synthesis and processing processes. Machine learning algorithms including Random Forest, LASSO, and XGBoost identified five downregulated genes (MTERF1, ACACA, COX15, OSGEPL1, and COQ9) as hub MitoDEGs for both EVLP and I/R processes. We confirmed the reduced expression of these hub MitoDEGs in endothelial cells during EVLP and observed mitochondrial damage in endothelial cells characterized by swollen morphology and cristae disappearance., Conclusions: Imbalance in mitochondrial homeostasis is a shared pathological process during EVLP and I/R-induced lung injury. The identified hub mitochondrial-related genes (MTERF1, ACACA, COX15, OSGEPL1, and COQ9) suggest promising therapeutic targets for lung injury during LTx. The downregulation of these genes indicates a significant disruption in mitochondrial function. This study provides potential mitochondrial-related therapeutic targets for I/R-induced lung injury and for donor lung repair during EVLP procedure in LTx., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Developing porous adsorbents for the complete sieving of propylene/propane mixtures represents an alternative method to energy-intensive cryogenic distillation processes. However, the similar physical properties of these molecules and the inherent trade-off among adsorption capacity, selectivity, diffusion kinetic and host-guest binding interactions in molecular sieving adsorbents makes their separation challenging. Here we report the separation of propylene/propane mixtures through a crystalline porous material (HAF-1) that features channels and shrinkage throats-the latter defined as narrower channels that connect the main channels and a molecular pocket-where the throat aperture is between the kinetic diameters of propylene and propane. Single-crystal X-ray diffraction and computational simulation reveal that the shrinkage channels and hanging molecular pockets are key to ensure high sieving efficiency and high propylene adsorption capacity. Dynamic breakthrough experiments show that HAF-1 enables the achievement of high-purity (≥99.7%) propylene with a productivity of 33.9 l kg -1 by just one adsorption-desorption circle from propylene/propane mixtures., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The rational installation of pharmacophores targeting HSP90 and LSD1 axes has achieved significant anti-cancer capacity in prostate and colorectal cancer. Among the series of hybrids, inhibitor 6 exhibited remarkable anti-proliferative activity against prostate cancer cell lines PC-3 and DU145, with GI 50 values of 0.24 and 0.30 μM, respectively. It demonstrated notable efficacy in combinatorial attack and cell death initiation towards apoptosis. The cell death process was mediated by PARP induction and γH2AX signaling, and was also characterized as caspase-dependent and Bcl-xL/Bax-independent. Notably, no difference in eye size or morphology was observed in the zebrafish treated with compound 6 compared to the reference group (AUY922). The profound treatment response in docetaxel-resistant PC-3 cells highlighted the dual inhibitory ability in improving docetaxel sensitivity. Additionally, at a minimum concentration of 1.25 μM, compound 6 effectively inhibited the growth of patient-derived colorectal cancer (CRC) organoids for up to 10 days in vitro. Together, the designed HSP90/LSD1 inhibitors present a novel route and significant clinical value for anti-cancer drug therapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jing-Ping Liou reports financial support was provided by National Science and Technology, Taiwan. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

The development of environmentally responsive biodegradable polymers is a promising solution for balancing the stability and degradability of biodegradable plastics. In this study, a commercial biodegradable polyester, poly(butylene adipate-co-butylene terephthalate) (PBAT), was used as the substrate and was synthetically modified with a small amount of anionic sodium 1-3-isophthalate-5-sulfonate (SIPA) to obtain the ionized random poly(butylene adipate-co-butylene terephthalate-co-butylene 5-sodiosulfoisophthalate) (PBATS). The introduction of the sodium sulfonate ionic group enhanced the mechanical and heat-resistant properties of the material, while significantly improving the hydrophilicity and water absorption of the copolyesters of PBATSs and endowing them with special pH-responsive degradation properties. Compared with PBAT, PBATS copolyesters could accelerate degradation in acidic or alkaline buffer solutions and natural seawater, while degradation was inhibited in neutral buffer solutions at pH 7.2. Degradation experiments in simulated gastric, intestinal, and body fluids revealed that the copolyester showed specific and rapid degradation in acidic gastric fluids. This environmentally-responsive degradable material greatly expands the special applications of biodegradable polyesters in the fields of environmental remediation and medical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Patients with gastrointestinal cancer have a higher risk of malnutrition and postoperative infection., Objective: To investigate the nutritional status of patients with gastrointestinal cancers and factors for postoperative infections., Method: Based on the nutritional risk status, 294 patients with gastrointestinal tumours were divided into a nutritional risk group and a non-nutritional risk group, and the differences between the two groups were compared., Results: Among the included patients, 128 were at preoperative nutritional risk (43.54%); there were significant differences between the two groups in terms of age (66.25 ± 11.73 vs. 58.36 ± 10.41 years, P < 0.001), percentage of gastric cancers (39.84% vs. 28.92%, P = 0.049), percentage of stage IV tumours (60.16% vs. 45.18%, P = 0.011), total protein (64.90 ± 6.82 vs. 67.21 ± 7.41 g/L, P = 0.007), albumin (38.32 ± 4.74 vs. 41.61 ± 5.10 g/L, P < 0.001) and haemoglobin (112.72 ± 22.63 vs. 125.11 ± 22.79 g/L, P < 0.001). Multivariate logistic regression analysis showed that risk factors for postoperative infections in patients included age ≥ 60 years (odds ratio [OR] = 2.266 95%CI = 1.357-4.134), Nutrition Risk Screening (NRS)-2002 score ≥ 3 (OR = 2.183, 95%CI = 1.218-4.102), alcohol history (OR = 2.505, 95%CI = 1.370-4.683), comorbid diabetes mellitus (OR = 2.110, 95%CI = 1.381-4.023) and surgical time ≥ 6 h (OR = 2.446, 95%CI = 1.359-4.758)., Conclusion: Patients with gastrointestinal cancers are at high incidence of preoperative nutritional risk, and those with an NRS-2002 score of > 3, history of alcohol consumption and surgical time of > 6 h have a higher risk of postoperative infections., Competing Interests: Declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki and approved by the Research Ethics Committee of General hospital of TISCO (ethical batch number: K202406), and informed consent was obtained from all participants. All methods were carried out in accordance with relevant guidelines and regulations. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Clinical trial number Not applicable., (© 2024. The Author(s).)

The maturation and installation of the active site metal cluster (FeMo-co, Fe 7 S 9 CMo- R -homocitrate) in Mo-dependent nitrogenase requires the protein product of the nifB gene for production of the FeS cluster precursor (NifB-co, [Fe 8 S 9 C]) and the action of the maturase complex composed of the protein products from the nifE and nifN genes. However, some putative diazotrophic bacteria, like Roseiflexus sp. RS-1, lack the nifEN genes, suggesting an alternative pathway for maturation of FeMo-co that does not require NifEN. In this study, the Roseiflexus NifH, NifB, and apo-NifDK proteins produced in Escherichia coli are shown to be sufficient for FeMo-co maturation and insertion into the NifDK protein to achieve active nitrogenase. The E. coli expressed NifDK RS contained P-clusters but was devoid of FeMo-co (referred to as apo-NifDK RS ). Apo-NifDK RS could be activated for N 2 reduction by addition of preformed FeMo-co. Further, it was found that apo-NifDK RS plus E. coli produced NifB RS and NifH RS were sufficient to yield active NifDK RS when incubated with the necessary substrates (homocitrate, molybdate, and S -adenosylmethionine [SAM]), demonstrating that these proteins can replace the need for NifEN in maturation of Mo-nitrogenase. The E. coli produced NifH RS and NifB RS proteins were independently shown to be functional. The reconstituted NifDK RS demonstrated reduction of N 2 , protons, and acetylene in ratios observed for Azotobacter vinelandii NifDK. These findings reveal a distinct NifEN-independent pathway for nitrogenase activation involving NifH RS , NifB RS , and apo-NifDK RS ., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objective: This study evaluates the risk of ocular adverse events (AEs) associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) using data from the FDA Adverse Event Reporting System (FAERS) and network pharmacology methods., Methods: FAERS data from 2004 to 2024 were analyzed for ocular AEs linked to GLP-1 RA treatments. Disproportionality analysis (Reporting Odds Ratio, ROR) was used to identify signals, and a drug-gene interaction network explored potential mechanisms., Results: Among 17,785,793 FAERS reports, semaglutide and lixisenatide were significantly associated with ocular AEs, with RORs of 1.25 (95% CI, 1.20-1.31) and 1.96 (95% CI, 1.70-2.27), respectively. Commonly reported AEs included blurred vision, visual impairment, and diabetic retinopathy, with some AEs occurring as early as 10 days after treatment initiation. Gene enrichment analysis highlighted potential links between GLP-1-related genes and ocular AEs., Conclusion: The widespread use of GLP-1 RAs has raised concerns regarding their ophthalmic safety. This study contributes new evidence from real-world data, suggesting that semaglutide and lixisenatide are associated with significant risks of ocular AEs. Further experimental studies are warranted to elucidate the underlying mechanisms and confirm these associations.

More than half of the global novel drugs are directly or indirectly derived from natural products (NPs) because of their better selectivity towards proteins. Traditional medicines perform multiple bioactivities through various NPs binding to drug targets, which highlights the opportunities of target discovery for drug development. However, detecting the binding relationship between NPs and targets remains challenging. Chemical proteomics, an interdisciplinary field of chemistry, proteomics, biology, and bioinformatics, has emerged as a potential approach for uncovering drug-target interactions. This review summarizes the principles and characteristics of the current widely applied chemical proteomic technologies, while delving into their latest applications in the target discovery of natural medicine. These endeavours demonstrate the potential of chemical proteomics for target discovery to supply dependable methodologies for the target elucidation of NPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cyclodehydrogenation is an important ring-formation reaction that can directly produce planar-conjugated carbon-based nanomaterials from nonplanar molecules. However, inherently high C-H bond energy necessitates a high temperature during dehydrogenation, and the ubiquity of C - H bonds in molecules and small differences in their bond energies hinder the selectivity of dehydrogenation. Here, we report a room-temperature cyclodehydrogenation reaction on Au(111) via radical addition of open-shell resonance structures and demonstrate that radical addition significantly decreases cyclodehydrogenation temperature and further improves the chemoselectivity of dehydrogenation. Using scanning tunneling microscopy and non-contact atomic force microscopy, we visualize the cascade reaction process involved in cyclodehydrogenation and determine atomic structures and molecular orbitals of the planar acetylene-linked oxa-nanographene products. The nonplanar intermediates observed during progression annealing, combined with density functional theory calculations, suggest that room-temperature cyclodehydrogenation involves the formation of transient radicals, intramolecular radical addition, and hydrogen elimination; and that the high chemoselectivity of cyclodehydrogenation arises from the reversibility and different thermodynamics of radical addition step., (© 2024. The Author(s).)

PFOA has garnered heightened scrutiny for its impact on denitrification, especially given its frequent detection in secondary effluent discharged from wastewater treatment plants. However, it is still unclear what potential risk PFOA release poses to a typical advanced treatment process, especially the sulfur-based autotrophic denitrification (SAD) process. In this study, different PFOA concentration were tested to explore their impact on denitrification kinetics and microbial dynamic responses of the SAD process. The results showed that an increase PFOA concentration from 0 to 1000 μg/L resulted in a decrease in nitrate removal rate from 9.52 to 7.73 mg-N/L·h. At the same time, it increased nitrite accumulation and N 2 O emission by 6.11 and 2.03 times, respectively. The inhibitory effect of PFOA on nitrate and nitrite reductase activity in the SAD process was linked to the observed fluctuations in nitrate and nitrite levels. It is noteworthy that nitrite reductase was more vulnerable to the influence of PFOA than nitrate reductase. Furthermore, PFOA showed a significant impact on gene expression and microbial community. Metabolic function prediction revealed a notable decrease in nitrogen metabolism and an increase in sulfur metabolism under PFOA exposure. This study highlights that PFOA has a considerable inhibitory effect on SAD performance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Cadmium (Cd) contamination in agricultural soil brings severe health risks through the dietary intake of Cd-polluted crops. The comprehensive role of pectin in lowering Cd accumulation is investigated through low Cd accumulated (L) and high Cd accumulated (H) cultivars of L. sativa. The significantly different Cd contents in the edible parts of two L. sativa cultivars are accomplished by different Cd transportations. The pectin is the dominant responsive cell wall component according to significantly increased uronic acid contents and the differential Cd absorption between unmodified and modified cell wall. The chemical structure characterization revealed the decreased methyl esterification in pectin under Cd treatment compared with control. Significantly brighter LM19 relative fluorescence density and 40.82% decreased methanol in the root pectin of L cultivar under Cd treatment (p < 0.05) supported that the de-methyl esterification of root pectin is more significant in L cultivar than in H cultivar. The pectin de-methyl esterification of L cultivar is achieved by the upregulation of pectin esterases and the downregulation of pectin esterase inhibitors under Cd treatments, which has facilitated the higher Cd-binding of pectin. Our findings provide deep insight into the differential Cd accumulation of L. sativa cultivars and contribute to the understanding the pollutant behaviors in plants., (© 2024 John Wiley & Sons Ltd.)

This study investigates the impact of polystyrene microplastics (PS-MPs) on the growth, immunity, oxidative stress, mitochondrial function, and intestinal health of Leuciscus waleckii (3.00 ± 0.02 g) juveniles over 8 weeks. Our findings indicate that exposure to PS-MPs negatively affected the growth of Leuciscus waleckii, resulting in digestive disturbances. Furthermore, PS-MPs triggered immune dysfunction and oxidative stress through the activation of the NF-κB pathway and suppression of the Nrf2 signaling cascade. PS-MPs damaged intestinal tissue and compromised the intestinal barrier. Additionally, mitochondrial homeostasis was disrupted, activating endogenous mitochondrial apoptotic pathways, ultimately leading to cell apoptosis. High-throughput 16S rRNA sequencing disclosed that PS-MPs provoked shifts in the intestinal microbiota. Mantel analysis indicates significant correlations between growth parameters and the activities of enzymes related to antioxidant defense, immunity, apoptosis, and mitochondria, as well as with the gut microbiota. In summary, our study reveals that PS-MPs induce intestinal inflammation and oxidative stress in Leuciscus waleckii by activating the NF-κB pathway and the intrinsic mitochondrial apoptotic pathway while repressing the Nrf2 signaling, ultimately leading to cellular apoptosis, mitochondrial dysfunction, intestinal microbiota imbalance, and growth inhibition., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cardiac ischaemia/reperfusion (I/R) impairs mitochondrial function, resulting in excessive oxidative stress and cardiomyocyte ferroptosis and death. Nuclear factor E2-related factor 2 (Nrf2) is a key regulator of redox homeostasis and has cardioprotective effects against various stresses. Here, we tested whether CBR-470-1, a noncovalent Nrf2 activator, can protect against cardiomyocyte death caused by I/R stress. Compared with vehicle treatment, the administration of CBR-470-1 (2 mg/kg) to mice significantly increased Nrf2 protein levels and ameliorated the infarct size, the I/R-induced decrease in cardiac contractile performance, and the I/R-induced increases in cell apoptosis, ROS levels, and inflammation. Consistently, the beneficial effects of CBR-470-1 on cardiomyocytes were verified in a hypoxia/reoxygenation (H/R) model in vitro, but this cardioprotection was dramatically attenuated by the GPX4 inhibitor RSL3. Mechanistically, CBR-470-1 upregulated Nrf2 expression, which increased the expression levels of antioxidant enzymes (NQO1, SOD1, Prdx1, and Gclc) and antiferroptotic proteins (SLC7A11 and GPX4) and downregulated the protein expression of p53 and Nlrp3, leading to the inhibition of ROS production and inflammation and subsequent cardiomyocyte death (apoptosis, ferroptosis and pyroptosis). In summary, CBR-470-1 prevented I/R-mediated cardiac injury possibly through inhibiting cardiomyocyte apoptosis, ferroptosis and pyroptosis via Nrf2-mediated inhibition of p53 and Nlrp3 and activation of the SLC7A11/GPX4 pathway. Our data also highlight that CBR-470-1 may serve as a valuable agent for treating ischaemic heart disease., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Gallbladder cancer (GBC) is highly aggressive and has poor prognosis, with most patients only diagnosed at an advanced stage. Furthermore, treatment options are limited, and their effect is unsatisfactory. Bromodomain-containing protein (BRD) is an epigenetic regulator that plays a carcinogenic role in several tumors, including squamous cell lung cancer, acute myeloid leukemia, synovial sarcoma, and malignant rhabdomyosarcoma. However, the expression, biological function, and molecular mechanisms of action of BRD9 in GBC are still unknown. Kaplan-Meier analysis, qRT-PCR, and analysis of clinical features were used to assess the clinical significance of BRD9 in GBC. Cell Counting Kit-8 and colony formation assays were performed to determine the effects of BRD9 on cell growth. The functional role of BRD9 in GBC was explored using qRT-PCR, western blotting, siRNA, and CHIP-qPCR. mRNA sequencing was performed to explore the underlying mechanisms of BRD9, and a nude mouse model of GBC was established to explore the anti-tumor effects of the BRD9 inhibitor I-BRD9 in vivo. BRD9 expression was elevated in GBC tissues compared with adjacent non-tumor tissues, and high BRD9 expression was associated with poor prognosis in patients with GBC. BRD9 knockdown by siRNA significantly decreased cell growth. Targeting BRD9 with I-BRD9 inhibited the proliferation of GBC cells without significant toxic effects. Additionally, I-BRD9 treatment suppressed CST1 expression in GBC cell lines, thereby inhibiting the PI3K-AKT pathway. The transcription factor FOXP1 was found to interact with BRD9 to regulate CST1 expression. Collectively, these results suggest that BRD9 may be a promising biomarker and therapeutic target for GBC., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate Animal experiments involving nude mice met the requirements and were approved by Xinhua Hospital of Shanghai Jiao Tong University School of Medicine (Animal experiment approval number: XHEC–NSFC–2021-093, approval date: February 24, 2021). The study was approved by the Ethics Committee of Xinhua Hospital, Shanghai Jiaotong University School of Medicine. Informed consent was obtained from the patients for this study. Consent for publication All authors have seen and approved the manuscript and consent publication., (© 2024. The Author(s).)

Background: Depression and anxiety disorders are prevalent psychiatric conditions, and currently utilized chemical drugs typically come with significant adverse effects. China boasts a wealth of medicinal and food herbs known for their safe and effective properties., Purpose: This study aimed to develop novel formulations with improved antidepressant and anxiolytic effects derived from medicinal and food herbs., Study Design: Screening combinations with antidepressant and anxiolytic effects using techniques such as network pharmacology and validating their effects in vitro and in vivo experiments., Methods: Utilizing network pharmacology and molecular docking, we identified the top ten medicinal herbs with anxiolytic and antidepressant potential. Herbs with cytoprotective effects and non-toxic characteristics were further screened to formulate the herbal blends. Subsequently, we established a PC12 cell injury model and a chronic unpredictable mild stress (CUMS) model in mice to assess the effects of our formulations., Results: Ten medicinal herbs were initially screened, and six of them were deemed suitable for formulating the blend, namely Gancao, Dazao, Gouqizi, Sangye, Huangqi, and Jinyinhua (GDGSHJ). The GDGSHJ formulation reduced Lactate Dehydrogenase (LDH) leakage, decreased apoptosis, and demonstrated a favorable antidepressant and antianxiety effect in the CUMS mouse model. Besides, GDGSHJ led to the upregulation of serum 5-Hydroxytryptamine (5-HT) content and brain tissue 5-HT, Gamma-aminobutyric acid (GABA), and Dopamine (DA) levels. It also downregulated the expression of SLC6A4 and SLC6A3 genes in the mouse hippocampus while upregulating HTR1A, DRD1, DRD2, and GABRA1 genes., Conclusion: Our formulation exhibited robust antidepressant and antianxiety effects without inducing substantial toxicity. This efficacy appears to be mediated by the expression of relevant genes within the hippocampus of mice. The formulation achieved this effect by balancing 5-HT levels in the serum and DA, GABA, and 5-HT levels within brain tissue., Competing Interests: Declaration of competing interest The authors have no financial interest or other potential conflict of interests., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Globally, streptococcal disease caused by Streptococcus agalactiae is known for its high mortality rate, which severely limits the development of the tilapia breeding industry. As a third-generation vaccine, DNA vaccines have shown great application prospects in the prevention and control of aquatic diseases, but their low immunogenicity limits their development. The combination of DNA vaccines and molecular adjuvants proved to be an effective method for inducing protective immunity. This study constructed recombinant plasmids encoding tilapia HSP70 and IL-1β genes (pcHSP70 and pcIL-1β) to verify their effectiveness as molecular adjuvants for S. agalactiae DNA vaccine (pcSIP) in the immunized tilapia model. The results revealed that serum-specific IgM production, enzyme activities, and immune-related gene expression in tilapia immunized with pcSIP plus pcHSP70 or pcIL-1β were significantly higher than those in tilapia immunized with pcSIP alone. It is worth noting that combination with molecular adjuvants improved the immune protection of DNA vaccines, with a relative percentage survival (RPS) of 51.72% (pcSIP plus pcHSP70) and 44.83% (pcSIP plus pcIL-1β), respectively, compared with that of pcSIP alone (24.14%). Thus, our study indicated that HSP70 and IL-1β in tilapia are promising molecular adjuvants of the DNA vaccine in controlling S. agalactiae infection., (© 2024 John Wiley & Sons Ltd.)

Cardiomyocytes are terminal differentiated cells and have limited ability to proliferate or regenerate. Condition like myocardial infarction causes massive death of cardiomyocytes and is the leading cause of death. Previous studies have demonstrated that cardiac fibroblasts can be induced to transdifferentiate into cardiomyocytes in vitro and in vivo by forced expression of cardiac transcription factors and microRNAs. Our previous study have demonstrated that full chemical cocktails could also induce fibroblast to cardiomyocyte transdifferentiation both in vitro and in vivo. With the development of tissue clearing techniques, it is possible to visualize the reprogramming at the whole-organ level. In this study, we investigated the effect of the chemical cocktail CRFVPTM in inducing in situ fibroblast to cardiomyocyte transdifferentiation with two strains of genetic tracing mice, and the reprogramming was observed at whole-heart level with CUBIC tissue clearing technique and 3D imaging. In addition, single-cell RNA sequencing (scRNA-seq) confirmed the generation of cardiomyocytes from cardiac fibroblasts which carries the tracing marker. Our study confirms the use of small molecule cocktails in inducing in situ fibroblast to cardiomyocyte reprogramming at the whole-heart level and proof-of-conceptly providing a new source of naturally incorporated cardiomyocytes to help heart regeneration., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Psoriasis is an inflammatory skin disease that relapses frequently. Keratinocyte apoptosis dysregulation plays a crucial role in the pathological mechanisms of psoriasis. PANoptosis is a process with intermolecular interaction among pyroptosis, apoptosis, and necroptosis. The mechanism of PANoptosis in the occurrence and development of psoriasis is still unclear. Here we present a novel approach by identifying PANoptosis-related signatures (PANoptosis-sig) from skin tissue of psoriasis patients and healthy controls on transcriptional and protein levels. Five PANoptosis-sig (TYMP, S100A8, S100A9, NAMPT, LCN2) were identified. Enrichment analysis showed they were mainly enriched in response to leukocyte aggregation, leukocyte migration, chronic inflammatory response and IL-17 signaling pathway. Single cell transcriptome analysis showed TYMP and NAMPT were expressed in almost all cell populations, while LCN2, S100A8 and S100A9 were significantly highly expressed in keratinocyte. We then constructed predictive and diagnostic models with the PANoptosis-sig and evaluated their performance. Finally, unsupervised consensus clustering analysis was conducted to ascertain psoriasis molecular subtypes by the PANoptosis-sig. The psoriasis cohort was divided into two distinct subtypes. Immune landscape showed that the stromal score of cluster 1 was significantly higher than cluster 2, while the immune and estimate scores of cluster 2 were expressively higher than cluster 1. Cluster 1 exhibited high expression of Plasma cells, Tregs and Mast cells resting, while cluster 2 showed high expression of T cells, Macrophages M1, Dendritic cells activated, and Neutrophils in immune infiltration analysis. And cluster 2 was more sensitive to immune checkpoints. In conclusion, our findings revealed potential biomarkers and therapeutic targets for the prevention, diagnosis, and treatment of psoriasis, enhancing our understanding of the molecular mechanisms underlying PANoptosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The employment of ultra-low permittivity materials in the configuration of antennas has been demonstrated to augment the antenna bandwidth and diminish signal delay effectively. This study presents three ultra-low permittivity metaphosphate microwave dielectric ceramics (MWDCs). The ALaP 4 O 12 (A = Li, Na, K) metaphosphate ceramics, which all belong to the monoclinic crystal system, exhibit extremely low permittivity (ε r ≈ 5) and excellent quality factor ( Q · f > 10,000 GHz) at a low sintering temperature ( T < 950 °C). Terahertz time-domain spectroscopy indicates that the ε r of ALaP 4 O 12 at terahertz frequencies is comparable to that observed in the microwave band and its value remains stable over an extensive frequency range. Furthermore, the relationship between the crystal structure and the dielectric properties of ALaP 4 O 12 has been analyzed through the lens of chemical bond theory. The highest Q · f value observed for LiLaP 4 O 12 can be attributed to the high chemical bond strength and stability of its crystal structure. The lowest ionic polarizability per unit volume is exhibited by NaLaP 4 O 12 , which results in the lowest pore-corrected permittivity. The thermal expansion of the chemical bonds within KLaP 4 O 12 is considerable, resulting in the highest coefficient of thermal expansion. Finally, the performance of a LiLaP 4 O 12 -based dielectric resonator antenna (DRA) excited by slot-coupled microstrip lines was designed and optimized by using different ceramic radius-to-height (RH) ratios. It was found that when the RH ratio of DRA reached 1.85, both the fundamental mode (HEM 11δ ) and the higher-order mode (HEM 12δ ) of DRA were simultaneously excited. The two modes overlap significantly, resulting in an ultra-wideband (UWB) of 46.8% (bandwidth = 7.93 GHz). Concurrently, the maximum radiation efficiency and gain of the DRA, obtained from the simulation, are 97.9% and 7.92 dBi, respectively. The findings of this study may inform the investigation of ultra-low permittivity phosphorus-based MWDCs and UWB DRAs.

Bacterial aromatic polyketides are compounds with multiple aromatic rings synthesized by bacterial type II polyketide synthases (PKSs), some of which have been developed into clinical drugs. Compounds containing aromatic polyketides synthesized by hybrid type I and type II PKSs are extremely rare. Here, we report the discovery of a gene cluster encoding both modular type I and type II PKSs as well as KAS III through extensive bioinformatics analysis, leading to the characterization of the hybrid polyketide, spirocycline A. The structure of spirocycline A is rare among all aromatic polyketides, featuring a unique starter unit and four spirocycles and forming a dimer. Biosynthetic studies indicate that the starter unit of this molecule is synthesized by type I PKS in collaboration with two trans -acting ketoreductase (KR) and enoylreductase (ER). It is then transferred by KAS III to the type II PKS system, which synthesizes the tricyclic aromatic polyketide backbone. The subsequent formation of the spirocycle and dimerization are carried out by four redox enzymes encoded in the gene cluster. Overall, the discovery of spirocycline A provides a new approach for identifying novel aromatic polyketides and offers potential enzymatic tools for the bioengineering of these hybrid polyketides.

Objective: The uncoupling protein 1 (UCP1) is induced in brown or "beige" adipocytes through catecholamine-induced cAMP signaling, which activates diverse transcription factors. UCP1 expression can also be enhanced by PPARγ agonists such as rosiglitazone (Rsg). However, it is unclear whether this upregulation results from de-novo differentiation of beige adipocytes from progenitor cells, or from the induction of UCP1 in pre-existing adipocytes. To explore this, we employed human adipocytes differentiated from progenitor cells and examined their acute response to Rsg, to the adenylate-cyclase activator forskolin (Fsk), or to both simultaneously., Methods: Adipocytes generated from primary human progenitor cells were differentiated without exposure to PPARγ agonists, and treated for 3, 6 or 78 h to Fsk, to Rsg, or to both simultaneously. Bulk RNASeq, RNAScope, RT-PCR, CRISPR-Cas9 mediated knockout, oxygen consumption and western blotting were used to assess cellular responses., Results: UCP1 mRNA expression was induced within 3 h of exposure to either Rsg or Fsk, indicating that Rsg's effect is independent on additional adipocyte differentiation. Although Rsg and Fsk induced distinct overall transcriptional responses, both induced genes associated with calcium metabolism, lipid droplet assembly, and mitochondrial remodeling, denoting core features of human adipocyte beiging. Unexpectedly, we found that Fsk-induced UCP1 expression was reduced by approximately 80% following CRISPR-Cas9-mediated knockout of PNPLA2, the gene encoding the triglyceride lipase ATGL. As anticipated, ATGL knockout suppressed lipolysis; however, the associated suppression of UCP1 induction indicates that maximal cAMP-mediated UCP1 induction requires products of ATGL-catalyzed lipolysis. Supporting this, we observed that the reduction in Fsk-stimulated UCP1 induction caused by ATGL knockout was reversed by Rsg, implying that the role of lipolysis in this process is to generate natural PPARγ agonists., Conclusions: UCP1 transcription is known to be stimulated by transcription factors activated downstream of cAMP-dependent protein kinases. Here we demonstrate that UCP1 transcription can also be acutely induced through PPARγ-activation. Moreover, both pathways are activated in human adipocytes in response to cAMP, synergistically inducing UCP1 expression. The stimulation of PPARγ in response to cAMP may result from the production of natural PPARγ activating ligands through ATGL-mediated lipolysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Azo molecules, being extensively studied as photoswitches, have demonstrated versatile photoswitching performance and applications in solution-phase systems. However, the dense molecular packing and insufficient conformational freedom in the solid/crystalline state typically pose a challenge to their E ⇆ Z isomerization. This study presents a breakthrough in solid-state azo chemistry, where the investigated azobispyrazole molecules are capable of achieving high E → Z photoconversion, ranging from 85% to nearly quantitative (96%), and quantitative Z → E photoswitching in their crystalline states. To the best of our knowledge, azobispyrazoles are the first photoswitchable azo crystals that achieve high-yield bidirectional conversions, particularly the challenging thermodynamically stable-to-metastable E → Z transformation. Crystallographic and computational analyses provide in-depth insights into the photoswitching mechanism and propose that locally distributed free spaces and weak intermolecular interactions within the crystal structures are key factors contributing to the crystalline-state conversion. This work opens up new avenues for the development of promising photoswitchable azo crystals and also underscores the potential application of azobispyrazole crystals as light-responsive materials.

Background: Brain structure injury was presented in acute lymphoblastic leukemia (ALL) after treatment; however, its alterations in new-onset stage are still unclear. We aim to explore white matter (WM) and grey matter (GM) alterations using surface-based morphometry (SBM) and tract-based spatial statistics (TBSS) in new-onset pediatric ALL., Methods: Thirty-five ALL and 33 typically developing (TD) children were prospectively recruited and underwent three-dimensional T1-weighted and diffusion tensor (DTI) imaging. DTI metrics, cortical GM features, and deep GM nuclei volume were compared between groups differences., Results: In ALL, the only increased FA in the body of corpus callosum (P FWE-corrected  = 0.023) and left superior corona radiata (P FWE-corrected  = 0.045) were presented. Relative to TDs, pediatric ALL presented a significant decrease in cortical surface area (CSA), thickness (CT), and volume in orbital gyri, supramarginal gyrus, middle temporal gyrus, and superior temporal gyrus (all CWP = 0.01). Additionally, increased CT and CSA were found in lingual gyrus and left sulcus intermedius primus, respectively (all CWP = 0.01). Smaller volumes in pediatric ALL were observed in bilateral thalamus, caudate, hippocampus, and right putamen (P FDR-corrected  < 0.05)., Conclusion: Widespread brain structural abnormalities were found in new-onset pediatric ALL, which suggest disease itself can cause brain structural injury., Impact: This study revealed the altered white matter integrity and gray matter morphology characteristics in childhood acute lymphoblastic leukemia on new-onset stage. It is suggested that there may be structural impairment before chemotherapy. MRI is a sensitive way for early detection on brain structural damage in childhood acute lymphoblastic leukemia., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and declare that J-LT is a BMJ clinical research editor.

Excessive fluoride ion (F - ) in the environment can affect health and even endanger life when ingested by the human body. However, most fluoride probes have the disadvantages of low sensitivity and long detection time. Herein, fluorescent probe 3a is successfully synthesized by linking two acetylenyltrimethylsilyl groups at both ends of the fluorinated benzothiadiazole core. After the addition of F - to 3a, the emission at 436 nm is significantly quenched and slightly blue-shifted. It is confirmed by electrospray ionization high-resolution mass spectrometry (ESI-HRMS) and density functional theory calculations (DFT) that these changes are due to the F - triggered Si-C bond cleavage and the subsequent inactivation of intramolecular charge transfer (ICT). The detection limit and response time of probe 3a for F - are 10 -8 mol/L and 25 s, respectively. Importantly, fluorescent material 3a can be processed into portable test tools for the visual detection of fluoride ion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To review and compare the efficacy of different delivery modes of decision aids (DAs), including computer-based, print-based, multimedia-based, video-based, and website-based on decision-making outcomes for prostate cancer screening compared to usual care (UC) and among the delivery modes., Methods: PubMed, the Excerpta Medica dataBASE (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Google Advanced Search, and Turning Research Into Practice (TRIP) Database were systematically searched from inception to August 2023. The primary outcomes were knowledge level, knowledge scores, participation in shared decision-making (SDM), decisional conflict, and preference for SDM participation. Secondary outcomes were the proportion of subjects who underwent screening (actual screening utilisation) and the proportion of subjects who intended to be screened (intention to undergo screening). Network and pairwise meta-analyses were performed using random-effects models., Results: Seven systematic reviews were included. Network meta-analysis found that multimedia (relative risk [RR] 1.51, 95% confidence interval [CI] 1.02-2.24), print (RR 1.82, 95% CI 1.23-2.69), and website-based (RR 1.99, 95% CI 1.32-3.01) DAs significantly increased participation in SDM compared to the computer-based DA. There was a significant reduction in the actual screening utilisation in the computer DA arm compared to the other delivery modes. No significant differences between all delivery modes were noted on knowledge levels, knowledge scores, decisional conflict, preference for SDM participation, and intention to undergo screening. The highest mean surface under the cumulative ranking curve for all primary outcomes showed that website-based was the most effective delivery mode, followed by print-based DA. The pairwise meta-analysis showed a significant increase in participants' knowledge level, knowledge scores, a reduced intention to undergo screening and actual screening utilisation compared to UC., Conclusions: The findings suggest that different types of DAs have varying levels of effectiveness in increasing knowledge level, knowledge scores, participation in SDM, and influencing screening behaviours. While website-based DA appeared the most effective, employing the print-based DA could be a practical solution in settings with limited resources., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

In this work, two novel probes 4a and 4b were synthesized through Suzuki-Miyaura coupling reaction, whose structures were further confirmed by 1 H NMR, 13 C NMR, high-resolution mass spectrometry (HRMS) and X-ray single crystal diffraction. The optical properties of the obtained molecules were investigated accordingly. Owing to different bridging fluorophores, there are certain differences in optical performance and detection ability between the two synthesized compounds. Especially, due to the subtle difference in orbitals energy and electron distribution displayed by the DFT calculations, 4a possesses the characteristics of dual-state emission (DSE) molecule, while 4b is an aggregation-induced emission (AIE) molecule. Interestingly, these two molecules can be developed into multifunctional detection probes, successfully applied for the fluorescence recognition of iron ions and common nitroaromatic compounds (NACs). At the same time, the probe molecules can also be applied to the detection of NACs in aqueous environment. What's more, they can also be loaded on test strips and thin-films for fluorescence identification of NACs, thus being expected to be developed into portable detection tools for NACs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The traditional Chinese medicine (TCM) formulation Shengqiyichang Decoction (SQYCD) has been reported to stimulate host immunity, and it has been administered for the treatment of colorectal cancer (CRC). Here, we applied network and bioinformatics analyses to elucidate the mechanisms by which SQYCD ameliorates CRC and validated its modes of action via in vivo and in vitro experiments. We identified 46 active compounds in SQYCD and selected 237 proteins as potential therapeutic targets in CRC, most notably p38 mitogen-activated protein kinase (p38⍺). Bioinformatics analyses demonstrated differential expression in CRC tissues and prognostic value of the genes encoding TNFα, MAPK14, CASP-3, MAPK1, AKT1, PRKACA, VEGF, IL-6, EGFR and ESR1. We then plotted receiver operating curves (ROC) and time-ROC for the differentially expressed genes (DEGs) ESR1 and AKT1 to predict the progress of CRC. We speculated that the AKT/p38α-MAPK signaling pathway is associated with the clinical prognosis of CRC. In a mouse model, we found that SQYCD inhibits CRC tumor growth by increasing CD4 + and CD8 + T cell abundance and decreasing the ratio of T-regulatory cells (Tregs) in the tumor microenvironment. In cultured mouse CRC cells, SQYCD selectively upregulated levels of the CRC-associated protein lymphocyte antigen 6 family member G6D, while the AKT activator SC-79 reversed this effect. The discoveries made herein suggest that SQYCD exerts a therapeutic effect in CRC by inhibiting Treg recruitment via inhibition of the AKT/p38α/LY6G6D signaling axis., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Author(s).)

Introduction: Macranthoidin B (MB) is a primary active component of Flos Lonicerae. In Chinese veterinary clinics, Flos Lonicerae is frequently used in combination with florfenicol to prevent and treat infections in livestock and poultry. However, potential interactions between Flos Lonicerae and florfenicol remain unclear. To systematically study these interactions, it is crucial to investigate the individual phytochemicals within Flos Lonicerae . Therefore, MB was selected for this study to assess its effect on the pharmacokinetics of florfenicol in vivo and to explore the underlying mechanisms involved., Methods: Male Sprague-Dawley rats were administered MB (60 mg/kg BW) or sterile water orally for 7 consecutive days. On the 8th day, a single oral dose of florfenicol (25 mg/kg BW) was given. Florfenicol pharmacokinetics were analyzed using ultra-high performance liquid chromatography. The hepatic expression levels of cytochrome P450 (CYP1A2, CYP2C11, CYP3A1), UDP-glucuronosyltransferase (UGT1A1), P-glycoprotein (P-gp), and nuclear receptors, including constitutive androstane receptor (CAR), pregnane X receptor (PXR), and retinoid X receptor alpha (RXRα), were quantified via reverse transcription-quantitative polymerase chain reaction and Western blotting (WB). Hepatic CYP1A2 and CYP2C11 activities were measured using a cocktail method. Additionally, the subcellular expression and localization of CAR, PXR, and RXRαin hepatocytes was assessed using WB and immunofluorescence staining., Results: MB significantly reduces the AUC (0-∞) and MRT (0-∞) of florfenicol. MB also markedly upregulates the mRNA and protein expression of hepatic CYP1A2 and CYP2C11, along with their catalytic activities. Substantial upregulation of CAR and PXR proteins occurs in the hepatocyte nucleus, along with significant nuclear colocalization of the transcriptionally active CAR/RXRα and PXR/RXRαheterodimers, indicating MB-induced nuclear translocation of both CAR and PXR., Discussion: These findings suggest that MB-induced alterations in florfenicol pharmacokinetics, particularly its accelerated elimination, may be due to increased expression and activities of CYP1A2 and CYP2C11, with CAR and PXR potentially involved in these regulatory effects. Further investigation is yet needed to fully elucidate the clinical implications of these interactions concerning the efficacy of florfenicol in veterinary medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Wang, Zhang, Yin, Yang, Li and Liang.)

Despite effective countermeasures, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists worldwide because of its ability to diversify and evade human immunity. This evasion stems from amino acid substitutions, particularly in the receptor binding domain (RBD) of the spike protein that confers resistance to vaccine-induced antibodies and antibody therapeutics. To constrain viral escape through resistance mutations, we combined antibody variable regions that recognize different RBD sites into multispecific antibodies. Here, we describe multispecific antibodies, including a trivalent trispecific antibody that potently neutralized diverse SARS-CoV-2 variants and prevented virus escape more effectively than single antibodies or mixtures of the parental antibodies. Despite being generated before the appearance of Omicron, this trispecific antibody neutralized all major Omicron variants through BA.4/BA.5 at nanomolar concentrations. Negative stain electron microscopy suggested that synergistic neutralization was achieved by engaging different epitopes in specific orientations that facilitated binding across more than one spike protein. Moreover, a tetravalent trispecific antibody containing the same variable regions as the trivalent trispecific antibody also protected Syrian hamsters against Omicron variants BA.1, BA.2, and BA.5 challenge, each of which uses different amino acid substitutions to mediate escape from therapeutic antibodies. These results demonstrated that multispecific antibodies have the potential to provide broad SARS-CoV-2 coverage, decrease the likelihood of escape, simplify treatment, and provide a strategy for antibody therapies that could help eliminate pandemic spread for this and other pathogens.

The selective construction of bridged bicyclic scaffolds has garnered increasing attention because of their extensive use as saturated bioisosteres of arene in pharmaceutical industry. However, in sharp contrast to their racemic counterparts, assembling chiral bridged bicyclic structures in an enantioselective and regioselective manner remains challenging. Herein, we describe our protocol for constructing chiral 2-oxa-3-azabicyclo[3.1.1]heptanes (BCHeps) by enantioselective [4π + 2σ] cycloadditions of bicyclo[1.1.0]butanes (BCBs) and nitrones taking advantage of a chiral copper(II) complex as a Lewis acid catalyst. This method features mild conditions, good functional group tolerance, high yield (up to 99%), and excellent enantioselectivity (up to 99% ee). Density functional theory (DFT) calculation elucidates the origin of the reaction's enantioselectivity and the mechanism of BCB activation by Cu(II) complex.