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Xiao-Dong Huang,1,* Jia-Bao Chen,2,* Xiao-Yun Dong,1 Wei-Long Wang,1 Jin Zhou,1 Zhen-Feng Zhou1 1Department of Anesthesiology, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital, Hangzhou First People’s Hospital Qianjiang New City Campus, Zhejiang Chinese Medical University), Hangzhou, People’s Republic of China; 2Department of Anesthesiology, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medicine College), Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen-Feng Zhou, Department of Anesthesiology, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital, Hangzhou First People’s Hospital Qianjiang New City Campus, Zhejiang Chinese Medical University), Hangzhou, 310008, People’s Republic of China, Tel +86-571-56005077, Email zhenfeng9853@163.comPurpose: This study aimed to investigate the influence of fentanyl on the effective dose of remimazolam-induced sedation in elderly female patients undergoing general anesthesia.Patients and Methods: Sixty female patients aged 65– 80 years undergoing selective general anesthesia were randomized into two groups: Group R+F received an initial dose of remimazolam (7.5 mg) with fentanyl (1 μg/kg), while Group R received remimazolam alone. Dosing adjustments (± 2.5 mg) were made based on the response of the preceding patient using the up-and-down allocation technique. The ED50 and ED95 were calculated using a sequential formula and probit regression. Probit regression was also used to assess the relative potency of remimazolam between groups. Sedation levels were evaluated using the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale.Results: The ED50 for remimazolam was significantly lower in Group R+F compared to Group R (p= 0.007). Probit regression estimated the ED50 and ED95 values for Group R+F at 4.878 mg (95% CI, 3.845– 5.859) and 8.184 mg (95% CI, 6.636– 13.546), respectively. In contrast, Group R demonstrated ED50 and ED95 values of 6.733 mg (95% CI, 5.533– 8.068) and 11.298 mg (95% CI, 9.101– 19.617), respectively.Conclusion: This study provides compelling evidence that the administration of 1 μg/kg of fentanyl significantly reduces the required sedative dose of remimazolam by approximately 30% during induction in elderly patients. Importantly, the concomitant use of 1 μg/kg of fentanyl does not increase the risk of adverse effects such as hypotension, respiratory depression.Keywords: remimazolam, fentanyl, effective dose, elderly

Guo-Yi Shen,1,* Peng-Jie Yang,2,* Wen-Shan Zhang,1 Jun-Biao Chen,1 Qin-Yong Tian,1 Yi Zhang,1 Bater Han2 1Department of Cardiothoracic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, People’s Republic of China; 2Department of Thoracic Surgery, Inner Mongolia Cancer Hospital & Affiliated People’s Hospital of Inner Mongolia Medical University, Huhhot, Inner Mongolia Autonomous Region, 010020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Zhang, Department of Cardiothoracic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, No. 59, Shengli West Road, Zhangzhou Xiangcheng District, Zhangzhou, 363000, People’s Republic of China, Tel +86-13906969033, Email zhangyi625@126.com Bater Han, Department of Thoracic Surgery, Inner Mongolia Cancer Hospital & Affiliated People’s Hospital of Inner Mongolia Medical University, No. 42, Zhaowuda Road, Saihan District, Huhhot, Inner Mongolia Autonomous Region, 010020, People’s Republic of China, Tel +86-13948120033, Email baterhanhbb@126.comBackground: Dysregulation of lipid metabolism is common in cancer. However, the molecular mechanism underlying lipid metabolism in esophageal squamous cell carcinoma (ESCC) and its effect on patient prognosis are not well understood. The objective of our study was to construct a lipid metabolism-related prognostic model to improve prognosis prediction in ESCC.Methods: We downloaded the mRNA expression profiles and corresponding survival data of patients with ESCC from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. We performed differential expression analysis to identify differentially expressed lipid metabolism-related genes (DELMGs). We used Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses to establish a risk model in the GEO cohort and used data of patients with ESCC from the TCGA cohort for validation. We also explored the relationship between the risk model and the immune microenvironment via infiltrated immune cells and immune checkpoints.Results: The result showed that 132 unique DELMGs distinguished patients with ESCC from the controls. We identified four genes (ACAA1, ACOT11, B4GALNT1, and DDHD1) as prognostic gene expression signatures to construct a risk model. Patients were classified into high- and low-risk groups as per the signature-based risk score. We used the receiver operating characteristic (ROC) curve and the Kaplan-Meier (KM) survival analysis to validate the predictive performance of the 4-gene signature in both the training and validation sets. Infiltrated immune cells and immune checkpoints indicated a difference in the immune status between the two risk groups.Conclusion: The results of our study indicated that a prognostic model based on the 4-gene signature related to lipid metabolism was useful for the prediction of prognosis in patients with ESCC.Keywords: biomarkers, esophageal squamous cell carcinoma, immune microenvironment, lipid metabolism, prognosis

Jin-Bor Chen,1,2 Chiung-Chih Chang,2,3 Sin-Hua Moi,4 Lung-Chih Li1,2 1Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and School of Medicine, Kaohsiung, 833, Taiwan, Republic of China; 2College of Medicine, Chang Gung University, Taoyuan, 330, Taiwan, Republic of China; 3Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and School of Medicine, Kaohsiung, 833, Taiwan, Republic of China; 4Center of Cancer Program Development, E-Da Cancer Hospital, I-Shou University, Kaohsiung, 833, Taiwan, Republic of ChinaCorrespondence: Jin-Bor Chen, Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 DaPei Road, Niao Song District, Kaohsiung, 833, Taiwan, Republic of China, Tel +886-7-7317123, ext 8306, Fax +886-7-7322402, Email chenjb1019@gmail.com; jbchen@cgmh.org.twPurpose: This study aimed to compare the plasma levels of nanoparticle-based neurodegenerative biomarkers between hemodialysis (HD) participants with grossly normal cognitive function and healthy controls.Patients and Methods: A cohort of participants undergoing maintenance HD and healthy controls were enrolled for comparison between July and October 2021. The immunomagnetic reduction method was used to measure plasma neurodegenerative biomarkers Aβ1-40, Aβ1-42, tau protein, and neurofilament light chain (NfL). The clinical dementia rating (CDR) was used to evaluate cognitive function. A receiver operating characteristic curve was used to discriminate between HD participants and healthy controls.Results: There were 52 and 18 participants in the HD and healthy control groups, respectively. The mean age of the HD participants was 62 years, and that of the healthy controls was 57 years. The mean HD vintage in the HD cohort was 11.8 years. HD participants demonstrated significantly higher plasma levels of Aβ1-42, tau protein, Aβ1-42 × tau, and NfL and Aβ1-42/Aβ1-40 ratio and significantly lower plasma Aβ1-40 levels than healthy controls. The measured plasma biomarkers could not discriminate between CDR0 and CDR0.5 HD participants. The area under the curve of the study biomarkers to discriminate HD participants from healthy controls ranged from 0.987 (Aβ1-42 × tau) to 0.889 (NfL).Conclusion: The plasma levels of nanoparticle-based neurodegenerative biomarkers were higher in HD participants with grossly normal cognitive function than in healthy controls. These findings imply that neurodegenerative changes appear in HD participants. A profile of plasma neurodegenerative biomarkers could be considered a potential surrogate for evaluating long-term cognitive function in HD participants.Graphical Abstract: Keywords: Aβ proteins, cognitive function, hemodialysis, tau protein

Lin Wang,1 Ming-Hui Xin,1 Yan Ma,1 Yu Wang,1 Meng-Yuan Hu,1 Qiang-Qiang Liu,1 Jin-Bor Chen2,3 1Department of Nephrology, Dalian University Affiliated Xinhua Hospital, Dalian, People’s Republic of China; 2Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan, Republic of China; 3School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of ChinaCorrespondence: Jin-Bor ChenDivision of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Niao Song District, Kaohsiung City, Taiwan, Republic of China, Tel +886-7-7317123, ext 8306, Fax +886-7-7322402, Email chenjb1019@gmail.comPurpose: There is a limited evidence of durable effect of parathyroidectomy (PTX) on the quality of life (QoL) in dialysis populations. We aimed to investigate this concern by comparing the QoL scores in the pre- and post-PTX periods in a cohort of dialysis patients.Patients and Methods: A total of 212 dialysis patients were enrolled in a hospital-facilitated dialysis center in China between July 1, 2016 and June 30, 2021. The mean age was 46.4 years; the male:female ratio was 96:116; hemodialysis 191, peritoneal dialysis 21. Informative data relating to demographics and dialysis were recorded for comparison. QoL was measured using the Chinese version of the Kidney Disease Quality of Life-36 (KDQOL-36™) and compared subscale scores between the pre-and post-PTX period. Appropriate statistical methods and Pearson’s correlation test were used for statistical analysis.Results: Nutritional markers, including hemoglobin and albumin, significantly increased post-PTX than pre-PTX. KDQOL-36 domain scale scores, including Symptoms and Problems of Kidney Disease, Burden of Kidney Disease, Effects of Kidney Disease (EKD), Physical Component Summary (PCS) score, and Mental Component Summary score, significantly increased post-PTX than pre-PTX. All patients were further stratified into three groups based on the PTX duration— 0– 2 years, > 2–< 5 years, and ≥ 5 years—and all KDQOL-36 domain scale scores increased in individual PTX durations. The PTX duration showed a significant negative correlation between PCS subscale scores and a positive correlation between EKD subscale scores.Conclusion: PTX could improve QoL in dialysis patients with medically refractory secondary hyperparathyroidism. The durable effects should be studied using a larger sample.Keywords: dialysis, Kidney Disease Quality of Life-36, parathyroidectomy

Jing-Xiao Li,1 Jin-Shu Pang,2 Bin-Tong Yin,1 Gang Chen,1 Jun-Hong Chen,1 Jia-Yuan Luo,1 Xia Yang,1 Li-Ting Qin,1 Jiang-Hui Zeng,3 Peng Chen,4 Jia-Bo Chen,4 Deng Tang1 1Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3Department of Clinical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/Nanning Second People’s Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530031, People’s Republic of China; 4Department of Pediatric Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530031, People’s Republic of ChinaCorrespondence: Deng TangDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaTel +86-7715356534Email tdnever@163.comPurpose: The molecular mechanisms and signal pathways of ferroptosis in hepatoblastoma (HB) have not yet been clarified. In previous studies, activating transcription factor 3 (ATF3) was reported to be correlated with several tumors, but the clinical significance of ATF3 has never been determined. Herein, we investigated the clinicopathological value and mechanisms of ATF3 in regulating ferroptosis in HB.Methods: The mRNA microarray and RNA-sequencing data of 402 samples from our hospital and public databases were used to estimate ATF3 expression and assess its clinical role in HB. The standard mean difference (SMD) and summary receiver operating characteristic curves were utilized to judge the discrimination ability of ATF3 between HB and non-HB liver tissues. We examined the expression variation of ATF3 in HB cells after the treatment with erastin. We also predicted the target genes of ATF3 as a transcriptional factor from public Chromatin Immunoprecipitation-sequencing data and selected the ferroptosis-related genes for a signaling pathway analysis.Results: In ten series, the pooled SMD for ATF3 was − 0.91, demonstrating that ATF3 expression was predominantly lower in HB than in non-HB liver tissues. ATF3 down-regulation showed moderate potential to distinguish HB from non-HB liver tissues (area under curves = 0.83, 95% confidence interval = 0.79– 0.86). Altogether, 4855 putative targets of ATF3 as a transcriptional factor were collected, among which, 60 genes were ferroptosis-related.Conclusion: The down-regulated ATF3 expression may play a vital role in the occurrence of HB possible partially by regulating ferroptosis.Keywords: transcription factor, ATF3, hepatoblastoma, ferroptosis

Yang-Xun Pan,1– 3,&ast; Xu-Qi Sun,1,2,&ast; Zi-Li Hu,1,2,&ast; Wa Xie,1,2 Ke-Xin Nie,4 Ai-Ping Fang,5 Ying-Yao Zhang,4 Yi-Zhen Fu,1,2 Jin-Bin Chen,1,2 Jun-Cheng Wang,1,2 Xin Wang,1,2 Yao-Jun Zhang,1,2 Dan-Dan Hu,1,2 Min-Shan Chen1,2 1Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China; 3Department of Oncology-Pathology, Karolinska Institutet, Solna, 17165, Sweden; 4Real World Study Team, BaseBit.ai, Shanghai, 200050, People’s Republic of China; 5Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dan-Dan Hu; Min-Shan ChenDepartment of Liver Surgery, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of ChinaTel +86-20-87343115; +86-20-87343117Fax +86-20-87343585; +86-20-8734358Email hudd@sysucc.org.cn; chenmsh@sysucc.org.cnBackground: The importance of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) in hepatocellular carcinoma (HCC) has been studied extensively in Japan, where hepatitis C virus is the predominant aetiology of HCC. The clinical profiles of HCC regarding the state of AFP and DCP in a hepatitis B virus epidemic area have not been comprehensively investigated, and the value of these tumour markers in evaluating the response to treatment and the detection of recurrence has yet to be determined.Patients and Methods: A total of 4792 patients treated in our centre were continuously analysed regarding accessible AFP and DCP data pre- and posttreatment. Baseline characteristics were summarized, and comparisons of progression-free survival (PFS) and overall survival (OS) rates were made independently. The prognostic significance of each factor was tested with the Cox proportional hazards model. Patients who had AFP and DCP data pretreatment, pre- and posttreatment, and those who were continuously monitored more than twice were analysed separately.Results: A total of 2600 patients (53.4%) were positive for AFP and DCP; 362 (7.6%) and 1211 (25.3%) patients were AFP- or DCP-positive, respectively, and 619 patients (12.9%) were negative for both AFP and DCP. Patients in the AFP single-positive or double-negative groups had the best OS (P< 0.001). Patients with less than 50% responses in AFP and DCP after treatments suffered from worse prognostic survival (P< 0.001). In the multivariate analysis, elevated AFP and DCP were identified as independent prognostic factors of PFS and OS. In addition, different tumour markers were related to different clinical and pathological traits.Conclusion: The present study comprehensively explored the clinical value of classical tumour markers for HCC using the “point-to-line” method. Positivity of pretreatment AFP and DCP or less than 50% treatment response rates exhibited more aggressive HCC, resulting in poor PFS and OS in HCC patients.Keywords: alpha-fetoprotein, des-gamma-carboxy prothrombin, hepatocellular carcinoma, clinical features

Both the coding and control regions of mitochondrial DNA (mtDNA) play roles in the generation of diabetes; however, no studies have thoroughly reported on the combined diabetogenic effects of variants in the two regions. We determined the mitochondrial haplogroup and the mtDNA sequence of the control region in 859 subjects with diabetes and 1,151 normoglycemic control subjects. Full-length mtDNA sequences were conducted in 40 subjects harboring specific diabetes-related haplogroups. Multivariate logistic regression analysis with adjustment for age, sex, and BMI revealed that subjects harboring the mitochondrial haplogroup B4 have significant association with diabetes (DM) (odds ratio [OR], 1.54 [95% CI 1.18-2.02]; P < 0.001), whereas subjects harboring D4 have borderline resistance against DM generation (0.68 [0.49-0.94]; P = 0.02). Upon further study, we identified an mtDNA composite group susceptible to DM generation consisting of a 10398A allele at the coding region and a polycytosine variant at nucleotide pair 16184-16193 of the control region, as well as a resistant group consisting of C5178A, A10398G, and T152C variants. The OR for susceptible group is 1.31 (95% CI 1.04-1.67; P = 0.024) and for the resistant group is 0.48 (0.31-0.75; P = 0.001). Our study found that mtDNA variants in the coding and control regions can have combined effects influencing diabetes generation. [ABSTRACT FROM AUTHOR]

Background and Purpose: ATP is a potent signalling molecule that regulates biological activities including increasing or decreasing proliferation in different types of cells. The aim of the present study was to investigate how ATP regulates the proliferation of human cardiac fibroblasts.Experimental Approach: Reverse transcription (RT)-PCR, Western blot analysis, cell proliferation and migration assays were employed to investigate the effects of ATP on human adult ventricular fibroblasts.Key Results: ATP increased cell proliferation in a concentration-dependent manner. Similarly, the P2X receptor agonist α,β-methylene ATP and P2Y receptor agonist ATP-γS also up-regulated cell proliferation. The P2 receptor antagonists suramin and reactive blue-2 prevented the ATP-induced increase in proliferation and RT-PCR and Western blot analysis revealed that mRNAs of P2X(4/7) and P2Y(2) are abundant in cardiac fibroblasts. ATP increased phosphorylated PKB (Akt) and ERK1/2 levels; an effect antagonized by suramin, reactive blue-2, the PI3-kinase inhibitor, wortmannin, PKB inhibitor, API-2, and MAPK inhibitor, PD98059. These kinase inhibitors also prevented the ATP-induced increase in proliferation. In addition, ATP enhanced the progression of cells from the G0/G1 phase to the S phase by increasing the expression of proteins for cyclin D1 and cyclin E. Silencing the P2X(4/7) and P2Y(2) receptors with siRNA targeting the corresponding receptor diminished ATP-stimulated proliferation and migration of the cardiac fibroblasts.Conclusion and Implication: ATP activates P2X(4/7) and P2Y(2) receptors and up-regulates the proliferation of human cardiac fibroblasts by promoting cell cycling progression. It also increases the migration of these cells. These effects of ATP may be involved in cardiac remodelling of injured hearts. [ABSTRACT FROM AUTHOR]

BACKGROUND: Inorganic arsenic has been linked to decreased kidney function through oxidative damage. Arsenic methylation is believed to be a pathway for arsenic metabolism. Lycopene is an antioxidant that reduces oxidative stress; however, the association between urinary arsenic species, plasma lycopene level, and chronic kidney disease (CKD) has seldom been evaluated. STUDY DESIGN: Case-control study. SETTING & PARTICIPANTS: 125 patients with CKD and 229 controls were recruited from a hospital-based pool. PREDICTOR: Urinary arsenic species and plasma lycopene level. OUTCOMES & MEASUREMENTS: CKD was defined as estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m(2), calculated by using the Modification of Diet in Renal Disease Study equation. Plasma lycopene was measured by means of high-performance liquid chromatography. Urinary arsenic species, including arsenite, arsenate, monomethylarsonic acid, and dimethylarsinic acid, were determined by means of high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. RESULTS: Lycopene level was associated positively with eGFR, and participants with a high serum lycopene level had a significant, inverse association with CKD (odds ratio, 0.41; 95% confidence interval, 0.21 to 0.81). Total arsenic level was associated significantly with CKD in a dose-response relationship, especially in participants with a total arsenic level greater than 20.74 compared with 11.78 mug/g creatinine or less (odds ratio, 4.34; 95% confidence interval, 1.94 to 9.69). Furthermore, participants with a high urinary total arsenic level or participants with a low percentage of dimethylarsinic acid had a positive association with CKD when their plasma lycopene level was low. LIMITATIONS: Because of the single spot evaluation of plasma antioxidants and urinary arsenic species and the small sample size, statistical significance should be interpreted with caution. CONCLUSIONS: This study shows that high urinary total arsenic or low plasma lycopene level is associated positively with CKD. Results suggest that the capacity for arsenic methylation may be associated with CKD in individuals who ingest low arsenic levels in drinking water and also have a low plasma lycopene level. [ABSTRACT FROM AUTHOR]

RIG-I-like receptors (RLRs) are cytosolic RNA sensors critical for antiviral immunity. RLR activation is regulated by polyubiquitination and oligomerization following RNA binding. Yet, little is known about how RLRs exploit subcellular organelles to facilitate their posttranslational modifications and activation. Endosomal adaptor TAPE regulates the endosomal TLR and cytosolic RLR pathways. The potential interplay between RIG-I signaling and endosomes has been explored. Here, we report that endosomes act as platforms for facilitating RIG-I polyubiquitination and complex formation. RIG-I was translocated onto endosomes to form signaling complexes upon activation. Ablation of endosomes impaired RIG-I signaling to type I IFN activation. TAPE mediates the interaction and polyubiquitination of RIG-I and TRIM25. TAPE-deficient myeloid cells were defective in type I IFN activation upon RNA ligand and virus challenges. Myeloid TAPE deficiency increased the susceptibility to RNA virus infection in vivo. Our work reveals endosomes as signaling platforms for RIG-I activation and antiviral immunity.

Background: The combined trans-oral and chest approach is a novel technique for endoscopic selective neck dissection (SND), with satisfactory oncological safety and cosmetic results. However, this hybrid approach is difficult, and the learning curve remains unclear. In this study, we aimed to evaluate the short-term outcomes for this hybrid approach, and to define the associated learning curve., Method: Clinical data and surgical outcomes of 58 PTC patients who underwent endoscopic SND via combined trans-oral and chest approach between September 2020 and April 2023 were retrospectively reviewed. The cumulative sum (CUSUM) sequential analysis technique is used to detect change, and has been applied for the evaluation of learning curves., Results: The study population included 58 patients (40 females, 18 males), with mean age of 38.9 ± 12.7 years and average body mass index of 22.6 ± 4.8 kg/m 2 . In all cases, the same surgical team performed endoscopic SND via combined trans-oral and chest approach. The numbers of positive/retrieved lymph nodes were 4.3 ± 3.2/27.8 ± 8.4 in the lateral compartment and 4.0 ± 3.5/8.4 ± 5.1 in the central compartment. The learning curve was evaluated in terms of an initial phase (20 cases) and a mature phase (38 cases). Operative time was longer during the initial phase, compared to the mature phase (375.2 vs. 274.6 min, p = 0.002). The frequency of operative complications was higher during the initial phase, compared to the mature phase (85% vs. 55.3%, p = 0.048)., Conclusions: After the experience acquired using endoscopic SND via combined trans-oral and chest approach to treat PTC in 20 patients, the number of complications decreased significantly. Compared to data collected for the initial phase, data collected for the mature phase showed trends toward decreased operating time., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The current throughput of conventional organic chemical synthesis is usually a few experiments for each operator per day. We develop a robotic system for ultra-high-throughput chemical synthesis, online characterization, and large-scale condition screening of photocatalytic reactions, based on the liquid-core waveguide, microfluidic liquid-handling, and artificial intelligence techniques. The system is capable of performing automated reactant mixture preparation, changing, introduction, ultra-fast photocatalytic reactions in seconds, online spectroscopic detection of the reaction product, and screening of different reaction conditions. We apply the system in large-scale screening of 12,000 reaction conditions of a photocatalytic [2 + 2] cycloaddition reaction including multiple continuous and discrete variables, reaching an ultra-high throughput up to 10,000 reaction conditions per day. Based on the data, AI-assisted cross-substrate/photocatalyst prediction is conducted., (© 2024. The Author(s).)

Anthropometric indexes play a crucial role in identifying obesity. However, as an internationally commonly used indicator of obesity diagnosis, BMI has limitations in distinguishing lean body mass from fat mass. The weight-adjusted waist index (WWI), a novel anthropometric index, assesses adiposity through standardized waist circumference for weight, which presents an excellent capacity to predict the morbidity and mortality risks of various diseases. However, research on WWI is still in the exploratory stage, and there is a lack of unified standards for using this indicator to determine obesity. In addition, its potential application in children and adolescents also urgently needs to be explored. Therefore, this article comprehensively summarizes and compares the distinctive characteristics between WWI and other obesity-related anthropometric indexes. Bibliometric methods are used to analyze the hotspots and trends of WWI-related research, and we focus on discussing the value of WWI in predicting adverse health outcomes, including cardiovascular disease, diabetes, liver and kidney diseases. We aim to promote the application of WWI in a broader field and fully demonstrate its important public health significance and broad application prospects.

Background: Endothelial dysfunction (ED), characterized by markedly reduced nitric oxide (NO) bioavailability, vasoconstriction, and a shift toward a proinflammatory and prothrombotic state, is an important contributor to hypertension, atherosclerosis, and other cardiovascular diseases. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is widely involved in cardiovascular development. Przewaquinone A (PA), a lipophilic diterpene quinone extracted from Salvia przewalskii Maxim, inhibits vascular contraction., Purpose: Herein, the goal was to explore the protective effect of PA on ED in vivo and in vitro, as well as the underlying mechanisms., Methods: A human umbilical vein endothelial cell (HUVEC) model of ED induced by angiotensin II (AngII) was used for in vitro observations. Levels of AMPK, endothelial nitric oxide synthase (eNOS), vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO), and endothelin-1 (ET-1) were detected by western blotting and ELISA. A mouse model of hypertension was established by continuous infusion of AngII (1000 ng/kg/min) for 4 weeks using osmotic pumps. Following PA and/or valsartan administration, NO and ET-1 levels were measured. The levels of AMPK signaling-related proteins in the thoracic aorta were evaluated by immunohistochemistry. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using the tail cuff method. Isolated aortic vascular tone measurements were used to evaluate the vasodilatory function in mice. Molecular docking, molecular dynamics, and surface plasmon resonance imaging (SPRi) were used to confirm AMPK and PA interactions., Results: PA inhibited AngII-induced vasoconstriction and vascular adhesion as well as activated AMPK signaling in a dose-dependent manner. Moreover, PA markedly suppressed blood pressure, activated vasodilation in mice following AngII stimulation, and promoted the activation of AMPK signaling. Furthermore, molecular simulations and SPRi revealed that PA directly targeted AMPK. AMPK inhibition partly abolished the protective effects of PA against endothelial dysfunction., Conclusion: PA activates AMPK and ameliorates endothelial dysfunction during hypertension., Competing Interests: Declaration of competing interest All the authors have declared that no conflicts of interest., (Copyright © 2024. Published by Elsevier GmbH.)

Salt stress severely inhibits plant growth. Understanding the mechanism of plant salt tolerance is highly important to improving plant salt tolerance. Previous studies have shown that nonselective cyclic nucleotide-gated ion channels ( CNGCs ) play an important role in plant salt tolerance. However, current research on CNGCs mainly focuses on CNGCs in glycophytic plants, and research on CNGCs in halophytes that exhibit special salt tolerance strategies is still scarce. This study used the halophilic plant Zoysia japonica , an excellent warm-season turfgrass, as the experimental material. Through bioinformatics analysis, 18 members of the CNGC family were identified in Zoysia japonica ; they were designated ZjCNGC1 through ZjCNGC18 according to their scaffold-level chromosomal positions. ZjCNGCs are divided into four groups (I-IV), with the same groups having differentiated protein-conserved domains and gene structures. ZjCNGCs are unevenly distributed on 16 scaffold-level chromosomes. Compared with other species, the ZjCNGCs in Group III exhibit obvious gene expansion, mainly due to duplication of gene segments. The collinearity between ZjCNGCs , OsCNGCs , and SjCNGCs suggests that CNGCs are evolutionarily conserved among gramineous plants. However, the Group III ZjCNGCs are only partially collinear with OsCNGCs and SjCNGCs , implying that the expansion of Group III ZjCNGC genes may have been an independent event occurring in Zoysia japonica . Protein interaction prediction revealed that ZjCNGCs, calcium-dependent protein kinase, H + -ATPase, outwardly rectifying potassium channel protein, and polyubiquitin 3 interact with ZjCNGCs. Multiple stress response regulatory elements, including those involved in salt stress, are present on the ZjCNGC promoter. The qPCR results revealed differences in the expression patterns of ZjCNGCs in different parts of the plant. Under salt stress conditions, the expression of ZjCNGCs was significantly upregulated in roots and leaves, with ZjCNGC8 and ZjCNGC13 showing the greatest increase in expression in the roots. These results collectively suggest that ZjCNGCs play an important role in salt tolerance and that their expansion into Group III may be a special mechanism underlying the salt tolerance of Zoysia japonica .

The design and synthesis of hybrid borates by the organic ligand modification method are urgent and undeveloped areas of research. It is difficult to directly integrate organoboronic acids within inorganic borate chemistry by adopting the traditional preparation approaches. This work reports a facile synthetic method to synthesize a large family of pyrazole molecule-protected borates in a rapid and precise manner under mild conditions. A unique cyclic eight-membered B 4 O 4 -ring has been identified as the cluster core for all these hybrid borates with two different conformations (boat and crown). This strategy can be applied to a system of pyrazolyl molecules to generate such hybrid borates in two independent routes from organoboronic or inorganic boric acids. Furtherly, the mechanism of 'click reaction' between boric acid and pyrazole induced by copper ions has been proposed based on the synthetic conditions and the structure of intermediate. Due to the bimetallic Cu sites and the functional surfaces, these materials can be used as electrocatalysts for CO 2 reduction reaction and efficiently enhance the selectivity of HCOOH and C 2 H 4 . Our strategy can be regarded as a typical template technique for organic molecule-protected borates., (© 2024 Wiley-VCH GmbH.)

Deep vein thrombosis (DVT) is a leading cause of morbidity and mortality after trauma. Here, we integrate plasma metabolomics and proteomics to evaluate the metabolic alterations and their function in up to 680 individuals with and without DVT after trauma (pt-DVT). We identify 28 metabolites and 2 clinical parameter clusters associated with pt-DVT. Then, we develop a panel of 9 metabolites (hexadecanedioic acid, pyruvic acid, L-Carnitine, serotonin, PE(P-18:1(11Z)/18:2(9Z,12Z)), 3-Hydroxycapric acid, 5,6-DHET, 3-Methoxybenzenepropanoic acid and pentanenitrile) that can predict pt-DVT with high performance, which can be verified in an independent cohort. Furthermore, the integration analysis of metabolomics and proteomics data indicates that the upregulation of glycolysis/gluconeogenesis-TCA cycle may promote thrombosis by regulating ROS levels in red blood cells, suggesting that interfering with this process might be potential therapeutic strategies for pt-DVT. Together, our study comprehensively delineates the metabolic and hematological dysregulations for pt-DVT, and provides potential biomarkers for early detection., (© 2024. The Author(s).)

With the increasing demand for trace sample analysis, injecting trace samples into liquid chromatography-mass spectrometry (LC-MS) systems with minimal loss has become a major challenge. Herein, we describe an in situ LC-MS analytical probe, the Falcon probe, which integrates multiple functions of high-pressure sample injection without sample loss, high-efficiency LC separation, and electrospray. The main body of the Falcon probe is made of stainless steel and fabricated by the computer numerical control (CNC) technique, which has ultrahigh mechanical strength. By coupling a nanoliter-scale droplet reactor made of polyether ether ketone (PEEK) material, the Falcon probe-based LC-MS system was capable of operating at mobile-phase pressures up to 800 bar, which is comparable to those of conventional ultraperformance liquid chromatography (UPLC) systems. Using the probe pressing microamount in situ (PPMI) injection approach, the Falcon probe-based LC-MS system showed high separation efficiency and good repeatability with relative standard deviations (RSDs) of retention time and peak area of 1.8% and 9.9%, respectively, in peptide mixture analysis ( n = 6). We applied this system to the analysis of a trace amount of 200 pg of HeLa protein digest and successfully identified an average of 766 protein groups ( n = 5). By combining in situ sample pretreatment at the nanoliter range, we further applied the present system in single-cell proteomic analysis, and 241 protein groups were identified in single 293 cells, which preliminarily demonstrated its potential in the analysis of trace amounts of samples with complex compositions.

Objective: In this study, we evaluated the efficacy and safety of 1 μg/kg dexmedetomidine as an adjuvant treatment to ropivacaine in children undergoing upper limb surgeries under ultrasound-guided axillary brachial plexus blocks and general anesthesia., Methods: We enrolled 90 children (aged 1-8 years; ASA I-II) undergoing closed reduction and internal fixation for upper extremity fractures at the Xiamen Children's Hospital and randomly assigned them to one of two groups: L (injection with 0.25% ropivacaine) or D (injection with 0.25% ropivacaine containing 1 μg/kg dexmedetomidine) using the random number table method. The main outcome indicators recorded were the facial expression, leg activity, position, crying, and Face, Legs, Activity, Cry, and Consolability (FLACC) scale scores of children after surgery and the duration of block and analgesia maintenance. The secondary outcome indicators were vital sign data at the time of ultrasound probe placement (T1), at the time of block completion (T2), prior to the beginning of surgery (T3), 5 min after the beginning of surgery (T4), and at the end of surgery (T5), as well as the time of postoperative recovery, the number of cases of remedial analgesia, and complications., Results: There was no statistical difference between the two groups in terms of general data, block completion time, postoperative recovery time, and complications (P > 0.05). Compared to the L group, the D group had significantly lower FLACC scores at 6 h after surgery, as well as significantly lower systolic blood pressure, diastolic blood pressure, and heart rate values at T4 and T5, and significantly longer duration of postoperative analgesia maintenance (all P < 0.05)., Conclusion: Dexmedetomidine (1 μg/kg) as a local anesthetic adjuvant to ropivacaine can alleviate pain at 6 h postoperatively, prolong analgesia maintenance, and reduce intraoperative blood pressure and heart rate in pediatric patients undergoing closed reduction and internal fixation for upper extremity fractures, with no obvious complications or delayed recovery., Clinical Registry Number: Registration website: www.chictr.org.cn, Registration number: ChiCTR2200065163, Registration date: October, 30, 2022., (© 2024. The Author(s).)

Grasslands, the largest carbon pool in China, possess enormous potential for carbon sequestration. Increasing the stomatal aperture to increase the CO 2 absorption capacity is a potential method to improve plant photosynthetic efficiency and ultimately enhance the carbon sequestration capacity of grass plants. Research on stomatal aperture regulation has focused mostly on Arabidopsis or crops, while research on grass plants in these areas is scarce, which seriously restricts the implementation of this grassland carbon sequestration strategy. Here, a widely used ecological grass, centipedegrass, was used as the experimental material. First, a convenient method for observing the stomatal aperture was developed. The leaves were floated in a potassium ion-containing open solution (67 mM KCl, pH 6.0) with the adaxial surface rather than the abaxial surface in contact with the solution and were cultivated under light for 1.5 h. Then, nail polish was applied on the adaxial surface, and a large number of open stomata were imprinted. Second, with the help of this improved method, the concentration‒response characteristics of the stomatal aperture to eleven environmental stimuli were tested. The stomatal aperture is dependent on these environmental stimuli in a concentration-dependent manner. The addition of 100 μM brassinolide led to the maximal stomatal aperture. This study provided a technical basis for manipulating stomatal opening to increase the carbon sequestration capacity of centipedegrass., 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 Masson SAS. All rights reserved.)

With the surge in the human coastal population and the increasing frequency of human activities along the coast, cases of marine envenomation, particularly jellyfish envenomation, have notably risen. Jellyfish stings can induce a spectrum of symptoms that vary in severity, encompassing skin injuries, acute systemic venom effects, delayed indirect sequelae, and even fatality, causing significant distress to patients. Among these manifestations, the occurrence of skin lesions following jellyfish stings is prevalent and substantial. These lesions are characterized by evident blister formation, development of bullae, subcutaneous hemorrhage, erythema, papules, wheal, ecchymosis, and ulceration or skin necrosis. Local cutaneous manifestations may persist for several weeks or even months after the initial sting. Despite aggressive treatment, many skin injuries still result in significant pigmentation or scarring after recovery. To address this issue effectively, it is imperative to conduct comprehensive evidence-based medical research, elucidate various components within jellyfish venom, and elucidate its pathogenic mechanism to develop targeted treatment programs. This article aims to review the skin symptoms, pathophysiology, and management of jellyfish stings. Such considerations can provide comprehensive guidance to medical professionals and the public and minimize the harm caused by jellyfish stings.

In the present study, the mitochondrial genomic characteristics of Acanthopsetta nadeshnyi have been reported and have depicted the phylogenetic relationship among Pleuronectidae. Combined with a comparative analysis of 13 PCGs, the TN93 model was used to review the neutral evolution and habitat evolution catalysis of the mitogenome to verify the distancing and purification selectivity of the mitogenome in Pleuronectidae. At the same time, a species differentiation and classification model based on mitogenome analysis data was established. This study is expected to provide a new perspective on the phylogenetic relationship and taxonomic status of A. nadeshnyi and lay a foundation for further exploration of environmental and biological evolutionary mechanisms.

The fundamental function of an optimal cervical pillow is to provide sufficient support to maintain normal spinal alignment and minimize biological stress on the contact surface throughout sleep. The recent advancements in cervical pillows have mainly focused on the subjective and objective evaluations of support comfort, as well as the relationship between pillow height and cervical vertebrae posture. However, only a few studies have addressed shape design guidelines and mechanical performances of the pillows themselves. In this study, a two-sectional contour cervical pillow comprising an arc and a Bezier curve is designed to support the head and neck. The design of the arc-shaped neck section incorporates the Cobb's angle and Borden value from healthy individuals to reflect the consistency of normal cervical anatomical features. The Bezier curve-based head section takes the head length and neck depth into account as significant individual differences. Static analysis and lattice optimization are performed in ANSYS Workbench to develop a variable-density cellular structure, aimed at improving air permeability and reducing the risk of pressure ulcers associated with the cervical pillow. The rapid prototyping technique fused deposition modeling (FDM) and thermoplastic material polylactic acid (PLA) are employed for fabricating different cellular structures. The results demonstrate that the neck section experiences less stress and greater deformation in comparison to the head section, indicating good comfort and support provided by the designed cervical pillow. Additionally, the compressive, bending, and cushion properties of the 3D-printed cervical pillow with variable-density cellular structure are experimentally validated, further confirming its effectiveness.

To investigate the efficacy of Ursolic acid in alleviating neuropathic pain in rats with spinal nerve ligation (SNL), the SNL rat model was surgically induced. Different concentrations of Ursolic acid and manipulated target mitogen-activated protein kinase 1 (MAPK1) were administered to the SNL rats. Fecal samples were collected from each group of rats for 16S rDNA analysis to examine the impact of gut microbiota. Molecular docking experiments were conducted to assess the binding energy between Ursolic acid and MAPK1. In vivo studies were carried out to evaluate the expression of inflammatory factors and signaling pathways in spinal cord and colon tissues. Ursolic acid was found to have a beneficial effect on pain reduction in rats by increasing plantar withdrawal latency (PWL) and paw withdrawal threshold (PWT). Comparing the Ursolic acid group with the control group revealed notable differences in the distribution of Staphylococcus, Allobaculum, Clostridium, Blautia, Bifidobacterium, and Prevotella species. Network pharmacology analysis identified MAPK1 and intercellular adhesion molecule-1 (ICAM1) as common targets for Ursolic acid, SNL, and neuropathic pain. Binding sites between Ursolic acid and these targets were identified. Additionally, immunofluorescent staining showed a decrease in GFAP and IBA1 intensity in the spinal cord along with an increase in NeuN following Ursolic acid treatment. Overexpression of MAPK1 in SNL rats led to an increase in inflammatory factors and a decrease in PWL and PWT. Furthermore, MAPK1 counteracted the pain-relieving effects of Ursolic acid in SNL rats. Ursolic acid was found to alleviate neuropathic pain in SNL rats by targeting MAPK1 and influencing gut microbiota homeostasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques. These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research. This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids, and patient-derived organoids. The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed. The construction of gastric organoids involves several key steps, including cell extraction and culture, three-dimensional structure formation, and functional expression. Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori . In addition, in drug screening and development, gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials. They can also be used for precision medicine according to the specific conditions of patients with gastric cancer, to assess drug resistance, and to predict the possibility of adverse reactions. However, despite the impressive progress in the field of gastric organoids, there are still many unknowns that need to be addressed, especially in the field of regenerative medicine. Meanwhile, the reproducibility and consistency of organoid cultures are major challenges that must be overcome. These challenges have had a significant impact on the development of gastric organoids. Nonetheless, as technology continues to advance, we can foresee more comprehensive research in the construction of gastric organoids. Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: This study aimed to analyze the expression and prognosis of SRY-box transcription factor 11 (SOX11) in neuroblastoma (NB), as well as the biological function and potential regulatory mechanism of SOX11 in NB., Methods: Public RNA sequencing was used to detect the expression level of SOX11. The Kaplan-Meier curve and hazard ratios (HR) were used to determine the prognostic value of SOX11 in NB. Functional analyses were performed using CCK8, wound healing assay, and transwell invasion assay. Finally, the potential target genes of SOX11 were predicted by Harmonizonme (Ma'ayan Laboratory) and Cistrome Data Browser (Cistrome Project) database to explore the potential molecular mechanism of SOX11 in NB., Results: Compared with normal adrenal tissue, the expression of SOX11 in NB tissue was significantly upregulated. The Kaplan-Meier curve showed that high expression of SOX11 was associated with poor prognosis in children with NB (HR, 1.719; P = 0.049). SOX11 knockdown suppressed the migration capacity of SK-N-SH cells but did not affect proliferation and invasion capacity. Enhancer of zeste homolog 2 ( EZH2 ) may be a potential downstream target gene for the transcription factor SOX11 to play a role in NB., Conclusion: The transcription factor SOX11 was significantly upregulated in NB. SOX11 knockdown suppressed the migration capacity of NB cell SK-N-SH. SOX11 may promote the progression of NB by targeting EZH2., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2024, the Korean Surgical Society.)

Characterizing the profiles of proteome and metabolome at the single-cell level is of great significance in single-cell multiomic studies. Herein, we proposed a novel strategy called one-shot single-cell proteome and metabolome analysis (scPMA) to acquire the proteome and metabolome information in a single-cell individual in one injection of LC-MS/MS analysis. Based on the scPMA strategy, a total workflow was developed to achieve the single-cell capture, nanoliter-scale sample pretreatment, one-shot LC injection and separation of the enzyme-digested peptides and metabolites, and dual-zone MS/MS detection for proteome and metabolome profiling. Benefiting from the scPMA strategy, we realized dual-omic analysis of single tumor cells, including A549, HeLa, and HepG2 cells with 816, 578, and 293 protein groups and 72, 91, and 148 metabolites quantified on average. A single-cell perspective experiment for investigating the doxorubicin-induced antitumor effects in both the proteome and metabolome aspects was also performed.

This study compared the therapeutic difference effects of the raw and scorched rhubarb for the treatment of ulcerative colitis(UC) and explored their difference in chemical components and mechanisms by using ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-QE-Orbitrap-MS) and network pharmacology. The UC therapeutic effects of Shaoyao Decoction with the raw rhubarb or the scorched rhubarb were evaluated by dextran sulfate sodium(DSS)-induced mouse model. The results showed that Shaoyao Decoction with either the raw rhubarb or the scorched rhubarb could relieve the UC symptoms of mice to different extents, while the scorched rhubarb-based formula showed advantages in reducing hemorrhagic diarrhea and inflammation levels. UPLC-QE-Orbitrap-MS was used to identify a total of 78 small molecules in the water decoction of the raw and scorched rhubarb. Multivariate statistical methods were used to screen components increasing significantly after the scorching process. The seven compounds included five free anthraquinones, gallic acid, and 5-hydroxymethylfurfural(HMF). Meanwhile, the nine compounds decreasing scorching were mainly combined anthraquinones and catechins-related compounds. Network pharmacology and molecular docking suggested that free anthraquinones, gallic acid, and 5-HMF may act on core targets such as B-cell lymphoma-2(BCL2), epidermal growth factor receptor(EGFR), tumor necrosis factor(TNF), and caspase-3(CASP3) and influence the signaling pathways such as phosphoinositide-3-kinase/protein kinase B(PI3K/Akt), hypoxia inducible factor-1(HIF-1), TNF, and mitogen-activated protein kinase(MAPK), so as to regulate the inflammation response, oxidative stress, and cell apoptosis to relieve UC symptoms. This study compared the therapeutic effects and chemical components of the raw and scorched rhubarb, providing the clinical reference for using rhubarb to treat UC.

Mycoplasma pneumoniae is a significant contributor to lower respiratory infections in children. However, the lipidomics and metabolics bases of childhood M. pneumoniae infections remain unclear. In this study, lipidomics and metabolomics analyses were conducted using UHPLC-LTQ-Orbitrap XL mass spectrometry and gas chromatography-triple quadrupole mass spectrometry on plasma (n = 65) and urine (n = 65) samples. MS-DIAL software, in combination with LipidBlast and Fiehn BinBase DB, identified 163 lipids and 104 metabolites in plasma samples, as well as 208 metabolites in urine samples. Perturbed lipid species (adjusted p < 0.05) were observed, including lysophosphatidylethanolamines, phosphatidylinositols, phosphatidylcholines, phosphatidylethanol amines, and triglycerides. Additionally, differential metabolites (adjusted p < 0.05) exhibited associations with amino acid metabolism, nucleotide metabolism, and energy metabolism. Thirteen plasma metabolites, namely l-hydroxyproline, 3-phosphoglycerate, citric acid, creatine, inosine, ribitol, α tocopherol, cholesterol, cystine, serine, uric acid, tagatose, and glycine, showed significant associations with disease severity (p < 0.05) and exhibited distinct separation patterns in M. pneumoniae-infected bronchitis and pneumonia, with an area under the curve of 0.927. Nine of them exhibited either positive or negative correlations with neutrophil or lymphocyte percentages. These findings indicated significant systemic metabolic shifts in childhood M. pneumoniae infections, offering valuable insights into the associated metabolic alterations and their relationship with disease severity., (© 2023 John Wiley & Sons Ltd.)

Neuromorphic simulation, i.e., the use of electronic devices to simulate the neural networks of the human brain, has attracted a lot of interest in the fields of data processing and memory. This work provides a new method for preparing a 1,3-dimethylimidazolium nitrate ([MMIm][NO 3 ]:H 2 O) microfluidic memristor that is ultralow cost and technically uncomplicated. Such a fluidic device uses capillaries as memory tubes, which are structurally similar to interconnected neurons by simple solution treatment. When voltage is applied, the transmission of anions and cations in the tube corresponds to the release of neurotransmitters from the presynaptic membrane to the postsynaptic membrane. The change of synaptic weights (plasticity) also can be simulated by the gradual change of conductance of the fluid memristor. The learning process of microfluidic memristors is very obvious, and the habituation and recovery behaviors they exhibit are extremely similar to biological activities, representing its good use for simulating neural synapses.

Abstract: To explore the impact of different imaging classifications of prostate cancer (PCa) with extracapsular extension (EPE) on positive surgical margins (PSM) after laparoscopic radical prostatectomy., Methods: Clinical data were collected for 114 patients with stage PT3a PCa admitted to Ningbo Yinzhou No. 2 Hospital from September 2019 to August 2023. Radiologists classified the EPE imaging of PCa into Type I, Type II, and Type III. A chi-square test or t-test was employed to analyze the factors related to PSM. Multivariate regression analysis was conducted to determine the factors associated with PSM. Receiver operating characteristic curve analysis was used to calculate the area under the curve and evaluate the diagnostic performance of our model. Clinical decision curve analysis was performed to assess the clinical net benefit of EPE imaging classification, biopsy grade group (GG), and combined model., Results: Among the 114 patients, 58 had PSM, and 56 had negative surgical margins. Multivariate analysis showed that EPE imaging classification and biopsy GG were risk factors for PSM after laparoscopic radical prostatectomy. The areas under the curve for EPE imaging classification and biopsy GG were 0.677 and 0.712, respectively. The difference in predicting PSM between EPE imaging classification and biopsy GG was not statistically significant (P>0.05). However, when used in combination, the diagnostic efficiency significantly improved, with an increase in the area under the curve to 0.795 (P<0.05). The clinical decision curve analysis revealed that the clinical net benefit of the combined model was significantly higher than that of EPE imaging classification and biopsy GG., Conclusions: EPE imaging classification and biopsy GG were associated with PSM after laparoscopic radical prostatectomy, and their combination can significantly improve the accuracy of predicting PSM., 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 Wang, Zhong, Zhang and Chen.)

Soil samples were collected in at different depths from the conflagration area in Liangshan Yi Autonomous Region, China, to investigate the distribution characteristics and ecological and human health risks of heavy metals after a wildfire. The samples collected comprise wildfire ash (WA) above the soil surface, ash soil (AS) 0-5 cm, and plain soil (PS) 5-15 cm below the soil surface. Additionally, reference soil (RS) was collected from a nearby unburned area at the same latitude as the conflagration area. The results showed that the concentrations of zinc (Zn), copper (Cu), lead (Pb), and cadmium (Cd) in the WA and AS were significantly higher than in reference soil (RS) (p < 0.05). Concentrations of Pb in the PS were 2.52 times higher than that in RS (17.9 mg kg -1 ) (p < 0.05). The AS and WA had the highest Index of potential ecological risks (RI > 600). In addition, The Cd in AS and WA contributed the most to the highest Improved nemerow index (INI) and RI with a contribution of more than 80%. The concentration of heavy metals was used to establish non-carcinogenic effects and cancer risks in humans via three exposure pathways: accident ingestion of soil, dermal contact with soil, and inhalation of soil particles. Hazard index (HI) values of each sample were all less than 1, indicating the non-carcinogenic risk was within the acceptable range and would not adversely affect the local population's health. The Cancer risk (CR) values of Cr, As, Cd, and Ni were all below 1 × 10 -6 , indicating that heavy metal pollution from this wildfire did not pose a cancer risk to residents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Landfill is reservoir containing antibiotic resistance genes (ARGs) that pose a threat to human life and health. Heavy metals impose lasting effects on ARGs. This review investigated and analyzed the distribution, composition, and abundance of heavy metals and ARGs in landfill. The abundance ranges of ARGs detected in refuse and leachate were similar. The composition of ARG varied with sampling depth in refuse. ARG in leachate varies with the distribution of ARG in the refuse. The ARG of sulI was associated with 11 metals (Co, Pb, Mn, Zn, Cu, Cr, Ni, Sb, As, Cd, and Al). The effects of the total metal concentration on ARG abundance were masked by many factors. Low heavy metal concentrations showed positive effects on ARG diffusion; conversely, high heavy metal concentrations showed negative effects. Organic matter had a selective pressure effect on microorganisms and could provide energy for the diffusion of ARGs. Complexes of heavy metals and organic matter were common in landfill. Therefore, the hypothesis was proposed that organic matter and heavy metals have combined effects on the horizontal gene transfer (HGT) of ARGs during landfill stabilization. This work provides a new basis to better understand the HGT of ARGs in landfill., 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 © 2023. Published by Elsevier B.V.)

As the only aquatic lineage of Pteridaceae, Parkerioideae is distinct from many xeric-adapted species of the family and consists of the freshwater Ceratopteris species and the only mangrove ferns from the genus Acrostichum . Previous studies have shown that whole genome duplication (WGD) has occurred in Parkerioideae at least once and may have played a role in their adaptive evolution; however, more in-depth research regarding this is still required. In this study, comparative and evolutionary transcriptomics analyses were carried out to identify WGDs and explore their roles in the environmental adaptation of Parkerioideae. Three putative WGD events were identified within Parkerioideae, two of which were specific to Ceratopteris and Acrostichum , respectively. The functional enrichment analysis indicated that the lineage-specific WGD events have played a role in the adaptation of Parkerioideae to the low oxygen concentrations of aquatic habitats, as well as different aquatic environments of Ceratopteris and Acrostichum , such as the adaptation of Ceratopteris to reduced light levels and the adaptation of Acrostichum to high salinity. Positive selection analysis further provided evidence that the putative WGD events may have facilitated the adaptation of Parkerioideae to changes in habitat. Moreover, the gene family analysis indicated that the plasma membrane H + -ATPase ( AHA ), vacuolar H + -ATPase ( VHA ), and suppressor of K + transport growth defect 1 ( SKD1 ) may have been involved in the high salinity adaptation of Acrostichum . Our study provides new insights into the evolution and adaptations of Parkerioideae in different aquatic environments., Competing Interests: The authors declare no conflicts of interest.

The shotgun proteomic analysis is currently the most promising single-cell protein sequencing technology, however its identification level of ~1000 proteins per cell is still insufficient for practical applications. Here, we develop a pick-up single-cell proteomic analysis (PiSPA) workflow to achieve a deep identification capable of quantifying up to 3000 protein groups in a mammalian cell using the label-free quantitative method. The PiSPA workflow is specially established for single-cell samples mainly based on a nanoliter-scale microfluidic liquid handling robot, capable of achieving single-cell capture, pretreatment and injection under the pick-up operation strategy. Using this customized workflow with remarkable improvement in protein identification, 2449-3500, 2278-3257 and 1621-2904 protein groups are quantified in single A549 cells (n = 37), HeLa cells (n = 44) and U2OS cells (n = 27) under the DIA (MBR) mode, respectively. Benefiting from the flexible cell picking-up ability, we study HeLa cell migration at the single cell proteome level, demonstrating the potential in practical biological research from single-cell insight., (© 2024. The Author(s).)

Total joint replacement (TJR) surgery in the ambulatory surgery centers (ASCs) has grown significantly over the past several years, along with the ability to improve the value of care. Standardization of high-quality, perioperative care is pivotal to the success of a TJR ASC program. As surgeons are experiencing increasing overhead with decreasing reimbursement, technology integration can provide major advantages. In this article, we will therefore highlight several examples of technologies that are changing the field and improving care in the preoperative, intraoperative, and postoperative settings., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Tracy M. Borsinger, MD, declares no potential conflicts of interest. James B Chen, MD, reports relationships with Canary Medical, OrthAlign, and Zimmer Biomet. Brian P. Chalmers, MD, reports relationships with Ortho Development, and Smith & Nephew. Eytan M. Debbi, MD, PhD, reports relationships with DePuy, Ortho Development, and Think Surgical., (© The Author(s) 2023.)

Objective: To explore the effects of pre-transplant controlling nutritional status (CONUT) and post-transplant minimal residual disease (MRD) on prognosis of patients with multiple myeloma (MM) after autologous hematopoietic stem cell transplantation (auto-HSCT)., Methods: The clinical data of 79 patients who received auto-HSCT from 2011 to 2020 in The First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The patients were divided into Low-CONUT group ( n =62) and High-CONUT group ( n =17) according to whether the CONUT score was less than 5. The differences in clinical features, hematopoietic reconstruction, adverse reactions, efficacy and survival between the two groups were compared. In addition, the prognostic risk factors were analyzed and verified by time-dependent ROC curve., Results: The proportions of male patients and bone marrow plasma cells>30% at initial diagnosis in High-CONUT group were both higher than those in Low-CONUT group (both P <0.05). While, there were no significant differences in hematopoietic reconstruction and adverse reactions (>grade 2) between the two groups. The complete response (CR) rate and CR+very good partial response (VGPR) rate before transplantation in Low-CONUT group were both significantly higher than those in High-CONUT group (both P <0.05). After 3 months of transplantation, the CR+VGPR rate still remained an advantage in Low-CONUT group compared with High-CONUT group ( P <0.01), but CR rate did not( P >0.05). The overall survival (OS) and progression-free survival (PFS) in Low-CONUT group were both superior to those in High-CONUT group (both P <0.05). Low CONUT score (0-4) before transplantation and negative MRD at 6 months after transplantation were favorable factors affecting OS and PFS (both P <0.05), while the International Myeloma Working Group (IMWG) high-risk at initial diagnosis and lactate dehydrogenase (LDH) level>250 U/L before transplantation were only risk factors for PFS (both P <0.05). Time-dependent ROC curve analysis showed that pre-transplant CONUT score and MRD status at 6 months after transplantation could independently or jointly predict 1- and 2-year OS and PFS, and the combined prediction was more effective., Conclusion: The combination of pre-transplant CONUT and post-transplant MRD can better predict the prognosis of MM patients.

Background: While robotic-assisted total hip arthroplasty (RA-THA) has been associated with improved accuracy of component placement, the perioperative and early postoperative outcomes of fluoroscopy-based RA-THA systems have yet to be elucidated., Methods: This retrospective cohort analysis included a consecutive series of patients who received manual, fluoroscopy-assisted THA (mTHA) and fluoroscopy-based RA-THA at a single institution. We compared rates of complications within 90 days of surgery, length of hospital stay (LOS), and visual analog scale (VAS) pain scores., Results: No differences existed between groups with respect to demographic data or perioperative recovery protocols. The RA-THA cohort had a significantly greater proportion of outpatient surgeries compared to the mTHA cohort (37.4% vs. 3.8%; p < 0.001) and significantly lower LOS (26.0 vs. 39.5 h; p < 0.001). The RA-THA cohort had a smaller 90-day postoperative complication rate compared to the mTHA cohort (0.9% vs. 6.7%; p = 0.029). The RA-THA cohort had significantly lower patient-reported VAS pain scores at 2-week follow-up visits (2.5 vs. 3.3; p = 0.048), but no difference was seen after 6-week follow visits (2.5 vs. 2.8; p = 0.468)., Conclusion: Fluoroscopy-based RA-THA demonstrates low rates of postoperative complications, improved postoperative pain profiles, and shortened LOS when compared to manual, fluoroscopy-assisted THA., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Reasonable nitrogen fertilizer application is an important strategy to maintain optimal growth of grasslands, thereby enabling them to better fulfil their ecological functions while reducing environmental pollution caused by high nitrogen fertilizer production and application. Optimizing the ammonium (NH 4 + ):nitrate (NO 3 - ) ratio is a common approach for growth promotion in crops and vegetables, but research on this topic in grass plants has not received sufficient attention. Centipedegrass, which is widely used in landscaping and ecological protection, was used as the experimental material. Different NH 4 + :NO 3 - ratios (0: 100, 25:75, 50:50, 75:25, 100:0) were used as the experimental treatments under hydroponic conditions. By monitoring the physiological and morphological changes under each treatment, the appropriate NH 4 + :NO 3 - ratio for growth and its underlying mechanism were determined. As the proportion of ammonium increased, the growth showed a "bell-shaped" response, with the maximum biomass and total carbon and nitrogen accumulation achieved with the NH 4 + :NO 3 - ratio of 50:50 treatment. Compared with the situation where nitrate was supplied alone, increasing the ammonium proportion increased the whole plant biomass by 93.2%, 139.7%, 59.0%, and 30.5%, the whole plant nitrogen accumulation by 44.9%, 94.6%, 32.8%, and 54.8%, and the whole plant carbon accumulation by 90.4%, 139.9%, 58.7%, and 26.6% in order. As a gateway for nitrogen input, the roots treated with an NH 4 + :NO 3 - ratio of 50:50 exhibited the highest ammonium and nitrate uptake rate, which may be related to the maximum total root length, root surface area, average root diameter, root volume, and largest root xylem vessel. As a gateway for carbon input, leaves treated with an NH 4 + :NO 3 - ratio of 50:50 exhibited the highest stomatal aperture, stomatal conductance, photosynthetic rate, transpiration rate, and photosynthetic products. The NH 4 + :NO 3 - ratio of 50:50 treatment had the largest stem xylem vessel area. This structure and force caused by transpiration may synergistically facilitate root-to-shoot nutrient translocation. Notably, the change in stomatal opening occurred in the early stage (4 hours) of the NH 4 + :NO 3 - ratio treatments, indicating that stomates are structures that are involved in the response to changes in the root NH 4 + :NO 3 - ratio. In summary, we recommend 50:50 as the appropriate NH 4 + :NO 3 - ratio for the growth of centipedegrass, which not only improves the nitrogen use efficiency but also enhances the carbon sequestration capacity., 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 © 2023 Hao, Zhou, Li, Qu, Li, Chen, Kong, Li, Li, Guo, Liu, Zong and Chen.)

This multicenter study aimed to explore the survival benefit of metastasectomy by first-line cetuximab-based chemotherapy in real-world patients with RAS wild-type metastatic colorectal cancer (mCRC). The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and metastasectomy rate. The exploratory endpoint was the optimal treatment cycle for better OS and PFS. Receiver operating characteristic curve with the area under curve (AUC) was used to identify the optimal cut-off cycle for survival outcomes. A total of 758 mCRC patients were enrolled in this study, with a median OS of 35.1 months, median PFS of 14.6 months, and metastasectomy rate of 21.4%. Left-sided mCRC had a significantly higher DCR (88.9% vs. 73.1%, P <0.001) and better OS (36.4 vs. 19.6 months, P <0.001). There were no significant differences in PFS and metastasectomy rate between left-sided and right-sided mCRC. However, mCRC patients who underwent metastasectomy over the course of treatment had better OS (54.9 vs. 28.6 months, P <0.001) and PFS (21.0 vs. 13.1 months, P <0.001) than those who did not. Notably, right-sided mCRC who benefited from first-line cetuximab-based chemotherapy to underwent metastasectomy also had favorable outcomes, on a par with left-sided mCRC. The optimal treatment cycle was 14 cycles (AUC: 0.779, P <0.001). Patients who received ≥14 cycles had higher metastasectomy rates (27.5% vs. 13.5%, P <0.001), favorable OS (42.6 vs. 23.4 months, P <0.001) and PFS (18.1 vs. 8.6 months, P <0.001), and, importantly, had comparable adverse events compared with patients who received <14 cycles of treatment. Patients who underwent metastasectomy after or during first-line cetuximab therapy have an improved OS in both left-sided and right-sided mCRC. Furthermore, patients receive ≥14 cycles of treatment whenever possible to achieve a higher likelihood of metastasectomy was associated with favorable survival outcomes., Competing Interests: None., (AJCR Copyright © 2023.)