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Xiaomin Liu,1,* Rui Hu,2,* Hongwei Lian,1,3 Yang Liu,4 Jing Liu,1 Jianwei Liu,1 Guimiao Lin,5 Liwei Liu,6 Xiaojian Duan,1 Ken-Tye Yong,2 Ling Ye1 1Institute of Gerontology and Geriatrics, Chinese PLA General Hospital, Beijing Key Lab of Aging and Geriatrics, Beijing, People’s Republic of China; 2School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore, Singapore; 3Department of Emergency Medicine, Peking University Third Hospital, Beijing, 4Department of Geriatric Nephrology, Chinese PLA General Hospital, Beijing, 5Key Lab of Biomedical Engineering, School of Medical Sciences, Shenzhen University, Shenzhen, 6School of Science, Changchun University of Science and Technology, Changchun, People’s Republic of China *These authors contributed equally to this work Abstract: Diabetes is one of the major chronic diseases diagnosed worldwide with a common complication of diabetic nephropathy (DN). There are multiple possible mechanisms associated with DN. Aldose reductase (AR) and Toll-like receptor 4 (TLR4) may be involved in the occurrence and development of DN. Here, we describe the distribution of AR and TLR4 in cells and renal tissues of diabetic rats through a quantum dot (QD)-based immunofluorescence technique and conventional immunohistochemistry. As a new type of nanosized fluorophore, QDs have been recognized in imaging applications and have broad prospects in biomedical research. The results of the reported study demonstrate that both the AR and the TLR4 proteins were upregulated in the renal tissues of diabetic rats. Further, to explore the relationship between AR and TLR4 in the pathogenesis of DN, a dual-color immunofluorescent labeling technique based on QDs was applied, where the expressions of AR and TLR4 in the renal tissues of diabetic rats were simultaneously observed – for the first time, as far as we are aware. The optimized QD-based immunofluorescence technique has not only shown a satisfying sensitivity and specificity for the detection of biomarkers in cells and tissues, but also is a valuable supplement of immunohistochemistry. The QD-based multiplexed imaging technology provides a new insight into the mechanistic study of the correlation among biological factors as well as having potential applications in the diagnosis and treatment of diseases. Keywords: diabetic nephropathy, TLR4, immunofluorescence, immunohistochemistry

Stephen W Pedersen,1 Martin Suedmeyer,2 Louis W C Liu,3 Dirk Domagk,4 Alison Forbes,5 Lars Bergmann,6 Koray Onuk,6 Ashley Yegin,6 Teus van Laar7 1Department of Neurology, Glostrup Hospital, University of Copenhagen, Glostrup, Copenhagen, Denmark; 2Department of Neurology, University of Düesseldorf, Düesseldorf, Germany; 3Division of Gastroenterology, Department of Medicine, University of Toronto, University Health Network, Toronto, ON, Canada; 4Department of Medicine I, Josephs-Hospital Warendorf, Academic Teaching Hospital, University of Muenster, Warendorf, Germany; 5PDNS consultant, AbbVie Inc., Roswell, GA, USA; 6Global Medical Affairs, AbbVie Inc., North Chicago, IL, USA; 7Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands Abstract: A multidisciplinary team (MDT) approach is increasingly recommended in Parkinson’s disease (PD) treatment guidelines, but no standard of care exists for such an approach, and the guidelines do not provide clarification on how it should be implemented. This paper reviews evidence of MDT interventions in people with PD and provides expert clinical perspectives for an MDT approach, with a focus on advanced PD and levodopa–carbidopa intestinal gel (carbidopa–levodopa enteral suspension in the USA). The key recommendations are to enable the best possible treatment of people with PD locally by facilitating a close structured collaboration of different health care professionals working in a fixed network structure; to refer people with PD to established MDT centers in a timely manner; to establish regular meetings for the MDT enabling interdisciplinary exchange and learning; to optimize individual treatment and carefully evaluate available treatment options; to ensure treatment decisions are agreed jointly between people with PD, their caregivers, family, and health care professional; and to include specialists outside of neurology from adjuvant medical departments as necessary when implementing advanced therapies. Keywords: Parkinson’s disease, multidisciplinary team, advanced therapy, levodopa–carbidopa intestinal gel, carbidopa–levodopa enteral suspension

The purpose of this study was to evaluate the resources and services of a pediatric consumer health library by analyzing data collected over a two-year period. Data gathered from May 1998 to May 2000 was analyzed under four major fields: number of requests, origin of requests, subjects of requests, sources of answers. There were a total of 359 reference questions asked. Some were initiated by patients or for patients by hospital staff (292); some were made by hospital employees (43), school nurses (11), insurance companies (8), and health agencies (5). Nurses made the most referrals to the library (78), followed by social workers and physicians (10). Birth defect questions were asked most often (88), followed by psychology (61), cancer (31), pulmonology (31), surgery (25), and others (123). Gale's Health Reference Center database was used 143 times, National Organization of Rare Diseases database was used 56 times, consumer books and videos were used 64 times, Internet was used 28 times, medical books and MEDLINE databases were used 47 times. There were seven questions that were not answered well, and seven others were not answered at all. Conclusion: Data gathered from the analysis demonstrated that the library collection was adequate in meeting the consumer health information needs in Arkansas Children's Hospital. [ABSTRACT FROM AUTHOR]

Background: Bacterial biofilm is a strong fortress for bacteria to resist harsh external environments, which can enhance their tolerance and exacerbate the drug/pesticide resistance risk. Currently, photopharmacology provides an advanced approach via precise spatiotemporal control for regulating biological activities by light-controlling the molecular configurations, thereby having enormous potential in the development of drug/pesticides., Results: To further expand the photopharmacology application for discovering new antibiofilm agents, we prepared a series of light-controlled azo-active molecules and explored their photo isomerization, fatigue resistance, and anti-biofilm performance. Furthermore, their mechanisms of inhibiting biofilm formation were systematically investigated. Overall, designed azo-derivative A11 featured excellent anti-Xoo activity with an half-maximal effective concentration (EC 50 ) value of 5.45 μg mL -1 , and the EC 50 value could be further elevated to 2.19 μg mL -1 after ultraviolet irradiation (converted as cis-configuration). The photo-switching behavior showed that A11 had outstanding anti-fatigue properties. An in-depth analysis of the action mechanism showed that A11 could effectively inhibit biofilm formation and the expression of relevant virulence factors. This performance could be dynamically regulated via loading with private light-switch property., Conclusion: In this work, designed light-controlled azo molecules provide a new model for resisting bacterial infection via dynamic regulation of bacterial biofilm formation. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

1D grain boundaries in transition metal dichalcogenides (TMDs) are ideal for investigating the collective electron behavior in confined systems. However, clear identification of atomic structures at the grain boundaries, as well as precise characterization of the electronic ground states, have largely been elusive. Here, direct evidence for the confined electronic states and the charge density modulations at mirror twin boundaries (MTBs) of monolayer NbSe 2 , a representative charge-density-wave (CDW) metal, is provided. The scanning tunneling microscopy (STM) measurements, accompanied by the first-principles calculations, reveal that there are two types of MTBs in monolayer NbSe 2 , both of which exhibit band bending effect and 1D boundary states. Moreover, the intrinsic CDW signatures of monolayer NbSe 2 are dramatically suppressed as approaching an isolated MTB but can be either enhanced or suppressed in the MTB-constituted confined wedges. Such a phenomenon can be well explained by the MTB-CDW interference interactions. The results reveal the underlying physics of the confined electrons at MTBs of CDW metals, paving the way for the grain boundary engineering of the functionality., (© 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Diabetes is a chronic disease that affects millions of humans worldwide. This review article provides an analysis of the recent advancements in non-invasive blood glucose monitoring, detailing methods and techniques, with a special focus on Electromagnetic wave microwave glucose sensors. While optical, thermal, and electromagnetic techniques have been discussed, the primary emphasis is focussed on microwave frequency sensors due to their distinct advantages. Microwave sensors exhibit rapid response times, require minimal user intervention, and hold potential for continuous monitoring, renders them extremely potential for real-world applications. Additionally, their reduced susceptibility to physiological interferences further enhances their appeal. This review critically assesses the performance of microwave glucose sensors by considering factors such as accuracy, sensitivity, specificity, and user comfort. Moreover, it sheds light on the challenges and upcoming directions in the growth of microwave sensors, including the need for reduction and integration with wearable platforms. By concentrating on microwave sensors within the broader context of non-invasive glucose monitoring, this article aims to offer significant enlightenment that may drive further innovation in diabetes care., Competing Interests: 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., (© 2024 The Authors.)

Background: The National Chest Pain Center Program (NCPCP) is a nationwide, quality enhancement program aimed at raising the standard of care for patients experiencing acute chest pain in China. The benefits of chest pain center (CPC) accreditation on acute coronary syndrome have been demonstrated. However, there is no evidence to indicate whether CPC accreditation improves outcomes for patients with acute aortic dissection (AAD)., Methods: We conducted a retrospective observational study of patients with AAD from 1671 hospitals in China, using data from the NCPCP spanning the period from January 1, 2016 to December 31, 2022. The patients were divided into 2 groups: pre-accreditation and post-accreditation admissions. The outcomes examined included in-hospital mortality, misdiagnosis, and Stanford type A AAD surgery. Multivariate logistic regression was employed to explore the relationship between CPC accreditation and in-hospital outcomes. Furthermore, we stratified the hospitals based on their geographical location (Eastern/Central/Western regions) or administrative status (provincial/non-provincial capital areas) to assess the impact of CPC accreditation on AAD patients across various regions., Results: The analysis encompassed a total of 40,848 patients diagnosed with AAD. The post-accreditation group exhibited significantly lower rates of in-hospital mortality and misdiagnosis (12.1% vs. 16.3%, P < 0.001 and 2.9% vs. 5.4%, P < 0.001, respectively) as well as a notably higher rate of Stanford type A AAD surgery (61.1% vs. 42.1%, P < 0.001) compared with the pre-accreditation group. After adjusting for potential covariates, CPC accreditation was associated with substantially reduced risks of in-hospital mortality (adjusted OR 0.644, 95% CI 0.599-0.693) and misdiagnosis (adjusted OR 0.554, 95% CI 0.493-0.624), along with an increase in the proportion of patients undergoing Stanford type A AAD surgery (adjusted OR 1.973, 95% CI 1.797-2.165). Following CPC accreditation, there were significant reductions in in-hospital mortality across various regions, particularly in Western regions (from 21.5 to 14.1%). Moreover, CPC accreditation demonstrated a more pronounced impact on in-hospital mortality in non-provincial cities compared to provincial cities (adjusted OR 0.607 vs. 0.713)., Conclusion: CPC accreditation is correlated with improved management and in-hospital outcomes for patients with AAD., (© 2024. The Author(s).)

Background: Bacterial virulence factors are involved in various biological processes and mediate persistent bacterial infections. Focusing on virulence factors of phytopathogenic bacteria is an attractive strategy and crucial direction in pesticide discovery to prevent invasive and persistent bacterial infection. Hence, discovery and development of novel agrochemicals with high activity, low-risk, and potent anti-virulence is urgently needed to control plant bacterial diseases., Results: A series of novel β-hydroxy pyridinium cation decorated pterostilbene derivatives were prepared and their antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) were systematacially assessed. Among these pterostilbene derivatives, compound 4S exhibited the best antibacterial activity against Xoo in vitro, with an half maximal effective concentration (EC 50 ) value of 0.28 μg mL -1 . A series of biochemical assays including scanning electron microscopy, crystal violet staining, and analysis of biofilm formation, swimming motility, and related virulence factor gene expression levels demonstrated that compound 4S could function as a new anti-virulence factor inhibitor by interfering with the bacterial infection process. Furthermore, the pot experiments provided convinced evidence that compound 4S had the high control efficacy (curative activity: 71.4%, protective activity: 72.6%), and could be used to effectively manage rice bacterial leaf blight in vivo., Conclusion: Compounds 4S is an attractive virulence factor inhibitor with potential for application in treating plant bacterial diseases by suppressing production of several virulence factors. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Benzimidazoles, the representative pharmacophore of fungicides, have excellent antifungal potency, but their simple structure and single site of action have hindered their wider application in agriculture. In order to extend the structural diversity of tubulin-targeted benzimidazoles, novel benzimidazole derivatives were prepared by introducing the attractive pyrimidine pharmacophore. 2-((6-(4-(trifluoromethyl)phenoxy)pyrimidin-4-yl)thio)-1 H -benzo[ d ]imidazole ( A 25 ) exhibited optimal antifungal activity against Sclerotinia sclerotiorum ( S. s. ), affording an excellent half-maximal effective concentration (EC 50 ) of 0.158 μg/mL, which was higher than that of the reference agent carbendazim (EC 50 = 0.594 μg/mL). Pot experiments revealed that compound A 25 (200 μg/mL) had acceptable protective activity (84.7%) and curative activity (78.1%), which were comparable with that of carbendazim (protective activity: 90.8%; curative activity: 69.9%). Molecular docking displayed that multiple hydrogen bonds and π-π interactions could be formed between A 25 and β-tubulin, resulting in a stronger bonding effect than carbendazim. Fluorescence imaging revealed that the structure of intracellular microtubules can be changed significantly after A 25 treatment. Overall, these remarkable antifungal profiles of constructed novel benzimidazole derivatives could facilitate the application of novel microtubule-targeting agents.

Objective: Explore the expression pattern of transcription factor activator protein 2C (TFAP2C) and identify the roles of Tfap2c during tooth development. Methods: Real-time fluorescence quantitative PCR (RT-qPCR) was used to analyze the relative expression level of Tfap2c in various organs of embryonic day(E)14.5 mouse embryos and mouse molar germs at E12.5-E18.5 and postnatal day (P)0-P7. The expression position of Tfap2c in mouse molar germs was demonstrated by frozen section immunofluorescence staining. Cultured mandibular molar germs were transfected with control small interfering RNA (siRNA) or Tfap2c siRNA to evaluate the effect of Tfap2c on tooth molar germs development, and RT-qPCR was used to detect the relative expression level of genes related to odontoblast expression. Dental mesenchymal cells were isolated from E14.5 molar germs and transfected with control siRNA or Tfap2c siRNA, cell counting kit 8 (CCK-8) and scratch healing test were applied to detect dental mesenchymal cell viability and migration. Results: Tfap2c was highly expressed in the early development period of mouse molar germs. Tfap2c was expressed in the epithelial and mesenchymal tissues of E13.5 mouse molar germs and there was no significant difference of relative expression of Tfap2c between them ( t =1.06, P =0.472). Tfap2c was expressed in mesenchymal tissues of E14.5 mouse molar germs and the relative expression of Tfap2c in mesenchymal tissues was significantly higher than epithelial tissues ( t =37.29, P <0.0001). For molar germs transfected with Tfap2c siRNA, the relative height of cusps (0.708±0.171) and the ratio of cusp height and crown height (0.321±0.068) was significantly lower than control group (1.000±0.287 and 0.483±0.166) ( t =2.79, P =0.012; t =2.85, P =0.015). But there was no significant difference in relative height (1.078±0.206, 0.993±0.254, t =0.83, P =0.419)and relative width (1.000±0.116, 0.999±0.122, t =0.01, P =0.992) of crowns between two groups. The relative expression level of genes related to odontoblast expression was decreased (Dspp: t =15.33, P <0.001; Dmp1: t =13.81, P <0.001). Tfap2c siRNA hinders cell migration in dental mesenchymal cells ( t =29.86, P =0.001), but there was no significant difference in CCK-8 absorbance value between two groups. The relative expression level of genes related to odontoblast expression was also decreased in dental mesenchymal cells transfected with Tfap2c siRNA (Dspp: t =3.86, P =0.031; Dmp1; t =4.36, P =0.022). Conclusions: Tfap2c highly expressed in the early morphogenesis period of mouse molar germs, mainly in mesenchymal tissues. Tfap2c affected the cusps formation of mouse molar germs and migration of dental mesenchymal cells.

Reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) serve as vital mediators essential for preserving intracellular redox homeostasis within the human body, thereby possessing significant implications across physiological and pathological domains. Nevertheless, deviations from normal levels of ROS, RNS, and RSS disturb redox homeostasis, leading to detrimental consequences that compromise bodily integrity. This disruption is closely linked to the onset of various human diseases, thereby posing a substantial threat to human health and survival. Small-molecule fluorescent probes exhibit considerable potential as analytical instruments for the monitoring of ROS, RNS, and RSS due to their exceptional sensitivity and selectivity, operational simplicity, non-invasiveness, localization capabilities, and ability to facilitate in situ optical signal generation for real-time dynamic analyte monitoring. Due to their distinctive transition from their spirocyclic form (non-fluorescent) to their ring-opened form (fluorescent), along with their exceptional light stability, broad wavelength range, high fluorescence quantum yield, and high extinction coefficient, rhodamine fluorophores have been extensively employed in the development of fluorescent probes. This review primarily concentrates on the investigation of fluorescent probes utilizing rhodamine dyes for ROS, RNS, and RSS detection from the perspective of different response groups since 2016. The scope of this review encompasses the design of probe structures, elucidation of response mechanisms, and exploration of biological 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 Elsevier B.V. All rights reserved.)

Introduction: Previous observational studies have shown that polycystic ovary syndrome (PCOS) was associated with adverse pregnancy and perinatal outcomes. However, it remains controversial whether PCOS is an essential risk factor for these adverse pregnancy and perinatal outcomes. We aimed to use instrumental variables in a two-sample Mendelian randomization (MR) study to determine causality between PCOS and adverse pregnancy and perinatal outcomes., Materials and Methods: Summary statistics were extracted from a recent genome-wide association study (GWAS) meta-analysis conducted in PCOS, which included 10,074 cases and 103,164 controls of European ancestry. Data on Adverse pregnancy and perinatal outcomes were summarized from the FinnGen database of European ancestry, which included more than 180,000 samples. The inverse variance weighted (IVW) method of MR was applied for the main outcome. To assess heterogeneity and pleiotropy, we conducted sensitivity analyses, including leave-one-out analysis, weighted median, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier), and MR-Egger regression., Results: Two-sample MR analysis with the IVW method suggested that PCOS exerted causal effects on the risk of hypertensive disorders of pregnancy [odds ratio (OR) 1.170, 95% confidence interval (CI) 1.051-1.302, p = 0.004], in particular gestational hypertension (OR 1.083, 95% CI 1.007-1.164, p = 0.031), but not other pregnancy and perinatal diseases (all p > 0.05). Sensitivity analyses demonstrated pleiotropy only in pre-eclampsia or eclampsia ( p = 0.0004), but not in other pregnancy and perinatal diseases (all p > 0.05). The results remained consistent after excluding two outliers (all p > 0.05)., Conclusions: We confirmed a causal relationship between PCOS and hypertensive disorders of pregnancy, in particular gestational hypertension, but no association with any other adverse pregnancy or perinatal outcome. Therefore, we suggest that women with PCOS who are pregnant should have their blood pressure closely monitored., 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 Ma, Cai, Liu, Wen, Huang, Hou, Wei, Xu, Xu, Wang and Mai.)

Background: Glove reuse poses risks, as chemicals can persist even after cleaning. Decontamination methods like thermal aeration, recommended by US OSHA, vary in effectiveness. Some studies show promising results, while others emphasize the importance of considering both permeation and tensile strength changes. This research advocates for informed glove reuse, emphasizing optimal thermal aeration temperatures and providing evidence to guide users in maintaining protection efficiency., Methods: The investigation evaluated Neoprene and Nitrile gloves (22 mils). Permeation tests with toluene and acetone adhered to American Society for Testing Materials (ASTM) F739 standards. Decontamination optimization involved aeration at various temperatures. The experiment proceeded with a maximum of 22 re-exposure cycles. Tensile strength and elongation were assessed following ASTM D 412 protocols. Breakthrough time differences were statistically analyzed using t -test and ANOVA., Results: At room temperature, glove residuals decreased, and standardized breakthrough time (SBT) 2 was significantly lower than SBT 1 , indicating reduced protection. Higher temperature decontamination accelerated residual removal, with ΔSBT (SBT 2 /SBT 1 ) exceeding 100%, signifying restored protection. Tensile tests showed stable neoprene properties postdecontamination. Results underscore thermal aeration's efficacy for gloves reuse, emphasizing temperature's pivotal role. Findings recommend meticulous management strategies, especially post-breakthrough, to uphold glove-protective performance., Conclusions: Thermal aeration at 100°C for 1 hour proves effective, restoring protection without compromising glove strength. The study, covering twenty cycles, suggests safe glove reuse with proper decontamination, reducing costs significantly. However, limitations in chemical-glove combinations and exclusive focus on specific gloves caution against broad generalization. The absence of regulatory directives on glove reuse highlight the importance of informed selection and rigorous decontamination validation for workplace safety practices., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 Occupational Safety and Health Research Institute. Published by Elsevier B.V. on behalf of Institute, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency.)

A synthetically useful approach to functionalized triazoles is described via the reaction of β-carbonyl phosphonates and azides. 1,4- and 1,5-disubstituted and 1,4,5-trisubstituted triazoles can be regio- and chemoselectively accessed under mild conditions in good to excellent yields (31 examples, up to 99%). A mechanism is proposed that rationalizes the avoidance of the 4-phosphonate byproducts, which is aligned with crystallographic and experimental evidence.

As a notorious phytopathogenic virus, the tobacco mosaic virus (TMV) severely reduced the quality of crops worldwide and caused critical constraints on agricultural production. The development of novel virucides is a persuasive strategy to address this predicament. Herein, a series of novel bisamide-decorated benzotriazole derivatives were elaborately prepared and screened. Biological tests implied that the optimized compound 7d possessed the most brilliant antiviral inactive profile (EC 50 = 157.6 μg/mL) and apparently surpassed that of commercial ribavirin (EC 50 = 442.1 μg/mL) 2.8-fold. The preliminary antiviral mechanism was elaborately investigated via transmission electron microscopy, microscale thermophoresis (MST) determination, RT-qPCR, and Western blot analysis. The results showed that compound 7d blocked the assembly of TMV by binding with coat protein ( K d = 0.7 μM) and suppressed TMV coat protein gene expression and biosynthesis process. Computational simulations indicated that 7d displayed strong H-bonds and pi interactions with TMV coat protein, affording a lower binding energy (Δ Gbind = -17.8 kcal/mol) compared with Ribavirin (Δ Gbind = -10.7 kcal/mol). Overall, current results present a valuable perception of bisamide decorated benzotriazole derivatives with appreciably virustatic competence and should be profoundly developed as virucidal candidates in agrochemical.

Background: We used computer-assisted image analysis to determine whether preexisting histological features of the cephalic vein influence the risk of non-maturation of wrist fistulas., Methods: This study focused on patients aged 20-80 years who underwent their first wrist fistula creation. A total of 206 patients participated, and vein samples for Masson's trichrome staining were collected from 134 patients. From these, 94 patients provided a complete girth of the venous specimen for automatic image analysis. Maturation was assessed using ultrasound within 90 days after surgery., Results: The collagen to muscle ratio in the target vein, measured by computer-assisted imaging, was a strong predictor of non-maturation in wrist fistulas. Receiver operating characteristic analysis revealed an area under the curve of 0.864 (95% confidence interval of 0.782-0.946, p < 0.001). The optimal cut-off value for the ratio was 1.138, as determined by the Youden index maximum method, with a sensitivity of 89.0% and specificity of 71.4%. For easy application, we used a cutoff value of 1.0; the non-maturation rates for patients with ratios >1 and ≤ 1 were 51.7% (15 out of 29 patients) and 9.2% (6 out of 65 patients), respectively. Chi-square testing revealed significantly different non-maturation rates between the two groups (X 2 (1, N = 94) = 20.9, p < 0.01)., Conclusion: Computer-assisted image interpretation can help to quantify the preexisting histological patterns of the cephalic vein, while the collagen-to-muscle ratio can predict non-maturation of wrist fistula development at an early stage., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objective: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with a high incidence of complications in the mid and late stages of gestation. This study investigates differences in the composition of intestinal flora among pregnant women diagnosed with ICP, employing Illumina MiSeq high-throughput sequencing technology., Methods: This case-control study obtained patient data from the hospital information system (HIS) and the laboratory information system (LIS). Fecal samples were collected from 25 pregnant women who did not undergo intestinal preparation before delivery between December 2020 and March 2021. Whole-genome analysis was performed. PCR was used to amplify the 16S rRNA V3-V4 variable region, which was then sequenced. Alpha and beta diversity were computed, and the maternal intestinal flora's abundance and composition characteristics were analyzed. Differences in intestinal flora between the two sample groups were examined., Results: Bacteroides and Proteobacteria exhibited positive correlations with TBIL and IBIL. Betaproteobacteria, Gammaproteobacteria, and Erysipeiotrichi showed positive correlations with TBIL, IBIL, and DBIL, while Lactobacillus , Delftia , and Odoribacter demonstrated positive correlations with ALT., Conclusion: The ICP group displayed significantly higher levels of total bile acid and ALT compared to the control group. The intestinal flora composition comprised four primary phyla: Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria. ICP patients exhibited a lower relative abundance of intestinal flora across different levels of community composition when compared to the control group. Specific correlations between certain intestinal flora and clinical liver parameters were identified., Competing Interests: 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., (© 2024 The Authors.)

Background: Naturally occurring alkaloids are particularly suitable for use as pesticide precursors and further modifications due to their cost-effectiveness, unique mechanism of action, tolerable degradation, and environmental friendliness. The famous tobacco mosaic virus (TMV) is a persistent plant pathogenic virus that can parasitize many plants and severely reduce crop production. To treat TMV disease, TMV helicase acts as a crucial target by hydrolyzing adenosine triphosphate (ATP) to provide energy for double-stranded RNA unwinding., Results: To seek novel framework alkaloid leads targeting TMV helicase, this work successfully established an efficient screening platform for TMV helicase inhibitors based on natural alkaloids. In vivo activity screening, enzyme activity detection, and binding assays showed that Rutaecarpine from Evodia rutaecarpa (Juss.) Benth exhibited excellent TMV helicase inhibitory properties [dissociation constant (K d ) = 1.1 μm, half maximal inhibitory concentration (IC 50 ) = 227.24 μm] and excellent anti-TMV ability. Molecular docking and dynamic simulations depicted that Rutaecarpine could stably bind in active pockets of helicase with low binding energy (ΔG bind  = -17.8 kcal/mol) driven by hydrogen bonding and hydrophobic interactions., Conclusion: Given Rutaecarpine's laudable bioactivity and structural modifiability, it can serve as a privileged building block for further pesticide discovery., (© 2023 Society of Chemical Industry.)

Salicylic acid (SA) is one of the chemical molecules, involved in plant growth and immunity, thereby contributing to the control of pests and pathogens, and even applied in fruit and vegetable preservation. However, only a few tools have ever been designed or executed to understand the physiological processes induced by SA or its function in plant immunity and residue detection in food. Hence, three Rh6G-based fluorogenic chemosensors were synthesized to detect phytohormone SA based on the "OFF-ON" mechanism. The probes showed high selectivity, ultrafast response time (<60 s), and nanomolar detection limit for SA. Moreover, the probe possessed outstanding profiling that can be successfully used for SA imaging of callus and plants. Furthermore, the fluorescence pattern indicated that SA could occur in the distal transport in plants. These remarkable results contribute to improving our understanding of the multiple physiological and pathological processes involved in SA for plant disease diagnosis and for the development of immune activators. In addition, SA detection in some agricultural products used probes to extend the practical application because its use is prohibited in some countries and is harmful to SA-sensitized persons. Interestingly, the as-obtained test paper displayed that SA could be imaged by ultraviolet (UV) and was directly visible to the naked eye. Given the above outcomes, these probes could be used to monitor SA in vitro and in vivo, including, but not limited to, plant biology, food residue detection, and sewage detection.

Background: Plant viral diseases, namely 'plant cancer', are extremely difficult to control. Even worse, few antiviral agents can effectively control and totally block viral infection. There is an urgent need to explore and discover novel agrochemicals with high activity and a unique mode of action to manage these refractory diseases., Results: Forty-one new phenothiazine derivatives were prepared and their inhibitory activity against tobacco mosaic virus (TMV) was assessed. Compound A 8 had the highest protective activity against TMV, with a half-maximal effective concentration (EC 50 ) of 115.67 μg/mL, which was significantly better than that of the positive controls ningnanmycin (271.28 μg/mL) and ribavirin (557.47 μg/mL). Biochemical assays demonstrated that compound A 8 could inhibit TMV replication by disrupting TMV self-assembly, but also enabled the tobacco plant to enhance its defense potency by increasing the activities of various defense enzymes., Conclusion: In this study, novel phenothiazine derivatives were elaborately fabricated and showed remarkable anti-TMV behavior that possessed the dual-action mechanisms of inhibiting TMV assembly and invoking the defense responses of tobacco plants. Moreover, new agrochemical alternatives based on phenothiazine were assessed for their antiviral activities and showed extended agricultural application. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

In the protracted "arms race" between host and plant pathogenic bacteria, host organisms have evolved powerful weapons known as host defense peptides (HDPs). However, natural HDPs are not suitable for large-scale applications; therefore, researchers have chosen to develop bespoke small-molecule functional mimics. Phenothiazine derivatives were developed as functional HDPs mimics, owing to their broad biological activity and high lipophilicity. The phenothiazine analogues designed in this study exhibited excellent in vitro bioactivity against the three Gram-negative bacteria Xanthomonas oryzae pv oryzae , Xanthomonas axonopodis pv citri , and Pseudomonas syringae pv actinidiae , with optimal EC 50 values of 0.80, 0.31, and 1.91 μg/mL, respectively. Preliminary evidence suggests that compound C 2 may act on bacterial cell membranes and interact with bacterial Deoxyribonucleic acid in the groove binding mode. In vivo trials showed that compound C 2 was highly effective against rice leaf blight (51.97-56.69%), with activity superior to those of bismerthiazol (40.7-43.4%) and thiodiazole copper (30.2-37.1%). Our study provides strong evidence to support the development of phenothiazine derivatives into pesticide candidates.

Research Question: Does blastocyst storage time have an impact on pregnancy and neonatal outcomes following the first single vitrified/warmed high-quality blastocyst transfer cycle for young women?, Design: Retrospective cohort study in a university-affiliated reproductive medical centre., Results: A total of 2938 patients undergoing their first frozen embryo transfer (FET) cycle with a single high-quality blastocyst (Day 5: 3BB and above; Day 6: 4BB and above) transferred were divided into five groups: Group A with storage time ≤3 months (n = 1621), Group B with storage time of 4-6 months (n = 657), Group C with storage time of 7-12 months (n = 225), Group D with storage time of 13-24 months (n = 104), and Group E with storage time of 25-98 months (n = 331). After adjusting for confounding factors by multivariate logistic regression, there were no significant differences in live birth rate [Group A as reference; Group B: adjusted odds ratio (aOR) 0.954 (95% CI 0.791- 1.151); Group C: aOR 0.905 (95% CI 0.674-1.214); Group D: aOR 0.727 (95% CI 0.474-1.114); Group E: aOR 1.185 (955 CI 0.873-1.608)], β-human-chorionic-gonadotropin-positive rate, clinical pregnancy rate and miscarriage rate between Group A and the other groups. Among all singletons born after FET, there were no significant differences with regards to gestational age, preterm birth, birthweight, low birthweight, high birthweight and macrosomia., Conclusion: Long-term cryostorage of human vitrified high-quality blastocysts does not affect pregnancy or neonatal outcomes., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Before the Song Dynasty, the main processing method of Pinelliae Rhizoma was soup washing. The "new method" in Taiping Huimin Heji JuFang is a processing method that concocted with Ginger,white alum and starter-making.The "Fa Banxia" in the Yuan Dynasty's Yuyuan Yaofang comes from the Taiping Huimin Heji JuFang , and the Fa Wen Banxia, Fa Bai Banxia, and Fa Hong Banxia are the processing methods of patent medicine with a variety of other herbs.Fa Banxia appeared in the Ming Dynasty, and its auxiliary materials were ginger and white alum, and medical formulary began to include formulas containing Fa Banxia. Bencao Gangmu abbreviates the Yuan Dynasty's Fabai Banxia as "Fa Banxia", and is elaborated under the item attached "prescription" item instead of the "treatment". In the literature of Materia Medica, it is recorded that the preparation of auxiliary materials in Fa Banxia increased, including lime, licorice, soap horn, and simple nitro.After Daoguang in the Qing Dynasty, the Fa Banxia in famous medical cases was more used, and at that time, Fa Banxia was Xian Banxia. There are two recipes for Xian Banxia: one is made with seven processes, and the other is soaked in alum licorice water. During the Republican period, Zhang Cigong also pointed out that Fa Banxia was sliced Xian Banxia after rinsing and boiling, while the preparation method of Xian Banxia was Banxia made of ginger and white alum.Ye Juquan pointed out that the so-called "fa" is neither an ancient method nor a new method, questioning the process of repeated immersion in Banxia. After 1949, the questioning of Fa Banxia continued unceasing.Influenced by this, the 1960 edition Beijing Traditional Chinese Medicine Slice Cutting Experience included the method of soaking alum, licorice ,lime water, and was included in the 1963 edition of the Pharmacopoeia of the People's Republic of China .The 1985 version reduced the soaking time and eliminated the soaking process of alum based on the 1963 version, and this method is still used today.

Objective: The authors aimed to use a large two-sample Mendelian randomization (MR) study to reveal the causality between age at menarche (AAM) and polycystic ovary syndrome (PCOS) incidence., Methods: The authors collected summary statistics from the hitherto largest genome-wide association studies conducted in AAM and PCOS in the same ancestry. MR with inverse variance weighting was conducted as the main analysis method, while weighted median and MR-Egger regression were used for comprehensive analysis. As for pleiotropy detection, inverse variance weighting, MR-Egger regression, Mendelian Randomization Pleiotropy Residual Sum and Outlier, as well as leave-one-out analysis were used to detect pleiotropy. Risk factor analysis was conducted to investigate the underlying mechanisms linking AAM to PCOS., Results: Each standard deviation increment in AAM was associated with a significantly lower incidence of PCOS (odds ratio, 0.86 [95% confidence interval, 0.75-0.98]). After adjustment in horizontal pleiotropy by eliminating four outliers, this pathogenic association was still statistically detected. All pleiotropy indexes were without statistical differences, which suggested the conclusions were robust. It showed the causal association between later AAM and lower body mass index, lower fasting insulin level and insulin resistance., Conclusion: Our MR analysis verified that a slightly later onset age (15 to 18 years) at menarche could reduce the risk of PCOS. A more comprehensive investigation in a prospective setting is strongly advised., (© 2023 International Federation of Gynecology and Obstetrics.)

Salicylic acid (SA) is a key hormone that regulates plant growth and immunity, and understanding the physiologic processes induced by SA enables the development of highly pathogen-resistant crops. Here, we report the synthesis of three new SA-sensors (R1-R3) from hydroxyphenol derivatives of a rhodamine-acylhydrazone scaffold and their characterization by NMR and HRMS. Spectroscopic analyses revealed that structural variations in R1-R3 resulted in sensors with different sensitivities for SA. Sensor R2 (with the 3-hydroxyphenyl modification) outperformed R1 (2-hydroxyphenyl) and R3 (4-hydroxyphenyl). The SA-detection limit of R2 is 0.9 μM with an ultra-fast response time (<60 s). In addition, their plant imaging indicated that designed sensor R2 is useful for the further study of SA biology and the discovery and development of new inducers of plant immunity.

PAHs (polycyclic aromatic hydrocarbons) accumulated in arable soils have significant impacts on farmland quality and human health, which has attracted wide attention from scientists and the public. A total of 22 arable soil samples were collected from Taiyuan, an old industrial city, including three districts (industrial zones, hilly areas, and sewage irrigation area), and the contents of 21 PAHs were detected using the GC-MS method. The sources of PAHs in soils were analyzed using the diagnostic ratios (DRs) method and positive matrix factorization (PMF) model, and the soil health risks were analyzed using the incremental lifetime cancer risk (ILCR) model. The results indicated that the average concentrations of Σ 21 PAHs and Σ 16 PAHs in arable soils of Taiyuan were 934.6 ng·g -1 and 787.7 ng·g -1 , respectively, which were lower than the soil pollution risk screening value of agricultural land stipulated in GB 15168-2018. 3-5 rings PAHs were the dominant components, accounting for~90% of the Σ 21 PAHs . Approximately 60% of sites in industrial zones, 13% in hilly areas, and 33% in the sewage irrigation area had high PAHs contents larger than 1000 ng·g -1 . The spatial distribution of PAHs showed that more severe PAHs pollution in the soil occurred in industrial areas than that in the other two districts. The DRs suggested that the combustion of coals, bio-masses, and traffic emissions were the dominant sources for PAHs pollution in arable soils in Taiyuan. The simulation results of the PMF model indicated that the sources and contribution rates of PAHs in cultivated soils were coal and biomass burning sources (59%), traffic sources (22%), and coking sources (19%). The risk assessment confirmed that the arable soils in Taiyuan had high potential carcinogenic risks; thus, more attention should be paid to the PAHs pollutions in arable soils.

Background: The white-backed planthopper (WBPH, Sogatella furcifera) is a major rice pest that exhibits condition dependent wing dimorphisms - a macropterous (long wing) form and a brachypterous (short wing) form. Although, the gene cascade that regulates wing development and dimorphic differentiation has been largely defined, the utility of these genes as targets for pest control has yet to be fully explored., Results: Five genes typically associated with the developmental signaling network, armadillo (arm), apterous A (apA), scalloped (sd), dachs (d), and yorkie (yki) were identified from the WBPH genome and their roles in wing development assessed following RNA interference (RNAi)-mediated knockdown. At 5 days-post injection, transcript levels for all five targets were substantially decreased compared with the dsGFP control group. Among the treatment groups, those injected with dsSfarm had the most pronounced effects on transcript reduction, mortality (95 ± 3%), and incidence (45 ± 3%) of wing deformities, whereas those injected with dsSfyki had the lowest incidence (6.7 ± 4%). To assess the utility of topical RNAi for Sfarm, we used a spray-based approach that complexed a large-scale, bacteria-based double-stranded RNA (dsRNA) expression pipeline with star polycation (SPc) nanoparticles. Rice seedlings infested with third and fourth instar nymphs were sprayed with SPc-dsRNA formulations and RNAi phenotypic effects were assessed over time. At 2 days post-spray, Sfarm transcript levels decreased by 86 ± 9.5% compared with dsGFP groups, and the subsequent incidences of mortality and wing defects were elevated in the treatment group., Conclusions: This study characterized five genes in the WBPH developmental signaling cascade, assessed their impact on survival and wing development via RNAi, and developed a nanoparticle-dsRNA spray approach for potential field control of WBPH. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Background: Various approaches using epidural analgesia have been employed for relieving labor pain and promoting spontaneous delivery. We aimed to evaluate the effect of nalbuphine and ropivacaine versus fentanyl and ropivacaine on the duration of delivery in parturients., Methods: Clinical data of 160 full-term primiparous women who received either nalbuphine or fentanyl in combination with ropivacaine infusion for epidural labor analgesia in our hospital from December 2020 to May 2022 were retrospectively analyzed. The participants were divided into two groups based on anesthesia methods: nalbuphine group (NR group, n = 78) received 0.2 mg/mL nalbuphine combined with 0.1% ropivacaine hydrochloride for patient-controlled epidural analgesia (PCEA) and fentanyl group (FR group, n = 82) received 2 ug/mL fentanyl citrate and 0.1% ropivacaine hydrochloride for PCEA. Both groups received an epidural blockade for labor analgesia at lumbar 2-3 interspace. The duration of the first, second, and third stages of labor, the onset of analgesia, and time before delivery (T0), 15 min of analgesia (T1), 30 min of analgesia (T2), full opening of the uterine opening (T3),exerts force during childbirth(T4), heart rate (HR), blood pressure (BP), blood saturation (SpO2), visual analogue pain scale (VAS) score, Ramsay sedation score, and modified Bromage score, and 5 min were recorded at 2 h postpartum (T5). The neonatal Apgar score, neonatal behavioral neurological assessment (NBNA) score, maternal nausea, vomiting, and itchy skin were recorded., Results: Compared with the FR group, the first stage of labor duration (p < 0.05) and total duration of labor (p < 0.05) were shortened and the onset of analgesia (p < 0.05) was increased in the NR group. NR group had lower incidence of urinary retention than FR group (p < 0.05). The maternal and neonatal investigational parameters and scores had no significant difference between the two groups., Conclusions: Nalbuphine combined with ropivacaine in epidural block labor has a faster onset of analgesia and has a lower incidence of urinary retention than fentanyl combined with ropivacaine, and nalbuphine shortens the duration of the first and total stages of labor. Both nalbuphine and fentanyl can reduce pain during labor, have little effect on maternal hemodynamics, and have no significant effect on neonatal Apgar or NBNA scores., (© 2023. The Author(s).)

Background: Plant pathogens have led to large yield and quality losses in crops worldwide. The discovery and study of novel agrochemical alternatives based on the chemical modification of bioactive natural products is a highly efficient approach. Here, two series of novel cinnamic acid derivatives incorporating diverse building blocks with alternative linking patterns were designed and synthesized to identify their antiviral capacity and antibacterial activity., Results: The bioassay results demonstrated that most cinnamic acid derivatives had excellent antiviral competence toward tobacco mosaic virus (TMV) in vivo, especially compound A 5 (median effective concentration [EC 50 ] = 287.7 μg mL -1 ), which had a notable protective effect against TMV when compared with the commercial virucide ribavirin (EC 50  = 622.0 μg mL -1 ). In addition, compound A 17 had a protective efficiency of 84.3% at 200 μg mL -1 against Xac in plants. Given these outstanding results, the engineered title compounds could be regarded as promising leads for controlling plant virus and bacterial diseases. Preliminary mechanistic studies suggest that compound A 5 could enhance the host's defense responses by increasing the activity of defense enzymes and upregulating defense genes, thereby suppressing phytopathogen invasion., Conclusion: This research lays a foundation for the practical application of cinnamic acid derivatives containing diverse building blocks with alternative linking patterns in pesticide exploration. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Background: Controlling bacterial infections in plants is a major challenge owing to the appearance of resistant strains. As a physical barrier, the bacterial biofilm helps bacterial infections acquire drug resistance by enabling bacteria to accommodate complex and volatile environmental conditions and avoid bactericidal effects. Thus, developing new antibacterial agents with antibiofilm potency is imperative., Results: A series of simple triclosan derivatives containing isopropanolamine moiety were elaborately designed and assessed for their antibacterial behavior. Bioassay results showed that some title compounds had excellent bioactivity against three destructive bacteria Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Pseudomonas syringae pv. actinidiae (Psa). Notably, compound C 8 displayed high bioactivities toward Xoo and Xac, with EC 50 values were 0.34 and 2.11 μg mL -1 , respectively. In vivo trials revealed that compound C 8 exhibited excellent protective activities against rice bacterial blight and citrus bacterial canker at 200 μg mL -1 , with control effectivenesses of 49.57% and 85.60%, respectively. Compound A 4 had remarkably inhibitory activity toward Psa, with an EC 50 value of 2.63 μg mL -1 , and demonstrated outstanding protective activity with a value of 77.23% against Psa in vivo. Antibacterial mechanisms indicated that compound C 8 dose-dependently prevented biofilm formation and extracellular polysaccharide production. C 8 also significantly weakened the motility and pathogenicity of Xoo., Conclusion: This study contributes to the development and excavation of novel bactericidal candidates with broad-spectrum antibacterial activity by targeting bacterial biofilm to control refractory plant bacterial diseases. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Objective: To observe the association between clinical phenotypes of hypertrophic cardiomyopathy (HCM) patients and a rare calcium channel and regulatory gene variation (Ca 2+ gene variation) and to compare clinical phenotypes of HCM patients with Ca 2+ gene variation, a single sarcomere gene variation and without gene variation and to explore the influence of rare Ca 2+ gene variation on the clinical phenotypes of HCM. Methods: Eight hundred forty-two non-related adult HCM patients diagnosed for the first time in Xijing Hospital from 2013 to 2019 were enrolled in this study. All patients underwent exon analyses of 96 hereditary cardiac disease-related genes. Patients with diabetes mellitus, coronary artery disease, post alcohol septal ablation or septal myectomy, and patients who carried sarcomere gene variation of uncertain significance or carried>1 sarcomere gene variation or carried>1 Ca 2+ gene variation, with HCM pseudophenotype or carrier of ion channel gene variations other than Ca 2+ based on the genetic test results were excluded. Patients were divided into gene negative group (no sarcomere or Ca 2+ gene variants), sarcomere gene variation group (only 1 sarcomere gene variant) and Ca 2+ gene variant group (only 1 Ca 2+ gene variant). Baseline data, echocardiography and electrocardiogram data were collected for analysis. Results: A total of 346 patients were enrolled, including 170 patients without gene variation (gene negative group), 154 patients with a single sarcomere gene variation (sarcomere gene variation group) and 22 patients with a single rare Ca 2+ gene variation (Ca 2+ gene variation group). Compared with gene negative group, patients in Ca 2+ gene variation group had higher blood pressure and higher percentage of family history of HCM and sudden cardiac death ( P <0.05); echocardiographic results showed that patients in Ca 2+ gene variation group had thicker ventricular septum ((23.5±5.8) mm vs. (22.3±5.7) mm, P <0.05); electrocardiographic results showed that patients in Ca 2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (400.6±47.2) ms, P <0.05) and higher RV5+SV1 ((4.51±2.26) mv vs. (3.50±1.65) mv, P <0.05). Compared with sarcomere gene variation group, patients in Ca 2+ gene variation group had later onset age and higher blood pressure ( P <0.05); echocardiographic results showed that there was no significant difference in ventricular septal thickness between two groups; patients in Ca 2+ gene variation group had lower percentage of left ventricular outflow tract pressure gradient>30 mmHg (1 mmHg=0.133 kPa, 22.8% vs. 48.1%, P <0.05) and the lower early diastolic peak velocity of the mitral valve inflow/early diastolic peak velocity of the mitral valve annulus (E/e') ratio ((13.0±2.5) vs. (15.9±4.2), P <0.05); patients in Ca 2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (399.0±43.0) ms, P <0.05) and lower percentage of ST segment depression (9.1% vs. 40.3%, P <0.05). Conclusion: Compared with gene negative group, the clinical phenotype of HCM is more severe in patients with rare Ca 2+ gene variation; compared with patients with sarcomere gene variation, the clinical phenotype of HCM is milder in patients with rare Ca 2+ gene variation.

As quorum sensing (QS) regulates bacterial pathogenicity, antiquorum sensing agents have powerful application potential for controlling bacterial infections and overcoming pesticide/drug resistance. Identifying anti-QS agents thus represents a promising approach in agrochemical development. In this study, the anti-QS potency of 53 newly prepared benzothiazole derivatives containing an isopropanolamine moiety was analyzed, and structure-activity relationships were examined. Compound D 3 exhibited the strongest antibacterial activity, with an in vitro EC 50 of 1.54 μg mL -1 against Xanthomonas oryzae pv oryzae ( Xoo ). Compound D 3 suppressed QS-regulated virulence factors (e.g., biofilm, extracellular polysaccharides, extracellular enzymes, and flagella) to inhibit bacterial infection. In vivo anti- Xoo assays indicated good control efficiency (curative activity, 47.8%; protective activity, 48.7%) at 200 μg mL -1 . Greater control efficiency was achieved with addition of 0.1% organic silicone or orange peel essential oil. The remarkable anti-QS potency of these benzothiazole derivatives could facilitate further novel bactericidal compound development.

Anti-infection strategies based on suppression of bacterial virulence factors represent a crucial direction for the development of new antibacterial agents to address the resistance triggered by traditional drugs'/pesticides' bactericidal activity. To identify and obtain more effective and diverse molecules targeting virulence, we prepared a series of 3-hydroxy-2-methyl-1-pyridin-4-(1 H )-one derivatives and evaluated their antibacterial behaviors. Compound B 6 exhibited the highest bioactivity, with half-maximal effective concentration (EC 50 ) values ranging fro9m 10.03 to 30.16 μg mL -1 against three plant pathogenic bacteria. The antibacterial mechanism showed that it could considerably reduce various virulence factors (such as extracellular enzymes, biofilm, and T3SS effectors) and inhibit the expression of virulence factor-related genes. In addition, the control efficiency of compound B 6 against rice bacterial leaf blight at 200 μg mL -1 was 46.15-49.15%, and their control efficiency was improved by approximately 12% after the addition of pesticide additives. Thus, a new class of bactericidal candidates targeting bacterial virulence factors was developed for controlling plant bacterial diseases.

The discovery of natural product-based pesticides is critical for agriculture. In this work, a series of novel tricyclic diterpenoid derivatives decorated with an amino alcohol moiety were elaborately prepared from natural abietic acid, and their antibacterial behavior was explored. Bioassay results indicated that compound C 2 exhibited the most promising bioactivity (EC 50 = 0.555 μg mL -1 ) against Xanthomonas oryzae pv. oryzae ( Xoo ), about 73 times higher than the effect of commercial thiodiazole copper (TC). Results of in vivo bioassays showed that compound C 2 displayed significantly higher control of rice bacterial leaf blight (curative activity: 63.8%; protective activity: 58.4%) than TC (curative activity: 43.6%; protective activity: 40.8%), and their bioactivity could be improved maximally 16% by supplementing the auxiliaries. Antibacterial behavior suggested that compound C 2 could suppress various virulence factors. Overall, these findings suggested that new botanical bactericide candidates could control intractable plant bacterial diseases by suppressing virulence factors.

Objective: To evaluate the impact of individual and combined assessment of age- and sex-specific brachial-ankle pulse wave velocity (baPWV) and pulse pressure (PP) on all-cause mortality. Methods: This study is a prospective cohort study. Individuals participated in the Kailuan Study and completed baPWV measurements between 2010 and 2016 were included in this study. After stratifying by sex, 75th percentile baPWV and PP values for different age group were calculated at five years interval. BaPWV and PP values below the 75th percentile were defined as normal, and those above or equal to the 75th percentile were defined as increased. The participants were allocated to four groups according to their PP and baPWV status: normal baPWV/PP group, high baPWV/normal PP group, normal baPWV/high PP group and high baPWV/PP group. The primary outcome was all-cause mortality during the follow-up period. Cox proportional hazards models were used to explore the impact of individual and combined assessment of baPWV and PP on all-cause mortality events. Results: A total of 39 339 participants were enrolled in this study, aged (49.3±12.8) years, of which 28 731 (73.03%) were males. There were 23 268, 6 025, 6 210 and 3 836 cases in the normal baPWV/PP group, high baPWV/normal PP group, normal baPWV/high PP group and high baPWV/PP group, respectively. The average follow-up duration was (4.98±2.53) years. During the follow-up period, all-cause mortality occurred in 998 individuals. Multivariate Cox regression analysis showed increased risk of all-cause mortality in the high baPWV/normal PP group ( HR =1.27, 95% CI 1.07-1.50), and in the high baPWV/PP group ( HR =1.33, 95%CI 1.08-1.65) compared to the normal baPWV/PP group. Increased pulse pressure alone had no impcat on all-cause death ( HR =1.06, 95% CI 0.87-1.29). Conclusions: The risk of all-cause mortality significantly increases with increased age-and sex-specific baPWV and PP values. BaPWV may be a better predictor of all-cause mortality than PP in this cohort.