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YiLin Luo, Xin Yue Bai, Lei Zhang, Qian Qian Hu, Ning Zhang, Jun Zhi Cheng, Ming Zheng Hou, Xiao Long Liu Yan ‘an Small Molecule Innovative Drug R&D Engineering Research Center, School of Medicine, Yan’an University, Yan’an, People’s Republic of ChinaCorrespondence: Xiao Long Liu, Email liuxiaolong@yau.edu.cnAbstract: Ferroptosis, a unique form of programmed cell death, is initiated by an excess of iron accumulation and lipid peroxidation-induced damage. There is a growing body of evidence indicating that ferroptosis plays a critical role in the advancement of tumors. The increased metabolic activity and higher iron levels in tumor cells make them particularly vulnerable to ferroptosis. As a result, the targeted induction of ferroptosis is becoming an increasingly promising approach for cancer treatment. This review offers an overview of the regulatory mechanisms of ferroptosis, delves into the mechanism of action of traditional small molecule ferroptosis inducers and their effects on various tumors. In addition, the latest progress in inducing ferroptosis using new means such as proteolysis-targeting chimeras (PROTACs), photodynamic therapy (PDT), sonodynamic therapy (SDT) and nanomaterials is summarized. Finally, this review discusses the challenges and opportunities in the development of ferroptosis-inducing agents, focusing on discovering new targets, improving selectivity, and reducing toxic and side effects.Keywords: ferroptosis inducers, small molecules, PROTACs, PDT, SDT, nanomaterials

Background: Dental impressions are essential for accurately capturing the detailed anatomy of teeth and surrounding oral structures. However, these impressions often become contaminated with saliva and blood, making proper disinfection necessary. The application of chemical disinfectants has been associated with negative side effects, leading to suboptimal disinfection practices in clinical settings., Objective: The purpose of this study was to evaluate the effectiveness of chlorogenic acid (CA) as a disinfectant for alginate impression materials, the impact of CA disinfection on the physical properties and dimensional accuracy of alginate impressions was also investigated., Methods: The physical properties of alginate impression materials, such as elastic recovery, strain-in-compression, initial setting time, and fluidity, were assessed after mixing the alginate impression materials with three different concentrations of CA solution (10 mg/mL, 15 mg/mL, 20 mg/mL). To evaluate the antimicrobial effect of CA, alginate impressions mixed with a 10 mg/mL CA solution and impressions mixed with distilled water (control group) were contaminated with four types of microorganism: Escherichia coli , Staphylococcus aureus , Candida albicans , and Streptococcus pneumoniae . Following a five-minute incubation period, a CA solution at a concentration of either 50 mg/mL, 55 mg/mL, or 60 mg/mL was sprayed on the samples for disinfection. Samples were collected at different time intervals (10 min, 20 min, 30 min) and cultured to determine the number of colony-forming units (CFU/mL), providing insight into the antimicrobial efficacy of these CA solutions. The dimensional accuracy of alginate impressions was assessed in three groups: one with alginate impressions mixed with distilled water, another with alginate impressions sterilized with available chlorine (2,000 mg/L) mixed with distilled water, and the last group consisting of alginate impressions mixed with 10 mg/mL CA solution and sprayed with 60 mg/mL CA solution. Both the standard model and the plaster model underwent 3D scanning, and the data were processed and compared by software. The root mean square (RMS) was used as a parameter to evaluate the deviation between models., Results: All alginate impression materials mixed with either 10 mg/mL, 15 mg/mL, or 20 mg/mL concentrations of CA solution met the ISO 21563 standard for elastic recovery, strain-in-compression, and fluidity. However, only the material mixed with a concentration of 10 mg/mL CA had an initial setting time within the range specified by the T-6505 Japanese industrial standard. The application of CA solution by mixing or spraying showed significant antimicrobial effects on Staphylococcus aureus, Escherichia coli, Candida albicans, and Streptococcus pneumoniae . There was no significant difference in the dimensional accuracy of the alginate impressions between the group of the CA solution applied, the blank group, or the chlorine intervention group., Competing Interests: The authors declare there are no competing interests., (©2024 Jiang et al.)

Severe acute pancreatitis (SAP) is an acute inflammatory injury disease with significant mortality rate and currently without effective strategy being available. Inflammation and oxidative stress play central roles in the etiology of SAP. Micheliolide (MCL), an active monomeric component isolated from Michelia champaca, has been proved its multiple therapeutic properties including anti-inflammatory, antioxidant and anti-cancer. Nevertheless, the therapeutic effect and underlying mechanism of MCL in SAP still remain unclear. Here, we found that caerulein with lipopolysaccharide (LPS)-induced SAP murine models exhibited severe pancreatic injury, including necrosis, edema, and vacuolation of acinar cells in the pancreas, elevated serum levels of amylase and lipase, and reduced number of the exocrine cells. As expected, MCL treatment alleviated these side effects. Mechanistically, MCL triggered nuclear factor erythroid 2-related factor 2 (Nrf2) activation, thereby activating Nrf2-regulated antioxidative pathways and inhibiting nuclear factor kappa B p65 (NF-κB p65)-mediated inflammatory response, resulting in protection against pancreatic injury in SAP mice. In addition, Nrf2 gene deficiency abolished the beneficial effects of MCL on SAP-induced pancreatic inflammation and oxidative stress and blocked the ability of MCL to alleviate the pancreatic injury in SAP mice. Collectively, these findings indicated that the suppression of SAP-induced pancreatic injury by MCL was at least in part due to Nrf2-mediated anti-oxidation effect and inhibition of inflammation., 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.)

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease with a challenging treatment landscape, due to its complex pathogenesis and limited availability of clinical drugs. Ferroptosis, an iron-dependent form of programmed cell death (PCD), stands distinct from apoptosis, necrosis, autophagy, and other cell death mechanisms. Recent studies have increasingly highlighted the role of iron deposition, reactive oxygen species (ROS) accumulation, oxidative stress, as well as systemic Xc- and glutamate accumulation in the antioxidant system in the pathogenesis of amyotrophic lateral sclerosis. Therefore, targeting ferroptosis emerges as a promising strategy for amyotrophic lateral sclerosis treatment. This review introduces the regulatory mechanism of ferroptosis, the relationship between amyotrophic lateral sclerosis and ferroptosis, and the drugs used in the clinic, then discusses the current status of amyotrophic lateral sclerosis treatment, hoping to provide new directions and targets for its treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Intracerebral hemorrhage, is a cerebrovascular disease with high morbidity, mortality, and disability. Due to the lack of effective clinical treatments, the development of new drugs to treat intracerebral hemorrhage is necessary. In recent years, ferroptosis has been found to play an important role in the pathophysiological process of intracerebral hemorrhage, which can be treated by inhibiting ferroptosis and thus intracerebral hemorrhage. This article aims to explain the mechanism of ferroptosis and its relationship to intracerebral hemorrhage. In the meantime, it briefly discusses the molecules identified to alleviate intracerebral hemorrhage by inhibiting ferroptosis, along with other clinical agents that are expected to treat intracerebral hemorrhage through this mechanism. In addition, a brief overview of the morphological alterations of different forms of cell death and their role in ICH is provided. Finally, the challenges that may arise in translating ferroptosis inhibitors from basic research to clinical use are presented. This article serves as a reference and provides insights to aid in the treatment of intracerebral hemorrhage in the clinic., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Synthesis of bicyclic scaffolds has gained significant attention in drug discovery due to their potential to mimic benzene bioisosteres. Here, we present a mild and scalable Sc(OTf) 3 -catalyzed [3+2] cycloaddition of bicyclo[1.1.0]butanes (BCBs) with ynamides, yielding a diverse array of polysubstituted 2-amino-bicyclo[2.1.1]hexenes in good to excellent yields. These products offer valuable starting materials for the construction of novel functionalized bicyclo[1.1.0]butanes. Preliminary mechanistic studies indicate that the reaction involves a nucleophilic addition of ynamides to bicyclo[1.1.0]butanes, followed by an intramolecular cyclization of in situ generated enolate and keteniminium ion. We expect that these findings will encourage utilization of complex bioisosteres and foster further investigation into BCB-based cycloaddition chemistry., (© 2024 Wiley-VCH GmbH.)

The dung beetle primarily feeds on the feces of herbivorous animals and play a crucial role in ecological processes like material cycles and soil improvement. This study aims to explore the diversity and composition of the gut microbiota of Catharsius molossus (a renowned dung beetle originating from China and introduced to multiple countries for its ecological value) and exploring whether these gut microbes are transmitted vertically across generations. Using 16S rRNA and ITS rRNA gene sequencing techniques, we described the diversity and composition of gut microbes in C. molossus from different localities and different developmental stages (Egg, young larvae and old larvae). We discovered that the diversity of gut microbiota of dung beetles varied obviously among different geographical localities and different developmental stages, and we also discussed the potential influencing factors. Interestingly, the microbial community structure within the brood balls is more similar to male dung beetle than to that of females, which is consistent with the observation that the brood ball is constructed by the male dung beetle, with the female laying egg in it at the final step. This unique breeding method facilitates offspring in inheriting microbial communities from both the mother and the father. Initially, the larvae's gut microbiota closely mirrors that of the parental gift in these brood balls. As larvae grow, significant changes occur in their gut microbiota, including an increase in symbiotic bacteria like Lactococcus and Enterococcus. Analysis of the gut bacteria of adult dung beetles across various localities and different developmental stages identified nine core genera in adults, contributing to 67.80% of the total microbial abundance, and 11 core genera in beetles at different developmental stages, accounting for 49.13% of the total. Notably, seven genera were common between these two core groups. Our results suggest that Parental gifts can play a role in the vertical transmission of microbes, and the abundance of probiotics increases with larval development, supporting the hypothesis that "larval feeding behavior occurs in two stages: larvae first feed on parental gifts to acquire necessary microbes, then enrich symbiotic microbiota through consuming their own feces.", Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The energy oriented mine ecological restoration mode of photovoltaic+ecological restoration provides a breakthrough for alleviating the dilemma of photovoltaic land development and solving the urgent need for restoration of abandoned mining land. Taking a mining area in central Liaoning Province as an example, we established three photovoltaic+mining ecological restoration modes, including forest-photovoltaic complementary, agriculture-photovoltaic, and grass photovoltaic complementation. Combined with the life cycle assessment method, we calculated and assessed the potential of photovoltaic+mining ecological restoration in carbon reduction and sink enhancement. The average annual carbon reduction and sink increase was 514.93 t CO 2 ·hm -2 under the photovoltaic+mining ecological restoration mode, while the average annual carbon reduction per megawatt photovoltaic power station was 1242.94 t CO 2 . The adoption of photovoltaic+ecological restoration mode in this mining area could make carbon reduction and sink enhancement 6.30-7.79 Mt CO 2 during 25 years. The carbon reduction and sink increment mainly stemmed from the photovoltaic clean power generation induced carbon reduction, accounting for 96.4%-99.4%, while the contribution of ecosystem carbon sink increment was small, accounting for only 0.6%-3.7% of the total. Among different photovoltaic+ecological restoration modes, the carbon reduction and sink increment was the largest in forest-photovoltaic complementary (7.11 Mt CO 2 ), followed by agriculture-photovoltaic (7.04 Mt CO 2 ), and the least in grass photovoltaic complementation (6.98 Mt CO 2 ). Constructing the development mode of "photovoltaic+mining ecological restoration" could effectively leverage the dual benefits of reducing emissions from photovoltaic power generation and increase sinks from mining ecological restoration, which would be helpful for achieving the goal of carbon neutrality in China.

Operationally simple and generally applicable arene nitration with cheap and easily accessible chemicals has been a long-sought transformation in the synthetic organic community. In this work, we realized this goal with nontoxic and inexpensive Fe(NO 3 ) 3 ·9H 2 O as the nitro source and easily recyclable solvent hexafluoroisopropanol as the promotor via a network of hydrogen-bonding interactions. As a result of the relative mildness and high reliability of this protocol, late-stage nitration of various highly functionalized natural products and commercially available drugs was realized.

A new layered metal sulfide, namely (C 6 H 15 N 3 ) 1.3 (NH 4 ) 1.5 H 1.5 In 3 SnS 8 (1, C 6 H 15 N 3 = N -(2-aminoethyl) piperazine), has been solvothermally synthesized and characterized. Compound 1 crystallizes in the monoclinic space group C 2/ c . Its structure features a two-dimensional layer of {In 3 SnS 8 } n 3 n - with the (4,4) topology net, which is formed by interlinking supertetrahedral T2 clusters as secondary building units. Band structure calculations revealed that 1 had a band gap of 2.7 eV. The photoelectric response of 1 showed steady and reversible on/off cycles with an "on" state of 121.13 nA cm -2 . Moreover, the activation of 1 by replacing the sluggish organic cations with harder K + ions endowed the material with improved adsorption performances for Sr 2+ ions from aqueous solutions.

Background: C2H2-zinc finger transcription factors comprise one of the largest and most diverse gene superfamilies and are involved in the transcriptional regulation of flowering. Although a large number of C2H2 zinc-finger proteins (C2H2-ZFPs) have been well characterized in a number of model plant species, little is known about their expression and function in Coptis teeta . C. teeta displays two floral phenotypes (herkogamy phenotypes). It has been proposed that the C2H2-zinc finger transcription factor family may play a crucial role in the formation of floral development and herkogamy observed in C. teeta . As such, we performed a genome-wide analysis of the C2H2-ZFP gene family in C. teeta . Results: The complexity and diversity of C. teeta C2H2 zinc finger proteins were established by evaluation of their physicochemical properties, phylogenetic relationships, exon-intron structure, and conserved motifs. Chromosome localization showed that 95 members of the C2H2 zinc-finger genes were unevenly distributed across the nine chromosomes of C. teeta , and that these genes were replicated in tandem and segmentally and had undergone purifying selection. Analysis of cis-acting regulatory elements revealed a possible involvement of C2H2 zinc-finger proteins in the regulation of phytohormones. Transcriptome data was then used to compare the expression levels of these genes during the growth and development of the two floral phenotypes (F-type and M-type). These data demonstrate that in groups A and B, the expression levels of 23 genes were higher in F-type flowers, while 15 genes showed higher expressions in M-type flowers. qRT-PCR analysis further revealed that the relative expression was highly consistent with the transcriptome data. Conclusion: These data provide a solid basis for further in-depth studies of the C2H2 zinc finger transcription factor gene family in this species and provide preliminary information on which to base further research into the role of the C2H2 ZFPs gene family in floral development in C. teeta ., Competing Interests: Author Q-QH was employed by Zhongshan Zhongzhi Pharmaceutical Group Co., Ltd. The remaining 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 Duan, Zhao, Yu, Xiang, Xiao, Cui, Hu, Baldwin, Lu and Liang.)

Introduction: The contamination of dental unit waterlines (DUWLs) poses a significant risk of cross-infection in dentistry. Although chemical disinfectants have been effective in reducing number of bacteria, they do have limitations., Methods: This study aimed to investigate the potential of chlorogenic acid, a natural substance with broadspectrum antibacterial properties, for treating DUWLs. Over a period of three months, we analyzed the microbial communities in 149 DUWLs samples collected from 5 dental units using high-throughput pyrophosphate sequencing., Results: The results revealed that chlorogenic acid treatment had a significant impact on the microbial community profile in the DUWLs, with the most significant changes occurring within the first 15 days and stabilization observed in the last 30 days. The predominant genera detected in the samples were Bacteroides, Lactobacillus, Streptococcus, Methylobacterium, and Phreatobacter. Additionally, the relative abundance of certain beneficial bacteria, such as Alloprevotella, Roseburia, and Blautia, increased, while the presence of opportunistic pathogens like Mycobacteria significantly decreased. The functional prediction analysis using the KEGG database indicated a decrease in the pathogenicity of the bacterial community in the DUWLs following chlorogenic acid treatment., Discussion: This study introduces a novel approach for the prevention and treatment of infections associated with dental care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Cai, Hu, Jiang, Chen, Hu, Yang and He.)

Background: Owing to the early suffering age and the rising incidence of type 1 diabetes (T1D), the resulting male reproductive dysfunction and fertility decline have become a disturbing reality worldwide, with no effective strategy being available. Icariin (ICA), a flavonoid extracted from Herba Epimedium, has been proved its promising application in improving diabetes-related complications including diabetic nephropathy, endothelial dysfunction and erectile dysfunction. Ensuring the future reproductive health of children and adolescents with T1D is crucial to improve global fertility. However, its roles in the treatment of T1D-induced testicular dysfunction and the potential mechanisms remain elusive., Purpose: The purpose of this present study was to investigate whether ICA ameliorates T1D-induced testicular dysfunction as well as its potential mechanisms., Methods: T1D murine model was established by intraperitoneal injection of STZ with or without treated with ICA for eleven weeks. Morphological, pathological and serological experiments were used to determine the efficacy of ICA on male reproductive function of T1D mice. Western blotting, Immunohistochemistry analysis, qRT-PCR and kit determination were performed to investigated the underlying mechanisms., Results: We found that replenishment of ICA alleviated testicular damage, promoted testosterone production and spermatogenesis, ameliorated apoptosis and blood testis barrier impairment in streptozotocin-induced T1D mice. Functionally, ICA treatment triggered adenosine monophosphate protein kinase (AMPK) activation, which in turn inhibited the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) to reduce inflammatory responses in the testis and activated nuclear factor erythroid 2-related factor 2(Nrf2), thereby enhancing testicular antioxidant capacity. Further studies revealed that supplementation with the AMPK antagonist Compound C or depletion of Nrf2 weakened the beneficial effects of ICA on testicular dysfunction of T1D mice., Conclusion: Collectively, these results demonstrate the feasibility of ICA in the treatment of T1D-induced testicular dysfunction, and reveal the important role of AMPK-mediated Nrf2 activation and NF-κB p65 inhibition in ICA-associated testicular protection during T1D., Competing Interests: Declaration of Competing Interest All authors have read and approve the content, and agree to submit for consideration for publication in the Journal of Phytomedicine. There is no conflict of interest of any authors in relation to the submission., (Copyright © 2023. Published by Elsevier GmbH.)

Diabetic neuropathic pain (DNP) is a common and destructive complication of diabetes mellitus. The discovery of effective therapeutic methods for DNP is vitally imperative because of the lack of effective treatments. Although 2 Hz electroacupuncture (EA) was a successful approach for relieving DNP, the mechanism underlying the effect of EA on DNP is still poorly understood. Here, we established a rat model of DNP that was induced by streptozotocin (STZ) injection. P2X4R was upregulated in the spinal cord after STZ-injection. The upregulation of P2X4R was mainly expressed on activated microglia. Intrathecal injection of a P2X4R antagonist or microglia inhibitor attenuated STZ-induced nociceptive thermal hyperalgesia and reduced the overexpression of brain-derived neurotrophic factor (BDNF), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the spinal cord. We also assessed the effects of EA treatment on the pain hypersensitivities of DNP rats, and further investigated the possible mechanism underlying the analgesic effect of EA. EA relieved the hyperalgesia of DNP. In terms of mechanism, EA reduced the upregulation of P2X4R on activated microglia and decreased BDNF, IL-1β and TNF-α in the spinal cord. Mechanistic research of EA's analgesic impact would be beneficial in ensuring its prospective therapeutic effect on DNP as well as in extending EA's applicability., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Constructing heterogeneous nanostructures is an efficient strategy to improve the electrical and ionic conductivity of metal chalcogenide-based anodes. Herein, ZnS/SnO 2 quantum dots (QDs) as p-n heterojunctions that are uniformly anchored to reduced graphene oxides (ZnS-SnO 2 @rGO) are designed and engineered. Combining the merits of fast electron transport via the internal electric field and a greatly shortened Li/Na ion diffusion pathway in the ZnS/SnO 2 QDs (3-5 nm), along with the excellent electrical conductivity and good structural stability provided by the rGO matrix, the ZnS-SnO 2 @rGO anode exhibits enhanced electronic and ionic conductivity, which can be proved by both experiments and theoretical calculations. Consequently, the ZnS-SnO 2 @rGO anode shows a significantly improved rate performance that simple counterpart composite anodes cannot achieve. Specifically, high reversible specific capacities are achieved for both lithium-ion battery (551 mA h g -1 at 5.0 A g -1 , 670 mA h g -1 at 3.0 A g -1 after 1400 cycles) and sodium-ion battery (334 mA h g -1 at 5.0 A g -1 , 313 mA h g -1 at 1.0 A g -1 after 400 cycles). Thus, this strategy to build semiconductor metal sulfides/metal oxide heterostructures at the atomic scale may inspire the rational design of metal compounds for high-performance battery applications., (© 2023 Wiley-VCH GmbH.)

Background: Food systems instantiate the complex interdependencies across humans, physical environments, and other organisms. Applying One Health approaches for agri-food system transformation, which adopts integrated and unifying approaches to optimize the overall health of humans, animals, plants, and environments, is crucial to enhance the sustainability of food systems. This study develops a potential assessment tool, named the global One Health index-Food Security (GOHI-FS), aiming to evaluate food security performance across countries/territories from One Health perspective and identify relevant gaps that need to be improved for sustainable food systems., Methods: We comprehensively reviewed existing frameworks and elements of food security. The indicator framework of GOHI-FS was conceptualized following the structure-process-outcome model and confirmed by expert advisory. Publicly available data in 2020 was collected for each indicator. The weighting strategy was determined by the Fuzzy Analytical Hierarchy Process. The data for each indicator was normalized and aggregated by weighted arithmetic mean. Linear regressions were performed to evaluate the associations of GOHI-FS with health and social-economic indicators., Results: The GOHI-FS includes 5 first-level indicators, 19 second-level indicators and 45 third-level indicators. There were 146 countries/territories enrolled for evaluation. The highest average score of first-level indicators was Nutrition (69.8) and the lowest was Government Support and Response (31.3). There was regional heterogeneity of GOHI-FS scores. Higher median scores with interquartile range (IQR) were shown in North America (median: 76.1, IQR: 75.5-76.7), followed by Europe and Central Asia (median: 66.9, IQR: 60.1-74.3), East Asia and the Pacific (median: 60.6, IQR: 55.5-68.7), Latin America and the Caribbean (median: 60.2, IQR: 57.8-65.0), Middle East and North Africa (median: 56.6, IQR: 52.0-62.8), South Asia (median: 51.1, IQR: 46.7-53.8), and sub-Saharan Africa (median: 41.4, IQR: 37.2-46.5). We also found significant associations between GOHI-FS and GDP per capita, socio-demographic index, health expenditure and life expectancy., Conclusions: GOHI-FS is a potential assessment tool to understand the gaps in food security across countries/territories under the One Health concept. The pilot findings suggest notable gaps for sub-Saharan Africa in numerous aspects. Broad actions are needed globally to promote government support and response for food security., (© 2023. National Institute of Parasitic Diseases.)

Background: One Health approach is crucial to tackling complex global public health threats at the interface of humans, animals, and the environment. As outlined in the One Health Joint Plan of Action, the international One Health community includes stakeholders from different sectors. Supported by the Bill & Melinda Gates Foundation, an academic community for One Health action has been proposed with the aim of promoting the understanding and real-world implementation of One Health approach and contribution towards the Sustainable Development Goals for a healthy planet., Main Text: The proposed academic community would contribute to generating high-quality scientific evidence, distilling local experiences as well as fostering an interconnected One Health culture and mindset, among various stakeholders on different levels and in all sectors. The major scope of the community covers One Health governance, zoonotic diseases, food security, antimicrobial resistance, and climate change along with the research agenda to be developed. The academic community will be supported by two committees, including a strategic consultancy committee and a scientific steering committee, composed of influential scientists selected from the One Health information database. A workplan containing activities under six objectives is proposed to provide research support, strengthen local capacity, and enhance global participation., Conclusions: The proposed academic community for One Health action is a crucial step towards enhancing communication, coordination, collaboration, and capacity building for the implementation of One Health. By bringing eminent global experts together, the academic community possesses the potential to generate scientific evidence and provide advice to local governments and international organizations, enabling the pursuit of common goals, collaborative policies, and solutions to misaligned interests., (© 2023. The Author(s).)

Background: Due to emerging issues such as global climate change and zoonotic disease pandemics, the One Health approach has gained more attention since the turn of the 21st century. Although One Health thinking has deep roots and early applications in Chinese history, significant gaps exist in China's real-world implementation at the complex interface of the human-animal-environment., Methods: We abstracted the data from the global One Health index study and analysed China's performance in selected fields based on Structure-Process-Outcome model. By comparing China to the Belt & Road and G20 countries, the advances and gaps in China's One Health performance were determined and analysed., Findings: For the selected scientific fields, China generally performs better in ensuring food security and controlling antimicrobial resistance and worse in addressing climate change. Based on the SPO model, the "structure" indicators have the highest proportion (80.00%) of high ranking and the "outcome" indicators have the highest proportion (20.00%) of low ranking. When compared with Belt and Road countries, China scores above the median in almost all indicators (16 out of 18) under the selected scientific fields. When compared with G20 countries, China ranks highest in food security (scores 72.56 and ranks 6th), and lowest in climate change (48.74, 11th)., Conclusion: Our results indicate that while China has made significant efforts to enhance the application of the One Health approach in national policies, it still faces challenges in translating policies into practical measures. It is recommended that a holistic One Health action framework be established for China in accordance with diverse social and cultural contexts, with a particular emphasis on overcoming data barriers and mobilizing stakeholders both domestically and globally. Implementation mechanisms, with clarified stakeholder responsibilities and incentives, should be improved along with top-level design., Competing Interests: The authors declare no conflicts of interest., (© 2023 Published by Elsevier B.V.)

Non-O1/non-O139 Vibrio cholerae (NOVC) causes various illnesses ranging in severity from mild to life-threatening but were ignored previously. Knowledge of the NOVC infection, particularly bacteremia, is limited because of its rarity. Here we first retrospectively reported the demographic, clinical, and therapy characteristics of patients with NOVC infection. Isolated NOVC stains were identified by a series of biochemical, mass spectrometry (MS), and serum agglutination tests. The results of 11 patients with NOVC infection (including 8 with bacteremia) with a median age of 68 years were included in this report. Most isolated NOVC strains had antibiotic susceptibility. Patients with NOVC-positive were distributed in various departments, most occurring in gastroenterology (6 cases). Hepatic disease was the most common comorbid disease, followed by diabetes (3 cases) and biliary tract disease (3 cases). Two cases were previously healthy. The most common symptom at presentation was fever. All patients presented with abnormal changes in hematology and inflammatory parameters. Cephalosporins were the most frequently used antibiotics. Ten patients had a favorable outcome after treatment; one died from complicated underlying diseases. In summary, we recommend the timely identification of NOVC strains using MALDI-TOF-MS. The suspicion of NOVC bacteremia cannot be ruled out regardless of the host's immune status. An alternative therapeutic regimen for this infection may be β-lactam antibiotics or combined with β-lactamase inhibitors. Regardless, the specific therapeutic regimen should be based on the antibiogram data.

Unveiling the structural evolution of single-crystalline compounds based on certain building units may help greatly in guiding the design of complex structures. Herein, a series of praseodymium antimony oxohalide crystals have been isolated under solvothermal conditions via adjusting the solvents used, that is, [HN(CH 2 CH 3 ) 3 ][Fe II (2,2'-bpy) 3 ][Pr 4 Sb 12 O 18 Cl 15 ]·EtOH ( 1 ) (2,2'-bpy = 2,2'-bipyridine), [HN(CH 2 CH 3 ) 3 ][Fe II (2,2'-bpy) 3 ] 2 [Pr 4 Sb 12 O 18 Cl 14 ) 2 Cl]·N(CH 2 CH 3 ) 3 ·2H 2 O ( 2 ), and (H 3 O)[Pr 4 Sb 12 O 18 Cl 12.5 (TEOA) 0.5 ]·2.5EtOH ( 3 ) (TEOA = mono-deprotonated triethanolamine anion). Single-crystal X-ray diffraction analysis revealed that all the three structures feature an anionic zig-zag chain of [Pr 4 Sb 12 O 18 Cl 15- x ] n as the tertiary building unit (TBU), which is formed by interconnections of praseodymium antimony oxochloride clusters (denoted as {Pr 4 Sb 12 }) as secondary building units. Interestingly, different arrangements or linkages of chain-like TBUs result in one-dimensional, two-dimensional layered, and three-dimensional structures of 1 , 2 , and 3 , respectively, thus demonstrating clearly the structural evolution of metal oxohalide crystals. The title compounds have been characterized by elemental analysis, powder X-ray diffraction, thermogravimetric analysis, and UV-Vis spectroscopy, and the photodegradation for methyl blue in an aqueous solution of compound 1 has been preliminarily studied. This work offers a way to deeply understand the assembly process of intricate lanthanide-antimony(III) oxohalide structures at the atomic level.

Diabetic neuropathic pain (DNP) is frequent among patients with diabetes. We previously showed that P2X3 upregulation in dorsal root ganglia (DRG) plays a role in streptozotocin (STZ)-induced DNP but the underlying mechanism is unclear. Here, a rat model of DNP was established by a single injection of STZ (65 mg/kg). Fasting blood glucose was significantly elevated from the 1 st to 3 rd week. Paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) in diabetic rats significantly reduced from the 2 nd to 3 rd week. Western blot analysis revealed that elevated p-CaMKIIα levels in the DRG of DNP rats were accompanied by pain-associated behaviors while CaMKIIα levels were unchanged. Immunofluorescence revealed significant increase in the proportion of p-CaMKIIα immune positive DRG neurons (stained with NeuN) in the 2 nd and 3 rd week and p-CaMKIIα was co-expressed with P2X3 in DNP rats. KN93, a CaMKII antagonist, significantly reduce mechanical hyperalgesia and thermal hyperalgesia and these effects varied dose-dependently, and suppressed p-CaMKIIα and P2X3 upregulation in the DRGs of DNP rats. These results revealed that the p-CaMKIIα upregulation in DRG is involved in DNP, which possibly mediated P2X3 upregulation, indicating CaMKIIα may be an effective pharmacological target for DNP management., (© 2021. The Author(s).)

Diabetic neuropathic pain (DNP) is highly common in diabetes patients. P2X receptors play critical roles in pain sensitization. We previously showed that elevated P2X3 expression in dorsal root ganglion (DRG) contributes to DNP. However, the role of other P2X receptors in DNP is unclear. Here, we established the DNP model using a single high-dose streptozotocin (STZ) injection and investigated the expression of P2X genes in the DRG. Our data revealed elevated P2X2, P2X4, and P2X7 mRNA levels in DRG of DNP rats. The protein levels of P2X4 and P2X7 in DNP rats increased, but the P2X2 did not change significantly. To study the role of P2X4 and P2X7 in diabetes-induced hyperalgesia, we treated the DNP rats with TNP-ATP (2',3'-O-(2,4,6-trinitrophenyl)-adenosine 5'-triphosphate), a nonspecific P2X1-7 antagonist, and found that TNP-ATP alleviated thermal hyperalgesia in DNP rats. 2 Hz electroacupuncture is analgesic against DNP and could downregulate P2X4 and P2X7 expression in DRG. Our findings indicate that P2X4 and P2X7 in L4-L6 DRGs contribute to diabetes-induced hyperalgesia, and that EA reduces thermal hyperalgesia and the expression of P2X4 and P2X7., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

As promising functional materials, organic-inorganic hybrid metal halide perovskites have attracted significant interest because of their excellent photovoltaic performance. However, although considerable efforts have been made, three-dimensional (3D) metal halide perovskites beyond lead halides have been rarely reported. Herein, a new 3D organic-inorganic hybrid ferroelectric material (Me-Hdabco)CsI 3 (1, Me-Hdabco = N -methyl-1,4-diazoniabicyclo[2.2.2]octane) was synthesized and characterized. 1 underwent a ferroelectric to paraelectric phase transition at T c = 441 K, which was investigated by differential scanning calorimetry (DSC), dielectric measurements, and variable temperature structural analyses. Moreover, 1 shows a clear ferroelectric domain switching recorded by piezoelectric force microscopy. More interestingly, the pristine colorless crystal of 1 has no photoluminescence properties, while 10% Sn(II):(Me-Hdabco)CsI 3 shows intense photoluminescence with a quantum yield of 8.90% under UV excitation. This finding will open up a new avenue to probe organic-inorganic hybrid multifunctional materials integrated ferroelectric and photoluminescence.

Background: The gibberellic acid-stimulated Arabidopsis (GASA) gene encodes a class of cysteine-rich functional proteins and is ubiquitous in plants. Most GASA proteins are influence the signal transmission of plant hormones and regulate plant growth and development, however, their function in Jatropha curcas is still unknown., Results: In this study, we cloned JcGASA6, a member of the GASA family, from J. curcas. The JcGASA6 protein has a GASA-conserved domain and is located in the tonoplast. The three-dimensional structure of the JcGASA6 protein is highly consistent with the antibacterial protein Snakin-1. Additionally, the results of the yeast one-hybrid (Y1H) assay showed that JcGASA6 was activated by JcERF1, JcPYL9, and JcFLX. The results of the Y2H assay showed that both JcCNR8 and JcSIZ1 could interact with JcGASA6 in the nucleus. The expression of JcGASA6 increased continuously during male flower development, and the overexpression of JcGASA6 was associated with filament elongation of the stamens in tobacco., Conclusion: JcGASA6, a member of the GASA family in J. curcas, play an important role in growth regulation and floral development (especially in male flower). It is also involved in the signal transduction of hormones, such as ABA, ET, GA, BR, and SA. Also, JcGASA6 is a potential antimicrobial protein determined by its three-dimensional structure., (© 2023. The Author(s).)

Since the approval by the Food and Drug Administration (FDA), ferumoxytol and other iron oxide nanoparticles (IONs) have been widely used as iron supplements for patients with iron deficiency. Meanwhile, IONs have also been used as contrast agents in magnetic resonance imaging and as drug carriers. Importantly, IONs have demonstrated a significant inhibitory effect on the growth of tumors, including hematopoietic and lymphoid tumors, such as leukemia. In this study, we further demonstrated the effect of IONs on inhibiting the growth of diffuse large B-cell lymphoma (DLBCL) cells by enhancing ferroptosis-mediated cell death. IONs treatment caused an accumulation of intracellular ferrous iron and the onset of lipid peroxidation in DLBCL cells as well as the suppressed expression of anti-ferroptosis protein Glutathione Peroxidase 4 (GPX4), thereby leading to increased ferroptosis. Mechanistically, IONs increased cellular lipid peroxidation through the generation of ROS via the Fenton reaction and regulating the iron metabolism-related proteins, such as ferroportin (FPN) and transferrin receptor (TFR), which elevated the intracellular labile iron pool (LIP). Hence, our findings suggest the potential therapeutic effect of IONs on the treatment of patients with DLBCL., Competing Interests: None., (AJCR Copyright © 2023.)

Diabetic neuropathic pain (DNP) is a common complication of diabetes. Streptozotocin (STZ)-induced changes of protein in dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) are critical for DNP genesis. However, which proteins change remains elusive. Here, the DNP model was established by a single intraperitoneal injection of STZ, accompanied by increased fasting blood glucose (FBG), decreased body weight (BW), and decreased paw withdrawal latency (PWL). Proteins change in L4-L6 DRGs and SCDH of rats were detected. Western blot and immunofluorescence results showed that expression levels of phosphorylated protein kinase C (p-PKC), transient receptor potential vanilloid-1 (TRPV1), Substance P (SP) and calcitonin gene-related peptide (CGRP) in the DRG and the SCDH of rats were increased after STZ injection. A preliminary study from our previous study showed that 2 Hz electroacupuncture (EA) effectively alleviates DNP. However, the analgesic mechanism of EA needs further elucidation. Here, EA at the bilateral Zusanli (ST36) and KunLun (BL60) acupoints was applied for one week, and to investigate the effect on DNP. EA reversed thermal hyperalgesia in DNP rats and downregulated the expression of p-PKC, TRPV1, SP, and CGRP in DRG and SCDH., Competing Interests: The authors declare no conflicts of interest for this work., (Copyright © 2023 Yi-qi Ma et al.)

Two efficient, scalable routes to bis-1,2,4-oxadiazole have been developed by tandem Staudinger/aza-Wittig reaction from the same starting material diaziglyoxime, isocyanates and triphenylphosphonium in good yields., Background: Two convenient and efficient routes for synthesizing diamino derivatives of bis-1,2,4- oxadiazoles were described., Objective: This study provides a simple protocol for the synthesis of bis-1,2,4-oxadiazoles., Methods: The two procedures were based on a tandem Staudinger/aza-Wittig reaction from the same starting material of diaziglyoxime, isocyanates and triphenylphosphonium., Results: In synthesis method I, diaziglyoxime 1 was treated with various aromatic or aliphatic isocyanates to give diazioxalimides 2 a high yield. Diazioxalimides 2 reacted with Ph3P to produce the iminophosphoranes 4; the reaction was directly heated from room temperature to 115 ℃ to get the desired diamino derivatives of bis-1,2,4-oxadiazole 4 in 72-92% yields. In synthesis method II, the same target compounds 4 were synthesized in a one-pot reaction by Ph3P and aromatic or aliphatic isocyanates in toluene for 10 h under 115 ℃ in 53-71% yields., Conclusion: The two procedures provide proficient methods of making nitrogen-containing heterocyclic rings. The structures of target compounds 4 were identified by IR, 1HNMR, 13CNMR and HRMS., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In recent years, CC chemokine receptor 2 (CCR2) has been found to be involved in tumor growth, angiogenesis, epithelial mesenchymal transition, metastasis, and immune escape. CCR2 overexpression was first identified as a poor prognostic predictor in diffuse large B-cell lymphoma (DLBCL) in our published article, but the mechanisms involved remain unknown. In this work, we collected data from another 138 patients with DLBCL data and verified the CCR2 expression level and its relationship to clinicopathological characteristics. Furthermore, we explored the possible mechanisms via in vitro and in vivo experiments. We showed that CCR2 overexpression was an independent prognostic marker and predicted shorter overall survival (OS) and progression-free survival (PFS) in patients with DLBCL. Blockade of CCR2 expression with a CCR2 antagonist inhibited tumor cell proliferation, migration, and anti-apoptosis ability in vitro by affecting the PI3K/Akt signaling pathway and the p38 MAPK signaling pathway. Furthermore, administration of a CCR2 antagonist decreased tumor growth and dissemination of DLBCL cells and increased survival time in the xenograft model. Our study demonstrates that CCR2 expression plays an important role in the development of DLBCL by stimulating cell proliferation, migration, and anti-apoptosis. Therefore, the inhibition of CCR2 may be a potential target for anticancer therapy in DLBCL., (© 2022. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.)

Objective: To study the clinical value of accelerated rehabilitation nursing (ARN) in improving the symptoms of PCa patients after surgery., Methods: This study included 80 cases of PCa treated surgically in our hospital from October 2020 to October 2021. We randomly divided the patients into two groups of an equal number to receive ARN and routine nursing care (the control group), respectively. We obtained the scores of the patients on IPSS, TCM syndromes, quality of life (QOL) and pain, incidence of postoperative complications, satisfaction with nursing care and Gleason scores, and compared them between the two groups., Results: The IPSS and TCM syndrome scores were significantly lower (P < 0.05 ), and the physical and psychological function score remarkably higher in the ARN than in the control group (P < 0.05), but there was no statistically significant difference in the social function scores between the two groups (P > 0.05). The postoperative pain score was also significantly lower in the ARN than in the control group (P < 0.05), and so was the incidence rate of postoperative complications (10% vs 37.5%, P < 0.05). The patients' satisfaction with nursing care was markedly higher in the former than in the latter group (90% vs 80%, P < 0.05). No statistically significant difference was observed in the Gleason scores between the two groups of patients., Conclusion: Accelerated rehabilitation nursing can effectively improve the symptoms of PCa patients after surgery and therefore deserves clinical application.

Objective: To evaluate the quality of life and influencing factors of patients with herpes zoster (HZ) seen in hospitals. Methods: Based on Zoster Brief Pain Inventory (ZBPI) and Five-level EuroQol Five-dimensional Questionnaire (EQ-5D-5L), a cross-sectional survey was conducted to evaluate the pain severity and quality of life of 332 HZ cases seen in 22 hospitals of Lu'an City (Anhui Province), Zibo City (Shandong Province) and Tongchuan City (Shaanxi Province) from October to December 2021. The censored least absolute deviations (CLAD) model was used to analyze the related factors affecting the changes of patients' health utility values. Results: The 45.5% of 332 HZ cases were male. The median ( Q 1 , Q 3 ) age was 59 (50, 68) years. 59.64% of them assessed by ZBPI had moderate to severe pain in the past 24 hours (worst pain score≥5), and that of PHN cases was 84.8%(39/46). 77.7% (258/332), 77.4% (257/332) and 74.1% (246/332) of all patients reported that pain interfered with sleep, mood and general activities, respectively. Aging [β 40-49y (95% CI )=-0.11 (-0.15, -0.08); β 50-59y (95% CI )=-0.03 (-0.05, 0.00); β 60-69y (95% CI )=-0.09 (-0.12, -0.06); β 70-90y (95% CI )=-0.16 (-0.19, -0.12)], working status (unemployed) [β farmer (95% CI )=0.15 (0.13, 0.18); β retirees (95% CI )=0.21 (0.18, 0.24); β employee (95% CI )=0.13 (0.10, 0.16) ], complications[β PHN (95% CI )=-0.08 (-0.13, -0.04); β other complications (95% CI )=-0.12 (-0.15, -0.08)], within 30 days after onset [β(95% CI )=-0.01 (-0.03, 0.01)] and treatment [β other complications (95% CI )=-0.09 (-0.11, -0.06)] were related factors for the decline of health utility value (all P values <0.05). Conclusions: More than half of the patients with HZ had moderate to severe pain in the past 24 hours, which had a serious negative impact on the physical and mental health of the patients. Elderly patients, acute patients and patients with complications had lower health utility values and worse health status. We suggest that eligible people be vaccinated with HZ vaccine as soon as possible.

Spider mites belonging to the genus Tetranychus infest many important agricultural crops in both fields and greenhouses worldwide and are diversified in their host plant range. How spider mites perceive their suitable host plants remains not completely clear. Here, through two-host-choice designs (bean vs. tomato, and bean vs. eggplant), we tested the efficacies of the olfactory and gustatory systems of five spider mite species ( T. urticae , T. truncatus , T. pueraricola , T. piercei , and T. evansi ), which differ in host plant range in sensing their suitable host plant, by Y-tube olfactometer and two-choice disc experiments. We found that spider mites cannot locate their suitable host plants by volatile odours from a long distance, but they can use olfactory sensation in combination with gustatory sensation to select suitable host plants at a short distance. Highly polyphagous species displayed strong sensitivity in sensing suitable host plants rather than the lowered sensitivity we expected. Intriguingly, our principal component analyses (PCAs) showed that the similarity among five spider mite species in the performance of perceiving suitable host plants was highly correlated with their relative phylogenetic relationships, suggesting a close relationship between the chemosensing system and the speciation of spider mites. Our results highlight the necessity of further work on the chemosensing system in relation to host plant range and speciation of spider mites.

AbstractObjective: To explore the distribution characteristics and clinical significance of peripheral blood monocyte subgroups in patients with diffuse large Bcell lymphoma(DLBCL)., Methods: The percentage of peripheral blood monocyte subsets of 82 DLBCL patients (including 32 newly diagnosis, 29 remission and 21 relapse) and 30 healthy controls were detected by flow cytometry, and the correlation with the clinical characteristics and its diagnostic value of DLBCL were analyzed., Results: The proportion of intermediate monocytes in patients with newly diagnosed DLBCL group was higher than that in healthy controls (t=5.888, P<0.01). The proportion in relapsed group was higher than those in newly diagnosed DLBCL group（t=2.106，P=0.04） and remission group （t=6.882， P＜0.01）, and the proportion of intermediate monocytes in newly diagnosed DLBCL group was higher than that in Remission group (t=3.969, P<0.01). With the increase of International Prognostic Index (IPI) score, the percentage of intermediate monocytes in patients with DLBCL increased (r=0.37). Furthermore, when the proportion of intermediate monocytes was 10.91% as the cutoff value, the sensitivity and specificity of the whole sample were 90.60% and 9100%, respectively., Conclusion: The disease progression is related to the increased intermediate monocytes, which can be used as a potential diagnostic index for DLBCL.

The clinical use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) is limited by its short serum half-life. In this study, a long-acting strategy for site-specific modification of rhG-CSF with 1-pentadecyl-1H-pyrrole-2,5-dione (C15 fatty chain-maleimide, C15-MAL) was studied in mixed DMSO-aqueous solutions. The factors influencing the conjugation reaction were investigated and optimized, and a high yield of the desired product (C15-rhG-CSF) was achieved. Subsequently, C15-rhG-CSF product was efficiently purified using preparative liquid chromatography, and further characterized. Circular dichroism spectroscopy analysis showed that the secondary structure of C15-rhG-CSF had no significant difference from unmodified rhG-CSF. C15-rhG-CSF retained 87.2% of in vitro bioactivity of unmodified rhG-CSF. The pharmacokinetic study showed that the serum half-life of C15-rhG-CSF in mice was 2.08-fold longer than that of unmodified rhG-CSF. Furthermore, C15-rhG-CSF by single-dose subcutaneous administration showed better in vivo efficacy than those of both PEG 10k -rhG-CSF by single-dose administration and rhG-CSF by multiple doses administration. This study demonstrated the potential of C15-rhG-CSF being developed into a novel drug candidate as well as an efficient process for the development of long-acting protein and peptide drugs., 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 © 2022 Wang, Yu, Liu, Du, Chen, Hu, Sun and Ying.)

Background: A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed., Methods: We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators., Results: The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8-65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible., Conclusions: GOHI-subject to rigorous validation-would represent the world's first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge., (© 2022. The Author(s).)

Objective: To observe the occurrence time of neuralgia and the expression of purinergic ligand-gated ion channel 7 receptor (P2X7R) in the dorsal horn of the spinal cord after intraperitoneal injection of streptozotocin (STZ) in diabetic rats, and to explore the effect of electroacupuncture (EA) and pretreatment of EA on the heat pain threshold and expression of P2X7R in the spinal dorsal horn in rats with diabetic neuropathic pain (DNP), and to explore the possible mechanism of EA for DNP., Methods: PartⅠ: Thirty male SD rats were randomly selected from 64 male SD rats as the control group; the remaining rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model, and 30 rats were successfully modeled as the model group. The control group and the model group were divided into three subgroups respectively at 7, 14 and 21 days, with 10 rats in each subgroup. Body mass, fasting blood glucose (FBG) and thermal pain threshold were recorded at 7, 14 and 21 days after injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot. PartⅡ: Eight SD rats were randomly selected from 35 male SD rats as the blank group, and the remaining 27 rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model. The 24 rats with successful diabetes model were randomly divided into a DNP group, an EA group and a pre-EA group, 8 rats in each group. Fifteen to 21 days after STZ injection, the EA group received EA at "Zusanli" (ST 36) and "Kunlun" (BL 60), continuous wave, frequency of 2 Hz, 30 min each time, once a day; the intervention method in the pre-EA group was the same as that in the EA group. The intervention time was 8 to 14 days after STZ injection. The body mass, FBG and thermal pain threshold were recorded before STZ injection and 7, 14 and 21 days after STZ injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot 21 days after injection., Results: PartⅠ: Compared with the control group, in the model group, the body mass was decreased and FBG was increased 7, 14 and 21 days after STZ injection ( P <0.01), and the thermal pain threshold was decreased 14 and 21 days after STZ injection ( P <0.05), and the expression of P2X7R in spinal dorsal horn was increased 7, 14 and 21 days after STZ injection ( P <0.05, P <0.01). PartⅡ: Compared with the blank group, in the DNP group, the body mass was decreased and fasting blood glucose were increased 7, 14 and 21 days after STZ injection ( P <0.01). Compared with the DNP group, in the pre-EA group, the heat pain threshold was increased 14 and 21 days after STZ injection ( P <0.05), while in the EA group, the heat pain threshold was increased 21 days after STZ injection ( P <0.01), and the expression of P2X7R in the dorsal horn in the EA group and the pre-EA group was decreased ( P <0.01)., Conclusion: The diabetic neuropathic pain is observed 14 days after STZ injection. EA could not only treat but also prevent the occurrence of DNP, and its mechanism may be related to down-regulation of P2X7R expression in the dorsal horn of the spinal cord.

Background: Reaching optimal vaccination rates is an essential public health strategy to control the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to simulate the optimal vaccination strategy to control the disease by developing an age-specific model based on the current transmission patterns of COVID-19 in Wuhan City, China., Methods: We collected two indicators of COVID-19, including illness onset data and age of confirmed case in Wuhan City, from December 2, 2019, to March 16, 2020. The reported cases were divided into four age groups: group 1, ≤ 14 years old; group 2, 15 to 44 years old; group 3, 44 to 64 years old; and group 4, ≥ 65 years old. An age-specific susceptible-exposed-symptomatic-asymptomatic-recovered/removed model was developed to estimate the transmissibility and simulate the optimal vaccination strategy. The effective reproduction number (R eff ) was used to estimate the transmission interaction in different age groups., Results: A total of 47 722 new cases were reported in Wuhan City from December 2, 2019, to March 16, 2020. Before the travel ban of Wuhan City, the highest transmissibility was observed among age group 2 (R eff  = 4.28), followed by group 2 to 3 (R eff  = 2.61), and group 2 to 4 (R eff  = 1.69). China should vaccinate at least 85% of the total population to interrupt transmission. The priority for controlling transmission should be to vaccinate 5% to 8% of individuals in age group 2 per day (ultimately vaccinated 90% of age group 2), followed by 10% of age group 3 per day (ultimately vaccinated 90% age group 3). However, the optimal vaccination strategy for reducing the disease severity identified individuals ≥ 65 years old as a priority group, followed by those 45-64 years old., Conclusions: Approximately 85% of the total population (nearly 1.2 billion people) should be vaccinated to build an immune barrier in China to safely consider removing border restrictions. Based on these results, we concluded that 90% of adults aged 15-64 years should first be vaccinated to prevent transmission in China., (© 2021. The Author(s).)

In this article, a new zinc-containing ionic liquid (IL) [HMMIm] 2 [ZnCl 4 ] (HMMIm = 1-hexyl-2,3-dimethyl-imidazolium) is designed, which acts as a multifunctional source for the interfacial engineering of ZnS nanodots (NDs). Given the electrostatic interaction driven by the imidazolium cation, the steric effect of the alkyl chain, and the in situ released Zn ion from the IL, [HMMIm] 2 [ZnCl 4 ] shows great advantages in controlling the formation of ZnS NDs. Based on this strategy, a nanocomposite consisting of homodispersed ZnS NDs anchored on sulfur/nitrogen dual-doped reduced graphene oxide (ZnS-NDs@SNG) is prepared. When evaluated as an anode material for lithium-ion batteries (LIBs), the nanocomposite delivers high reversible specific capacity, excellent high-rate performance, and superior cycling life. In particular, a discharge capacity of 648.1 mA h g -1 can be achieved at a high current density (10.0 A g -1 ) over 5000 cycles. Benefitting from the multifunctional IL and the simple synthesis protocol, the IL-assisted interfacial engineering strategy will enable a new avenue for the controllable synthesis of metal-sulfide-based anode materials.

An efficient iodine-imine synergistic promoted Povarov-type multicomponent reaction was reported for the synthesis of a practical 2,2'-biquinoline scaffold. The tandem annulation has reconciled iodination, Kornblum oxidation, and Povarov aromatization, where the methyl group of the methyl azaarenes represents uniquely reactive input in the Povarov reaction. This method has broad substrate scope and mild conditions. Furthermore, these 2,2'-biquinoline derivatives had been directly used as bidentate ligands in metal-catalyzed reactions.

The plant root is an important storage organ that stores indole-3-acetic acid (IAA) from the apical meristem, as well as nitrogen, which is obtained from the external environment. IAA and nitrogen act as signaling molecules that promote root growth to obtain further resources. Fluctuations in the distribution of nitrogen in the soil environment induce plants to develop a set of strategies that effectively improve nitrogen use efficiency. Auxin integrates the information regarding the nitrate status inside and outside the plant body to reasonably distribute resources and sustainably construct the plant root system. In this review, we focus on the main factors involved in the process of nitrate- and auxin-mediated regulation of root structure to better understand how the root system integrates the internal and external information and how this information is utilized to modify the root system architecture., 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 © 2021 Hu, Shu, Li and Wang.)

ZnS/carbon nanocomposites have potential electrochemical applications due to their improved conductivity and more active sites through modification of the carbon materials. Herein, we report a facile method to synthesize the nanocomposites comprising ZnS nanoparticles and nitrogen-doped carbon (ZnS@NC). The inorganic-organic hybrid ZnS-amine material ZnS(ba) (ba = n -butylamine) is synthesized on a large scale by a reflux method, which effectively shortens the reaction time while maintaining the high yield compared with the solvothermal method. Then ZnS(ba) is used as precursor for obtaining ZnS@NC nanocomposites via a vacuum pyrolysis route, in which the content of carbon and nitrogen can be controlled by adjusting the pyrolysis temperature. Further, a series of ZnS-amine hybrid materials ZnS(ha), ZnS(en) 0.5 and ZnS(pda) 0.5 (ha = n -hexylamine; en = ethylenediamine; pda = 1,3-propanediamine) are synthesized and used as precursors for the preparation of ZnS@NC materials, indicating the universality of this method. Moreover, the as-synthesized ZnS@NC materials exhibit remarkable lithium storage performance with outstanding cycling stability, high-rate capability and remarkable pseudo-capacitance characteristics., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The high expression of sonic hedgehog ligand (SHh) is closely correlated to the metastasis, drug resistance and poor prognosis of hepatocellular carcinoma (HCC). Therefore, sensitive, specific and efficient detection methods for SHh are needed for the early diagnosis and assessment of prognosis. Herein, an aptamer, AP32 that specifically binds to SHh (K D  = 25.7 ± 4.1 nM) was obtained by SELEX technology with further optimization. In vivo experiments confirmed that AP32 has the potential to be an imaging probe for Huh-7 cell-derived xenograft. The interaction mode in 3-dimensional configuration between the aptamer and SHh was established by molecular simulation and confirmed by mutations at key sites of the aptamer. An aptasensor-based assay was successfully developed by conjugating Texas-Red-labeled AP32 to microbeads, and was used to analyze SHh content in hepatoma cell lysates, serum and HCC specimens. The method exhibited a broad detection range from 0.07 to 62.5 nM with a low detection limit of 69 pM, and a recovery rate of 104.6 ± 3.9% in serum. When the assay was used to measure SHh content in tissue lysates, the results demonstrated that it possessed 57.1% positivity, 100% specificity in distinguishing 28 HCC specimens from normal tissues, and was compensatory for detection of HCC in AFP-negative cases. Moreover, elevated SHh levels are indicative of portal vein invasion at 77.8% positive rate. This novel aptasensor-based SHh assay may offer a reliable means in predicting early metastasis and poor prognosis in hepatocellular carcinoma., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also called 2019-nCoV) causes different morbidity risks to individuals in different age groups. This study attempts to quantify the age-specific transmissibility using a mathematical model., Methods: An epidemiological model with five compartments (susceptible-exposed-symptomatic-asymptomatic-recovered/removed [SEIAR]) was developed based on observed transmission features. Coronavirus disease 2019 (COVID-19) cases were divided into four age groups: group 1, those ≤ 14 years old; group 2, those 15 to 44 years old; group 3, those 45 to 64 years old; and group 4, those ≥ 65 years old. The model was initially based on cases (including imported cases and secondary cases) collected in Hunan Province from January 5 to February 19, 2020. Another dataset, from Jilin Province, was used to test the model., Results: The age-specific SEIAR model fitted the data well in each age group (P < 0.001). In Hunan Province, the highest transmissibility was from age group 4 to 3 (median: β 43  = 7.71 × 10 - 9 ; SAR 43  = 3.86 × 10 - 8 ), followed by group 3 to 4 (median: β 34  = 3.07 × 10 - 9 ; SAR 34  = 1.53 × 10 - 8 ), group 2 to 2 (median: β 22  = 1.24 × 10 - 9 ; SAR 22  = 6.21 × 10 - 9 ), and group 3 to 1 (median: β 31  = 4.10 × 10 - 10 ; SAR 31  = 2.08 × 10 - 9 ). The lowest transmissibility was from age group 3 to 3 (median: β 33  = 1.64 × 10 - 19 ; SAR 33  = 8.19 × 10 - 19 ), followed by group 4 to 4 (median: β 44  = 3.66 × 10 - 17 ; SAR 44  = 1.83 × 10 - 16 ), group 3 to 2 (median: β 32  = 1.21 × 10 - 16 ; SAR 32  = 6.06 × 10 - 16 ), and group 1 to 4 (median: β 14  = 7.20 × 10 - 14 ; SAR 14  = 3.60 × 10 - 13 ). In Jilin Province, the highest transmissibility occurred from age group 4 to 4 (median: β 43  = 4.27 × 10 - 8 ; SAR 43  = 2.13 × 10 - 7 ), followed by group 3 to 4 (median: β 34  = 1.81 × 10 - 8 ; SAR 34  = 9.03 × 10 - 8 )., Conclusions: SARS-CoV-2 exhibits high transmissibility between middle-aged (45 to 64 years old) and elderly (≥ 65 years old) people. Children (≤ 14 years old) have very low susceptibility to COVID-19. This study will improve our understanding of the transmission feature of SARS-CoV-2 in different age groups and suggest the most prevention measures should be applied to middle-aged and elderly people.

Aiming at the problem of heavy metal Cd pollution in mining wasteland under the high background value and superposition area of the historical mining source, a total of 30 samples were collected from the reclaimed soil of a historical sulfur mine in Southwest China. The total contents of Cadmium (Cd), Chromium (Cr), Nickel (Ni), Arsenic (As), and Mercury (Hg) in soil samples were analyzed. Scanning electron microscopy-electron diffraction spectroscopy (SEM-EDS) and BCR method for continuous extraction of heavy metals were used to analyze the occurrence of Cd under different soil thicknesses. The effectiveness of heavy metal Cd was evaluated by the risk assessment coding method (RAC), and the ratio of secondary phase and primary phase (RSP) was obtained. In addition, the changes in Cd morphology under different physicochemical properties were discussed. The results show that the concentration factor of Cd in the five heavy metals is the highest over 4. Through the morphological characteristics, it can be found that there are mainly subangular and angular particles in the samples. The resulting energy spectrum characteristics at different depths were similar, and all sampled contained Cd, Fe, S, and As. Isomorphs of Cd element were observed. According to the potential risk assessment of Cd, the RAC results show that the risk is medium or below, while the RSP results may lead to serious pollution except for the bottom layer. The total amount of heavy metals is the most important factor affecting the distribution of Cd forms, followed by pH, organic matter, and CEC. The results of this study can provide scientific basis for further understanding the activity, migration rule, biological toxicity, and occurrence form of Cd in profile soil.

Objective: The aim of the present study was to evaluate the effects of ethyl acetate extract of Polygonum orientale L. (POE) on ameliorating postmenopausal osteoporosis in ovariectomized (OVX) rats. Methods: Six-month-old female rats were randomly divided into seven groups: sham-operated; OVX; OVX with estradiol valerate; OVX with alendronate; and OVX with POE in graded doses (3.75, 5.0, or 7.5 g/kg/day). Administration began at week 6 after ovariectomy for 12 weeks. A comprehensive assessment of bone quality was performed, including serum biochemical markers, serum inflammatory factors, bone oxidative stress markers, bone mechanics, and bone histomorphometry. Results: POE treatment significantly decelerated OVX-induced body weight gain without affecting the uterus index and produced a significant decrease in the levels of serum bone turnover markers ( p  < 0.05 or p  < 0.01). Biomechanical testing demonstrated that POE (5.0 and 7.5 g/kg/day) treatments significantly prevented the reduction in maximum stress and Young's modulus in OVX rats ( p  < 0.05). Compared with the OVX group, POE (3.75, 5.0, or 7.5 g/kg/day) treatments significantly increased trabecular bone mineral density by 35.03, 38.42, and 42.02%, respectively. Conclusion: Our findings suggest that POE has potential effects in regulation of bone metabolism and prevention of bone loss in postmenopausal osteoporosis.

Objective: To detect the clinicopathological features, immunophenotype, diagnosis, and differential diagnosis of composite pheochromocytoma(CP). Methods: Five cases of CP were collected at Zhejiang Provincial People's Hospital from January 2011 to January 2019. The clinical, radiological, histologic, immunohistochemical and outcome data were analyzed; the diagnosis and differential diagnosis were discussed. Results: The patients' age range was 52-68 years (mean 59 years, median 54 years), There were 4 males and 1 female, and the male to female ratio was 4∶1. Tumor size was 3-4 cm (mean 3.6 cm, median 3.5 cm). The most common clinical manifestation was adrenal mass. Histologically, the classical feature was two distinct morphologic components, one with tumor cells arranged in irregular nests, and with fine granular and basophilic oramphophilic cytoplasm; the other was composed of scattered ganglion cells in the background of Schwann cells organized in interwoven bundles. The components of pheochromocytoma expressed PHOX2B(5/5), synaptophysin (5/5), CgA (5/5), the sustentacular cells expressed S-100 protein; the components of ganglioneuroma expressed S-100 protein (5/5), NF (5/5), the ganglion cells were weakly positive for PHOX2B, synaptophysin and CgA. All the cases were surgically resected and all patients were free of recurrence at follow-up. Conclusions: CP is rare adrenal tumor, and it has typical histologic features but no specific clinical manifestations. Attention should be paid to its characteristic histomorphology with the use of PHOX2B, CgA, synaptophysin and S-100 protein immunohistochemistry that is helpful for its diagnosis.

Ethylene insensitive 3 (EIN3), a key transcription factor in ethylene signal transduction, play important roles in plant stress signaling pathways. In this study, we isolated and characterized an EIN3-like gene from cotton (Gossypium hirsutum), designated as GhEIN3. GhEIN3 is highly expressed in vegetative tissues, and its expression is induced by 1-aminocyclopropane-1-carboxylic acid (ACC) and NaCl. Ectopic expression of GhEIN3 in Arabidopsis elevated plants' response to ethylene, which exhibit smaller leaves, more root hairs, shorter roots and hypocotyls. The germination rate, survival rate and root length of GhEIN3 transgenic plants were significantly improved compared to wild type under salt stress. GhEIN3 transgenic plants accumulated less H 2 O 2 and malondialdehyde (MDA), while higher superoxide dismutase (SOD) and peroxidase (POD) activities were detected under salt stress. In addition, expression of several genes related to reactive oxygen species (ROS) pathway and ABA signaling pathway was increased in the GhEIN3 transgenic plants under salt stress. In contrast, virus-induced gene silencing (VIGS) of GhEIN3 in cotton enhanced the sensitivity of transgenic plants to salt stress, accumulating higher H 2 O 2 and MDA and lower SOD and POD activities compared to control plants. Collectively, our results revealed that GhEIN3 might be involved in the regulation of plant response to salt stress by regulating ABA and ROS pathway during plant growth and development., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

The different hydrogen bond interactions in two organic-inorganic hybrid manganese halide compounds, namely [A]2[MnBr4] (A = N-butyl-N-methylpyrrolidinium ([P14]+) for (1) and N-butyl-N-methylpiperidinium ([PP14]+) for (2)), lead to distinct photoluminescence quantum yields (81% for 1; 55% for 2). Further applications of luminescent 1 are also developed.

Exploring the composition and accumulation of antibiotics in agricultural land soil for soil for quality management of agricultural land and control of antibiotic pollution is of great significance. A total of 95 soil samples were collected from farmland soil in a typical agricultural and sideline production base of northern China. In this study, the concentrations of 10 antibiotics, including tetracycline antibiotics (TCs), macrolide antibiotics (MLs), and sulfonamide antibiotics (SAs), were determined in soil samples from different land use types using HPLC-MS/MS. In addition, the composition and spatial distribution of the antibiotics were compared. The relationships between the concentration distributions and the distance from livestock farms, highways, and rivers were analyzed. Moreover, the composition and accumulation of antibiotics in the soil with different planting patterns and soil properties were preliminarily discussed. The results showed that the concentrations of antibiotics in the soil were low-level, while the detection rate was high; in particular, the detection rate of the total amount of antibiotics was as high as 100%. In the study area, TCs were the dominant antibiotic types, accounting for 94% of the total. The coefficient variation (CV) was high, which reflected a significant difference in the spatial variation of these antibiotics. The spatial distribution and accumulation of antibiotics in the soil in this area were affected by the intensity of human activity. The detection rate and concentrations of the various antibiotics decreased with increasing distance between the soil sample and livestock farms, highways, and rivers. Among these, there was a significant negative correlation between the concentration of antibiotics and the distance between livestock farms and the soil samples ( P <0.05). The detection rate of three types of antibiotics in soil samples from within 50 meters of a river reached 100%. The total concentration of the 10 antibiotics was the highest in orchards, followed by vegetable plots, and mixed fruit and vegetable areas. Furthermore, the sources and concentrations of antibiotics in a peach orchard and open-air vegetable field were significantly different from those in a walnut orchard, greenhouse vegetable field, and mixed field. Moreover, the soil pH, soil organic matter (SOM), cation exchange capacity (CEC), total nitrogen (TN), available phosphorus (AP), and available potassium (AK) were selected to characterize soil properties. Redundancy analysis showed that soil properties such as pH, SOM, CEC, AP, AK have a greater impact on the distribution of antibiotics. The distribution of antibiotics was most closely related to AK, and the effect of TN was relatively weak. The results of this study suggested that the composition and accumulation of soil antibiotics in the area were affected by human activities and soil properties.