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Abstract The impact of microplastics on antibiotic resistance has attracted widespread attention. However, previous studies primarily focused on the effects of individual microplastics. In reality, diverse microplastic types accumulate in soil, and it remains less well studied whether microplastic diversity (i.e., variations in color, shape or polymer type) can be an important driver of increased antibiotic resistance gene (ARG) abundance. Here, we employed microcosm studies to investigate the effects of microplastic diversity on soil ARG dynamics through metagenomic analysis. Additionally, we evaluated the associated potential health risks by profiling virulence factor genes (VFGs) and mobile genetic elements (MGEs). Our findings reveal that as microplastic diversity increases, there is a corresponding rise in the abundance of soil ARGs, VFGs and MGEs. We further identified microbial adaptive strategies involving genes (changed genetic diversity), community (increased specific microbes), and functions (enriched metabolic pathways) that correlate with increased ARG abundance and may thus contribute to ARG dissemination. Additional global change factors, including fungicide application and plant diversity reduction, also contributed to elevated ARG abundance. Our findings suggest that, in addition to considering contamination levels, it is crucial to monitor microplastic diversity in ecosystems due to their potential role in driving the dissemination of antibiotic resistance through multiple pathways.

Abstract Background Liver cancer (LC) screening, such as AFP test and abdominal ultrasound, is an effective way to prevent LC, one of the most common cancers worldwide. Despite the proven screening benefits, screening participation among high-risk populations for LC remains low. This suggests that targeted, systematic, and effective interventions should be provided to improve knowledge and awareness related to LC screening, enhance screening intentions, and thereby promote screening behaviors. Telephone is people’s main medium of daily communication and mHealth-based programs offer a potential and effective solution for promoting health behaviors. The purpose of this study is to develop and implement a mHealth (WeChat app) based intervention guided by Fogg’s Behavior Model (FBM) to augment the knowledge of LC prevention among people at risk of LC and enhance their motivation for screening, and to validate its effectiveness in improving LC screening. Methods We propose a two-arm, single-blind randomized controlled trial with 82 at-risk individuals of LC, delivering a 6-month mHealth-based intervention program with optional health counseling. Recruitment will be through tertiary hospitals and community organizations in 4 districts in Heng Yang. In total, 82 individuals at high risk for HCC will be randomized 1:1 to intervention or control (usual care) groups. The intervention group will receive intervention, whose contents are based on the FBM model, via multiple forms of media including PowerPoint presentation, multimedia video, health information booklet and screening message, which is delivered in the WeChat Applet. Control dyads will be provided with usual health education. Outcomes will be assessed at baseline and post-intervention. Discussion The findings of this study will provide evidence of the benefits of utilizing mHealth-based approaches in intervention development to enhance the effectiveness of screening adherence for high-risk people of LC. Further, the findings would provide reference to the potential incorporation of the targeted intervention in local community organizations. Trial registration Chinese Clinical Trial Registry (ChiCTR2400080530) Date registered: 31/1/2024.

BackgroundChronic coronary syndromes (CCS) is a common clinical condition that increases the risk of cardiovascular events at any time. Tongxinluo capsules (TXL) are widely used in China for treating CCS.ObjectivesTo systematically evaluate the therapeutic effects and safety of adding TXL to Western medical treatment (WM) for CCS.MethodsWe searched PubMed, Cochrane Library, CNKI, VIP, and Wanfang databases up to August 2024 for randomized controlled trials (RCTs) investigating the therapeutic effects and safety of combining TXL with WM compared to WM alone for CCS. Data analyses were conducted using RevMan 5.4 software.ResultsTwenty studies involving 2091 participants were identified. Evidence supports the use of TXL plus WM for reducing angina frequency [SMD −2.50, 95% CI (−3.53, −1.48)], improving seattle angina questionnaire scores (P

ABSTRACTThe emergence of Anaplasma bovis or A. bovis-like infection in humans from China and the United States of America has raised concern about the public health importance of this pathogen. Although A. bovis has been detected in a wide range of ticks and mammals in the world, no genome of the pathogen is available up to now, which has prohibited us from better understanding the genetic basis for its pathogenicity. Here we describe an A. bovis genome from metagenomic sequencing of an infected goat in China. Anaplasma bovis had the smallest genome of the genus Anaplasma, and relatively lower GC content. Phylogenetic analysis of single-copy orthologue sequence showed that A. bovis was closely related to A. platys and A. phagocytophilum, but relatively far from intraerythrocytic Anaplasma species. Anaplasma bovis had 116 unique orthogroups and lacked 51 orthogroups in comparison to other Anaplasma species. The virulence factors of A. bovis were significantly less than those of A. phagocytophilum, suggesting less pathogenicity of A. bovis. When tested by specific PCR assays, A. bovis was detected in 23 of 29 goats, with an infection rate up to 79.3% (95% CI: 64.6% ∼94.1%). The phylogenetic analyses based on partial 16S rRNA, gltA and groEL genes indicated that A. bovis had high genetic diversity. The findings of this study lay a foundation for further understanding of the biological characteristics and genetic diversity of A. bovis, and will facilitate the formulation of prevention and control strategies.

Ticks are important vectors of zoonotic pathogens, and represent an increasing threat for human and animal health. Considering the complex natural environments of Ningxia Hui Autonomous Region, China, we expect the diverse tick species in this region. Here, we conduct a field survey on parasitic and host-seeking ticks. A total of 10,419 ticks were collected, which belonged to nine species of four genera. There were significant differences in terms of vegetation index, altitude, and seven climatic factors among the four tick genera —Hyalomma, Dermacentor, Haemaphysalis, and Ixodes, except between Haemaphysalis and Ixodes, where no significant differences were observed in these factors. The ecological niche modelling revealed that the suitable habitats for Hyalomma asiaticum was in the northwest Ningxia, with annual ground surface temperature as the most important factor. The suitable area for Dermacentor nuttalli was in the southwest and eastern regions of Ningxia with elevation as the highest contribution. D. silvarum was best suited to the southern Ningxia also with elevation as the most important factor. The four tick species including Haemaphysalis longicornis, Hae. qinghaiensis, Hae. japonica, and Ixodes persulcatus were best suited to the southernmost Ningxia with annual precipitation as the main factors for Hae. longicornis and elevation for the other three ticks. The results of predicted potential distribution of different tick species provide a scientific basis for the prevention and control of ticks and tick-borne diseases in the region. Furthermore, the subsequent impacts of the Greening Program to regain forests and grasslands from former agricultural lands in Ningxia on tick population dynamics deserve further investigation.

This research examines the correlation between the COVID-19 pandemic and the desire to engage in compensatory consuming behaviors, specifically emphasizing emotional eating as a psychological coping strategy, particularly with respect to snacks and sweets. Conducting sentiment analysis by using a Natural Language Processing (NLP) method on posts from Sina Weibo, a leading Chinese social media platform, the research identifies three distinct phases of consumer behavior during the pandemic: anxiety, escapism, and compensatory periods. These stages are marked by varying degrees of emotional eating tendencies, illustrating a psychological trajectory from initial shock to seeking comfort through food as a means of regaining a sense of normalcy and control. The analysis reveals a notable increase in posts expressing a desire for compensatory consumption of snacks and sweets in 2020 compared to 2019, indicating a significant shift towards emotional eating amid the pandemic. This shift reflects the broader psychological impacts of the crisis, offering insights into consumer behavior and the role of digital platforms in capturing public sentiment during global crises. The findings have implications for policymakers, health professionals, and the food industry, suggesting the need for strategies to address the psychological and behavioral effects of natural disasters.

BackgroundPrevious research has demonstrated the validity of the triglyceride-glucose (TyG) index as a robust measure of insulin resistance (IR) and its association with coronary artery disease (CAD). The objective of this study is to elucidate the relationship between the TyG index and the prognosis of patients underwent percutaneous coronary intervention (PCI) through a comprehensive systematic review and meta-analysis. Our goal is to provide a thorough analysis of the available evidence to offer more clarity on this association.MethodsA systematic and thorough search was carried out in the PubMed, Embase, Cochrane Library, and Web of Science databases, covering studies published in English from the beginning until October 1, 2023. The focus of the search was to gather relevant studies pertaining to the occurrence of major adverse cardiovascular events (MACE). To address the variability among the included studies, random or fixed effect models were utilized to summarize the hazard ratios (HR). In cases where heterogeneity was detected, subgroup or sensitivity analyses were performed to explore potential sources. To evaluate publication bias, the Egger or Begg test was employed.ResultsThis study incorporated a total of 17 studies. Individuals with the highest TyG index exhibited an elevated risk of major adverse cardiovascular events (MACEs) compared to those with the lowest TyG index (HR = 1.69; 95% CI: 1.47–1.95; P

Abstract There has been increasing global concern about the spillover transmission of pangolin-associated microbes. To assess the risk of these microbes for emergence as human pathogens, we integrated data from multiple sources to describe the distribution and spectrum of microbes harbored by pangolins. Wild and trafficked pangolins have been mainly recorded in Asia and Africa, while captive pangolins have been reported in European and North American countries. A total of 128 microbes, including 92 viruses, 25 bacteria, eight protists, and three uncharacterized microbes, have been identified in five pangolin species. Out of 128 pangolin-associated microbes, 31 (including 13 viruses, 15 bacteria, and three protists) have been reported in humans, and 54 are animal-associated viruses. The phylogenetic analysis of human-associated viruses carried by pangolins reveals that they are genetically close to those naturally circulating among human populations in the world. Pangolins harbor diverse microbes, many of which have been previously reported in humans and animals. Abundant viruses initially detected in pangolins might exhibit risks for spillover transmission.

Abstract Myodural bridge (MDB) is a dense connective tissue between suboccipital muscle and dura mater. However, there are few reports on the development and maturation of the human MDB. This study aims to explore the developmental relationship between suboccipital muscle and MDB. 30 head and neck specimens from human fetuses (F) ranging from the 12th to 41st week (W) were made into histological sections. The F12W sections showed evidence that the dura mater dominated by fibroblasts, attached to the posterior atlanto-axial membrane (PAAM) which completely sealed the atlanto-axial space. In the F13W stage, myofibrils of the suboccipital muscle fibers increased significantly in number. At the F14W stage, a gap was observed at the caudal end of the PAAM. Numerous myodural bridge-like structures were observed blending into the dura mater through the gap. At the F19W stage, muscle cells mature. Starting at the F21W stage, the MDB were observed as fibroblasts that cross the atlanto-axial interspace and attach to the dura mater. Therefore, the traction generated by the suboccipital muscles seems to promote the maturity of MDB. This study will provide new morphological knowledge to support future research on the function of the human MDB and regulating the development mechanism of MDB.

Soft ticks (Ixodida: Argasidae) are ectoparasites of terrestrial vertebrates with worldwide distributions. As one representative group of Argasidae, the genus Argas has an important vectorial role in transmitting zoonotic diseases. However, our knowledge of the subgenus Argas in China is still limited, as most literature only lists occurrence records or describes specific case reports without providing detailed morphological characteristics and further molecular data. This study aims to characterize Argas vulgaris through complete mitochondrial sequencing and morphological diagnostic techniques based on a batch of adult specimens collected from Ningxia Hui Autonomous Regions (NXHAR), North China. The morphology and microstructures of Ar. vulgaris and other lectotypes of argasid ticks in the subgenus Argas were also observed using a stereomicroscope. Following DNA extraction and sequencing, a complete mitochondrial sequence of Ar. vulgaris was assembled and analyzed within a phylogenetic context. The 14,479 bp mitogenome of Ar. vulgaris consists of 37 genes, including 13 genes for protein coding, two for ribosomal RNA, 22 for transfer RNA, and one for control region (D-loops). Phylogenetic analysis of Ar. vulgaris showed 98.27%–100% nucleotide identity with Ar. japonicus, indicating a close relationship between the two tick species. The morphological diagnostic features to differentiate Ar. vulgaris from other ticks within the subgenus Argas included the location of the anus and setae on the anterior lip of the female genital aperture. This study provided high-resolution scanning electron microscope images of female Ar. vulgaris and corresponding molecular data, representing valuable resources for future accurate species identification.

Objectives: The aim of the study was to comprehensively analyze the effects of whey protein (WP)-enriched supplement intake with or without resistance training (RT) in older patients, either from the community or hospital, who were diagnosed with sarcopenia according to the EWGSOP or AWGS criteria. Methods: This meta-analysis study was registered in PROSPERO (CRD42023407885). We searched the PubMed, Embase, Web of Science, and Cochrane Library databases for RCTs up to June 1, 2023. Standardized mean differences (SMD) with 95% confidence intervals (CI) were used to estimate the pooled results. Results: Ten RCT studies, including 1154 participants, were included and analyzed. The primary outcomes were the changes in muscle mass, strength, and physical performance. In WP group versus (vs.) Isocaloric placebo (PLA)/Routine consultation (RC) group, WP significantly increased the appendicular skeletal muscle mass index (SMD: 0.47, 95%CI: 0.23, 0.71), appendicular skeletal muscle mass (SMD: 0.28, 95%CI: 0.11, 0.45) and gait speed (SMD: 1.13, 95%CI: 0.82, 1.44) in older patients with sarcopenia. In WP with RT group vs. PLA/ RC group, there was significant increase in handgrip strength (SMD: 0.67, 95%CI: 0.29, 1.04). In addition, in the secondary outcomes, WP significantly reduced interleukin-6, significantly increased insulin-like growth factor-1 and albumin, promoted participants' intake of total energy and protein, enhanced activities of daily living scores in patients, and had no significant effect on BMI, weight, or fat mass. Conclusion: This review confirms that WP can improve various aspects of older adult with sarcopenia, thereby enhancing their overall physical condition. More studies should be conducted to validate this result and further explore the effects of WP and RT in patients with sarcopenia.

Abstract Background Acute diarrhea with fever can potentially represent a more severe form of the disease compared to non-febrile diarrhea. This study was to investigate the epidemiological characteristics and enteric pathogen composition of febrile-diarrheal patients, and to explore factors including pathogens associated with fever by age group. Methods A nationwide surveillance study of acute diarrheal patients of all ages was conducted in 217 sentinel hospitals from 31 provinces (autonomous regions or municipalities) in China between 2011 and 2020. Seventeen diarrhea-related pathogens, including seven viruses and ten bacteria, were investigated and their association with occurrence of fever symptoms was assessed using multivariate logistic analysis. Results A total of 146,296 patients with acute diarrhea (18.6% with fever) were tested. Th diarrheal children below 5 years had the highest frequency of fever (24.2%), and related to significantly higher prevalence of viral enteropathogens (40.2%) as compared with other age groups (P

Abstract Background Long-term use of anti-resorptive or anti-angiogenic drugs in cancer patients with odontogenic infections may lead to medication-related osteonecrosis of the jaw (MRONJ). This study investigated whether anti-angiogenic agents aggravate MRONJ occurrence in anti-resorptive-treated patients. Methods The clinical stage and jawbone exposure of MRONJ patients caused by different drug regimens were analyzed to ascertain the aggravation effect of anti-angiogenic drugs on anti-resorptive drug-based MRONJ. Next, a periodontitis mice model was established, and tooth extraction was performed after administering anti-resorptive and/or anti-angiogenic drugs; the imaging and histological change of the extraction socket were observed. Moreover, the cell function of gingival fibroblasts was analyzed after the treatment with anti-resorptive and/or anti-angiogenic drugs in order to evaluate their effect on the gingival tissue healing of the extraction socket. Results Patients treated with anti-angiogenic and anti-resorptive drugs had an advanced clinical stage and a bigger proportion of necrotic jawbone exposure compared to patients treated with anti-resorptive drugs alone. In vivo study further indicated a greater loss of mucosa tissue coverage above the tooth extraction in mice treated with sunitinib (Suti) + zoledronate (Zole) group (7/10) vs. Zole group (3/10) and Suti group (1/10). Micro-computed tomography (CT) and histological data showed that the new bone formation in the extraction socket was lower in Suti + Zole and Zole groups vs. Suti and control groups. In vitro data showed that the anti-angiogenic drugs had a stronger inhibitory ability on the proliferation and migration function of gingival fibroblasts than anti-resorptive drugs, and the inhibitory effect was obviously enhanced after combining zoledronate and sunitinib. Conclusion Our findings provided support for a synergistic contribution of anti-angiogenic drugs to anti-resorptive drugs-based MRONJ. Importantly, the present study revealed that anti-angiogenic drugs alone do not induce severe MRONJ but aggravate the degree of MRONJ via the enhanced inhibitory function of gingival fibroblasts based on anti-resorptive drugs.

Primary headache is a very common and burdensome functional headache worldwide, which can be classified as migraine, tension-type headache (TTH), trigeminal autonomic cephalalgia (TAC), and other primary headaches. Managing and treating these different categories require distinct approaches, and accurate diagnosis is crucial. Functional magnetic resonance imaging (fMRI) has become a research hotspot to explore primary headache. By examining the interrelationships between activated brain regions and improving temporal and spatial resolution, fMRI can distinguish between primary headaches and their subtypes. Currently the most commonly used is the cortical brain mapping technique, which is based on blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). This review sheds light on the state-of-the-art advancements in data analysis based on fMRI technology for primary headaches along with their subtypes. It encompasses not only the conventional analysis methodologies employed to unravel pathophysiological mechanisms, but also deep-learning approaches that integrate these techniques with advanced statistical modeling and machine learning. The aim is to highlight cutting-edge fMRI technologies and provide new insights into the diagnosis of primary headaches.

Abstract Recently, self‐driven soft robotics based on biomimetics, capable of mimicking biological motion, has attracted attention. Soft actuators using intrinsically soft organic materials are expected to be applied to haptic devices, artificial muscles, and micropumps. Ferroelectric polymers can aid in the realization of such soft actuators. However, actuators using such materials encounter problems in terms of the response frequency to an applied voltage. In this study, a soft actuator is fabricated by a printing process using a unique composite material comprising P(VDF‐TrFE), nano‐carbon material (single‐walled carbon nanotubes (SWCNT) and graphene oxide (GO)), and conductive polymer. To characterize the actuator using a minimum substrate thickness of 25 µm, hysteresis curves in the ferroelectric properties and driving characteristics according to the applied frequency are clarified. In addition, the mechanical life of the actuator under continuous voltage sweep is clarified considering it as a mechanical property. Subsequently, a simple haptics system is constructed using the fabricated actuators, and a human‐sensitive actuator demonstration system is constructed wherein the phase of the sweep frequency is variable.

Abstract Robotic machine interfaces with sensor devices in robotics applications can facilitate the proper handling of objects. The wide‐range responses of the sensors are important for achieving statement of recognition in tactile sensing systems. Thus, this study proposes a novel micro‐pore‐induced soft pressure sensor via wide‐range response by synthesizing functional composite materials with ether‐surfactant and conductive materials. The aim is to produce soft pressure sensors that are highly responsive and exhibit a wide sensitivity range for the detection of an applied pressure. The sensor comprises a multiwalled‐carbon nanotube, an ether‐based surfactant, and polymeric soft materials, which exhibit high‐speed response characteristics because of the microporous structure of the sensing layer. Moreover, a novel wearable robotic machine interface for facilitating object manipulation is achieved. Furthermore, the findings of this study in terms of the performance of the robotic‐tactile sensing sensor confirm its suitability for the machine interface of an artificial perception system. Furthermore, a real‐time tactile sensing system using the manufactured sensor in the form of wearable e‐skins is experimentally demonstrated.

Abstract Background To quantitatively assess the impact of the onset-to-diagnosis interval (ODI) on severity and death for coronavirus disease 2019 (COVID-19) patients. Methods This retrospective study was conducted based on the data on COVID-19 cases of China over the age of 40 years reported through China’s National Notifiable Infectious Disease Surveillance System from February 5, 2020 to October 8, 2020. The impacts of ODI on severe rate (SR) and case fatality rate (CFR) were evaluated at individual and population levels, which was further disaggregated by sex, age and geographic origin. Results As the rapid decline of ODI from around 40 days in early January to

In combination with the digital and green development needs of the foundry industry, this article proposes a digital patternless freezing casting method. In this method, mixed water green sand particles are frozen and transformed to a certain strength in a low-temperature environment, which are then directly cut through a sand mold CAD three-dimensional model. Pouring to obtain castings with dimensional accuracy that meets the requirements, this is a new technology, new process, and new method in the field of casting. With the fast development of the rapid and sub-rapid solidification technology of metals, the nonequilibrium solidification theory of liquid–solid transformation during the preparation of metals and alloy materials has been developed by leaps and bounds. Using some special nonequilibrium solidification techniques to prepare metal parts, and to make metal parts with a special structure that traditional casting does not have, can improve the materials’ properties and structures. The nonequilibrium solidification mechanism based on the freezing casting technology is not yet clear. Based on the nonequilibrium solidification process of the freezing casting principle, a higher cooling rate will considerably affect the heat transfer and mass transfer behavior of casting during solidification, which will then considerably affect the alloy micro component distribution and fracture morphology, ultimately affecting the service performance of the alloy material. Based on the digital precision forming technology of patternless frozen casting, this paper realized the rapid forming of the frozen sand mold. Frozen casting flat castings were obtained by pouring the A356 high-temperature aluminum alloy. The distribution of trace elements in frozen and resin sand castings was characterized by electron probe microanalysis, and the fracture morphology of frozen and resin sand castings was analyzed. Results show that the solubility of the Si element in the aluminum matrix phase of freeze casting is significantly higher than that of resin sand casting. In addition, the distribution of the Mg element in freeze casting is more uniform than that in resin sand casting, and there are more segregation areas of the Mg element composition in resin sand casting specimens. The fracture morphology of freeze-cast specimens is a mixed fracture mode of toughness and brittleness. Meanwhile, the fracture morphology of resin sand casting specimens has a cleavage step failure morphology and rectangular tear structure morphology, and the alloy tends to exhibit a brittle fracture.

Porous structures and micropatterning surfaces play a crucial role in the development of highly sensitive force sensors. However, achieving these two conductive architectures typically requires the synthesis of complex materials and expensive manufacturing processes. In this study, we introduce a novel conductive composite film featuring a microporous/micropyramid hybrid conductive architecture, which is achieved through a straightforward process of materials mixing and one-step screen printing. By utilizing a deep eutectic solvent in the ink component, micropores are induced in the printed composite, while the mesh of the screen mask acts as a template, resulting in a micropyramid film surface. We have successfully realized highly sensitive flexible force sensors (0.15 kPa−1) with multifunctional capabilities for perceiving normal force and shear force.

Abstract Background Acute gouty arthritis (GA) is the main clinical manifestation and the most common initial symptom of gout. The treatment of acute GA involves the use of colchicine, non-steroidal anti-inflammatory drugs, and corticosteroids. Because of the side effects of these drugs, their clinical applications are limited. The use of traditional Chinese medicine for the treatment of acute GA has unique advantages. The aim of this trial is to clarify the treatment efficacy, safety, and recurrence control efficacy of Huzhang granules (HZG) in patients with GA showing dampness-heat syndrome. Methods/design This double-blind, randomized, controlled trial was planned to be conducted between July 1, 2020, and December 31, 2022. A sample size of 267 participants (89 per group) with GA will be randomly assigned to three treatment groups in the ratio of 1:1:1: HZG, etoricoxib, and placebo groups. The study duration is 13 days, including a 1-day screening period, 5-day intervention period, and 1-week follow-up period. The primary outcome is analgesic effectiveness, assessed as pain in the worst-affected joint, which will be measured using the visual analog scale. Secondary outcomes include the patient’s assessment of pain in the primary study joint, patient’s global assessment of response to therapy, investigator’s global assessment of response to therapy, investigator’s assessment of tenderness and swelling of the study joint, and TCM syndromes. Furthermore, the number, nature, and severity of adverse events will be recorded. Discussion This study will provide evidence regarding the clinical efficacy and safety of Chinese medicine treatment for acute gouty arthritis. This study will provide noteworthy findings. Trial registration ClinicalTrials.gov NCT04462666 . Registered on July 05, 2020 (first version).

Background/aim: Hypertensive nephropathy (HN) is a common complication of hypertension. Traditional Chinese medicine has long been used in the clinical treatment of Hypertensive nephropathy. However, botanical drug prescriptions have not been summarized. The purpose of this study is to develop a prescription for improving hypertensive nephropathy, explore the evidence related to clinical application of the prescription, and verify its molecular mechanism of action.Methods: In this study, based on the electronic medical record data on Hypertensive nephropathy, the core botanical drugs and patients’ symptoms were mined using the hierarchical network extraction and fast unfolding algorithm, and the protein interaction network between botanical drugs and Hypertensive nephropathy was established. The K-nearest neighbors (KNN) model was used to analyze the clinical and biological characteristics of botanical drug compounds to determine the effective compounds. Hierarchical clustering was used to screen for effective botanical drugs. The clinical efficacy of botanical drugs was verified by a retrospective cohort. Animal experiments were performed at the target and pathway levels to analyze the mechanism.Results: A total of 14 botanical drugs and five symptom communities were obtained from real-world clinical data. In total, 76 effective compounds were obtained using the K-nearest neighbors model, and seven botanical drugs were identified as Gao Shen Formula by hierarchical clustering. Compared with the classical model, the Area under the curve (AUC) value of the K-nearest neighbors model was the best; retrospective cohort verification showed that Gao Shen Formula reduced serum creatinine levels and Chronic kidney disease (CKD) stage [OR = 2.561, 95% CI (1.025–6.406), p < 0.05]. With respect to target and pathway enrichment, Gao Shen Formula acts on inflammatory factors such as TNF-α, IL-1β, and IL-6 and regulates the NF-κB signaling pathway and downstream glucose and lipid metabolic pathways.Conclusion: In the retrospective cohort, we observed that the clinical application of Gao Shen Formula alleviates the decrease in renal function in patients with hypertensive nephropathy. It is speculated that Gao Shen Formula acts by reducing inflammatory reactions, inhibiting renal damage caused by excessive activation of the renin-angiotensin-aldosterone system, and regulating energy metabolism.

ABSTRACT Wild rice has been demonstrated to possess enriched genetic diversity and multiple valuable traits involved in disease/pest resistance and abiotic stress tolerance, which provides a potential resource for sustainable agriculture. However, unlike the plant compartments such as rhizosphere, the structure and assembly of phyllosphere microbial communities of wild rice remain largely unexplored. Through amplicon sequencing, this study compared the phyllosphere bacterial and fungal communities of wild rice and its neighboring cultivated rice. The core phyllosphere microbial taxa of both wild and cultivated rice are dominated with Pantoea, Methylobacterium, Nigrospora, and Papiliotrema, which are potentially beneficial to rice growth and health. Compared to the cultivated rice, Methylobacterium, Sphingomonas, Phaeosphaeria, and Khuskia were significantly enriched in the wild rice phyllosphere. The potentially nitrogen-fixing Methylobacterium is the dominated wild-enriched microbe; Sphingomonas is the hub taxon of wild rice networks. In addition, the microbiota of wild rice was more governed by deterministic assembly with a more complicated and stable community network than the cultivated rice. Our study provides a list of the beneficial microbes in the wild rice phyllosphere and reveals the microbial divergence between wild rice and cultivated rice in the original habitats, which highlights the potential selective role of wild rice in recruiting specific microbiomes for enhancing crop performance and promoting sustainable food production. IMPORTANCE Plant microbiota are being considered a lever to increase the sustainability of food production under a changing climate. In particular, the microbiomes associated with ancestors of modern cultivars have the potential to support their domesticated cultivars. However, few efforts have been devoted to studying the biodiversity and functions of microbial communities in the native habitats of ancestors of modern crop species. This study provides a list of the beneficial microbes in the wild rice phyllosphere and explores the microbial interaction patterns and the functional profiles of wild rice. This information could be useful for the future utilization of the plant microbiome to enhance crop performance and sustainability, especially in the framework of sustainable agroecosystems.

Natural polysaccharides (NPs) possess numerous health-promoting effects, such as liver protection, kidney protection, lung protection, neuroprotection, cardioprotection, gastrointestinal protection, anti-oxidation, anti-diabetic, and anti-aging. Nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway is an important endogenous antioxidant pathway, which plays crucial roles in maintaining human health as its protection against oxidative stress. Accumulating evidence suggested that Nrf2 antioxidant pathway might be one of key regulatory targets for the health-promoting effects of NPs. However, the information concerning regulation of NPs on Nrf2 antioxidant pathway is scattered, and NPs show different regulatory behaviors in their different health-promoting processes. Therefore, in this article, structural features of NPs having regulation on Nrf2 antioxidant pathway are overviewed. Moreover, regulatory effects of NPs on this pathway for health-promoting effects are summarized. Furthermore, structure-activity relationship of NPs for health-promoting effects by regulating the pathway is preliminarily discussed. Otherwise, the prospects on future work for regulation of NPs on this pathway are proposed. This review is beneficial to well-understanding of underlying mechanisms for health-promoting effects of NPs from the view angle of Nrf2 antioxidant pathway, and provides a theoretical basis for the development and utilization of NPs in promoting human health.

Abstract Background Stress-induced neuroinflammation was considered to play a critical role in the pathogenesis of depression. Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder. The anti-inflammatory signal of vagus nerve is mediated by α7 nicotinic acetylcholine receptor (α7nAchR), and the hippocampus, the region with the most distribution of α7nAchR, regulates emotions. Here, we investigated the role of α7nAchR mediating hippocampal neuroinflammation in taVNS antidepressant effect though homozygous α7nAChR (−/−) gene knockout and α7nAchR antagonist (methyllycaconitine, MLA). Methods There were control, model, taVNS, α7nAChR(−/−) + taVNS, hippocampus (Hi) MLA + taVNS and Hi saline + taVNS groups. We used the chronic unpredicted mild stress (CUMS) method to establish depressive model rats for 42 days, excepting control group. After the successful modeling, except the control and model, the rats in the other groups were given taVNS, which was applied through an electroacupuncture apparatus at the auricular concha (2/15 Hz, 2 mA, 30 min/days) for 21 days. Behavioral tests were conducted at baseline, after modeling and after taVNS intervention, including sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST). These tests are widely used to evaluate depression-like behavior in rats. The samples were taken after experiment, the expressions of α7nAchR, NF-κB p65, IL-1β and the morphology of microglia were detected. Results Depression-like behavior and hippocampal neuroinflammation in CUMS model rats were manifested by down-regulated expression of α7nAchR, up-regulated expression of NF-κB p65 and IL-1β, and the morphology of microglia was in amoebic-like activated state. TaVNS could significantly reverse the above-mentioned phenomena, but had rare improvement effect for α7nAChR(−/−) rats and Hi MLA rats. Conclusion The antidepressant effect of taVNS is related to hippocampal α7nAchR/NF-κB signal pathway.

BackgroundAcupuncture is widely used as adjuvant therapy for major depressive disorder (MDD). There is robust evidence that inflammation is closely associated with MDD. To date, only a few numbers of studies have investigated the potential relationship between acupuncture and the change of inflammatory biomarkers in patients with MDD. Additionally, the results are inconsistent among studies. The current study aims to provide a comprehensive, systematic review of the association between acupuncture and changes in peripheral inflammation of patients with MDD, and clarify the alterations of inflammatory cytokines before and after acupuncture treatment by meta-analysis.Methods and analysisThis study will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible randomized controlled trials (RCTs) reporting acupuncture, with inflammatory cytokines as the outcome measured before and after intervention in patients with MDD, were searched in electronic databases, such as PubMed, Embase, Cochrane, SINOMED, Wanfang, China national knowledge infrastructure (CNKI), and Chongqing VIP (CQVIP). Primary outcomes of interest will be validated to measure the levels of inflammatory cytokines before and after acupuncture treatment in patients with MDD.DiscussionAcupuncture can drive anti-inflammatory effects, as well as symptom changes in MDD, which may represent a viable, multi-faceted treatment approach in MDD.Systematic review registration[PROSPERO], identifier [CRD42021289207 on 04 December 2021].

China operates a national surveillance program for acute respiratory infections and sampled over 200,000 patients between 2009–2019. Here, the authors present results from this program and describe patterns by age, pathogen type, presence of pneumonia, and season.

Lotus (Nelumbo nucifera Gaertn.) is a well-known food and medicinal plant. Lotus seedpod (Receptaculum Nelumbinis) is the by-products during lotus products processing, which is considered as waste. Numerous studies have been conducted on its phytochemicals, biological activity and industrial application. However, the information on lotus seedpod is scattered and has been rarely summarized. In this review, summaries on preparation and identification of phytochemicals, the biological activities of extracts and phytochemicals, and applications of raw material, extracts and phytochemicals for lotus seedpod were made. Meanwhile, the future study trend was proposed. Recent evidence indicated that lotus seedpods extracts, obtained by non-organic and organic solvents, possessed several activities, which were influenced by extraction solvents and methods. Lotus seedpods were rich in phytochemicals categorized as different chemical groups, such as proanthocyanidins, oligomeric procyanidins, flavonoids, alkaloids, terpenoids, etc. These phytochemicals exhibited various bioactivities, including ameliorating cognitive impairment, antioxidation, antibacterial, anti-glycative, neuroprotection, anti-tyrosinase and other activities. Raw material, extracts and phytochemicals of lotus seedpods could be utilized as sources for biochar and biomass material, in food industry and as dye. This review gives well-understanding on lotus seedpod, and provides theoretical basis for its future research and application.

Twelve new guaianolide sesquiterpene lactones (1–12), along with ten known analogs (13–22) were isolated from an EtOH extract of the dried aerial parts of Artemisia vulgaris L. The new structures were elucidated via abundant spectroscopic data analyses (HRESIMS, IR, 1D, and 2D NMR), and the absolute configurations of these compounds were determined by X-ray crystallography and ECD calculations. The compounds (1−22) were identified as guaiane-type sesquiterpenes with characteristic α-methylene-γ-lactone and α,β-unsaturated carbonyl moieties. All compounds were tested for their inhibitory activity against NO production in lipopolysaccharide-stimulated RAW264.7 macrophages. The isolated sesquiterpenoids dose-dependently exhibited an NO production inhibitory activity by inhibiting the expression of inducible NO oxidase (iNOS) and cyclooxygenase-2 (COX-2) with IC50 values ranging from 1.0 to 3.6 μM. The inhibitory effect on the NO production of the compounds (1–4 and 6–22) is better than that of the positive control (dexamethasone). The different substitutions of compounds on C-8 influence anti-inflammatory effects, as evidenced by the in silico analysis of related binding interactions of new compounds (1–12) with iNOS.

Acrostalagmus is known for its ability to produce numerous bioactive natural products, making it valuable in drug development. This review provides information on the sources, distribution, chemical structure types, biosynthesis, and biological activities of the compounds isolated from the genus Acrostalagmus in the family Plectosphaerellaceae from 1969 to 2022. The results show that 50% of the compounds isolated from Acrostalagmus are new natural products, and 82% of the natural products derived from this genus are from the marine Acrostalagmus. The compounds isolated from Acrostalagmus exhibit diverse structures, with alkaloids being of particular importance, accounting for 56% of the natural products derived from this genus. Furthermore, within the alkaloid class, 61% belong to the epipolythiodioxopiperazine family, highlighting the significance of epipolythiodioxopiperazine as a key characteristic structure within Acrostalagmus. Seventy-two percent of natural products derived from Acrostalagmus display bioactivities, with 50% of the bioactive compounds exhibiting more significant or comparable activities than their positive controls. Interestingly, 89% of potent active compounds are derived from marine fungi, demonstrating their promising potential for development. These findings underscore Acrostalagmus, particularly the marine-derived genus Acrostalagmusas, a valuable source of new bioactive secondary metabolites, and emphasize the vast resource importance of the ocean.

We present a high-performance flexible bending strain sensor for directional motion detection of human hands and soft robotic grippers. The sensor was fabricated using a printable porous conductive composite composed of polydimethylsiloxane (PDMS) and carbon black (CB). The utilization of a deep eutectic solvent (DES) in the ink formulation induced a phase segregation between the CB and PDMS and led to a porous structure inside the printed films after being vapored. This simple and spontaneously formed conductive architecture provided superior directional bend-sensing characteristics compared to conventional random composites. The resulting flexible bending sensors displayed high bidirectional sensitivity (gauge factor of 45.6 under compressive bending and 35.2 under tensile bending), negligible hysteresis, good linearity (>0.99), and excellent bending durability (over 10,000 cycles). The multifunctional applications of these sensors, including human motion detection, object-shape monitoring, and robotic perceptions, are demonstrated as a proof-of-concept.

Diarrhoea is a major cause of morbidity and mortality in China. Here, the authors present results from a large sentinel surveillance scheme from 217 hospitals in all 31 provinces in mainland China, including ~150,000 patients with acute diarrhoea and covering years 2009-2018.

In our previous study, we prepared the granules by embedding artemisinin into alginate-chitosan using microcapsule technology. These granules can release artemisinin sustainably and have a strong inhibitory effect on the growth of both single Microcystis aeruginosa and mixed algae. To safely and effectively use artemisinin sustained-release granules to control algal blooms, the ecotoxicity was studied by assessing their acute and chronic toxicity to Daphnia magna (D. magna) and Danio rerio (D. rerio), along with their antioxidant activities. The results showed that the 48-h median effective concentration (EC50) of pure artemisinin to D. magna was 24.54 mg/L and the 96-h median lethal concentration (LC50) of pure artemisinin to D. rerio was 68.08 mg/L. Both values were classified as intermediate toxicity according to the Organization for Economic Co-operation and Development (OECD). The optimal algae inhibitory concentration of artemisinin sustained-release granules (1 g/L) had low acute toxicity to both D. magna and D. rerio. The sustained-release granules had higher chronic toxicity to D. magna than to D. rerio. Partial indices of D. magna were inhibited by granules when the concentrations were larger than 0.1 g/L. Low granule concentration had an inductive effect on antioxidant enzyme activities in D. magna and D. rerio. With the increase of the exposure concentration and time, the enzyme activity presented a trend of first increasing and then decreasing, and the overall changes were significant. The change trend and range of enzyme activity indicated that the granules could cause serious oxidative stress to D. magna and D. rerio, and the changes were consistent with the results of toxicity experimentation.

With the new coronavirus (2019-nCoV) infected pneumonia spreading across the country in December 2019, social collaborative control of the 2019-nCoV infected pneumonia is a hot research topic. What about public awareness of non-drug control measures? Based on the evidence-based social science, this study carried out the retrieval, extraction, evidence classification and analysis of non-drug measures for the prevention and treatment of infectious diseases, and finally puts forward policy suggestions from the individual level, social level and national level, in order to put forward reasonable suggestions for the coordinated prevention and treatment of this epidemic and provide available evidence for future research.

Eco-friendly flexible humidity sensors with high sensing performance are desired for the next-generation wearable electronics. In this work, we developed a high-performance fully printed flexible humidity sensor using all-carbon functional materials. The electrodes and sensing layer of the sensor were printed using all-carbon-based cellulose nanofiber/graphene nanoplatelet (CNF/GNP) composites. The newly developed CNF/GNP ink can be prepared by simple mixing without any complex processes. These sensors showed a high resistive response of 240% over the relative humidity (RH) range of 30% to 90%, with response and recovery times of 17 s and 22 s, respectively, and good mechanical flexibility. Since CNF and GNPs are abundant in nature, degradable, and biocompatible, this work suggests the possibility of manufacturing inexpensive, eco-friendly sensors with high performances. As a proof-of-concept, we demonstrate the application of our sensor in human respiration detection, non-contact proximity sensing, and baby-diaper wetness monitoring.

Long-term fertilization is known to impact the biodiversity and community structures of soil organisms, which are responsible for multiple soil ecosystem functions (multifunctionality). However the relationship between the alterations of soil organisms and ecosystem multifunctionality remains unclear, especially in the case of long-term fertilization. To explore the contribution of soil organismal biodiversity and community structures to ecosystem multifunctionality, we took soil samples from a nearly 25-year field fertilization experiment. Organic matter significantly improved the soil ecosystem multifunctionality. Ecosystem multifunctionality was found to be closely linked to the biodiversity and communities of soil organisms within the major ecological clustering of soil organisms (Module 1) according to the trophic co-occurrence network, rather than the entire community of soil organisms. This indicated that ecological clusters of soil organisms within the network were critical in maintaining soil ecosystem multifunctionality. The application of organic fertilization could enrich specialized soil organisms and increase interactions of soil organisms in the ecological cluster. As a result, our findings emphasize the role of ecological clusters in the soil organismal co-occurrence network in controlling soil multifunctionality after long-term fertilization, presenting a novel perspective on the link between soil biodiversity and ecosystem multifunctionality.

Summary: Background: Acute meningitis or encephalitis (AME) results from a neurological infection causing high case fatality and severe sequelae. AME lacked comprehensive surveillance in China. Methods: Nation-wide surveillance of all-age patients with AME syndromes was conducted in 144 sentinel hospitals of 29 provinces in China. Eleven AME-causative viral and bacterial pathogens were tested with multiple diagnostic methods. Findings: Between 2009 and 2018, 20,454 AME patients were recruited for tests. Based on 9,079 patients with all-four-virus tested, 28.43% (95% CI: 27.50%‒29.36%) of them had at least one virus-positive detection. Enterovirus was the most frequently determined virus in children

Antarctic krill (Euphausia superba) of the Euphausiidae family comprise one of the largest biomasses in the world and play a key role in the Antarctic marine ecosystem. However, the study of E. superba-derived microbes and their secondary metabolites has been limited. Chemical investigation of the secondary metabolites of the actinomycetes Nocardiopsis sp. LX-1 (in the family of Nocardiopsaceae), isolated from E. superba, combined with molecular networking, led to the identification of 16 compounds a–p (purple nodes in the molecular network) and the isolation of one new pyrroline, nocarpyrroline A (1), along with 11 known compounds 2–12. The structure of the new compound 1 was elucidated by extensive spectroscopic investigation. Compound 2 exhibited broad-spectrum antibacterial activities against A. hydrophila, D. chrysanthemi, C. terrigena, X. citri pv. malvacearum and antifungal activity against C. albicans in a conventional broth dilution assay. The positive control was ciprofloxacin with the MIC values of 1 and compounds 7, 10, and 11 displayed antifungal activities against F. fujikuroi and D. citri, respectively, in modified agar diffusion test. Prochloraz was used as positive control and showed the inhibition zone radius of 17 mm and 15 mm against F. fujikuroi and D. citri, respectively. All the annotated compounds a–p by molecular networking were first discovered from the genus Nocardiopsis. Nocarpyrroline A (1) features an unprecedented 4,5-dihydro-pyrrole-2-carbonitrile substructure, and it is the first pyrroline isolated from the genus Nocardiopsis. This study further demonstrated the guiding significance of molecular networking in the research of microbial secondary metabolites.

The complete chloroplast genome sequence of rare and endangered Camellia lungzhouensis (Theaceae) was reported in this study. The cp genome was 157,110 bp in length with a GC content of 62.70%, including LSC (86,653 bp), SSC (18,277 bp), and two reverse repeat sequence regions (26,090 bp). The genome encoded 136 functional genes, including 84 protein-coding genes, 44 tRNA genes, and eight rRNA genes. The phylogenetic analysis showed that C. lungzhouensis was closely related to C. petelotii and C. nitidissima.

Ferroptosis, a form of programmed cell death process driven by iron-dependent lipid peroxidation, plays an important role in tumor suppression. Although previous study showed that intracellular Merlin-Hippo signaling suppresses ferroptosis of epithelial tumor cells through the inactivation of YAP signaling, it remains elusive if the proto-oncogenic transcriptional co-activator YAP could serve as a potential biomarker to predict cancer cell response to ferroptosis-inducing therapies. In this study, we show that both total YAP staining and nuclear YAP staining were more prevalent in HCC tissues than in nontumorous regions. Compared to low-density HCC cells, high-density cells showed decreased nuclear localization of YAP and conferred significant resistance to ferroptosis. Oncogenic activation of YAP signaling by overexpression of YAP(S127A) mutant sensitized ferroptosis of HCC cells cultured in confluent density or in the 3D tumor spheroid model. Furthermore, we validated the lipoxygenase ALOXE3 as a YAP-TEAD target gene that contributed to YAP-promoted ferroptosis. Overexpression of ALOXE3 effectively increased the vulnerability of HCC cells to ferroptotic cell death. In an orthotopic mouse model of HCC, genetic activation of YAP rendered HCC cells more susceptible to ferroptosis. Finally, an overall survival assay further revealed that both a high expression of YAP and a low expression of GPX4 were correlated with increased survival of HCC patients with sorafenib treatment, which had been proven to be an inducer for ferroptosis by inhibition of the xc-amino acid antiporter. Together, this study unveils the critical role of intracellular YAP signaling in dictating ferroptotic cell death; it also suggests that pathogenic alterations of YAP signaling can serve as biomarkers to predict cancer cell responsiveness to future ferroptosis-inducing therapies.

Background: Non pharmaceutical interventions (NPI) including hand washing directives were implemented in China and worldwide to combat the COVID-19 pandemic, which are likely to have had impacted a broad spectrum of enteric pathogen infections. Methods: Etiologically diagnostic data from 45 937 and 67 395 patients with acute diarrhea between 2012 and 2020, who were tested for seven viral pathogens and 13 bacteria respectively, were analyzed to assess the changes of enteric pathogen infections in China during the first COVID-19 pandemic year compared to pre-pandemic years. Findings: Test positive rates of all enteric viruses decreased during 2020, compared to the average levels during 2012−2019, with a relative decrease of 71•75% for adenovirus, 58•76% for norovirus, 53•50% for rotavirus A, and 72•07% for the combination of other four uncommon viruses. In general, a larger reduction of positive rate in viruses was seen among adults than pediatric patients. A rebound of rotavirus A was seen after September 2020 in North China rather than South China. Test positive rates of bacteria decreased during 2020, compared to the average levels during 2012−2019, excepting for nontyphoidal Salmonella and Campylobacter coli with 66•53% and 90•48% increase respectively. This increase was larger for pediatric patients than for adult patients. Interpretation: The activity of enteric pathogens changed profoundly alongside the NPIs implemented during the COVID-19 pandemic in China. Greater reductions of the test positive rates were found for almost all enteric viruses than for bacteria among acute diarrhea patients, with further large differences by age and geography. Lifting of NPIs will lead to resurgence of enteric pathogen infections, particularly in children whose immunity may not have been developed and/or waned. Funding: China Mega-Project on Infectious Disease Prevention; National Natural Science Funds.

Spinal cord injury (SCI) is a devastating medical condition, often accompanied by motor and sensory dysfunction. The Hedgehog (Hh) pathway has a protective role in pathological injury after SCI. However, the specific mechanism remains unclear. The present study aimed to confirm the effects of the mitogen-activated protein kinase kinase-2 (MEKK2)/MEKK3/JNK/Hh pathway on SCI. SCI rat models were established and then inoculated with plasmids overexpressing MEKK2/MEKK3 or with small interfering RNA (siRNA) against MEKK2/MEKK3. The expression of MEKK2 and -3 was detected in dorsal root ganglia (DRG) cells. The motor function of hindlimbs, the expression of the c-Jun N-terminal kinase (JNK)- and Hh-pathway-related genes, and the level of neurofilament-200 (NF-200) and glial fibrillary acidic protein (GFAP) were measured. MEKK2 and -3 were expressed at a high level in DRG cells. The silencing of MEKK2/MEKK3 in rats caused an increase in the expression of glioma-associated oncogene homolog-1 (Gli-1), Nestin, smoothened (Smo), and Sonic Hedgehog (Shh). The Basso, Beattie, and Bresnahan (BBB) rating and the level of NF-200 protein also increased. However, the expression of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1β (MIP-1β), MIP-3α, p-JNK/JNK, and p-c-Jun/c-Jun and the level of GFAP were reduced. Downregulation of MEKK2/MEKK3 ameliorated the symptoms of SCI by promoting neural progenitor cell differentiation via activating the Hh pathway and disrupting the JNK pathway. The findings in this study reveal a potential biomarker for SCI treatment. Keywords: spinal cord injury, Hedgehog signaling pathway, MEKK2/MEKK3, JNK signaling pathway, neural progenitor cell differentiation

Tactile sensing is desirable for skillful object handling in soft robotics applications. Real‐time measurement and identification of dynamic shear forces are crucial for slip detection and object interaction. This study proposes a soft sensor with a closed‐loop feedback system for dynamic shear force detection to address object slippage in a soft robotic gripper. The sensor is made of a ferroelectric polymer with nanocarbon materials because of the resulting improved crystallinity and good sensitivity. The sensor shows high performance and high‐speed response for detecting dynamic shear forces when fragile objects (e.g., vegetables) slip from the soft gripper. The artificial cutaneous sensor shows high sensitivity for grasping such objects with the gripper. Furthermore, the feedback system provides a control system for operations and avoids the need for training for various tasks, thus demonstrating the potential of the proposed system for novel soft robotics applications such as biomimetic electronic skin.

Actinomycetes are currently one of the major sources of bioactive secondary metabolites used for medicine development. Accumulating evidence has shown that Nocardiopsis, a key class of actinomycetes, has the ability to produce novel bioactive natural products. This review covers the sources, distribution, bioactivities, biosynthesis, and structural characteristics of compounds isolated from Nocardiopsis in the period between March 2018 and 2021. Our results reveal that 67% of Nocardiopsis-derived natural products are reported for the first time, and 73% of them are isolated from marine Nocardiopsis. The chemical structures of the Nocardiopsis-derived compounds have diverse skeletons, concentrating on the categories of polyketides, peptides, terphenyls, and alkaloids. Almost 50% of the natural products isolated from Nocardiopsis have been discovered to display various bioactivities. These results fully demonstrate the great potential of the genus Nocardiopsis to produce novel bioactive secondary metabolites that may serve as a structural foundation for the development of novel drugs.

Many studies have demonstrated that cancer stem cells (CSCs) or tumor-initiating cells (TICs) are responsible for tumor cell proliferation, chemotherapy resistance, metastasis, and relapse in various cancers. We, and others, have previously shown that the signal transducer and activator of transcription 3 (STAT3) signaling pathway is responsible for CSCs and TICs growth. Recent reports have indicated that the heat shock protein 90 (Hsp90) is also essential for the survival of CSCs and TICs. SNX-2112 is an Hsp90 inhibitor. However, it remains unclear whether proliferation of esophageal cancer stem-like cells (ECSLCs) is suppressed by SNX-2112 with knockdown of STAT3 (shSTAT3). Here, we explored the association between SNX-2112 with shSTAT3 and the suppression of ECSLCs growth. We found that the expression level of both STAT3 and p-STAT3 was higher in clinical esophageal cancer tissue than in the adjacent normal tissue, using western blot and qPCR analysis. Furthermore, differential expression analysis demonstrated that STAT3 was overexpressed in clinical specimens. We demonstrated that SNX-2112 inhibited cancer cell proliferation, decreased ABCB1 and ABCG2 gene expression levels and reduced the colony formation capacity of ECSLCs, which was enhanced by STAT3 silencing. Flow cytometry analysis revealed that the combination of SNX-2112 and shSTAT3 significantly induced apoptosis and cell cycle arrest at G2/M phase in ECSLCs. Levels of proliferation pathway proteins, including p38, c-Jun N-terminal kinase (JNK), and extracellular signal–regulated kinase (ERK) which were also client proteins of Hsp90, were also reduced. In addition, SNX-2112 with shSTAT3 inhibited the proliferation of ECSLCs in vivo. Finally, STAT3 overexpression eliminated the apoptotic and antiproliferative effects of SNX-2112 on ECSLCs. Hence, these results provide a rationale for the therapeutic potential of the combination of SNX-2112 with shSTAT3 in esophageal cancer, and may indicate new targets for clinical intervention in human cancer.

Abstract Background A model was constructed using clinical and serum variables to discriminate between chronic hepatitis B (CHB) patients with and without significant necroinflammatory activity (score 4–18 vs. score 0–3). Methods Consecutive CHB patients who underwent liver biopsy were divided into two sequential groups: a training group (n = 401) and a validation group (n = 401). Multivariate analysis identified alanine aminotransferase, γ-glutamyltransferase, prothrombin time and albumin as independent predictors of necroinflammatory activity. Results The area under the receiver operating characteristic curve was 0.826 for the training group and 0.847 for the validation group. Using a cut-off score of H ≤ 0.375, significant necroinflammatory activity (score 4–18) was excluded with high accuracy [78.2% negative predictive value (NPV), 72% positive predictive value (PPV), and 90.8% sensitivity] in 238 (59.4%) of 401 patients in the training group and with the same certainty (88.1% NPV, 61.2% PPV, and 95.1% sensitivity) among 204 (50.9%) of 401 patients in the validation group. Similarly, applying a cut-off score of H > 0.720, significant necroinflammatory activity was correctly identified with high accuracy (90.8% PPV, 57.7% NPV, and 92.0% specificity) in 150 (37.4%) of 401 patients in the training group and with the same certainty (91.8% PPV, 64.6% NPV, and 95.4% specificity) in 188 (46.9%) of 401 patients in the validation group. Conclusions A predictive model based on easily accessible variables identified CHB patients with and without significant necroinflammatory activity with a high degree of accuracy. This model may decrease the need for liver biopsy for necroinflammatory activity grading in 72.1% of CHB patients.