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Edaravone Dexborneol (EDB), comprised of edaravone and (+)- bornel, has been demonstrated to have synergistic effects of antioxidant and anti-inflammatory, which makes it to be applied for stroke as a protectant. However, the underlying mechanism of neuroprotection of EDB has not been fully elucidated. Increasing evidence has shown that neurotoxic A1 astrocytes were closely related to neuronal death after cerebral ischemia. However, whether EDB could provide neuroprotection by modulating the activation of astrocytes has not yet been elucidated. The present study aimed to explore whether EDB afforded neuroprotection by modulating A1 polarization of astrocytes and the down-stream signaling after cerebral ischemia. We first validated the neuroprotective effects of EDB in mice suffering focal cerebral ischemia via evaluating behavioral test, infarct volumes and neuronal survival. As for the down-stream signaling, our data further showed that EDB alleviated neuronal death by suppressing activation of neurotoxic A1 astrocytes via inhibition of NF-κB signaling pathway in vitro. Additionally, administration of EDB reduced the number of A1 reactive astrocytes in mice of focal cerebral ischemia. The above findings demonstrated that EDB provided neuroprotective effect by inhibiting neurotoxic activation of A1 astrocytes in animal model of cerebral ischemia, which indicated that EDB-mediated phenotypic regulation of astrocytes is a potential research direction to promote neurological recovery in central nervous system (CNS) diseases., Competing Interests: Declaration of Competing Interest All authors declare that there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study investigated the expression of Zip6, a gene predominantly located in the placenta, breast, and prostate tissues, in patients with Kashin-Beck disease (KBD). Environmental risk factor models for KBD were developed using low selenium (Se) feeding (with a Se content of 0.02 mg Se/kg in the feed) and exposure to T-2 toxin (200 ng/g*BW/D). Additionally, the study examined the alterations in Se and Zn 2+ levels, along with the mRNA and protein expression levels of Zip6 and KBD related genes, including Mtf1, Mmp3, Mmp13, Adamts5, and Col2a1. Differentially expressed genes (DEGs) were examined by transcriptome sequencing to elucidate the mechanism by which Zip6 induces metabolic disorder of the extracellular matrix (ECM), subsequently leading to cartilage injury under the influence of Se deficiency and T-2 toxin. The findings indicated that the expression levels of Zip6 in adult and pediatric KBD chondrocytes were not synchronized. In the animal study, there was a notable increase in the Zn 2+ level in the comprehensive exposure (CE) group. Moreover, in both the T-2 exposure (T-2) and CE groups, there was a significant decrease in the expression of Zip6 in each zone, and the expression of Adamts5 in the middle zone exhibited a significant increase (P < 0.05) correlating with varying degrees of cartilage tissue damage in each group. Sequencing results revealed that the significantly up-regulated DEGs in the CE group included Zimz2. This study suggested that Se and T-2 toxin may influence the expression of Zip6, and it investigated the role of Zn 2+ in the pathogenesis of KBD, thereby providing a novel scientific foundation for understanding the pathogenesis of KBD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Initiation of endoplasmic reticulum (ER) stress is pivotal to the advancement of osteoarthritis (OA). We aimed to explore the function of ER-resident selenoprotein M (SELM) in cartilage-forming chondrocytes, investigating how SELM participates in cartilage extracellular matrix (ECM) metabolism and ER stress modulation., Methods: Articular cartilage samples with knee OA undergoing total knee arthroplasty were categorised into OA-smooth and OA-damaged groups, with primary chondrocytes extracted from smooth areas. Destabilization of the medial meniscus was induced in male C57BL6/J mice, with sham operations on the left knee as controls. After 8 weeks, knee joint tissues were collected for analysis. Histology and immunohistochemistry examined cartilage damage. Molecular biology techniques investigated how SELM affects ECM metabolism and ER stress regulation. RNA sequencing revealed the pathway changes after SELM intervention. AlphaFold demonstrated how SELM interacts with other molecules. Cultured cartilage explants helped determine the effects of SELM supplementation., Results: SELM expression was reduced in the damaged cartilage. Increasing SELM levels positively impacted ECM equilibrium. Decreasing SELM expression activated genes linked to degenerative ailments and impaired the cellular response to misfolded proteins, initiating the PERK/P-EIF2A/ATF4 pathway and exacerbating GSH/GSSG imbalance via the ATF4/CHAC1 axis. SELM likely participated in protein folding and modification by leveraging its thioredoxin domains. In vitro SELM supplementation mitigated IL-1β effects on damaged cartilage explants and suppressed beneficial chondrocyte phenotypes., Conclusions: Our results confirm the involvement of SELM in ER stress-induced cartilage damage as well as protein folding, pointing to new directions in molecular therapy for degenerative diseases., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Exploring the spatial-temporal changes, driving forces, and future development tendency of the carbon sequestration service function of the Three-River-Source National Park ecosystem has great significance for regional ecological protection and sustainable development. Historical land-use data of Three-River-Source National Park from 1990 to 2020 were selected at five-year intervals, and based on the PLUS-InVEST-Geodector model, the spatial-temporal changes of historical carbon storage were analyzed, and the driving forces of spatial-temporal variation were explored combined with multiple factors. The carbon storage of Three-River-Source National Park in 2030 was predicted under the scenarios of natural development and ecological protection. The results showed that： ① The carbon storage of Three-River-Source National Park showed a fluctuating characteristic of increase-decrease-increase-decrease from 1990 to 2020, the carbon storage was increased by 41.85×10 6 t overall, and the grassland took the largest contribution. ② The spatial distribution characteristics of carbon storage in Three-River-Source National Park had little change between 1990 to 2020, and the evolution of the spatial distribution was relatively stable. The contribution ratio of the Yangtze River source park, Lancang River source park, and Yellow River source park was 7∶1∶2, which was roughly equivalent to the park area. ③ The major driving factors of the spatial-temporal variation of carbon storage in Three-River-Source National Park from 1990 to 2020 were： FVC, soil type, and annual precipitation. The interactive detection of each driving factor showed dual-factor enhancement and nonlinear enhancement. ④ The carbon storage of Three-River-Source National Park was predicted to decrease by 4.87% and 3.98% from 2020 to 2030 under the scenarios of natural development and ecological protection, respectively, and the carbon storage reduction under the ecological protection scenario had a significant inhibitory effect. The findings can provide data support for national spatial planning of Three-River-Source National Park and the enhancement of terrestrial ecosystem carbon storage.

To eliminate the epidemic of coal-burning-borne endemic arsenism (CBBA), our study organized and implemented comprehensive measures including high-arsenic coal ban, improved cook-stoves, and health education. We also aimed to promote the application value of these measures in preventing and controlling CBBA to the world. From 2004 to 2005, through a stratified random sampling method, we selected 58,256 individuals to investigate the prevalence of CBBA and the arsenic levels in 1287 environmental and biological specimens. The prevalence of CBBA was 19.26 % and significantly associated with the arsenic levels in coal, pepper, corn and hair, which were at or exceeded national upper limits. To timely prevent and control the disease, the comprehensive measures have been implemented since 2005 to present. Comparison and correlation analyses were utilized to evaluate the effectiveness of these measures in reducing the prevalence of CBBA. According to statistics, 73 high-arsenic coal mines were banned and over 99 % households in endemic areas accepted stove improvements and diversified health education. Monitoring studies during 2010-2019 has confirmed that these measures led to a decrease in urine arsenic levels among endemic residents, and they developed novel dietary practices, such as properly drying, storage, and washing of food. Additionally, the awareness rate of CBBA increased from less than 70 % to over 95 %. Finally, the prevalence of CBBA has decreased to 0.153 % investigated by a census involving 2.076 million endemic residents in 2019. In summary, CBBA in northwest China has been successfully controlled through banning on high-arsenic coal, introducing improved cook-stoves, and providing health education., 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.)

Background: Reports on coronavirus disease 2019 (COVID-19) in neonates are limited, especially in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) Omicron variant. This study aims to analyze the clinical characteristics and identify risk factors associated with severe COVID-19 in neonates infected with Omicron variant., Methods: The study population was represented by neonates with COVID-19, who were admitted to The Affiliated Children's Hospital of Xi'an Jiaotong University in northwest China, from December 10, 2022 to January 20, 2023. Chinese Center for Disease Control and Prevention (CDC) announced that all local COVID-19 cases were infected with Omicron variant during the study period. Clinical and laboratory data were collected retrospectively. We used logistic regression analysis to investigate the risk factors for severe COVID-19, and derived odds ratios (ORs) and the corresponding 95% confidence intervals (CIs)., Results: A total of 108 neonates, with median age of 18.1 days (interquartile range 9.4-23.0), were affected by COVID-19, of whom 84 had a mild disease, while 24 a severe one (22.2%). Of them, 6.5% were premature. No deaths were observed in the study population. The most common clinical manifestations were fever (88.9%) and cough (55.6%), with 5 cases (4.6%) complicated by pneumonia. 4 cases (3.7%) received respiratory support, including 2 cases of high-flow oxygen and 2 cases of continuous positive airway pressure. Gestational age at birth (OR: 0.615; 95% CI: 0.393-0.961), neutrophil count (NEU) (OR:0.576; 95% CI : 0.344-0.962) and lymphocyte count (LYM) (OR: 0.159; 95% CI: 0.063-0.401) were independent risk factors for severe COVID-19. The combination of NEU and LYM had the largest receiver operating characteristic area under the curve [0.912 (95% CI:0.830-0.993)] for identifying severe COVID-19, with a sensitivity of 0.833 and a specificity of 0.917., Conclusions: The general presentations and outcomes of neonatal COVID-19 caused by Omicron variant were not severe, and very few patients required respiratory support. The simultaneous decrease in NEU and LYM can be used to identify severe infection., (© 2024. The Author(s).)

Dexmedetomidine (Dex) is widely used in the sedation in intensive care units and as an anesthetic adjunct. Considering the anti-inflammatory and antioxidant properties of Dex, we applied in vivo rat model as well as in vitro cardiomyocyte models (embryonic rat cardiomyocytes H9c2 cells and neonatal rat cardiomyocytes, NRCMs) to evaluate the effects of Dex against myocardial ischemia reperfusion (I/R) injury. Transcriptomic sequencing for gene expression in heart tissues from control rats and Dex-treated rats identified that genes related to fatty acid metabolism were significantly regulated by Dex. Among these genes, the elongation of long-chain fatty acids (ELOVL) family member 6 (Elovl6) was most increased upon Dex-treatment. By comparing the effects of Dex on both wild type and Elovl6-knockdown H9c2 cells and NRCMs under oxygen-glucose deprivation/reoxygenation (OGD/R) challenge, we found that Elovl6 knockdown attenuated the protection efficiency of Dex, which was supported by the cytotoxicity endpoints (cell viability and lactate dehydrogenase release) and apoptosis as well as key gene expressions. These results indicate that Dex exhibited the protective function against myocardial I/R injury via fatty acid metabolism pathways and Elovl6 plays a key role in the process, which was further confirmed using palmitate exposure in both cells, as well as in an in vivo rat model. Overall, this study systematically evaluates the protective effects of Dex on the myocardial I/R injury and provides better understanding on the fatty acid metabolism underlying the beneficial effects of Dex., 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.)

Community detection has become a prominent task in complex network analysis. However, most of the existing methods for community detection only focus on the lower order structure at the level of individual nodes and edges and ignore the higher order connectivity patterns that characterize the fundamental building blocks within the network. In recent years, researchers have shown interest in motifs and their role in network analysis. However, most of the existing higher order approaches are based on shallow methods, failing to capture the intricate nonlinear relationships between nodes. In order to better fuse higher order and lower order structural information, a novel deep learning framework called motif-based contrastive learning for community detection (MotifCC) is proposed. First, a higher order network is constructed based on motifs. Subnetworks are then obtained by removing isolated nodes, addressing the fragmentation issue in the higher order network. Next, the concept of contrastive learning is applied to effectively fuse various kinds of information from nodes, edges, and higher order and lower order structures. This aims to maximize the similarity of corresponding node information, while distinguishing different nodes and different communities. Finally, based on the community structure of subnetworks, the community labels of all nodes are obtained by using the idea of label propagation. Extensive experiments on real-world datasets validate the effectiveness of MotifCC.

Muscle quality index (MQI) is a novel indicator reflecting the quality of skeletal muscles. The association between MQI and the development of advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is unknown. We investigated the association of low MQI with advanced fibrosis among adults with NAFLD using a nationally representative sample of the US population. Adults with NAFLD who participated in the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were included. Sex-specific standard was used to define low and extremely low MQI. Univariate and multivariate logistic regressions were used to assess the association between MQI level and advanced fibrosis. In the study, 3758 participants with NAFLD were included. The prevalence of low and extremely low MQI was 11.7% (95% CI 10.4-13.0%) and 2.2% (95% CI 1.6-2.8%), respectively. Among these participants, 96 were assessed to have advanced fibrosis. Individuals with low [(odds ratio (OR) 2.45, 95% confidence interval (CI) 1.22-4.91)] and extremely low MQI (OR 10.48, 95% CI 3.20-34.27) were associated with advanced fibrosis in multivariable analysis. A linear trend relationship was also observed between MQI level and the risk of advanced fibrosis (P trend  = 0.001). Subgroup and sensitivity analyses yielded similar results to the main analyses. Decreased MQI is highly prevalent, and is associated with an increased risk of advanced fibrosis in adult US population with NAFLD., (© 2024. The Author(s).)

Background: Older patients with cancer have a higher risk for malnutrition and impaired quality of life (QoL). The present study aimed to investigate the relationship between malnutrition diagnosed according to the Global Leadership Initiative Malnutrition (GLIM) criteria and QoL across various tumor types, and to evaluate the combined prognostic value of malnutrition and QoL in predicting survival among older patients with cancer., Methods: This multicenter, observational cohort study included 5310 older patients with cancer and 2184 with malnutrition (moderate stage, n = 1023; severe stage, n = 1161). An empirical cumulative distribution curve was performed to illustrate the correlation between malnutrition and QoL. The primary objective was to investigate the association between malnutrition and QoL using logistic regression analysis. Survival analyses were performed to assess the combined prognostic value of malnutrition and QoL., Results: The median age of the patients (66.9% male, 33.1% female) was 70 years (interquartile range [IQR] 67-74 years) years. The median QoL score was highest in patients without malnutrition (91.88 [IQR 84.44-97.44]), followed by those with moderate (86.15 [IQR 76.18-93.85) and severe (82.31 [IQR 69.87-91.11]) malnutrition. Logistics regression revealed that the risk for developing impaired QoL increased 1.98 (95% confidence interval [CI] 1.64-2.38; P < 0.001) and 2.33 (95% CI 1.93-2.81; P < 0.001) times in patients with moderate and severe malnutrition, respectively. Kaplan-Meier curves showed that QoL in combination with GLIM criteria demonstrated a significant discriminative performance for survival and served as an independent prognostic factor among older patients with cancer, especially for lung and gastric cancers., Conclusions: Malnutrition diagnosed according to the GLIM criteria was a predictor of impaired QoL. Additionally, the combination of QoL and malnutrition demonstrated utility for predicting survival outcomes in older patients with cancer., (Copyright © 2024. Published by Elsevier Masson SAS.)

Obg-like ATPase 1 (OLA1) is a binding protein of Breast cancer gene 1 (BRCA1), germline pathogenic variants of which cause hereditary breast cancer. Cancer-associated variants of BRCA1 and OLA1 are deficient in the regulation of centrosome number. Although OLA1 might function as a tumor suppressor, the relevance of OLA1 deficiency to carcinogenesis is unclear. Here, we generated Ola1 knockout mice. Aged female Ola1 +/- mice developed lymphoproliferative diseases, including malignant lymphoma. The lymphoma tissues had low expression of Ola1 and an increase in the number of cells with centrosome amplification. Interestingly, the proportion of cells with centrosome amplification in normal spleen from Ola1 +/- mice was higher in male mice than in female mice. In human cells, estrogen stimulation attenuated centrosome amplification induced by OLA1 knockdown. Previous reports indicate that prominent centrosome amplification causes cell death but does not promote tumorigenesis. Thus, in the current study, the mild centrosome amplification observed under estrogen stimulation in Ola1 +/- female mice is likely more tumorigenic than the prominent centrosome amplification observed in Ola1 +/- male mice. Our findings provide a possible sex-dependent mechanism of the tumor suppressor function of OLA1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: While radiation therapy remains pivotal in esophageal squamous cell carcinoma (ESCC) treatment, the perplexing phenomenon of post-radiation metastasis presents a formidable clinical challenge. This study investigates the role of fibrinogen-like protein 1 (FGL1) in driving ESCC metastasis following radiation exposure., Methods: FGL1 expression in post-radiation ESCC cells was meticulously examined using qRT-PCR, western blotting, and immunofluorescence. The impact of FGL1 on ESCC cell invasion and migration was assessed through Transwell and wound healing assays. In vivo, the metastatic potential of ESCC in response to FGL1 was scrutinized using nude mice models. Comprehensive RNA sequencing and functional experiments elucidated the intricate mechanism associated with FGL1., Results: Radiation induced upregulation of FGL1 in ESCC cells through FOXO4, intensifying ESCC cell invasion and migration. Targeted knockdown of FGL1 effectively alleviated these characteristics both in vitro and in vivo. FGL1 depletion concurrently suppressed IMPDH1 expression. Rescue experiments underscored that IMPDH1 knockdown robustly reversed the pro-invasive effects induced by FGL1 in ESCC cells. ESCC tissues exhibited heightened IMPDH1 mRNA levels, demonstrating a correlation with patient survival., Conclusions: Radiation-induced upregulation of FGL1 propels ESCC metastasis through IMPDH1, proposing a potential therapeutic target to mitigate post-radiotherapy metastasis in ESCC patients., (© 2024. The Author(s).)

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28 days and younger than 18 years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30 days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5-8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556-0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004-1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799-1.000), indicating that these factors can accurately predict a poor prognosis.          Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Gastroesophageal reflux disease (GERD) in the elderly is characterized by atypical symptoms, relatively severe esophageal injury, and more complications, and when GERD is treated, it is also necessary to fully consider the general health condition of the elderly patients. This consensus summarized the epidemiology, pathogenesis, clinical manifestations, and diagnosis and treatment characteristics of GERD in the elderly, and provided relevant recommendations, providing guidance for medical personnel to correctly understand and standardize the diagnosis and treatment of GERD in the elderly., Competing Interests: Zheng Songbai is the Editorial Board member of the journal and was excluded from the peer‐review process and all editorial decisions related to the publication of this article. Other authors have nothing to disclose., (© 2024 The Authors. Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.)

Objectives: To assess and compare the effectiveness of various treatment approaches for laryngeal contact granulomas (LCG)., Methods: A retrospective analysis was conducted on a cohort of 45 patients diagnosed with LCG at the Second Affiliated Hospital of Xi'an Jiaotong University from October 2017 to May 2023. Based on the treatment modalities administered, patients were categorized into three groups: acid suppression alone, hormone injection combined with acid suppression, and surgery combined with acid suppression. Subsequently, the study compared differences in treatment efficacy and average healing time among these three groups, using various indicators., Results: The findings indicate that the granuloma size in LCG patients with hoarseness (0.126, 95% CI 0.087-0.288) was significantly greater compared to LCG patients without hoarseness (0.047, 95% CI 0.014-0.083) (P = 0.001). However, there were no significant variations in age, morphology (unlobulated/lobulated), laterality ratio (left/right), sex ratio (male/female), history of tracheal intubation (non-intubation/intubation), and RFS score (RFS > 7/RFS ≤ 7) (P > 0.05), regardless of the presence of hoarseness symptoms. At the treatment observation endpoint of 3 months, the curative ratio in the group receiving hormone injection combined with acid suppression was found to be significantly higher compared to the group receiving acid suppression alone (P = 0.018). In addition, the average healing time of patients in the hormone injection combined with acid suppression group was notably shorter than that of the acid suppression alone group (P = 0.007)., Conclusions: The combination of hormonal injections and acid suppression may enhance the curative ratio and expedite the healing time of LCG., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fluoride can be widely ingested from the environment, and its excessive intake could result in adverse effects. Dental fluorosis is an early sign of fluoride toxicity which can cause esthetic and functional problems. Though apoptosis in ameloblasts is one of the potential mechanisms, the specific signal cascade is in-conclusive. High-throughput sequencing and molecular biological techniques were used in this study to explore the underlying pathogenesis of dental fluorosis, for its prevention and treatment. A fluorosis cell model was established. Viability and apoptosis rate of mouse ameloblast-derived cell line (LS8 cells) was measured using cell counting kit-8 (CCK-8) assay and flow cytometry analysis. Cells were harvested with or without 2-mM sodium fluoride (NaF) stimulation for high-throughput sequencing. Based on the sequencing data, subcellular structures, endoplasmic reticulum stress (ERS), and apoptosis related biomarkers were verified using transmission electron microscopy, quantitative real-time polymerase chain reaction, and Western blotting techniques. Expression of ERS markers, apoptosis related proteins, and enamel formation enzymes were detected using Western blotting after addition of 4-phenylbutyrate (4-PBA). NaF-inhibited LS8 cells displayed time- and dose- dependent viability. Additionally, apoptosis and morphological changes were observed. RNA-sequencing data showed that protein processing in endoplasmic reticulum was obviously affected. ERS and apoptosis were induced by excessive NaF. Downregulation of kallikrein-related peptidase 4 (KLK4) was also observed. Inhibition of ERS by 4-PBA rescued the apoptotic and functional protein changes in cells. Excessive fluoride induces apoptosis by activating ERS, which is mediated by GRP-78/PERK/CHOP signaling. Key proteinase is present in maturation-stage enamel; KLK4 was also affected by fluoride, but rescued by 4-PBA. This study presents a possibility for therapeutic strategies for dental fluorosis, while further exploration is required., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim of this study was to construct rat models of environmental risk factors for Kashin-Beck disease (KBD) with low selenium and T-2 toxin levels and to screen the differentially expressed genes (DEGs) between the rat models exposed to environmental risk factors. The Se-deficient (SD) group and T-2 toxin exposure (T-2) group were constructed. Knee joint samples were stained with hematoxylin-eosin, and cartilage tissue damage was observed. Illumina high-throughput sequencing technology was used to detect the gene expression profiles of the rat models in each group. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis were performed and five differential gene expression results were verified by quantitative real-time polymerase chain reaction (qRT‒PCR). A total of 124 DEGs were identified from the SD group, including 56 upregulated genes and 68 downregulated genes. A total of 135 DEGs were identified in the T-2 group, including 68 upregulated genes and 67 downregulated genes. The DEGs were significantly enriched in 4 KEGG pathways in the SD group and 9 KEGG pathways in the T-2 group. The expression levels of Dbp, Pc, Selenow, Rpl30, and Mt2A were consistent with the results of transcriptome sequencing by qRT‒PCR. The results of this study confirmed that there were some differences in DEGs between the SD group and the T-2 group and provided new evidence for further exploration of the etiology and pathogenesis of KBD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Our aim was to assess the trend in gynaecologic cancer (GC) mortality in the period from 2010 to 2022 in the United States, with focus on the impact of the pandemic on increased deaths., Methods: GC mortality data were extracted from the Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) platform. We analysed mortality trends and evaluated observed vs. predicted mortality for the period from 2020 to 2022 with joinpoint regression and prediction modelling analyses., Results: A total of 334,382 deaths among adults aged 25 years and older with gynaecologic cancer were documented from 2010 to 2022. The overall age-standardised mortality rate (ASMR, per 100,000 persons) for ovarian cancer-related death decreased gradually from 7.189 in 2010 to 5.517 in 2019, yielding an APC (annual percentage change) of -2.8%. However, the decrease in ovarian cancer-related mortality slowed down by more than 4-fold during the pandemic. Cervical cancer -related mortality decreased slightly prior to the pandemic and increased during the pandemic with an APC of 0.6%, resulting in excess mortality of 4.92%, 9.73% and 2.03% in 2020, 2021 and 2022, respectively. For uterine corpus cancer, the ASMR increased from 1.905 in 2010 to 2.787 in 2019, and increased sharply to 3.079 in 2021 and 3.211 in 2022. The ASMR rose steadily between 2013 and 2022, yielding an APC of 6.9%., Conclusions: Overall, we found that GC-related mortality increased during the COVID-19 pandemic, and this increase was not specific to age, race, or ethnicity., (© 2024. The Author(s).)

Acquired drug resistance is a main reason for limiting the application of sorafenib in HCC treatment. This study aimed to explore the role and mechanisms of a novel long non-coding RNA (lncRNA), lnc-TSI, in sorafenib resistance of HCC. The interaction between lnc-TSI and miR-4726-5p, and miR-4726-5p and KCNMA1 were predicted using bioinformatic tools. Expression of the molecules in the lnc-TSI/miR-4726-5p/KCNMA1 axis in clinical samples and cell lines, as well as the sorafenib resistant HCC cell lines, was determined using qRT-PCR or western blotting. Expressions of lnc-TSI, miR-4726-5p, and KCNMA1 were manipulated in HepG2 and Huh7 cells through plasmid transfection or lentivirus infection. The CCK-8, flow cytometry, and Tunel assays were employed to determine the role of this axis on sorafenib resistance of HCC. A xenograft model was established using sorafenib-resistant HepG2 and Huh7 cells followed by in vivo sorafenib treatments to confirm the in vitro findings. Lnc-TSI and KCNMA1 expressions were significantly downregulated in HCC clinical samples and cell lines, especially in sorafenib resistance ones, while mi-4726-5p presented a reversed expression pattern. Lnc-TSI interacted with miR-4726-5p, and Lnc-TSI acts as a ceRNA via sponging miR-4726-5p in HCC cells. Overexpression of lnc-TSI and KCNMA1 promoted apoptosis and decreased cell viability of sorafenib-treated HCC cells, thus alleviated sorafenib resistance. miR-4726-5p mimic reversed the KCNMA1-mediated sorafenib sensitivity-promoting effect, while additional overexpression of lnc-TSI reversed the effect of miR-4726-5p. In vivo analysis also showed that overexpression of ln-TSI diminished sorafenib resistance in mice inoculated with sorafenib-resistant HCC cells via increasing KCNMA1 expression and decreasing miR-4726-5p expression. The lnc-TSI/miR-4726-5p/KCNMA1 axis plays a critical role in regulating the resistance of HCC to sorafenib, and might serve as a therapeutic target to manage sorafenib resistance of HCC in clinic., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Accumulation studies have found that adipose-derived stem cell (ADSC) exosomes have anti-oxidant and anti-inflammatory characteristics. The current study verified their therapeutic potential to elucidate mechanisms of ADSC exosome actions in ultraviolet B (UVB) light-induced skin injury. Exosomes were isolated from ADSCs and hypoxic pretreated ADSCs. Next-generation sequencing (NGS) was applied to characterize differential mRNA expression. A UV-induced mice skin injury model was generated to investigate therapeutic effects regarding the exosomes via immunofluorescence and ELISA analysis. Regulatory mechanisms were illustrated using luciferase report analysis and in vitro experiments. The results demonstrated that exosomes from hypoxic pretreated ADSCs (HExos) inhibited UVB light-induced vascular injury by reversing reactive oxygen species, inflammatory factor expression and excessive collagen degradation. NGS showed that HExos inhibits UV-induced skin damage via GLRX5 delivery, while GLRX5 downregulation inhibited the therapeutic effect of HExos on UV-induced skin damage. GLRX5 upregulation increased the protective Exo effect on UV-induced skin and EPC damage by inhibiting ferroptosis, inflammatory cytokine expression and excessive collagen degradation. Therefore, the data indicate that HExos attenuate UV light-induced skin injury via GLRX5 delivery and ferroptosis inhibition., (© 2023. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

Taking a previously discovered indazole derivative 1 as a lead, systematic structural modifications were performed with an indazole core at the 1- and 6-positions to improve its aqueous solubility. Among the designed indazole derivatives, 6-methylpyridin-3-yl indazole derivative 8l and 1H-indol-4-yl indazole derivative 8m exhibited high potency in the low nanomolar range against A549, Huh-7, and T24 cancer cells, including Taxol-resistant variant cells (A549/Tax). As a hydrochloride salt, 8l exhibited much improved aqueous solubility, and its log P value fell into a favorable range. In mechanistic studies, 8l impeded tubulin polymerization through interacting with the colchicine site, resulting in cell cycle arrest and cellular apoptosis. In addition, compared to lead compound 1, 8l reduced cell migration and led to more potent inhibition of tumor growth in vivo without apparent toxicity. In summary, indazole derivative 8l could work as a potential anticancer agent and deserves further investigation for cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The aim of this study was to analyze the differences in gut microbiota between selenium deficiency and T-2 toxin intervention rats. Knee joint and fecal samples of rats were collected. The pathological characteristics of knee cartilage were observed by safranin O/fast green staining. DNA was extracted from fecal samples for PCR amplification, and 16S rDNA sequencing was performed to compare the gut microbiota of rats. At the phylum level, Firmicutes (81.39% vs. 77.06%) and Bacteroidetes (11.11% vs. 14.85%) were dominant in the Se-deficient (SD) group and T-2 exposure (T-2) groups. At the genus level, the relative abundance of Ruminococcus&#95;1 (12.62%) and Ruminococcaceae&#95;UCG-005 (10.31%) in the SD group were higher. In the T-2 group, the relative abundance of Lactobacillus (11.71%) and Ruminococcaceae&#95;UCG-005 (9.26%) were higher. At the species level, the high-quality bacteria in the SD group was Ruminococcus&#95;1&#95;unclassified , and Ruminococcaceae&#95;UCG-005&#95;unclassified in the T-2 group. Lactobacillus&#95;sp&#95;&#95;L&#95;YJ and Lactobacillus&#95;crispatus were the most significant biomarkers in the T-2 group. This study analyzed the different compositions of gut microbiota in rats induced by selenium deficiency and T-2 toxin, and revealed the changes in gut microbiota, so as to provide a certain basis for promoting the study of the pathogenesis of Kashin-Beck disease (KBD).

This umbrella review aimed to evaluate the effectiveness of pragmatic language interventions and existing competing views in improving pragmatic language skills in persons with pragmatic language impairment (PLI). A comprehensive search was conducted to identify qualitative and quantitative systematic reviews that included diagnostic criteria, features, development and course, risk and prognostic factors, differential diagnosis of PLI, and existing interventions, views, and arguments to improve the pragmatic language abilities/skills of persons with PLI. Syntheses were critically appraised by two independent reviewers using the JBI Critical Appraisal Checklist for Systematic Reviews and Research Syntheses. This umbrella review was registered with PROSPERO on 9th December 2022 under the registration number CRD42022378690. Out of 3,609 studies, 42 reviews were included in this umbrella review. The extracted findings were categorized based on theoretical intervention perspectives, which included behavioral, social-pragmatic, and cognitive-linguistic approaches. The studies revealed that pragmatic language interventions had a positive impact on improving pragmatic language skills in persons with PLI. However, competing views on pragmatic language interventions were also identified, suggesting the need for a more comprehensive approach that includes both behavioral and cognitive-linguistic components. In conclusion, cognitive-linguistic approach was the most documented intervention method, and suiting intervention methods to the complex nature of PLI is crucial. The documented intervention methods reflected competing views on the nature of PLI, highlighting the need for tailored interventions.

Skin scarring is a frequent complication of the wound healing process. Bacterial contamination and prolonged inflammation in wounds are thought to play significant roles during scar formation, but little is known about their specific mechanisms of action. In this study, hypertrophic scar derived fibroblasts (HSFs) and paired normal skin derived fibroblasts (NSFs) were used to evaluate the effects of lipopolysaccharide (LPS) on inflammation-induced skin scarring and explore the inflammation-mediated mechanism of activity of LPS on dermal fibroblasts. LPS was found to significantly upregulate the expression of the proinflammatory molecules TLR4, Myd88, TRAF6, and p65, and the fibrosis-related proteins Col I, Col III, and α-SMA, in NSFs. Blocking Myd88 expression with T6167923 downregulated the expression of Col I, Col III, and α-SMA, whereas activating Myd88 expression with CL075 significantly upregulated their expression in LPS-treated NSFs. LPS was found to delay wound healing and increase skin scarring in cell and mouse models. These results showed that LPS could induce scar formation through the TLR4/Myd88 signaling pathway in dermal fibroblasts, suggesting that the downregulation of excessive inflammation in wound tissues inhibits skin scarring and improves scar appearance., Competing Interests: Declaration of Competing Interest The authors have no conflicts relative to this manuscript., (Copyright © 2023 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Objective: To analyze the risk factors for recurrence of laryngeal amyloidosis (LA)., Methods: The clinical data of patients with LA admitted in the Otolaryngology Head and Neck Surgery Department of the Second Affiliated Hospital of Xi'an Jiaotong University from August 2009 to June 2022 were analyzed retrospectively; then, the risk factors for recurrence and their impacts on the recurrence time were also analyzed., Results: Of the 44 patients with LA, the majority (38 cases, 86.4%) only involved one anatomical region and the others (6 cases, 13.6%) involved two laryngeal regions concurrently. Overall, the glottic region was the most commonly affected area (28 cases, 63.6%), followed by the supraglottic region (16 cases, 36.4%) and subglottic region (6 cases, 13.6%). In addition, all the lesions were categorized as isolated nodule (31.8%), submucosal localized deposition (52.3%), and submucosal diffuse deposition (15.9%) according to their morphologies under electronic laryngoscope. Finally, six patients (13.6%) had recurrence after operation with a median recurrence time of 24.5 months, and subglottic involvement was confirmed to be an independent risk factor for recurrence of LA by univariate and multivariate logistic regression analyses (P < 0.05). Meanwhile, the patients with subglottic involvement presented as submucosal diffuse deposition had a considerable shorter recurrence time (t = 5.759, P = 0.005)., Conclusion: The subglottic involvement is an independent risk factor for recurrence of LA., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To explore the mechanism of effects of total saponin fraction from Dioscorea Nipponica Makino (TSDN) on M1/M2 polarization of monocytes/macrophages and arachidonic acid (AA) pathway in rats with gouty arthritis (GA)., Methods: Seventy-two Sprague Dawley rats were randomly divided into 4 groups (n=18 in each): normal, model, TSDN at 160 mg/kg, and celecoxib at 43.3 mg/kg. Monosodium urate crystal (MSU) was injected into the rats' ankle joints to induce an experimental GA model. Blood and tissue samples were collected on the 3rd, 5th, and 8th days of drug administration. Histopathological changes in the synovium of joints were observed via hematoxylin and eosin (HE) staining. The expression levels of arachidonic acid (AA) signaling pathway were assessed via real-time polymerase chain reaction (qPCR) and Western blot. Flow cytometry was used to determine the proportion of M1 and M2 macrophages in the peripheral blood. An enzyme-linked immunosorbent assay (ELISA) was used to detect interleukine (IL)-1 β, tumor necrosis factor-alpha (TNF-α), IL-4, IL-10, prostaglandin E 2 (PGE 2 ), and leukotriene B4 (LTB4)., Results: HE staining showed that TSDN improved the synovial tissue. qPCR and Western blot showed that on the 3rd, 5th and 8th days of drug administration, TSDN reduced the mRNA and protein expressions of cyclooxygenase (COX)2, microsomal prostaglandin E synthase-1 derived eicosanoids (mPGES-1), 5-lipoxygenase (5-LOX), recombinant human mothers against decapentaplegic homolog 3 (Smad3), nucleotide-binding oligomerization domain-like receptor protein 3 (NALP3), and inducible nitric oxide synthase (iNOS) in rats' ankle synovial tissues (P<0.01). TSDN decreased COX1 mRNA and protein expression on 3rd and 5th day of drug administration and raised it on the 8th day (both P<0.01). It lowered CD68 protein expression on days 3 (P<0.01), as well as mRNA and protein expression on days 5 and 8 (P<0.01). On the 3rd, 5th, and 8th days of drug administration, TSDN elevated the mRNA and protein expression of Arg1 and CD163 (P<0.01). Flow cytometry results showed that TSDN decreased the percentage of M1 macrophages while increasing the percentage of M2 in peripheral blood (P<0.05 or P<0.01). ELISA results showed that on the 3rd, 5th, and 8th days of drug administration, TSDN decreased serum levels of IL-1 β, TNF-α, and LTB4 (P<0.01), as well as PGE 2 levels on days 3rd and 8th days (P<0.05 or P<0.01); on day 8 of administration, TSDN increased IL-4 serum levels and enhanced IL-10 contents on days 5 and 8 (P<0.05 or P<0.01)., Conclusion: The anti-inflammatory effect of TSDN on rats with GA may be achieved by influencing M1/M2 polarization through AA signaling pathway., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Obstructive sleep apnea (OSA) is a globally prevalent disease with a complex diagnostic method. Severe OSA is associated with multi-system dysfunction. We aimed to develop an interpretable machine learning (ML) model for predicting the risk of severe OSA and analyzing the risk factors based on clinical characteristics and questionnaires., Methods: This was a retrospective study comprising 1656 subjects who presented and underwent polysomnography (PSG) between 2018 and 2021. A total of 23 variables were included, and after univariate analysis, 15 variables were selected for further preprocessing. Six types of classification models were used to evaluate the ability to predict severe OSA, namely logistic regression (LR), gradient boosting machine (GBM), extreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), bootstrapped aggregating (Bagging), and multilayer perceptron (MLP). All models used the area under the receiver operating characteristic curve (AUC) was calculated as the performance metric. We also drew SHapley Additive exPlanations (SHAP) plots to interpret predictive results and to analyze the relative importance of risk factors. An online calculator was developed to estimate the risk of severe OSA in individuals., Results: Among the enrolled subjects, 61.47% (1018/1656) were diagnosed with severe OSA. Multivariate LR analysis showed that 10 of 23 variables were independent risk factors for severe OSA. The GBM model showed the best performance (AUC = 0.857, accuracy = 0.766, sensitivity = 0.798, specificity = 0.734). An online calculator was developed to estimate the risk of severe OSA based on the GBM model. Finally, waist circumference, neck circumference, the Epworth Sleepiness Scale, age, and the Berlin questionnaire were revealed by the SHAP plot as the top five critical variables contributing to the diagnosis of severe OSA. Additionally, two typical cases were analyzed to interpret the contribution of each variable to the outcome prediction in a single patient., Conclusions: We established six risk prediction models for severe OSA using ML algorithms. Among them, the GBM model performed best. The model facilitates individualized assessment and further clinical strategies for patients with suspected severe OSA. This will help to identify patients with severe OSA as early as possible and ensure their timely treatment., Trial Registration: Retrospectively registered., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Extracellular vesicular miRNAs (EV-miRNAs) play essential roles as intercellular communication molecules in knee Osteoarthritis (OA). We isolated cartilage-derived extracellular vesicles (EVs), to perform miRNA sequencing, which revealed EV-miRNA profiles and identified differentially expressed miRNAs (DE-miRNAs) between cartilage injury and cartilage non-injury groups. The target genes of known and novel DE-miRNAs were predicted with multiMiR package in 14 miRNA-target interaction databases. Meanwhile, single-cell RNA sequencing (scRNA-seq) was performed to identify chondrocyte clusters and their gene signatures in knee OA. Then we performed comparative analysis between target genes of the cartilage-derived EV-DE-miRNAs target genes and cluster-specific maker genes of characteristic chondrocyte clusters. Finally, the functional analysis of the cartilage-derived EVs DE-miRNA target genes and cluster-specific marker genes of each cell population were performed. The EV-miRNA profile analysis identified 13 DE-miRNAs and 7638 target genes. ScRNA-seq labelled seven clusters by cell type according to the expression of multiple characteristic markers. The results identified 735, 184, 303 and 879 common genes between EV-DE-miRNA target genes and cluster-specific marker genes in regulatory chondrocytes (RegCs), fibrocartilage chondrocytes (FC), prehypertrophic chondrocytes (PreHTCs) and mitochondrial chondrocytes (MTC), respectively. We firstly integrated the association between the cartilage-derived EV-DE-miRNA target genes and distinguished cluster-specific marker genes of each chondrocyte clusters. KEGG pathway analysis further identified that the DE-miRNAs target genes were significantly enriched in MAPK signaling pathway, Focal adhesion and FoxO signaling pathway. Our results provided some new insights into cartilage injury and knee OA pathogenesis which could improve the new diagnosis and treatment methods for OA., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The paper explored the extent to which hospital appointed official root cause analysis (RCA) panels consider antecedent and proximal events when they investigate communication related sentinel events (CRSEs) in hospitals. It also explored which CRSEs are most common in the hospital setting in Hong Kong and the communication modes most commonly associated with CRSEs. The data consisted of Risk Alert and Annual Report on SEs issued by the Hong Kong Hospital Authority from October 2007 to September 2017. Over the period studied, there were 379 reported sentinel events (SEs). In 186 of these SEs we identified communication as a contributing factor. We examined the RCA panels' reports on contributing factors and subsequent recommendations in these 186 SEs and found that their recommendations only highlighted the proximal contributing factors and not antecedent factors that may be relevant. RCA panels most often recommended that communication should be enhanced or documentation improved. We propose that it is time to review the RCA process to recognize that many CRSEs may occur because of antecedent factors that result from the complex hospital organizational structure and its associated hierarchical culture. We suggest two ways forward, 1) applying a language and social psychology perspective to the investigations of CRSEs and, 2) the involvement of experts from different disciplines who can work with clinicians during RCA investigations.

Background: Ventricular septal defect (VSD) is the most common subtype of congenital heart disease. In the present study, we aimed to determine whether chromosome aberration was associated with the occurrence of VSD and evaluate the association of VSD size, location and chromosome aberration with adverse outcomes in the Chinese fetuses., Methods: Fetuses with VSD and comprehensive follow-up data were included and evaluated retrospectively. Medical records were used to collect epidemiological data and foetal outcomes. For VSD fetuses, conventional karyotype and microarray analysis were conducted. After adjusting confounding factors by using multivariable logistic regression analyses, the association between chromosome variations and VSD occurrence was explored. The association between defect size, location and chromosome aberrations and adverse foetal outcomes was also investigated., Results: Chromosome aberration was the risk factor for VSD occurrence, raising 6.5-fold chance of developing VSD. Chromosome aberration, peri-membranous site and large defect size of VSD were significant risk factors of adverse fetal outcome. Chromosome aberrations, including pathogenic copy number variations (CNVs) and variations of uncertain significance (VUS), were both risk factors, increasing the risk of the adverse fetal outcome by 55.9 times and 6.7 times, respectively. The peri-membranous site would increase 5.3-fold risk and defects larger than 5 mm would increase the 7.1-fold risk for poor fetal outcome., Conclusions: The current investigation revealed that chromosomal abnormalities, large defects, and the peri-membranous site were all risk factors for poor fetal outcomes. Our study also indicated that chromosome aberration was one of risk factors for the VSD occurrence., (© 2023. BioMed Central Ltd., part of Springer Nature.)

There is a lack of effective programmed cell death protein 1 (PD-1)-targeted immunotherapy with good tolerability in patients with advanced hepatocellular carcinoma (HCC) and severely compromised liver function. We assessed patient outcomes after combined camrelizumab and molecular targeted therapy in a multicenter cohort study in China. The study included 99 patients with advanced HCC (58 Child-Pugh A and 41 Child-Pugh B), 84 of them received camrelizumab combined with molecular targeted therapy from January 10, 2019, to March 31, 2021. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were assessed. The median follow-up was 12.1 months. For patients with Child-Pugh B, the OS probability at 12-months, ORR and DCR were 49.7%, 31.7% and 65.9%, respectively, and the median PFS was 5.1 months [95% confidence interval (CI) 3.0-7.1], which were comparable with Child-Pugh A patients, although median OS was shorter in Child-Pugh B patients (20.5 vs.13.4 months, P = 0.12). In multivariate analysis, macrovascular infiltration (MVI), but not sex, age, hepatitis B virus etiology, extrahepatic metastasis, Child-Pugh B, or AFP > 400 ng/ml, was associated with 12-months OS [hazard ratio (HR) 2.970, 95% CI 1.276-6.917, P = 0.012] and ORR (HR 2.906, 95% CI 1.18-7.16, P = 0.020). Grade 3/4 immune-related AEs occurred in 26.8% of Child-Pugh B patients, including one potentially treatment-related death. In both groups, the most common AEs were immune thrombocytopenia and hepatotoxicity. Camrelizumab combined with targeted therapy showed favorable effectiveness and tolerability with manageable toxicities in Chinese HCC patients, regardless of Child-Pugh A/B liver function. MVI was associated with suboptimal immunotherapy response and poor prognosis., (© 2023. The Author(s).)

Purpose: Our aim is to establish an AI model for distinguishing color fundus photographs (CFP) of RVO patients from normal individuals., Methods: The training dataset included 2013 CFP from fellow eyes of RVO patients and 8536 age- and gender-matched normal CFP. Model performance was assessed in two independent testing datasets. We evaluated the performance of the AI model using the area under the receiver operating characteristic curve (AUC), accuracy, precision, specificity, sensitivity, and confusion matrices. We further explained the probable clinical relevance of the AI by extracting and comparing features of the retinal images., Results: Our model achieved an average AUC was 0.9866 (95% CI: 0.9805-0.9918), accuracy was 0.9534 (95% CI: 0.9421-0.9639), precision was 0.9123 (95% CI: 0.8784-9453), specificity was 0.9810 (95% CI: 0.9729-0.9884), and sensitivity was 0.8367 (95% CI: 0.7953-0.8756) for identifying fundus images of RVO patients in training dataset. In independent external datasets 1, the AUC of the RVO group was 0.8102 (95% CI: 0.7979-0.8226), the accuracy of 0.7752 (95% CI: 0.7633-0.7875), the precision of 0.7041 (95% CI: 0.6873-0.7211), specificity of 0.6499 (95% CI: 0.6305-0.6679) and sensitivity of 0.9124 (95% CI: 0.9004-0.9241) for RVO group. There were significant differences in retinal arteriovenous ratio, optic cup to optic disc ratio, and optic disc tilt angle (p = 0.001, p = 0.0001, and p = 0.0001, respectively) between the two groups in training dataset., Conclusion: We trained an AI model to classify color fundus photographs of RVO patients with stable performance both in internal and external datasets. This may be of great importance for risk prediction in patients with retinal venous occlusion., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Esophageal squamous cell carcinoma (ESCC) is a highly prevalent and aggressive cancer with poor treatment outcomes. Despite the critical role of tight junction proteins in tumorigenesis, the involvement of Claudin5 in ESCC remains poorly understood. Thus, this study aimed to investigate the role of Claudin5 in ESCC malignant progression and radioresistance, as well as the underlying regulatory mechanisms., Methods: The expression of Claudin5 was evaluated in esophageal cancer tissue using both public databases and 123 clinical samples. CCK-8, transwell invasion, wound healing and clonogenic survival assays were used to examine the proliferation, invasion, migration and radiosensitivity of ESCC cells in vitro. Xenograft and animal lung metastasis experiments were conducted to examine the impact of Claudin5 on tumor growth and lung metastasis in vivo. The effect of Claudin5 on autophagy was detected via transmission electron microscopy, western blotting and autophagy flux. Immunohistochemical staining was used to detect Claudin5 expression in ESCC patient samples. The statistical difference was assessed with Student t test or one-way ANOVA. The correlation between Claudin5 expression and radiotherapy response rate was performed by the Chi-square test. The significance of Kaplan-Meier curves was evaluated by the Logrank test., Results: Claudin5 expression was downregulated in ESCC tissues. Downregulation of Claudin5 promoted ESCC cell proliferation, invasion, and migration both in vitro and in vivo. Downregulation of Claudin5 decreased the radiosensitivity of ESCC cells. Moreover, downregulation of Claudin5 promoted autophagy and the expression of Beclin1. Beclin1 knockdown reversed the effect of Claudin5 downregulation on autophagy induction and the promotion of ESCC cell malignant progression and radioresistance. Additionally, low expression of Claudin5 in ESCC cancer tissues was associated with poor radiotherapy response and prognosis., Conclusions: In summary, these findings suggest that downregulation of Claudin5 promotes ESCC malignant progression and radioresistance via Beclin1-autophagy activation and may serve as a promising biomarker for predicting radiotherapy response and patient outcome in ESCC., (© 2023. The Author(s).)

Background and Aims: Accurate evaluation of intraductal papillary mucinous neoplasm (IPMN) is necessary to inform clinical decision-making. But it is still difficult to distinguish benign and malignant IPMN preoperatively. This study aims to evaluate the utility of EUS to predict the pathology of IPMN., Methods: Patients with IPMN who underwent endoscopic ultrasound within 3 months before surgery were collected from six centers. Logistic regression model and random forest model were used to determine risk factors associated with malignant IPMN. In both models, 70% and 30% of patients were randomly assigned to the exploratory group and validation group, respectively. Sensitivity, specificity, and ROC were used in model assessment., Results: Of the 115 patients, 56 (48.7%) had low-grade dysplasia (LGD), 25 (21.7%) had high-grade dysplasia (HGD), and 34 (29.6%) had invasive cancer (IC). Smoking history (OR = 6.95, 95%CI: 1.98-24.44, p = 0.002), lymphadenopathy (OR = 7.91, 95%CI: 1.60-39.07, p = 0.011), MPD > 7 mm (OR = 4.75, 95%CI: 1.56-14.47, p = 0.006) and mural nodules > 5 mm (OR = 8.79, 95%CI: 2.40-32.24, p = 0.001) were independent risk factors predicting malignant IPMN according to the logistic regression model. The sensitivity, specificity, and AUC were 0.895, 0.571, and 0.795 in the validation group. In the random forest model, the sensitivity, specificity, and AUC were 0.722, 0.823, and 0.773, respectively. In patients with mural nodules, random forest model could reach a sensitivity of 0.905 and a specificity of 0.900., Conclusions: Using random forest model based on EUS data is effective to differentiate benign and malignant IPMN in this cohort, especially in patients with mural nodules., (© 2023. The Author(s).)

Abdominal pain in Crohn's disease (CD) has been known to be associated with changes in the central nervous system. The periaqueductal gray (PAG) plays a well-established role in pain processing. However, the role of PAG-related network and the effect of pain on the network in CD remain unclear.Resting-state functional magnetic imaging (fMRI) data were collected from 24 CD patients in remission with abdominal pain, 24 CD patients without abdominal pain and 28 healthy controls (HCs). Using the subregions of PAG (dorsomedial (dmPAG), dorsolateral (dlPAG), lateral (lPAG) and ventrolateral (vlPAG)) as seeds, the seed-based FC maps were calculated and one-way analysis of variance (ANOVA) was performed to investigate the differences among the three groups.Results showed that the group differences were mainly involved in the FC of the vlPAG with the precuneus, medial prefrontal cortex (mPFC) as well as orbitofrontal cortex (OFC), and the FC of the right lateral PAG (lPAG) with the precuneus, inferior parietal lobule (IPL), angular gyrus and premotor cortex. The FC values of all these regions decreased successively in the order of HCs, CD without abdominal pain and CD with abdominal pain. The pain score was negatively correlated with the FC of the l/vlPAG with the precuneus, angular gyrus and mPFC in CD patients with abdominal pain.This study implicated the disrupt communication between the PAG and the default mode network (DMN). These findings complemented neuroimaging evidence for the pathophysiology of visceral pain in CD patients., (Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Neuroinflammation triggered by chronic cerebral ischemia-induced microglial pyroptosis is a significant contributor to vascular cognitive impairment. It has been shown that emodin possesses anti-inflammatory and neuroprotective properties, however, it's potential molecular and signaling transduction pathway remains to be illuminated. This study researched the neuroprotective mechanisms of emodin focussing on emodin effects on lipopolysaccharide/adenosine triphosphate (LPS/ATP)-caused pyroptosis in BV2 cells and HT-22 hippocampal neurons., Methods: To explore the neuroprotective effect of emodin, Emodin was applied to BV2 cells, HT-22 hippocampal neurons, and BV2/HT-22 co-cultures stimulated with LPS/ATP to evaluate the cell morphology, levels of inflammatory factors, NLRP3 inflammatory inflammasome activity and focal pyroptosis-related protein expression, as same as neuronal apoptosis., Results: Emodin alleviated LPS/ATP-induced pyroptosis of BV2 cells by preventing the activity of the NLRP3 inflammasome and the cleavage of pyroptosis executive protein Gasdermin D (GSDMD). Furthermore, levels of interleukin (IL)-18, IL-1β and tumor necrosis factor (TNF)-α were reduced, the apoptosis of HT-22 hippocampal neurons was attenuated, and cell viability was restored., Conclusions: Emodin can antagonize microglial neurotoxicity by inhibiting microglial pyroptosis, thereby exerting anti-inflammatory and neuroprotective effects., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

In this paper, the effects of material removal strategies and initial stress states on the machining deformation of aluminum alloy plates were investigated through a combination of finite element simulation and experiments. We developed different machining strategies described by Tm+Bn, which removal m mm materials form top and n mm materials from the bottom of the plate. The results demonstrate that the maximum deformation of structural components with the T10+B0 machining strategy could reach 1.94 mm, whereas with the T3+B7 machining strategy was only 0.065 mm, decreasing by more than 95%. The asymmetric initial stress state had a significant impact on the machining deformation of the thick plate. The machined deformation of thick plates increased with the increase in the initial stress state. The concavity of the thick plates changed with the T3+B7 machining strategy due to the asymmetry of the stress level. The deformation of frame parts was smaller when the frame opening was facing the high-stress level surface during machining than when it was facing the low-stress level. Moreover, the modeling results for the stress state and machining deformation were accurate and in good accordance with the experimental findings.

Kashin-Beck disease (KBD) is a serious, endemic chronic osteochondral disease characterized by symmetrical enlargement of the phalanges, brachydactyly, joint deformity, and even dwarfism. To investigate the urinary metabolomic profiles of KBD patients, we performed an untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS). Adult urinary specimens were collected from 39 patients with KBD and 19 healthy subjects; the children's urinary specimens were collected from 5 patients with KBD, 25 suspected KBD cases and 123 healthy subjects in the KBD endemic area during a three consecutive year study. We identified 10 upregulated and 28 downregulated secondary level metabolites highly associated with aetiology and pathogenesis of KBD between adult KBD and adult controls. A total of 163, 967 and 795 metabolites were significantly different in the urine among children with KBD, suspected children with KBD cases and healthy child controls, respectively, for each year in three consecutive years. HT-2 toxin, Se-adenosylselenomethionine (AdoSeMet), the toxin T2 tetrol, and many kinds of amino acids were identified as differential metabolites in this study. Amino sugar and nucleotide sugar metabolism, fructose and mannose metabolism, arachidonic acid metabolism, D-glutamine and D-glutamate metabolism, ubiquinone and other terpenoid-quinone biosynthesis, and D-glutamine and D-glutamate metabolism were perturbed pathways in adult and child KBD patients. Our study provides new insight into the underlying mechanisms of KBD, and suggests that we should pay more attention to these differences in small-molecule metabolites and metabolic pathways in the environmental aetiology and pathogenesis of KBD.

Objectives: This study aims to retrospectively evaluate the survival rate of pulpectomy performed under dental general anesthesia (DGA) through long-term follow-up and to explore the risk factors associated with treatment failure., Methods: The medical records of the children who were diagnosed with S-ECC and received pulpectomy treatment under general anesthesia (GA) from 1 August 2014 to 1 December 2019, in the Stomatological Hospital of Xi'an Jiaotong University, were collected. Two dentistry postgraduates extracted the necessary information and filled in a predesigned excel form. Survival analysis was performed using the Kaplan-Meier method. The shared frailty model was used to explore possible factors affecting the success rate of pulpectomy in primary teeth., Results: A total of 381 children (mean age 3.49 ± 0.90) with S-ECC and 1220 teeth were included in the study, including 590 primary anterior teeth and 630 primary molars. The overall 35-month survival rate was 38.5%, which was 52.9% for anterior teeth and 31.1% for molars. The overall median survival time was 31 months, in which anterior teeth were 35 months and molars were 26 months. The older the children were, the greater the risk of treatment failure (HR 1.56, 95% CI 1.09, 2.24). The risk of pulpectomy failure of primary molars was 1.9 times that of primary anterior teeth (95% CI 1.36, 2.65) and the teeth with abnormal radiological findings before treatment was 1.41 times higher than that of teeth without imaging abnormalities (95% CI 1.74, 3.36)., Conclusion: The survival rate of primary tooth pulpectomy is acceptable but decreased gradually with time. The failure rate of pulpectomy in primary molars is higher than that of primary anterior teeth. When the primary caries has extended to the pulp and resulted in a nonvital lesion, pulpectomy could be an option for maximum retention of the primary tooth.

Objective: Communication at the end-of-life (EOL) is complex and multidimensional. Although culture is acknowledged as a key influence, there remains a gap in knowledge about intracultural aspects of EOL communication in the Chinese context. This review presents a synthesis of practitioners' accounts of communication at the EOL in Hong Kong, Mainland China and Taiwan., Methods: This review was registered prospectively on PROSPERO (CRD42021297052). Five databases were systematically searched using the terms 'communication', 'End-of-Life', 'Hong Kong', 'China' and 'Taiwan'. Empirical research published between 2015 and 2021 was downloaded and appraised. Fifteen articles were included in the review., Results: Findings highlight the influence of Chinese culture and philosophy, inadequate communication skills training and psychological support for practitioners and legislative and organisational factors., Conclusion: Education and training for practitioners and public education about the EOL needs strengthening. Enhanced understanding of how culture influences EOL communication will strengthen service delivery and enhance awareness in multicultural communities., Practice Implications: EOL workers need practical and workplace-based support to engage in meaningful communication practices. The influence of culture and the readiness of patients and families to engage in communication are also important considerations., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Radiotherapy is one of the main treatments for esophageal squamous cell carcinoma (ESCC), but its efficacy is limited by radioresistance. MicroRNAs play a crucial role in posttranscriptional regulation, which is linked to the cancer response to radiation., Methods: We successfully established a radioresistant cell line model by using fractionated irradiation. qRT-PCR was adopted to detect the expression of miR-4443 in human normal esophageal cell lines, tumor cells, and radioresistant cells. Next, CCK-8, colony formation, apoptosis, and cell cycle assays were used to assess the biological effect of miR-4443. Weighted gene coexpression network analysis (WGCNA) was performed to identify potential radiosensitivity-related genes. Additionally, we predicted the probable targets of the miRNA using bioinformatic methods and confirmed them using Western blot., Results: miR-4443 was significantly upregulated in radioresistant ESCC cells. Enhancement of miR-4443 further decreased the radiosensitivity of ESCC cells, while inhibition of miR-4443 increased the radiosensitivity of ESCC cells. Notably, miR-4443 modulated radiosensitivity by influencing DNA damage repair, apoptosis, and G2 cycle arrest. By using WGCNA and experimental validation, we identified PTPRJ as a key target for miRNA-4443 to regulate radiosensitivity. The effects of miR-4443 overexpression or inhibition could be reversed by increasing or decreasing PTPRJ expression., Conclusion: In this study, miR-4443 is found to promote radiotherapy resistance in ESCC cells by regulating PTPRJ expression, which provides a new perspective and clue to alleviate radioresistance., (© 2022. The Author(s).)

The purpose of this study was to evaluate the feasibility of opportunistic screening for osteoporosis in postmenopausal females using the dual-energy CT(DECT)-derived hydroxyapatite (HAP) concentration and CT value of L1-vertebra. 239 consecutive postmenopausal female patients were enrolled and underwent both chest DECT and Dual energy X-ray absorptiometry (DXA). According to the T-score of the 1st lumbar vertebra on DXA, patients were divided into the osteoporosis group (T [Formula: see text]- 2.5, n = 112) and non-osteoporosis group (T [Formula: see text] - 2.5, n = 127). The HAP values of the 1st lumbar vertebra were measured from the coronal-view HAP(Fat)-based material decomposition(MD) images, and CT values were measured on the 75 keV monochromatic image. The cutoff values of using HAP and CT value for diagnosing osteoporosis were obtained by drawing receiver operating characteristic (ROC) curves. Both HAP and CT value of the 1st lumbar vertebra had moderate-high correlation with bone-mineral-density measurement on DXA (HAP, r = 0.614; CT value, r = 0.625; all p < 0.01). The area-under-the-curve (AUC), sensitivity, specificity, PPV and NPV for diagnosing osteoporosis was 0.754, 0.714, 0.693, 0.68 and 0.752 using HAP (cutoff value: 142.05 mg/cm 3 ) and 0.766, 0.741, 0.7, 0.685 and 0.754 using CT value (cutoff value: 132HU), respectively. HAP measurements on HAP(Fat)-based MD images in DECT could provide reasonably accurate BMD quantification for diagnosing osteoporosis in postmenopausal females. DECT prescribed for lung cancer screening could also provide opportunistic screening for osteoporosis, extending the clinical application of DECT without additional radiation to patients., (© 2022. The Author(s).)

Background: Ferroptosis is a non-apoptotic form of programmed cell death and has been found in ischemic stroke. Increasing evidence revealed that ELAVL1 is associated with ferroptosis, but it remains largely unclear whether ELAVL1 is involved in ischemic stroke. Here, we aimed to investigate the biological role and mechanism of ELAVL1 in cerebral ischemia/reperfusion (I/R) injury., Methods: ELAVL1 shRNA were intravenously injected into rat brain, and then ischemic/reperfusion (I/R) model was constructed in rats to detect infarct volume, neurobehavioral deficit, and several ferroptosis factors (GSH, GPX4, SLC7A11, MDA, ROS, iron ion) in vivo. Oxygen-glucose deprivation/reperfusion (OGD/R) treated pheochromocytoma-12 (PC12) cells were used as in vitro models of I/R. RIP, biotin pull-down and ChIP assays was used to explore the relationship among ELAVL1, DNMT3B, and PINK1., Results: ELAVL1 was highly expressed in rat brain tissue after I/R injury. Compared with those in the I/R group, the injection of RSL3 (30 mg/kg) or ferrostatin-1 (10 mg/kg) aggravated or alleviated infarct volume, neurobehavioral impairments, and increased or decreased ferroptosis factor levels, respectively. ELAVL1 silencing ameliorated brain damage in I/R-treated rats by inhibiting ferroptosis. Moreover, ELAVL1 silencing observably facilitated cell viability, GSH content, GPX4 and SLC7A11 expression, and reduced iron ion concentration, ROS and MDA levels in OGD/R-treated PC12 cells. ELAVL1 bound with DNMT3B mRNA 3'UTR and promoted DNMT3B expression. ELAVL1 inhibited PINK1 expression through stabilizing DNMT3B mRNA and blocking DNMT3B-mediated DNA methylation of PINK1 promoter. PINK1 knockdown reversed the effects of ELAVL1 inhibition on cell viability, GSH, GPX4, SLC7A11, iron ion concentration, ROS and MDA levels in OGD/R-treated PC12 cells., Conclusion: ELAVL1 plays a critical role in protecting against ferroptosis-induced cerebral I/R and subsequent brain damage via DNMT3B/PINK1 axis, thus providing a new potential target for ischemic stroke treatment., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Selenium (Se) as well as selenoproteins are vital for osteochondral system development. Se deficiency (SeD) has a definite impact on the expression and activity of histone deacetylases (HDACs). Abnormal expression of some HDACs affects cartilage development. This current study aims to explore the relationship between differentially expressed HDACs and cartilage development, especially extracellular matrix (ECM) homeostasis maintenance, under SeD conditions., Materials and Methods: Dark Agouti rats and C28/I2 cell line under SeD states were used to detect the differently expressed HDAC by RT-qPCR, western blotting and IHC staining. Meanwhile, the biological roles of the above HDAC in cartilage development and homeostasis maintenance were confirmed by siRNA transfection, western blotting, RNA sequence and inhibitor treatment experiments., Results: HDAC2 exhibited lower expression at protein level in both animals and chondrocytes during SeD condition. The results of cell-level experiments indicated that forkhead box O3A (FOXO3A), which was required to maintain metabolic homeostasis of cartilage matrix, was reduced by HDAC2 knockdown. Meanwhile, induced HDAC2 was positively associated with FOXO3A in rat SeD model. Meanwhile, knockdown of HDAC2 and FOXO3A led to an increase of intracellular ROS level, which activated NF-κB pathway. Se supplementary significantly inhibited the activation of NF-κB pathway with IL-1β treatment., Conclusion: Our results suggested that low expression of HDAC2 under SeD condition increased ROS content by decreasing FOXO3A in chondrocytes, which led to the activation of NF-κB pathway and ECM homeostasis imbalance., (© 2022. The Japanese Society Bone and Mineral Research.)

To alleviate the sparsity issue, many recommender systems have been proposed to consider the review text as the auxiliary information to improve the recommendation quality. Despite success, they only use the ratings as the ground truth for error backpropagation. However, the rating information can only indicate the users' overall preference for the items, while the review text contains rich information about the users' preferences and the attributes of the items. In real life, reviews with the same rating may have completely opposite semantic information. If only the ratings are used for error backpropagation, the latent factors of these reviews will tend to be consistent, resulting in the loss of a large amount of review information. In this article, we propose a novel deep model termed deep rating and review neural network (DRRNN) for recommendation. Specifically, compared with the existing models that adopt the review text as the auxiliary information, DRRNN additionally considers both the target rating and target review of the given user-item pair as ground truth for error backpropagation in the training stage. Therefore, we can keep more semantic information of the reviews while making rating predictions. Extensive experiments on four publicly available datasets demonstrate the effectiveness of the proposed DRRNN model in terms of rating prediction.

Spodoptera frugiperda (J. E. Smith), is commonly known as fall armyworm, native to tropical and subtropical regions of America, is an important migratory agricultural pest. It is important to understand the resistance and internal mechanism of action of S. frugiperda against lufenuron in China. Lufenuron is one of the main insecticides recommended for field use in China and has a broad prospect in the future. We conducted a bioassay using the diet-overlay method and found that the current S. frugiperda in China are still at a low level of resistance to lufenuron. Secondly, we examined whether the mutation I1040M (I1042M in Plutella xylostella), associated with lufenuron resistance, was produced in the field. And then we tested the expression of chitin synthase SfCHSA and SfCHSB in different tissues, and the changes of these two genes after lufenuron induction. The results showed that there is still no mutation generation in China and there is a significant change in the expression of SfCHSA under the effect of lufenuron. In conclusion, our study suggests that field S. frugiperda populations in 2019 and 2020 were less resistant to lufenuron. In fall armyworm, chitin synthases included SfCHSA and SfCHSB genes, and after induction treatment with lufenuron, the expression of the SfCHSA gene was significantly increased. In SfCHSA, no mutation has been detected in the site associated with lufenuron resistance. Secondly, in S. frugiperda larvae, the SfCHSA gene was the highest in the head of the larvae, followed by the integument; while the SfCHSB gene was mainly concentrated in the midgut. Therefore, we believe that the SfCHSA gene plays a greater role in the resistance of S. frugiperda to lufenuron than the SfCHSB gene. It is worth noting that understanding the level of resistance to lufenuron in China, the main mechanism of action of lufenuron on larvae, and the mechanism of resistance to lufenuron in S. frugiperda will help in crop protection as well as in extending the life span of this insecticide.

Recent studies have indicated that the plant volatile methyl benzoate (MB) exhibits significant insecticidal bioactivity against several common insects. However, the potential environmental hazards of MB and its safety to non-target organisms is poorly understood. In the present study, these characteristics were investigated through laboratory experiments and field investigations. The results revealed that MB was highly toxic to the agricultural pest, fall armyworm Spodoptera frugiperda. Compared with the commercial pesticide lambda-cyhalothrin, the toxicities of MB against S. frugiperda larvae and adults were comparable and 3.41 times higher, respectively. Behavioral bioassays showed that the percentage repellency of MB to S. frugiperda larvae was 56.72 %, and MB induced 69.40 % oviposition deterrence rate in S. frugiperda female adults. Furthermore, in terms of median lethal concentration (LC 50 ) and median lethal doses (LD 50 ), MB exhibited non-toxic effects on non-target animals with 3-d LC 50 of > 1 % to natural predators (Coccinella septempunctata and Harmonia axyridis), 3-d LD 50 of 467.86 µg/bee to the bumblebee Bombus terrestris, 14-d LC 50 of 971.09 mg/kg to the earthworm Eisenia fetida, and 4-d LC 50 of 47.30 mg/L to the zebrafish Brachydanio rerio. The accumulation of MB in the soil and earthworms was found to be extremely limited. Our comparative study clearly demonstrated that MB is effective as a selective botanical pesticide against S. frugiperda and it is safe to use in the tested environment, with no toxic effects on non-target animals and natural predators., 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 © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The Chinese wheat aphid Sitobion miscanthi (CWA) is an important harmful pest in wheat fields. Imidacloprid plays a critical role in controlling pests with sucking mouthparts. However, imidacloprid-resistant pests have been observed after insecticide overuse. Point mutations and low expression levels of the nicotinic acetylcholine receptor β1 (nAchRβ1) subunit are the main imidacloprid-resistant mechanisms. However, the regulatory mechanism underlying nAChRβ1 subunit expression is poorly understood. In this study, a target of miR-263b was isolated from the 5'UTR of the nAchRβ1 subunit in the CWA. Low expression levels were found in the imidacloprid-resistant strain CWA. Luciferase reporter assays showed that miR-263b could combine with the 5'UTR of the nAChRβ1 subunit and suppress its expression by binding to a site in the CWA. Aphids treated with the miR-263b agomir exhibited a significantly reduced abundance of the nAchRβ1 subunit and increased imidacloprid resistance. In contrast, aphids treated with the miR-263b antagomir exhibited significantly increased nAchRβ1 subunit abundance and decreased imidacloprid resistance. These results provide a basis for an improved understanding of the posttranscriptional regulatory mechanism of the nAChRβ1 subunit and further elucidate the function of miRNAs in regulating susceptibility to imidacloprid in the CWA. These results provide a better understanding of the mechanisms of posttranscriptional regulation of nAChRβ1 and will be helpful for further studies on the role of miRNAs in the regulation of nAChRβ1 subunit resistance in homopteran pests., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)