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De-Bin Liu,1,&ast; You-Fu He,2– 4,&ast; Gui-Jian Chen,1 Hua Huang,1 Xu-Ling Xie,1 Wan-Jun Lin,1 Zhi-Jian Peng1 1Department of Cardiology, The Second People’s Hospital of Shantou, Shantou, Guangdong Province, People’s Republic of China; 2Department of Cardiology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, People’s Republic of China; 3Guizhou Provincial Cardiovascular Disease Clinical Medicine Research Center, Guiyang, Guizhou Province, People’s Republic of China; 4Medical College, Guizhou University, Guiyang, Guizhou Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Jian Peng, Department of Cardiology, The Second People’s Hospital of Shantou, Shantou, 515000, Guangdong Province, People’s Republic of China, Tel +86 18316056382, Fax +86-754 88983534, Email 983247770@qq.comBackground: Aortic dissection (AD) is a rare and lethal disorder with its genetic basis remains largely unknown. Many studies have confirmed that circRNAs play important roles in various physiological and pathological processes. However, the roles of circRNAs in AD are still unclear and need further investigation. The present study aimed to elucidate the underlying molecular mechanisms of circRNAs regulation in AD based on the circRNA-associated competing endogenous RNA (ceRNA) network.Methods: Expression profiles of circRNAs (GSE97745), miRNAs (GSE92427), and mRNAs (GSE52093) were downloaded from Gene Expression Omnibus (GEO) databases, and the differentially expressed RNAs (DERNAs) were subsequently identified by bioinformatics analysis. CircRNA–miRNA–mRNA ceRNA network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to predict the potential functions of circRNA-associated ceRNA network. RNA was isolated from human arterial blood samples after which qRT-PCR was performed to confirm the DERNAs.Results: We identified 14 (5 up-regulated and 9 down-regulated) differentially expressed circRNAs (DEcircRNAs), 17 (8 up-regulated and 9 down-regulated) differentially expressed miRNAs (DEmiRNAs) and 527 (297 up-regulated and 230 down-regulated) differentially expressed mRNAs (DEmRNAs) (adjusted P-value < 0.05 and | log2FC | > 1.0). KEGG pathway analysis indicated that DEmRNAs were related to focal adhesion and extracellular matrix receptor interaction signaling pathways. Simultaneously, the present study constructed a ceRNA network based on 1 circRNAs (hsa_circRNA_082317), 1 miRNAs (hsa-miR-149-3p) and 10 mRNAs (MLEC, ENTPD7, SLC16A3, SLC7A8, TBC1D16, PAQR4, MAPK13, PIK3R2, ITGA5, SERPINA1). qRT-PCR demonstrated that hsa_circRNA_082317 and ITGA5 were significantly up-regulated, and hsa-miR-149-3p was dramatically down-regulated in AD (n = 3).Conclusion: This is the first study to demonstrate the circRNA-associated ceRNA network is altered in AD, implying that circRNAs may play important roles in regulating the onset and progression and thus may serve as potential biomarkers for the diagnosis and treatment of AD.Keywords: circRNA, miRNA, mRNA, ceRNA, aortic dissection, bioinformatics analyses

Xin-Li Xie,* Yan Liu,* Bing Cheng, Xiao-Guang Du, Qiao Ruan, Xing-Min Han Department of Nuclear Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People’s Republic of China*These authors contributed equally to this work.Correspondence: Xing-Min HanDepartment of Nuclear Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Of Jianshe East Road, Erqi District, Zhengzhou, 450052, Henan, People’s Republic of ChinaTel +86 371 66915504Fax +86 371 66913059Email hanxingmin_cn@126.comObjective: The aim of the study was to explore the nature of a V-shaped sign in the backbone of the fifth lumbar vertebra revealed by whole-body bone scintigraphy (WBBS).Methods: A local single-photon emission computed tomography (SPECT) scan plus a computed tomography (CT) scan were performed on 41 patients in our department who had a V-shaped sign in the backbone of the fifth lumbar vertebra detected by WBBS. Image fusion was conducted to understand the manifestations of the changes in the V-shaped sign in the CT images in WBBS and to determine the nature of the lesion.Results: All 41 patients presented with degenerative changes observed in the bilateral posterior zygapophysial joint of the fifth lumbar vertebra in the CT imaging bone window, bone hyperplasia of the articular process, joint surface hardening, and a joint gap. The vacuum sign could also be seen in some of these patients.Conclusion: The typical V-shaped sign in the posterior zygapophysial joint of the fifth lumbar vertebra revealed by WBBS suggests degenerative changes in the zygapophysial joint of the fifth lumbar vertebra.Keywords: lumbar, zygapophysial joints, degeneration, bone radionuclide imaging, MDP, single-photon emission computed tomography (SPECT)-CT, diagnosis

The effects of l-arginine (Arg) supplementation on intestinal mucosal immune barrier function in weaned pigs after Escherichia coli LPS challenge were evaluated. Twenty-four weaned pigs were allotted to four treatments including: (i) non-challenged control; (ii) LPS-challenged control; (iii) LPS + 0.5% Arg; and (iv) LPS + 1.0% Arg. On d 16, pigs in the LPS, LPS + 0.5% Arg and LPS + 1.0% Arg groups were challenged by injection with 100 µg/kg of body mass LPS, whereas the control group were given sterile saline. At 48 h post-challenge, all pigs were sacrificed for evaluation of small intestinal morphology and mucosal immune barrier function. In the jejunum and ileum, LPS caused villous atrophy and intestinal morphology disruption, whereas 0.5% or 1.0% Arg supplementation mitigated villus atrophy and intestinal morphology impairment caused by LPS challenge. Arg (0.5%) supplementation increased the numbers of IgA-secreting cells, CD8+ and CD4+ T cells in the ileum (P < 0.05). Arg supplementation prevented the elevation of mast cell numbers induced by LPS challenge (P < 0.05). Dietary supplementation of Arg caused a decreased lymphocyte apoptosis of Peyer’s patches in pigs challenged by LPS (P < 0.05). These results indicated that Arg supplementation protects and enhances intestinal mucosal immune barrier function and maintains intestinal integrity in weaned pigs after E. coli LPS challenge. [ABSTRACT FROM AUTHOR]

Ethnopharmacological Relevance: Blumea balsamifera (L.) DC. (BB), the source of Blumea balsamifera oil (BBO), is an aromatic medicinal plant, renowned for its pharmacological properties and its traditional use in Southeast Asian countries such as China, Thailand, Vietnam, Malaysia, and the Philippines for centuries. Traditionally, BB has been used as a raw herbal medicine for treating various skin conditions like eczema, dermatitis, athlete's foot, and wound healing for skin injuries., Aim of the Study: This research aimed to explore the inhibitory effects of BBO on skin aging using two models: in vitro analysis with human dermal fibroblasts (HDF) under UVB-induced stress, and in vivo studies on UVA-induced dorsal skin aging in mice. The study sought to uncover the mechanisms behind BBO's anti-aging effects, specifically, its impact on cellular and tissue responses to UV-induced skin aging., Materials and Methods: We applied doses of 10-20 μL/mL of BBO to HDF cells that had been exposed to UVB radiation to simulate skin aging. We measured cell viability, and levels of reactive oxygen species (ROS), SA-β-gal, pro-inflammatory cytokines, and matrix metalloproteinases (MMPs). In addition, we investigated the involvement of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathways in mediating the anti-aging effects of BBO. Histopathological and biochemical analyses were conducted in a mouse model to examine the effects of BBO on UV-induced photoaging., Results: UV exposure accelerated aging, and caused cellular damage and inflammatory responses through ROS-mediated pathways. In HDF cells, BBO treatment countered the UVB-induced senescence, and the recovery of cell viability was correlated to notable reductions in SA-β-gal, ROS, pro-inflammatory cytokines, and MMPs. Mechanistically, the anti-aging effect of BBO was associated with the downregulation of the JNK/NF-κB signaling pathways. In the in vivo mouse model, BBO exhibited protective capabilities against UV-induced photoaging, which were manifested by the enhanced antioxidant enzyme activities and tissue remodeling., Conclusions: BBO effectively protects fibroblasts from UV-induced photoaging through the JNK/NF-κB pathway. Recovery from photoaging involves an increase in dermal fibroblasts, alleviation of inflammation, accelerated synthesis of antioxidant enzymes, and slowed degradation of ECM proteins. Overall, BBO enhances the skin's defensive capabilities against oxidative stress, underscoring its potential as a therapeutic agent for oxidative stress-related skin aging., 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.)

We report a sortase-based site-specific antibody-drug conjugation strategy, which involves an affinity peptide-directed acyl transfer reaction and sortase-mediated peptide ligation. Through the affinity peptide-mediated acyl transfer reaction, an LPXTG-containing peptide is conjugated to a specific Lys side chain of an antibody. Under the assistance of sortase, a protein drug bearing a GG motif reacts specifically with the LPXTG moiety to produce an antibody-drug conjugate. Our strategy for antibody conjugation can be applied not only to chemically synthesized drugs, but also to biologically expressed proteins, and will provide a new sortase-based strategy for the preparation of antibody-drug conjugates.

PCB126, a type of polychlorinated biphenyl (PCB), is a persistent pollutant found in both biotic and abiotic environments and poses significant public health risks due to its potential to cause cardiac damage with prolonged exposure. Hypoxia-inducible factor-2α (HIF-2α) is part of the hypoxia-inducible factor (HIF) transcription complex family. Previous studies have shown that knocking out or inhibiting HIF-2α expression can ameliorate pulmonary hypertension and right ventricular dysfunction. This study aimed to investigate whether cardiac-specific knockout of HIF-2α can alleviate the cardiotoxicity caused by PCB126. In this study, cardiac-specific knockout mice and wild-type mice were orally administered PCB126 or corn oil (50 μg/kg/week) for eight weeks. Our findings indicated that PCB126 induces cardiotoxicity and myocardial injury, as evidenced by elevated cardiac enzyme levels and increased cardiac collagen fibers. RNA sequencing revealed that PCB126-induced cardiotoxicity involves the PI3K/Akt and p53 signaling pathways, which was confirmed by western blot analysis. Notably, cardiac-specific knockout of HIF-2α mitigated the damage caused by PCB126, reducing the expression of cardiac enzymes, inflammatory cytokines, and myocardial collagen fibers. Under normal conditions, conditional knockout (CKO) of the HIF-2α gene in cardiomyocytes did not affect the morphology or function of the mouse heart. However, HIF-2α CKO in the heart reduced the cardiotoxic effects of PCB126 by decreasing apoptosis through the PI3K/Akt and p53 signaling pathways. In conclusion, inhibiting HIF-2α expression in cardiomyocytes attenuated PCB126-induced cardiotoxicity by modulating apoptosis through these signaling pathways., 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 Authors. Published by Elsevier Inc. All rights reserved.)

2-Ethylhexyl diphenyl phosphate (EHDPHP), a widely used organophosphorus flame retardant (OPFR), is ubiquitous in daily life because of its extensive application in plastic production. EHDPHPs, which are only superficially applied and not chemically bonded to products, are released into the environment, posing potential health risks. With increasing environmental concentrations, EHDPHP is a growing threat, particularly to individuals with preexisting health conditions who are more susceptible to environmental pollutants. This study examined the effects of EHDPHP exposure in a colitis model, reflecting a rising chronic health issue, by assessing changes in neuroinflammation and neurobehavioral abnormalities. Healthy and dextran sulfate sodium (DSS)-induced colitis C57BL/6 J mice were treated with either 0.2 % Tween or EHDPHP solution (10 mg/kg body weight/day) for 28 days. The study revealed significant increases in the serum and expression levels of TNFα and IL-1β, accompanied by depressive and anxiety-like behaviors. Coexposure to EHDPHP and DSS exacerbated these neurobehavioral impairments. RNA sequencing confirmed that EHDPHP triggered inflammation via the PI3K-Akt-NF-κB and Wnt/GSK3β signaling pathways, as confirmed by Western blot analysis. These findings suggest that EHDPHP aggravates colitis-induced neuroinflammation and neurobehavioral abnormalities, highlighting the harmful impact of EHDPHP, particularly in individuals with preexisting inflammatory conditions., 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 Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study is to evaluate the effectiveness and frequency factors of endoscopic bougie dilatation in treating postoperative anastomotic stenosis of congenital esophageal atresia (CEA)., Methods: The clinical data of patients of anastomotic stenosis with endoscopic bougie were retrospectively analyzed. According to the number of dilation times (ND), patients were divided into two groups (Group 0: ND < 3; Grooup1: ND ≥ 3), and the differences in multiple clinical data were compared. Lasso regression and Ridge regression were used to screen important variables. Classification models were built utilizing various machine learning algorithms and their performance were evaluated. Finally, Kaplan-Meier model was used to estimate the probable-time distribution of children achieving normal feeding., Results: Seventy-five patients underwent a total of 210 times of dilation, with a median of 3 times of dilation. The overall effectiveness was 98.67% (74/75), with perforation in 2 case (0.95%), and obvious bleeding in 3 cases (1.43%). Initial diameter of bougie, final diameter of bougie, treatment pattern (Regular: dilation each 4weeks; Wait-and-see: dilation until symptoms present), age at final dilation, esophageal obstruction by food were the factors related to ND. Random Forest (RF) and Logistic regression (LR) model were excellent models for predicting ND. The median age for achieving normal eating in Group0 was 120 days (95% CI: 90-160), while it was 270 days (95% CI: 240-460) in Group1 with a statistically significant difference ( P  < 0.0001)., Conclusion: Endoscopic bougie dilatation is a safe and effective treatment for anastomotic stenosis. Selecting the appropriate bougie, using symptoms as the criterion for dilation, and minimizing the dilations under 3 times constitute a rational strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 He, Xiong, Deng, Yang, Yan, Zhang, Shang, Xie, Liu and Li.)

Current studies for brain-muscle modulation often analyze selected properties in electrophysiological signals, leading to a partial understanding. This article proposes a cross-modal generative model that converts brain activities measured by electroencephalography (EEG) to corresponding muscular responses recorded by electromyography (EMG). Examining the generation process in the model highlights how the motor cue, representing implicit motor information hidden within brain activities, modulates the interaction between brain and muscle systems. The proposed model employs a two-stage generation process to bridge the semantic gap in cross-modal signals. Initially, the shared movement-related information between EEG and EMG signals is extracted using a contrastive learning framework. These shared representations act as conditional vectors in the subsequent EMG generation stage based on generative adversarial networks (GANs). Experiments on a self-collected multimodal electrophysiological signal data set show the algorithm's superiority over existing time series generative methods in cross-modal EMG generation. Further insights derived from the model's inference process underscore the brain's strategy for muscle control during movements. This research provides a data-driven approach for the neuroscience community, offering a comprehensive perspective of brain-muscular modulation.

GenX, a substitute for perfluorooctanoic acid, has demonstrated potential enterotoxicity. The enterotoxic effects of GenX and effective interventions need further investigation. In the present study, the mice were administered GenX (2 mg/kg/day) with or without inulin supplementation (5 g/kg/day) for 12 weeks. Histopathological assessments revealed that GenX induced colonic gland atrophy, inflammatory cell infiltration, a reduction in goblet cell numbers, and decreased mucus secretion. Furthermore, a significant decrease in the protein levels of ZO-1, occludin, and claudin-5 indicated compromised barrier integrity. Transcriptomic analysis identified 2645 DEGs, which were mapped to 39 significant pathways. The TGF-β, BMP6, and β-catenin proteins were upregulated in the intestinal mucosa following GenX exposure, indicating activation of the TGF-β pathway. Conversely, the protein expression of PAK3, CyclinD2, contactin1, and Jam2 decreased, indicating disruptions in cell cycle progression and cell adhesion. Inulin cotreatment ameliorated these GenX-induced alterations, partially through modulating the MAPK pathway, as evidenced by the upregulation of the cell cycle and cell adhesion proteins. Collectively, these findings suggested that GenX exposure triggered intestinal injury in mice by activating the TGF-β pathway and disrupting proteins crucial for the cell cycle and cell adhesion, whereas inulin supplementation mitigated this injury by modulating the MAPK pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Nanoplastics (NPs) pollution has become a global environmental problem, raising numerous health concerns. However, the cardiotoxicity of NPs exposure and the underlying mechanisms have been understudied to date. To address this issue, we comprehensively evaluated the cardiotoxicity of polystyrene nanoplastics (PS-NPs) in both healthy and pathological states. Briefly, mice were orally exposed to four different concentrations (0 mg/day, 0.1 mg/day, 0.5 mg/day, and 2.5 mg/day) of 100-nm PS-NPs for 6 weeks to assess their cardiotoxicity in a healthy state. Considering that individuals with underlying health conditions are more vulnerable to the adverse effects of pollution, we further investigated the cardiotoxic effects of PS-NPs on pathological states induced by isoprenaline. Results showed that PS-NPs induced cardiomyocyte apoptosis, cardiac fibrosis, and myocardial dysfunction in healthy mice and exacerbated cardiac remodeling in pathological states. RNA sequencing revealed that PS-NPs significantly upregulated homeodomain interacting protein kinase 2 (HIPK2) in the heart and activated the P53 and TGF-beta signaling pathways. Pharmacological inhibition of HIPK2 reduced P53 phosphorylation and inhibited the activation of the TGF-β1/Smad3 pathway, which in turn decreased PS-NPs-induced cardiotoxicity. This study elucidated the potential mechanisms underlying PS-NPs-induced cardiotoxicity and underscored the importance of evaluating nanoplastics safety, particularly for individuals with pre-existing heart conditions., 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.)

Objectives: To explore the diagnostic efficacy of serum 14-3-3β protein combined with fractional exhaled nitric oxide (FeNO) and conventional ventilatory lung function parameters in diagnosing bronchial asthma (referred to as "asthma") in children., Methods: A prospective study included 136 children initially diagnosed with asthma during an acute episode as the asthma group, and 85 healthy children undergoing routine health checks as the control group. The study compared the differences in serum 14-3-3β protein concentrations between the two groups, analyzed the correlation of serum 14-3-3β protein with clinical indices, and evaluated the diagnostic efficacy of combining 14-3-3β protein, FeNO, and conventional ventilatory lung function parameters for asthma in children., Results: The concentration of serum 14-3-3β protein was higher in the asthma group than in the control group ( P <0.001). Serum 14-3-3β protein showed a positive correlation with the percentage of neutrophils and total serum immunoglobulin E, and a negative correlation with conventional ventilatory lung function parameters ( P <0.05). Cross-validation of combined indices showed that the combination of 14-3-3β protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume had an area under the curve of 0.948 for predicting asthma, with a sensitivity and specificity of 88.9% and 93.7%, respectively, demonstrating good diagnostic efficacy ( P <0.001). The model had the best extrapolation., Conclusions: The combination of serum 14-3-3β protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume can significantly improve the diagnostic efficacy for asthma in children. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 723-729 .

Background: The relationship between the intake of dietary fatty acids (FA) and bone mineral density (BMD) has been the subject of prior investigations. However, the outcomes of these studies remain contentious. The objective of this research is to examine the link between dietary FA consumption among adolescents and BMD., Methods: This study utilized high-quality data from the National Health and Nutrition Examination Survey database, spanning 2011 to 2018, to explore the association between dietary fatty acids and bone health indicators in adolescents, including BMD and bone mineral content (BMC). Analyses were performed using weighted multivariate linear regression models, incorporating detailed subgroup analysis., Results: The study included 3440 participants. Analysis demonstrated that intake of saturated fatty acids (SFA) was positively correlated with total BMD, left arm BMD, total BMC, and left arm BMC. Monounsaturated fatty acid (MUFA) intake was positively correlated with BMC across most body parts, though it showed no correlation with BMD. Intake of polyunsaturated fatty acids (PUFA) was significantly inversely correlated with both BMD and BMC in most body parts. Additionally, subgroup analysis indicated that variables such as sex, age, standing height, and race significantly influenced the correlation between FA intake and BMD., Conclusions: Our study indicates that dietary intake of SFA may benefit to BMD in adolescents, in contrast to PUFA and MUFA. Therefore, we recommend that adolescents maintain a balanced intake of SFA to promote optimal bone mass development while preserving metabolic health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Fang and Xie.)

Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility., 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 Authors. Published by Elsevier Inc. All rights reserved.)

Background: Sheep and goats have undergone domestication and improvement to produce similar phenotypes, which have been greatly impacted by structural variants (SVs). Here, we report a high-quality chromosome-level reference genome of Asiatic mouflon, and implement a comprehensive analysis of SVs in 897 genomes of worldwide wild and domestic populations of sheep and goats to reveal genetic signatures underlying convergent evolution., Results: We characterize the SV landscapes in terms of genetic diversity, chromosomal distribution and their links with genes, QTLs and transposable elements, and examine their impacts on regulatory elements. We identify several novel SVs and annotate corresponding genes (e.g., BMPR1B, BMPR2, RALYL, COL21A1, and LRP1B) associated with important production traits such as fertility, meat and milk production, and wool/hair fineness. We detect signatures of selection involving the parallel evolution of orthologous SV-associated genes during domestication, local environmental adaptation, and improvement. In particular, we find that fecundity traits experienced convergent selection targeting the gene BMPR1B, with the DEL00067921 deletion explaining ~10.4% of the phenotypic variation observed in goats., Conclusions: Our results provide new insights into the convergent evolution of SVs and serve as a rich resource for the future improvement of sheep, goats, and related livestock., (© 2024. The Author(s).)

Acupuncture is one of the most effective complementary therapies for allergic rhinitis (AR) and has been recommended by several clinical practice guidelines (CPGs) for AR. However, these CPGs mentioned acupuncture without making recommendations for clinical implementation and therapeutic protocols, therefore limiting the applicability of acupuncture therapies for AR. Hence, for the benefit of acupuncture practitioners around the world, the World Federation of Acupuncture-moxibustion Societies have initiated a project to develop the CPG for the use of acupuncture and moxibustion to treat AR. This CPG was developed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development. During the development of the CPG, the guideline development group (GDG) played an important role. The clinical questions, recommendations and therapeutic protocols were all formulated by the GDG using the modified Delphi method. The CPG contains recommendations for 15 clinical questions about the use of acupuncture and moxibustion interventions. These include one strong recommendation for the intervention based on high-quality evidence, three conditional recommendations for either the intervention or standard care, and 11 conditional recommendations for the intervention based on very low quality of evidence. The CPG also provides one filiform needle acupuncture protocol and five moxibustion protocols extracted based on the protocols presented in randomized controlled trials reviewed by the GDG. Please cite this article as: Du SH, Chen S, Wang SZ, Wang GQ, Du S, Guo W, Xie XL, Peng BH, Yang C, Zhao JP. Clinical practice guideline for acupuncture and moxibustion: Allergic rhinitis. J Integr Med. 2024; 22(3): 245-257., (Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

Urinary incontinence (UI) is a common problem worldwide. It has a major impact on physical and social activities and interpersonal relationships. UI is common in women, but is under-reported and under-treated. It affects the quality of life of female patients severely. Acupuncture and moxibustion have been proposed as potentially effective interventions for female UI. Hence, for the benefit of acupuncture practitioners around the world, the World Federation of Acupuncture-moxibustion Societies initiated a project to develop a clinical practice guideline (CPG) for the use of acupuncture and moxibustion to treat female UI. This CPG was developed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development. During the development of the CPG, the guideline development group (GDG) played an important role. The clinical questions, recommendations and therapeutic protocols were all formulated by GDG using the modified Delphi method. This CPG contains ten recommendations about the use of acupuncture and moxibustion interventions for ten clinical questions, which include nine conditional recommendations for the intervention and one conditional recommendation for either the intervention or the comparison. This CPG also provides one protocol for conventional filiform needle therapy, two therapy protocols for deep needling stimulation on lumbosacral acupoints, and four moxibustion therapy protocols, based on the protocols presented in randomized controlled trials reviewed by the GDG. Please cite this article as: Yang C, Wang SZ, Chen S, Du S, Wang GQ, Guo W, Xie XL, Peng BH, Du SH, Zhao JP. Clinical practice guideline for acupuncture and moxibustion: Female urinary incontinence. J Integr Med. 2024; 22(3): 258-269., (Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

Organophosphorus flame retardants (OPFRs), such as 2-ethylhexyl diphenyl phosphate (EHDPHP), are ubiquitously used, leading to pervasive environmental contamination and human health risks. While associations between EHDPHP and health issues such as disruption of hormones, neurotoxic effects, and toxicity to reproduction have been recognized, exposure to EHDPHP during perinatal life and its implications for the intestinal health of dams and their pups have largely been unexplored. This study investigated the intestinal toxicity of EHDPHP and the potential for which inulin was effective. Dams were administered either an EHDPHP solution or a corn oil control from gestation day 7 (GD7) to postnatal day 21 (PND21), with inulin provided in their drinking water. Our results indicate that inulin supplementation mitigates damage to the intestinal epithelium caused by EHDPHP, restores mucus-secreting cells, suppresses intestinal hyperpermeability, and abates intestinal inflammation by curtailing lipopolysaccharide leakage through reshaping of the gut microbiota. A reduction in LPS levels concurrently inhibited the inflammation-associated TLR4/NF-κB pathway. In conclusion, inulin administration may ameliorate intestinal toxicity caused by EHDPHP in dams and pups by reshaping the gut microbiota and suppressing the LPS/TLR4/NF-κB pathway. These findings underscore the efficacy of inulin as a therapeutic agent for managing health risks linked to EHDPHP exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Pancreaticoduodenectomy (PD) is a complex procedure and easily accompanied by healthcare-associated infections (HAIs). This study aimed to assess the impact of PBD on postoperative infections and clinical outcomes in PD patients., Methods: The retrospective cohort study were conducted in a tertiary hospital from January 2013 to December 2022. Clinical and epidemiological data were collected from HAIs surveillance system and analyzed., Results: Among 2842 patients who underwent PD, 247 (8.7%) were diagnosed with HAIs, with surgical site infection being the most frequent type (n = 177, 71.7%). A total of 369 pathogenic strains were detected, with Klebsiella pneumoniae having the highest proportion, followed by Enterococcu and Escherichia coli. Although no significant association were observed generally between PBD and postoperative HAIs, subgroup analysis revealed that PBD was associated with postoperative HAIs in patients undergoing robotic PD (aRR = 2.174; 95% CI:1.011-4.674; P = 0.047). Prolonging the interval between PBD and PD could reduce postoperative HAIs in patients with cholangiocarcinoma (≥4 week: aRR = 0.292, 95% CI 0.100-0.853; P = 0.024) and robotic PD (≤2 week: aRR = 3.058, 95% CI 1.178-7.940; P = 0.022). PBD was also found to increase transfer of patients to ICU (aRR = 1.351; 95% CI 1.119-1.632; P = 0.002), extended length of stay (P < 0.001) and postoperative length of stay (P = 0.004)., Conclusion: PBD does not exhibit a significant association with postoperative HAIs or other outcomes. However, the implementation of robotic PD, along with a suitable extension of the interval between PBD and PD, appear to confer advantages concerning patients' physiological recuperation. These observations suggest potential strategies that may contribute to enhanced patient outcomes., (© 2024. The Author(s).)

The prediction of potential protein-protein interactions (PPIs) is a critical step in decoding diseases and understanding cellular mechanisms. Traditional biological experiments have identified plenty of potential PPIs in recent years, but this problem is still far from being solved. Hence, there is urgent to develop computational models with good performance and high efficiency to predict potential PPIs. In this study, we propose a multi-source molecular network representation learning model (called MultiPPIs) to predict potential protein-protein interactions. Specifically, we first extract the protein sequence features according to the physicochemical properties of amino acids by utilizing the auto covariance method. Second, a multi-source association network is constructed by integrating the known associations among miRNAs, proteins, lncRNAs, drugs, and diseases. The graph representation learning method, DeepWalk, is adopted to extract the multisource association information of proteins with other biomolecules. In this way, the known protein-protein interaction pairs can be represented as a concatenation of the protein sequence and the multi-source association features of proteins. Finally, the Random Forest classifier and corresponding optimal parameters are used for training and prediction. In the results, MultiPPIs obtains an average 86.03% prediction accuracy with 82.69% sensitivity at the AUC of 93.03% under five-fold cross-validation. The experimental results indicate that MultiPPIs has a good prediction performance and provides valuable insights into the field of potential protein-protein interactions prediction. MultiPPIs is free available at https://github.com/jiboyalab/multiPPIs ., (© 2024. The Author(s).)

Chronic total occlusion (CTO) is one of the most severe and sophisticated vascular stenosis because of complete blockage, greater operation difficulty, and lower procedural success rate. This study proposes a hydraulic-driven soft robot imitating the earthworm's locomotion to assist doctors or operators in actively opening thrombi in coronary or peripheral artery vessels. Firstly, a three-actuator bionic soft robot is developed based on earthworms' physiological structure. The soft robot's locomotion gait inspired by the earthworm's mechanism is designed. Secondly, the influence of structure parameters on actuator deformation, stress, and strain is explored, which can help us determine the soft actuators' optimal structure parameters. Thirdly, the relationship between hydraulic pressure and actuator deformation is investigated by performing finite element analysis using the bidirectional fluid-structure interaction (FSI) method. The kinematic models of the soft actuators are established to provide a valuable reference for the soft actuators' motion control.

Background: Ginkgo biloba L. preparations (GBLPs) are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke (IS). Recently, several systematic reviews (SRs) and meta-analyses (MAs) of GBLPs for IS have been published., Objective: This overview aims to assess the quality of related SRs and MAs., Search Strategy: PubMed, Embase, Cochrane Library, Web of Science, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Journals databases were searched from their inception to December 31, 2022., Inclusion Criteria: SRs and MAs of randomized controlled trials (RCTs) that explored the efficacy of GBLPs for patients with IS were included., Data Extraction and Analysis: Two independent reviewers extracted data and assessed the methodological quality, risk of bias (ROB), reporting quality, and credibility of evidence of the included SRs and MAs using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Additionally, descriptive analysis and data synthesis were conducted., Results: Twenty-nine SRs/MAs involving 119 outcomes were included in this review. The overall methodological quality of all SRs/MAs was critically low based on AMSTAR 2, and 28 had a high ROB based on the ROBIS. According to the PRISMA statement, the reporting items of the included SRs/MAs are relatively complete. The results based on GRADE showed that of the 119 outcomes, 8 were rated as moderate quality, 24 as low quality, and 87 as very low quality. Based on the data synthesis, GBLPs used in conjunction with conventional treatment were superior to conventional treatment alone for decreasing neurological function scores., Conclusion: GBLPs can be considered a beneficial supplemental therapy for IS. However, because of the low quality of the existing evidence, high-quality RCTs and SRs/MAs are warranted to further evaluate the benefits of GBLPs for treating IS. Please cite this article as: Meng TT, You YP, Li M, Guo JB, Song XB, Ding JY, Xie XL, Li AQ, Li SJ, Yin XJ, Wang P, Wang Z, Wang BL, He QY. Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses. J Integr Med. 2024;22(2): 163-179., 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. Published by Elsevier B.V.)

Heterostructure engineering and oxygen vacancy engineering are the most promising modification strategies to reinforce the Zn 2+ ion storage of vanadium oxides. Herein, a rare mixed-dimensional material ( VO x ), composed of V 2 O 5 (2D), V 3 O 7 (3D), and V 6 O 13 (3D) heterostructures, rich in oxygen vacancies, was synthesized via thermal decomposition of layered ammonium vanadate. The VO x cathode provides an exceptional discharge capacity (411 mA h g -1 at 0.1 A g -1 ) and superior cycling stability (the capacity retention remains close to 100% after 800 cycles at 2 A g -1 ) for aqueous zinc-ion batteries (AZIBs). Ex situ characterizations confirm that the byproduct Zn 3 V 2 O 7 (OH) 2 · n H 2 O is generated/decomposed during discharge/charge processes. Furthermore, VO x demonstrates reversible intercalation/deintercalation of H + /Zn 2+ ions, enabling efficient energy storage. Remarkably, a reversible crystal-to-amorphous transformation in the V 2 O 5 phase of VO x during charge-discharge was observed. This investigation reveals that mixed-dimensional heterostructured vanadium oxide, with abundant oxygen vacancies, serves as a highly promising electrode material for AZIBs, further advancing the comprehension of the storage mechanism within vanadium-based cathode materials.

Lung cancer is the leading cause of cancer-related deaths worldwide, of which non-small cell lung cancer (NSCLC) is the most common type, and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are widely used for the treatment of NSCLC. EGFR-TKIs are known to develop a drug-resistant response after a certain number of cycles of dosing, and how to alleviate or even reverse EGFR-TKI resistance is an urgent problem at present. This review focuses on the role of ncRNAs in the resistance of NSCLC to EGFR-TKIs and the potential mechanisms underlying the development of NSCLC resistance to EGFR-TKIs. NcRNAs are involved in NSCLC resistance to EGFR-TKIs by mediating cellular drug efflux, epithelial-mesenchymal transition, apoptosis, autophagy, and EGFR mutation. ncRNAs play a crucial role in NSCLC resistance to EGFR-TKIs. Hopefully, the results will provide some guidance and help for the treatment and prognosis of NSCLC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Perfluorooctanoic acid (PFOA) is a widely used industrial compound that has been found to induce intestinal toxicity. However, the underlying mechanisms have not been fully clarified and effective interventions are rarely developed. Inulin, a prebiotic, has been used as a supplement in human daily life as well as in gastrointestinal diseases and metabolic disorders. In this study, male mice were exposed to PFOA with or without inulin supplementation to investigate the enterotoxicity and potential intervention effects of inulin. Mice were administered PFOA at 1 mg/kg/day, PFOA with inulin at 5 g/kg/day, or Milli-Q water for 12 weeks. Histopathological analysis showed that PFOA caused colon shortening, goblet cell reduction, and inflammatory cell infiltration. The expression of the tight junction proteins ZO-1, occludin and claudin5 significantly decreased, indicating impaired barrier function. According to the RNA-sequencing analysis, PFOA exposure resulted in 917 differentially expressed genes, involving 39 significant pathways, such as TNF signaling and cell cycle pathways. In addition, the protein expression of TNF-α, IRG-47, cyclinB1, and cyclinB2 increased, while Gadd45γ, Lzip, and Jam2 decreased, suggesting the involvement of the TNF signaling pathway, cell cycle, and cell adhesion molecules in PFOA-associated intestinal injury. Inulin intervention alleviated PFOA-induced enterotoxicity by activating the PI3K/AKT/mTOR signaling pathway and increasing the protein expression of Wnt1, β-catenin, PI3K, Akt3, and p62, while suppressing MAP LC3β, TNF-α, and CyclinE expression. These findings suggested that PFOA-induced intestinal injury, including inflammation and tight junction disruption, was mitigated by inulin through modifying the PI3K/AKT/mTOR signaling pathways. Our study provides valuable insights into the enterotoxic effects of PFOA and highlights the potential therapeutic role of inulin., 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 Ltd. All rights reserved.)

Ammonium perfluoro (2-methyl-3-oxahexanoate) (GenX), a replacement for perfluorooctanoic acid (PFOA), has been detected in multiple environmental media and biological samples worldwide. Accumulated evidence implies that GenX exposure might exert adverse health effects, although the underlying mechanisms have not been fully revealed. In this study, pregnant BALB/c mice were exposed to GenX (2 mg/kg/day), PFOA (1 mg/kg/day), or Milli-Q water by gavage from the first day of gestation (GD0) until GD21. Necropsy and tissue collection were conducted in pups at 4 weeks of age. PFOA and GenX induced similar histopathological changes in both the liver and the intestinal mucosa, accompanied by higher serum levels of alanine and aspartate aminotransferase. Moreover, the capacity of hepatic glycogen storage and intestinal mucus secretion were significantly decreased, suggesting dysfunction of liver metabolism and the intestinal mucosal barrier. A total of 637 and 352 differentially expressed genes (DEGs) were identified in the liver tissues of GenX and PFOA group, respectively. Most of the enriched pathways from the DEGs by KEGG enrichment analysis were metabolism-associated. Moreover, overexpression of CYP4A14, Sult2a1, Cpt1b, Acaa1b, Igfbp1, Irs-2 and decreased expression of Gys2 were observed in livers of GenX exposed pups, supporting the hypothesis that there was metabolic disruption. Furthermore, DNA damage and cell cycle arrest proteins (Gadd45β, p21, Ppard) were significantly increased, while cell proliferation-related proteins (Cyclin E, Myc, EGFR) were decreased by gestational GenX exposure in the pups' liver. In addition, imbalance of gut microbiota and dysfunction of the intestinal mucosa barrier might contribute to hepatotoxicity at least in part. Taken together, our results suggested that gestational GenX exposure triggered metabolic disorder, which might be responsible for the hepatotoxicity in the pups in addition to dysfunction of the intestinal mucosa barrier. This study enriches the mechanisms of GenX-induced developmental hepatotoxicity by associating metabolic disorder with intestinal homeostasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Prenatal exposure to methamphetamine (METH) is an issue of global concern due to its adverse effects on offspring, particularly its impact on liver health, an area still not fully understood. Inulin, a recognized prebiotic, is thought to potentially ameliorate these developmental disorders and toxic injuries in progeny. To investigate the effects of prenatal METH exposure on the liver and the role of gut microbiota, we established a murine model, the subjects of which were exposed to METH prenatally and subsequently treated with inulin. Our findings indicate that prenatal METH exposure causes liver damage in offspring, as evidenced by a decreased liver index, histopathological changes, diminished glycogen synthesis, hepatic dysfunction, and alterations in mRNA profiles. Furthermore, it impairs the antioxidant system and induces oxidative stress, possibly due to changes in cecal microbiota and dysregulation of bile acid homeostasis. However, maternal inulin supplementation appears to restore the gut microbiota in offspring and mitigate the hepatotoxic effects induced by prenatal METH exposure. Our study provides definitive evidence of METH's transgenerational hepatotoxicity and suggests that maternal inulin supplementation could be an effective preventive strategy., 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. No potential conflict of interest was reported by the authors., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Percutaneous coronary intervention (PCI) has increasingly become the main treatment for coronary artery disease. The procedure requires high experienced skills and dexterous manipulations. However, there are few techniques to model PCI skill so far. In this study, a learning framework with local and ensemble learning is proposed to learn skill characteristics of different skill-level subjects from their PCI manipulations. Ten interventional cardiologists (four experts and six novices) were recruited to deliver a medical guidewire to two target arteries on a porcine model for in vivo studies. Simultaneously, translation and twist manipulations of thumb, forefinger, and wrist are acquired with electromagnetic (EM) and fiber-optic bend (FOB) sensors, respectively. These behavior data are then processed with wavelet packet decomposition (WPD) under 1-10 levels for feature extraction. The feature vectors are further fed into three candidate individual classifiers in the local learning layer. Furthermore, the local learning results from different manipulation behaviors are fused in the ensemble learning layer with three rule-based ensemble learning algorithms. In subject-dependent skill characteristics learning, the ensemble learning can achieve 100% accuracy, significantly outperforming the best local result (90%). Furthermore, ensemble learning can also maintain 73% accuracy in subject-independent schemes. These promising results demonstrate the great potential of the proposed method to facilitate skill learning in surgical robotics and skill assessment in clinical practice.

During intravascular interventional surgery, the 3D surgical navigation system can provide doctors with 3D spatial information of the vascular lumen, reducing the impact of missing dimension caused by digital subtraction angiography (DSA) guidance and further improving the success rate of surgeries. Nevertheless, this task often comes with the challenge of complex registration problems due to vessel deformation caused by respiratory motion and high requirements for the surgical environment because of the dependence on external electromagnetic sensors. This article proposes a novel 3D spatial predictive positioning navigation (SPPN) technique to predict the real-time tip position of surgical instruments. In the first stage, we propose a trajectory prediction algorithm integrated with instrumental morphological constraints to generate the initial trajectory. Then, a novel hybrid physical model is designed to estimate the trajectory's energy and mechanics. In the second stage, a point cloud clustering algorithm applies multi-information fusion to generate the maximum probability endpoint cloud. Then, an energy-weighted probability density function is introduced using statistical analysis to achieve the prediction of the 3D spatial location of instrument endpoints. Extensive experiments are conducted on 3D-printed human artery and vein models based on a high-precision electromagnetic tracking system. Experimental results demonstrate the outstanding performance of our method, reaching 98.2% of the achievement ratio and less than 3 mm of the average positioning accuracy. This work is the first 3D surgical navigation algorithm that entirely relies on vascular interventional robot sensors, effectively improving the accuracy of interventional surgery and making it more accessible for primary surgeons.

Background: Oxaliplatin (Oxa) is the first-line chemotherapy drug for colorectal cancer (CRC), and Oxa resistance is crucial for treatment failure. Prostaglandin F 2α synthase (PGF 2α ) (PGFS), an enzyme that catalyzes the production of PGF 2α , is involved in the proliferation and growth of a variety of tumors. However, the role of PGFS in Oxa resistance in CRC remains unclear., Aim: To explore the role and related mechanisms of PGFS in mediating Oxa resistance in CRC., Methods: The PGFS expression level was examined in 37 pairs of CRC tissues and paracancerous tissues at both the mRNA and protein levels. Overexpression or knockdown of PGFS was performed in CRC cell lines with acquired Oxa resistance (HCT116-OxR and HCT8-OxR) and their parental cell lines (HCT116 and HCT8) to assess its influence on cell proliferation, chemoresistance, apoptosis, and DNA damage. For determination of the underlying mechanisms, CRC cells were examined for platinum-DNA adducts and reactive oxygen species (ROS) levels in the presence of a PGFS inhibitor or its products., Results: Both the protein and mRNA levels of PGFS were increased in the 37 examined CRC tissues compared to the adjacent normal tissues. Oxa induced PGFS expression in the parental HCT116 and HCT8 cells in a dose-dependent manner. Furthermore, overexpression of PGFS in parental CRC cells significantly attenuated Oxa-induced proliferative suppression, apoptosis, and DNA damage. In contrast, knockdown of PGFS in Oxa-resistant HCT116 and HCT8 cells (HCT116-OxR and HCT8-OxR) accentuated the effect of Oxa treatment in vitro and in vivo . The addition of the PGFS inhibitor indomethacin enhanced the cytotoxicity caused by Oxa. Treatment with the PGFS-catalyzed product PGF 2α reversed the effect of PGFS knockdown on Oxa sensitivity. Interestingly, PGFS inhibited the formation of platinum-DNA adducts in a PGF 2α -independent manner. PGF 2α exerts its protective effect against DNA damage by reducing ROS levels., Conclusion: PGFS promotes resistance to Oxa in CRC via both PGF 2α -dependent and PGF 2α -independent mechanisms., Competing Interests: Conflict-of-interest statement: The authors declare that there are no conflicts of interest in our study., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Organophosphorus flame retardants (OPFRs), including 2-ethylhexyl diphenyl phosphate (EHDPHP), are prevalent in everyday life due to their broad usage in fields such as healthcare, electronics, industry, and sports. These compounds, added to polymers through physical mixing, can leach into the environment, posing a risk to humans through direct contact or the food chain. Despite known associations with health issues like endocrine disruption, neurotoxicity, and reproductive toxicity, the implications of perinatal EHDPHP exposure on both mothers and offspring are still unclear. This study aimed to investigate the neuroinflammatory effects of EHDPHP and the potential mitigating role of inulin. Pregnant C57 mice were administered either a corn oil control or an EHDPHP solution (300 μg/kg bw/d) from gestation day 7 (GD7) to postnatal day 21 (PND21). Concurrently, mice were provided either regular drinking water or water supplemented with 1% inulin. We found that EHDPHP significantly increased the serum levels of IL-1β, IL-6, and MDA, but decreased SOD levels in both mothers and pups. These effects were reversed by inulin supplementation. RNA-sequencing revealed that EHDPHP induced inflammation and oxidative stress through the TLR4/NF-κB pathway, which was mitigated by inulin. In conclusion, inulin ameliorated EHDPHP-induced neuroinflammation and oxidative stress in both mothers and offspring, highlighting its potential therapeutic role., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Polystyrene microplastics (PS-MPs) have emerged as a concerning pollutant in modern society due to their widespread production and usage. Despite ongoing research efforts, the impact of PS-MPs on mammalian behavior and the mechanisms driving these effects remain incompletely elucidated. Consequently, effective strategies for prevention have yet to be developed. To fill these gaps, C57BL/6 mice were orally administered with 5 μm PS-MPs for 28 consecutive days in this study. The open-field test and the elevated plus-maze test were performed to evaluate the anxiety-like behavior, 16S rRNA sequencing and untargeted metabolomics analysis were used to detect the changes of gut microbiota and serum metabolites. Our results indicated that PS-MPs exposure activated hippocampal inflammation and induced anxiety-like behavior in mice. Meanwhile, PS-MPs disturbed the gut microbiota, impaired the intestinal barrier, and aroused peripheral inflammation. Specifically, PS-MPs increased the abundance of pathogenic microbiota Tuzzerella, while lowered the abundance of probiotics Faecalibaculum and Akkermansia. Interestingly, eliminating the gut microbiota protected against the deleterious effects of PS-MPs on intestinal barrier integrity, reduced the levels of peripheral inflammatory cytokines, and ameliorated anxiety-like behavior. Additionally, green tea's primary bioactive constituent, epigallocatechin-3-gallate (EGCG), optimized gut microbial composition, improved intestinal barrier function, reduced peripheral inflammation, and exerted anti-anxiety effects by inhibiting the hippocampal TLR4/MyD88/NF-κB signaling cascade. EGCG also remodeled serum metabolism, especially modulated purine metabolism. These findings suggested that gut microbiota participates in PS-MPs-induced anxiety-like behavior by modulating the gut-brain axis, and that EGCG could serve as a potential preventive strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Gastric cancer (CC) is a disease with high incidence and mortality rate. Immunotherapy is an important method for gastric cancer while lack of effective predictor. Integrins play an important role in the development. We aimed to explore the predictive value of β1 integrin (ITGB1) as a predictor of immunnotherapy in gastric cancer., Methods: Differential expression analysis was conducted using the Gene Expression Profiling Interactive Analysis (GEPIA) 2.0 and GEO databases. GEPIA data were used to evaluate the prognostic value of ITGB1 in gastric cancer (GC). Transcriptomic and clinical data of GC and normal tissues were downloaded from The Cancer Genome Atlas database, and the TIMER database was used to evaluate the association between ITGB1 and immune infiltration. Time-dependent receiver operating characteristic (ROC) curve analysis was used to determine the prognostic value of ITGB1. To verify ITGB1 expression at the protein level, immunohistochemical staining was conducted. In addition, to analyze the correlation of ITGB1 with PD-1 and PD-L1, we examined levels of PD-1 and PD-L1 by IHC and determined the predictive value of ITGB1 for anti-PD-1 therapy in GC by ROC curve analysis., Results: Compared with normal tissues, analysis of GEPIA and data at protein levels showed significantly higher expression of ITGB1 in GC. In addition, higher expression of ITGB1 was associated with worse pathological G-staging and tumor T-staging, which suggested that ITGB1 is a risk factor for poor prognosis in GC. The level of ITGB1 expression was positively correlated with CD8 + T cells, neutrophils, macrophages, and dendritic cells. ITGB1 expression was also correlated with PD-L1 expression, and this was further verified at the protein level by immunohistochemical analysis. The area under the ROC curve was 0.808., Conclusion: ITGB1 may be a promising prognostic biomarker and effective predictor for anti-PD-1 therapy in GC., Trial Registration: Retrospectively registered., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Increases in the prevalence of food allergy and vitamin D deficiency have been observed in recent years. The association between vitamin D levels and food allergy remains to be fully elucidated, and research focused on the prevalence of vitamin D insufficiency in infants with food protein-induced gastrointestinal disease in Chengdu, Sichuan is lacking. Thus, the present study aimed to determine the prevalence and clinical characteristics of serum 25 hydroxyvitamin D [25-(OH)D] insufficiency and sufficiency in infants with food protein-induced gastrointestinal disease. The present study also aimed to identify the potential predisposing factors of 25-(OH)D insufficiency. The present retrospective study analyzed data obtained from Chengdu Women's and Children's Central Hospital spanning between June 2021 and February 2022. Children with a confirmed diagnosis of food protein-induced gastrointestinal disease were enrolled in the present study. Blood indicators, including serum 25-(OH)D, serum total immunoglobulin E (IgE), specific IgE against allergens, and hemoglobin were measured during the course of the disease. Clinical characteristics of patients and blood examination results were obtained from the hospital electronic database. A total of 361 patients were included in the study group and 45 healthy individuals were included in the control group. The results of the present study demonstrated that serum 25-(OH)D levels of infants with protein-induced gastrointestinal disease were significantly lower compared with the control group. Notably, female participants with higher serum total IgE levels exhibited insufficient serum 25-(OH)D levels. However, the results of the logistic regression analysis revealed no predisposing factors associated with serum 25-(OH)D insufficiency. In conclusion, infants with food protein-induced gastrointestinal disease may exhibit a higher risk of low serum 25-(OH)D levels and this risk may be greater in females with higher total IgE., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Zhou et al.)

Hospital patients can have catheters and lines inserted during the course of their admission to give medicines for the treatment of medical issues, especially the central venous catheter (CVC). However, malposition of CVC will lead to many complications, even death. Clinicians always detect the malposition based on position detection of CVC tip via X-ray images. To reduce the workload of the clinicians and the percentage of malposition occurrence, we propose an automatic catheter tip detection framework based on a convolutional neural network (CNN). The proposed framework contains three essential components which are modified HRNet, segmentation supervision module, and deconvolution module. The modified HRNet can retain high-resolution features from start to end, ensuring the maintenance of precise information from the X-ray images. The segmentation supervision module can alleviate the presence of other line-like structures such as the skeleton as well as other tubes and catheters used for treatment. In addition, the deconvolution module can further increase the feature resolution on the top of the highest-resolution feature maps in the modified HRNet to get a higher-resolution heatmap of the catheter tip. A public CVC Dataset is utilized to evaluate the performance of the proposed framework. The results show that the proposed algorithm offering a mean Pixel Error of 4.11 outperforms three comparative methods (Ma's method, SRPE method, and LCM method). It is demonstrated to be a promising solution to precisely detect the tip position of the catheter in X-ray images., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hak-Keung Lam reports was provided by King’s College London., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Most naturally occurring indole diterpenes share a 6/5/5/6/6/6 hexacyclic ring system, while a 6/8/6/6/6 pentacyclic skeleton is occasionally observed. In this study, we demonstrate the formation of an eight-membered C-N heteroring via nonenzymatic flavin-catalyzed oxidative indole ring opening. More interestingly, 18 O-labeled experiments proved that the two incorporated oxygen atoms are predominantly originated from water instead of molecular oxygen. In this process, the oxidized form of flavin catalyzes two successive oxidations of amines to imines with involvement of hydrolysis for the ring expansion. The reduced flavin is then regenerated by oxidation with molecular oxygen to form H 2 O 2 .

We report here a robust and practical strategy for chemical protein synthesis using an o -nitrobenzyl group as a temporary protective group for an N-terminal cysteine residue of intermediate hydrazide fragments. By reinvestigating the photoremoval of an o -nitrobenzyl group, we establish a robust and reliable strategy for its quantitative photodeprotection. The o -nitrobenzyl group is completely stable to oxidative NaNO 2 treatment and has been applied to the convergent chemical synthesis of programmed death ligand 1 fragment, providing a practical avenue for hydrazide-based native chemical ligation.

With three representative types of gynecological diseases (dysmenorrhea, pelvic inflammation, polycystic ovary syndrome) as examples, the application methods of meridian and acupoint diagnosis for gynecological diseases treated with acupuncture and moxibustion are discussed. During clinical diagnosis and treatment, it is recommended to examine the patient's leg segment along the three yin meridians of foot, aiming to explore the positive reactions of the meridians and acupoints (color, shape, skin temperature, sensory abnormalities, etc.). Acupuncture and moxibustion treatment at this positive reaction place can improve the clinical efficacy. Meridian and acupoint diagnosis could provide basis for meridian syndrome differentiation, thus guiding the selection of acupoint prescriptions; it is also helpful to clarify the deficiency, excess, cold and heat of the disease nature, thus guiding the selection of acupuncture and moxibustion methods. In addition, it is an auxiliary method to estimate the prognosis and outcome of the disease.

Introduction: Burn injury has been shown to lead to changes in the composition of the gut microbiome and cause other damage in patients. However, little is known about how the gut microbial community evolves in individuals who have recovered from burn injury., Methods: In this study, we established a model of deep partial-thickness burn in mice and collected fecal samples at eight time points (pre-burn, 1, 3, 5, 7, 14, 21, and 28 days post-burn) for 16S rRNA amplification and high-throughput sequencing., Results: The results of the sequencing were analyzed using measures of alpha diversity, and beta diversity and taxonomy. We observed that the richness of the gut microbiome declined from day 7 post-burn and that the principal component and microbial community structure varied over time. On day 28 after the burn, the microbiome composition largely returned to the pre-burn level, although day 5 was a turning point for change. Some probiotics, such as the Lachnospiraceae&#95;NK4A136&#95;group, decreased in composition after the burn but were restored in the later recovery period. In contrast, Proteobacteria showed an opposite trend, which is known to include potential pathogenic bacteria., Conclusion: These findings demonstrate gut microbial dysbiosis after burn injury and provide new insights into the burn-related dysbiosis of the gut microbiome and strategies for improving the treatment of burn injury from the perspective of the microbiota., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Liu, Yang, Lin, Hsu, Zhang, Liu, Li, Li, Yang, Chen, Zeng, Xie, Xu and Wang.)

Objective: To investigate the effect and possible mechanism of Y-box-binding protein 1 (YB-1) on sorafenib resistance in hepatoma cells. Methods: Lentiviral vectors with YB-1 overexpression and knockdown were constructed, respectively, to stimulate human hepatoma cell lines (HepG2 and Huh7) alone or in combination with sorafenib.The overexpression part of the experiment was divided into four groups: overexpression control group (Lv-NC), YB-1 overexpression group (Lv-YB-1), overexpression control combined with sorafenib resistance group (Lv-NC+sorafenib), YB-1 overexpression combined with sorafenib resistance group (Lv-YB-1 + sorafenib). The knockdown part of the experiment was also divided into four groups: knockdown control group (Lv-shNC), YB-1 knockdown group (Lv-shYB-1), knockdown control combined with sorafenib resistance group (Lv-shNC + sorafenib), YB-1 knockdown combined with sorafenib resistance group (Lv-shYB-1 + sorafenib). The occurrence of cell apoptosis was detected by TUNEL. The protein expression levels of phosphorylated (p)-ERK and ERK, key proteins in the extracellular regulatory protein kinase (ERK) signaling pathway, were detected by Western blot and quantified by ImageJ software. Subcutaneous tumorigenesis experiments were performed in nude mice. The effect of YB-1 on the efficacy of sorafenib was verified in vivo. The comparison between the two sets of data was carried out by an independent sample t-test. One-way ANOVA was used for comparisons between the three groups of data above. Results: Sorafenib had accelerated the occurrence of apoptosis in hepatoma cells, while YB-1 overexpression had inhibited cell apoptosis, and at the same time also inhibited the apoptosis-accelerating impact of sorafenib. On the contrary, YB-1 knockdown accelerated cell apoptosis and amplified the induction effect of sorafenib on apoptosis. Furthermore, sorafenib resistance had down-regulated p-ERK levels (HepG2: Lv-NC 0.685 ± 0.143, Lv-NC + sorafenib 0.315 ± 0.168, P < 0.05; Huh7: Lv-NC 0.576 ± 0.078, Lv-NC + sorafenib 0.150 ± 0.131, P < 0.01), whereas YB-1 overexpression had inhibited sorafenib resistance p-ERK reduction (HepG2: Lv-NC + sorafenib 0.315 ± 0.168, Lv-YB-1 + sorafenib 0.688 ± 0.042, P < 0.05; Huh7: Lv-NC + sorafenib 0.150 ± 0.131, Lv-YB-1 + sorafenib 0.553 ± 0.041, P < 0.05). YB-1 knockdown further increased sorafenib-induced p-ERK downregulation (HepG2: Lv-shNC + sorafenib 0.911 ± 0.252, Lv-shYB-1 + sorafenib 0.500 ± 0.201, P < 0.05; Huh7: Lv-shNC + sorafenib 0.577 ± 0.082, Lv-shYB-1 + sorafenib 0.350 ± 0.143, P < 0.05), which was further verified in naked mice (Lv-shNC + sorafenib 0.812 ± 0.279, Lv-shYB-1 + sorafenib 0.352 ± 0.109, P < 0.05). Conclusion: YB-1 mediates the occurrence of sorafenib resistance via the ERK signaling pathway in hepatoma cells.

Introduction: Depression is a common mental disorder that affects approximately 350 million people worldwide. Much remains unknown about the molecular mechanisms underlying this complex disorder. Sigma-1 receptor (Sig-1R) is expressed at high levels in the central nervous system. Increasing evidence has demonstrated a close association between the Sig-1R and depression. Recently, research has suggested that the gut microbiota may play a crucial role in the development of depression., Methods: Male Sig-1R knockout (Sig-1R KO) and wild-type (WT) mice were used for this study. All transgenic mice were of a pure C57BL/6J background. Mice received a daily gavage of vancomycin (100 mg/kg), neomycin sulfate (200 mg/kg), metronidazole (200 mg/kg), and ampicillin (200 mg/kg) for one week to deplete gut microbiota. Fecal microbiota transplantation (FMT) was conducted to assess the effects of gut microbiota. Depression-like behaviors was evaluated by tail suspension test (TST), forced swimming test (FST) and sucrose preference test (SPT). Gut microbiota was analyzed by 16s rRNA and hippocampal transcriptome changes were assessed by RNA-seq., Results: We found that Sig-1R knockout induced depression-like behaviors in mice, including a significant reduction in immobility time and an increase in latency to immobility in the FST and TST, which was reversed upon clearance of gut microbiota with antibiotic treatment. Sig-1R knockout significantly altered the composition of the gut microbiota. At the genus level, the abundance of Alistipes, Alloprevotella, and Lleibacterium decreased significantly. Gut microbiota dysfunction and depression-like phenotypes in Sig-1R knockout mice could be reproduced through FMT experiments. Additionally, hippocampal RNA sequencing identified multiple KEGG pathways that are associated with depression. We also discovered that the cAMP/CREB/BDNF signaling pathway is inhibited in the Sig-1R KO group along with lower expression of neurotrophic factors including CTNF, TGF-α and NGF. Fecal bacteria transplantation from Sig-1R KO mice also inhibited cAMP/CREB/BDNF signaling pathway., Discussion: In our study, we found that the gut-brain axis may be a potential mechanism through which Sig-1R regulates depression-like behaviors. Our study provides new insights into the mechanisms by which Sig-1R regulates depression and further supports the concept of the gut-brain axis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Liu, Li, Liu, Yang, Chen, Zhang, Xie and Wang.)

Methamphetamine (Meth) abuse can cause severe anxiety disorder and interfere with gut homeostasis. Obeticholic acid (OCA) has emerged as a protective agent against diet-related anxiety that improves gut homeostasis. The potential for OCA to ameliorate Meth-induced anxiety, and the microbial mechanisms involved, remain obscure. Here, C57/BL6 mice were intraperitoneally injected with Meth (15 mg/kg) to induce anxiety-like behavior. 16 S rRNA sequence analysis and fecal microbiome transplantation (FMT) were used to profile the gut microbiome and evaluate its effects, respectively. Orally administered OCA was investigated for protection against Meth-induced anxiety. Results indicated that Meth mediated anxiety-like behavior, aroused hippocampal neuroinflammation through activation of the TLR4/MyD88/NF-κB pathway, weakened intestinal barrier and disturbed the gut microbiome. Specifically, abundance of anxiety-related Rikenella was increased. FMT from Meth-administrated mice also weakened intestinal barrier and elevated serum LPS, inducing hippocampal neuroinflammation and anxiety-like behavior in recipient mice. Finally, OCA pretreatment ameliorated Meth-induced impairment of gut homeostasis by reshaping the microbial composition and improving the intestinal barrier. Meth-induced anxiety-like behavior and hippocampal neuroinflammation were also ameliorated by OCA pretreatment. These preliminary findings reveal the crucial role of gut microbiota in Meth-induced anxiety-like behavior and neuroinflammation, highlighting OCA as a potential candidate for the prevention of Meth-induced anxiety., 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 B.V. All rights reserved.)

Background: We evaluated the JAK2V617F mutation and p-JAK2, SOCS-1, SHP-1 expression in JAK2V617F positive myeloproliferative neoplasms (MPNs) patients and the role of JAK/STAT pathway in human erythroleukemia (HEL) cells, which had JAK2V617F mutation., Methods: Protein expression of p-JAK2, SOCS-1, SHP-1 in bone marrow biopsies (BMBs) were detected by immunohistochemical staining methods. Cell apoptosis and cell cycle were detected by flow cytometry and Caspase 3/7 assay kits., Results: 1. The p-JAK2, SOCS-1, and SHP-1 expressions were significantly different between JAK2V617F positive MPN and control patients (p < 0.01); 2. After being treated for 3 months, the p-JAK2, SOCS-1, and SHP-1 expressions were significantly different compared with newly diagnosed patients (p < 0.01). 3. HEL cell viabilities were significantly different after being treated with different concentrations of ruxolitinib. Ruxolitinib had a significant effect on the cell apoptosis, viability, and the protein activity of caspase-3 and -7 of HEL cells. 3. The mRNA and protein expressions of JAK2 and the protein expression of p-JAK2 were gradually decreased (p ＜ 0.01, p ＜ 0.05), while the mRNA and protein expressions of SOCS1 and SHP1 were gradually increased (all p ＜ 0.01).

Objective: The objective of this study is to analyze and verify the main drug components and targets of "Fuzi-Guizhi" in the treatment of osteoarthritis by using the network pharmacology platform., Methods: The integrated pharmacology of "Fuzi-Guizhi" was analyzed by using the platform of integrated pharmacology of traditional Chinese medicine to explore its mechanism in the treatment of osteoarthritis. By establishing an arthritis model in vitro, the pharmacological effect of "aconitecassia twigs" on articular cartilage was evaluated and conducted for molecular docking., Results: 28 candidate active components, 37 compound targets, and 583 osteoarthritis-related potential targets were screened, and 10 key target processes were screened in the protein interaction network model. Enrichment analysis showed that the 10 core targets involved 958 GO biologic function items and 76 KEGG signal pathways, which were mainly related to apoptosis and mitochondrial functional metabolism and "Fuzi-Guizhi" drug-containing serum inhibited the expression of Caspase-3 mRNA and protein in chondrocytes and promoted the synthesis of ATP., Conclusion: Our research is preliminary that the mechanism of action of "Fuzi-Guizhi" may inhibit chondrocyte degeneration by resisting mitochondrial apoptosis, and further experimental research is required to determine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)