Search

Sodium p-perfluorous nonenoxybenzene sulfonate (OBS) is a prominent alternative to perfluorooctanesulfonic acid (PFOS). Numerous studies have demonstrated hepatotoxicity and neurotoxicity of OBS and PFOS in mammals. The lungs, as a sensitive organ, are among the potential target organs for OBS and PFOS exposure. However, their toxic effects on the lungs remain unclear. In the present study, three-dimensional (3D) spheroids constructed from A549 cells were exposed to OBS and PFOS for 7 days to evaluate pulmonary toxicity through morphological examination, growth kinetics, transcriptomic profiling, and biochemical assays. Our results showed that OBS significantly reduced the diameter, volume, and growth fraction of the spheroids compared to PFOS. Transcriptomic analysis revealed a notable enrichment of the IL-17 signaling pathway after 7 days of OBS exposure. Significant differences in the transcription of genes within this pathway were observed between OBS and PFOS exposure. OBS reduced the transcription of tnfaip3, nfkbiα, map3k8, enpp2, jun, il6, cxcl1, cxcl2, cxcl3, and cxcl8 in the IL-17 signaling pathway, while PFOS enhanced the transcription of nfkbiα. Additionally, OBS decreased the level of IL-8, whereas PFOS had a minor effect. Cluster analysis confirmed significant differences in the pulmonary toxicity between OBS and PFOS. Our study demonstrated the utility of spheroids as an in vitro cell model complemented with omics technology, for comparing the pulmonary toxicity of OBS and PFOS. It provided a novel approach for evaluating the pulmonary toxicity of new pollutants like OBS., 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.)

To identify the genetic determinants of domestication and productivity of Asian water buffaloes (Bubalus bubalis), 470 genomes of domesticated river and swamp buffaloes along with their putative ancestors, the wild water buffaloes (Bubalus arnee) are sequenced and integrated. The swamp buffaloes inherit the morphology of the wild buffaloes. In contrast, most river buffaloes are unique in their morphology, but their genomes cluster with the wild buffaloes. The levels of genomic diversity in Italian river and Indonesian swamp buffaloes decrease at opposite extremes of their distribution range. Purifying selection prevented the accumulation of harmful loss-of-function variants in the Indonesian buffaloes. Genes that evolved rapidly (e.g., GKAP1) following differential selections in the river and swamp buffaloes are involved in their reproduction. Genes related to milk production (e.g., CSN2) and coat color (e.g., MC1R) underwent strong selections in the dairy river buffaloes via soft and hard selective sweeps, respectively. The selective sweeps and single-cell RNA-seq data revealed the luminal cells as the key cell type in response to artificial selection for milk production of the dairy buffaloes. These findings show how artificial selection has been driving the evolutionary divergence and genetic differentiation in morphology and productivity of Asian water buffaloes., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Repetitive use of morphine (MF) and other opioids can trigger two major pain-related side effects: opioid-induced hypersensitivity (OIH) and analgesic tolerance, which can be subclassified as mechanical and thermal. The central mechanisms underlying mechanical OIH/tolerance remain unresolved. Here, we report that a brain-to-spinal opioid pathway, starting from μ-opioid receptor (MOR)-expressing neuron in the lateral parabrachial nucleus (lPBN MOR+ ) via dynorphin (Dyn) neuron in the paraventricular hypothalamic nucleus (PVH Dyn+ ) to κ-opioid receptor (KOR)-expressing GABAergic neuron in the spinal dorsal horn (SDH KOR-GABA ), controls repeated systemic administration of MF-induced mechanical OIH and tolerance in mice. The above effect is likely mediated by disruption of dorsal horn gate control for MF-resistant mechanical pain via silencing of the Dyn-positive GABAergic neurons in the SDH (lPBN MOR+ → PVH Dyn+ → SDH KOR-GABA → SDH Dyn-GABA ). Repetitive binding of MF to MORs during repeated MF administration disrupted the above circuits. Targeting the above brain-to-spinal opioid pathways rescued repetitive MF-induced mechanical OIH and tolerance., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hydrogen sulfide (H 2 S) is a potent redox-active signaling molecule commonly dysregulated in disease states. The production of H 2 S and its involvement in various pathological conditions associated with mitochondrial dysfunction has been extensively documented. During stress, cystathionine gamma-lyase and cystathionine beta-synthase enzymes residing in cytosol are copiously translocated into the mitochondria to boost H 2 S production, confirming its pivotal role in mitochondrial activities. However, report on H 2 S levels in tissue, cells and organelles are lacking, mainly due to the absence of precise and accurate detection tools. Thus, there is a need to determine and monitor the levels of H 2 S in this important organelle. Recently, fluorescent probes have been identified as efficient tools for detecting and monitoring the levels of various biomolecules of medical importance including biological thiols. The development of fluorescent probes is a multi-pronged approach involving coupling of fluorophores with responsive sites. The use of fluorescent probes for monitoring mitochondrial H 2 S levels has recently received more attention, resulting in numerous publications depicting their synthesis, mechanism of action, application, and potential challenges. Fluorescent probes offer precise and timely results, high sensitivity, and selectivity, low biotoxicity, and minimal background interference. In this review, we aim to report designs of such probes, reaction mechanisms and their application in detecting mitochondrial H 2 S levels. Fluorescent probes can help uncover physio/pathological levels of H 2 S in essential organelles, its interactions with various biomarkers and associated consequences in biological systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Aim: This study was designed to investigate the response of the respiratory structures to orthognathic surgery in patients with Class III malocclusion, with a specific emphasis on the vertical placement of the hyoid bone. The correlations of these changes were also analysed, followed by further subgroup analyses based on preoperative conditions., Materials and Methods: Dolphin software was used to obtain cephalometric landmarks, airway and hyoid bone measurements from pre- and postoperative CBCT scans of 31 patients. Statistical analyses included paired t-tests and Pearson's correlation analysis., Results: Stomatological mandibular values and the nasopharynx height showed significant changes. Pearson's correlation identified significant correlations between changes in B and H horizontal coordinates (p < 0.05), as well as between changes in H longitudinal coordinates and specific airway dynamics (p < 0.05). Patients with a lower preoperative hyoid position experienced a more pronounced decrease in hypopharyngeal airway volume after surgery compared to those with a higher preoperative hyoid position, as evidenced by the significant mean differences and p values (p < 0.01)., Conclusions: Class III patients experienced airway constriction following orthognathic surgery, particularly those with a lower preoperative hyoid bone position, who showed a more significant decrease in hypopharyngeal airway volume postsurgery compared to those with a higher preoperative hyoid position. These findings underscored the importance of individualised surgical planning and highlighted the need for further research with dynamic assessments to optimise respiratory outcomes., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cystathionine β-synthase (CBS) occupies a key position as the initiating and rate-limiting enzyme in the sulfur transfer pathway and plays a vital role in health and disease. CBS is responsible for regulating the metabolism of cysteine, the precursor of glutathione (GSH), an important antioxidant in the body. Additionally, CBS is one of the three enzymes that produce hydrogen sulfide (H 2 S) in mammals through a variety of mechanisms. The dysregulation of CBS expression in cancer cells affects H 2 S production through direct or indirect pathways, thereby influencing cancer growth and metastasis by inducing angiogenesis, facilitating proliferation, migration, and invasion, modulating cellular energy metabolism, promoting cell cycle progression, and inhibiting apoptosis. It is noteworthy that CBS expression exhibits complex changes in different cancer models. In this paper, we focus on the CBS synthesis and metabolism, tissue distribution, potential mechanisms influencing tumor growth, and relevant signaling pathways. We also discuss the impact of pharmacological CBS inhibitors and silencing CBS in preclinical cancer models, supporting their potential as targeted cancer therapies., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

17α-Ethinylestradiol (EE2) is known for its endocrine-disrupting effects on embryonic and adult fish. However, its impact on juvenile zebrafish has not been well established. In this study, juvenile zebrafish were exposed to EE2 at concentrations of 5 ng/L (low dose, L), 10 ng/L (medium dose, M), and 50 ng/L (high dose, H) from 21 days post-fertilization (dpf) to 49 dpf. We assessed their growth, development, behavior, transcriptome, and metabolome. The findings showed that the survival rate in the EE2-H group was 66.8 %, with all surviving fish displaying stunted growth and swollen, transparent abdomens by 49 dpf. Moreover, severe organ deformities were observed in the gills, kidneys, intestines, and heart of fish in both the EE2-H and EE2-M groups. Co-expression analysis of mRNA and lncRNA revealed that EE2 downregulated the transcription of key genes involved in the cell cycle, DNA replication, and Fanconi anemia signaling pathways. Additionally, metabolomic analysis indicated that EE2 influenced metabolism and development-related signaling pathways. These pathways were also significantly identified based on the genes regulated by lncRNA. Consequently, EE2 induced organ deformities and mortality in juvenile zebrafish by disrupting signaling pathways associated with development and metabolism. The results of this study offer new mechanistic insights into the adverse effects of EE2 on juvenile zebrafish based on multiomics analysis. The juvenile zebrafish are highly sensitive to EE2 exposure, which is not limited to adult and embryonic stages. It is a potential model for studying developmental toxicity., 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 Inc. All rights reserved.)

Thalamic pain can be understood as a network reorganization disorder. This study aimed to investigate functional connectivity (FC) in human patients and a macaque model of thalamic pain. In humans, resting-state FC was compared between patients with thalamic pain and healthy individuals. Furthermore, resting-state FC was compared in macaques, before and after the induction of thalamic pain in the same individuals. FC between the amygdala of the unaffected hemisphere and the brainstem was significantly higher in patients with thalamic pain. More specifically, a significantly higher FC was observed between the basolateral amygdala and the ventral tegmental area, which also significantly predicted the value of a visual analog scale of pain intensity in individual patients. The macaque model of thalamic pain also exhibited a significantly higher FC between the amygdala of the unaffected hemisphere and the brainstem, particularly between the basolateral amygdala and the midbrain. Furthermore, the previously reported significantly higher FC between the amygdala and the mediodorsal nucleus of the thalamus in macaques with thalamic pain was also reproduced in the human patients. Therefore, the present results suggest that the FC changes in the regions associated with emotion, memory, motivation, and reward are part of the underlying mechanisms of thalamic pain onset present in both human patients and model macaques. This cross-species convergence provides new insights into the neurological mechanisms underlying thalamic pain, paving the way for further studies and the development of therapeutic strategies. PERSPECTIVE: This article presents that the FC changes in the regions associated with emotion, motivation, and reward are part of the underlying mechanisms of thalamic pain in humans and macaques., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Rationale and Objectives: The objective of this study was to measure the safety and efficacy of thermal ablation, including radiofrequency ablation (RFA) and microwave ablation (MWA), for patients with stage I non-small cell lung cancer (NSCLC)., Materials and Methods: The databases PubMed was searched from inception to November 2023 to identify relevant studies. Statistical analyses were performed with R version 3. 6. 3., Results: Thirty-three studies involving 1400 patients were finally included. According to our study, the incidence of patients with stage I NSCLC who were older than 60 years old was 98 % (95 % CI [94-100 %]); the lesions were mostly located in RUL (Right Upper Lobe) and LUL (Left Upper Lobe), and the incidence of the two sites was 29 % (95 % CI [23-35 %]) and 27 % (95 % CI [21-33 %]), respectively; the types of lung cancers mainly included adenocarcinoma, squamous carcinoma, and large-cell lung cancer, of which adenocarcinoma accounted for the largest proportion of 63 % (95 % CI [56-70 %]); the causes of death were mainly categorized into cancer-related (57 %, 95 %CI[40-74 %]) and noncancer-related (40 %, 95 %CI [23-58 %]); the common complications in the postoperative period were pneumothorax and pain, with the incidence of 33 % (95 %CI[24-44 %]) and 33 % (95 %CI[19-50 %]), and the rate of the postoperative complications in MWA was slightly higher than those in RFA; the local recurrence rate was 23 % (95 %CI[17-29 %]) and the distant recurrence rate was 18 % (95 %CI[7-32 %]); the pooling result showed the rate of 1-, 2-, 3-, and 5-year survival rate were 96 %, 81 %, 68 %, and 42 %, the Cancer-specific survival (CSS) rates at 1, 2, 3, and 5 years were 98 %, 88 %, 75 %, and 58 %, Disease-free survival (DFS) rates at 1, 2, 3, and 5 years were 87 %, 63 %, 57 %, and 42 %, there were no significant differences existed between the RFA group and MWA group in survival rate, CSS and DFS., Conclusion: Ablation therapy is safe and effective for stage I NSCLC patient. MWA and RFA have comparable efficacy, safety, and prognosis, which could be recommended for patients with stageⅠNSCLC, especially for patients who cannot tolerate open surgery., 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 Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis during chronic stress is essential for the pathogenesis of depression, and increased activity of cAMP response element binding protein (CREB)-regulated transcription co-activator 1 (CRTC1) in the paraventricular nucleus (PVN) plays a critical role. As a well-investigated microRNA (miRNA), miR-184 has two forms, miR-184-3p and miR-184-5p. Recently, miRNAs target genes predictive analysis and dual-luciferase reporter assays identified an inhibitory role of miR-184-3p on CRTC1 expression. Therefore, we speculated that miR-184-3p regulation was responsible for the effects of chronic stress on CRTC1 in the PVN. Various methods, including the chronic social defeat stress (CSDS) model of depression, behavioral tests, Western blotting, co-immunoprecipitation (Co-IP), quantitative real-time reverse transcription PCR (qRT-PCR), immunofluorescence, and adeno-associated virus (AAV)-mediated gene transfer, were used. CSDS evidently downregulated the level of miR-184-3p, but not miR-184-5p, in the PVN. Genetic knockdown and pharmacological inhibition of miR-184-3p in the PVN induced various depressive-like symptoms (e.g., abnormal behaviors, HPA hyperactivity, enhanced CRTC1 function in PVN neurons, downregulation of hippocampal neurogenesis, and decreased brain-derived neurotrophic factor (BDNF) signaling) in naïve male C57BL/6J mice. In contrast, genetic overexpression and pharmacological activation of miR-184-3p in the PVN produced significant beneficial effects against CSDS. MiR-184-3p in the PVN was necessary for the antidepressant actions of two well-known SSRIs, fluoxetine and paroxetine. Collectively. miR-184-3p was also implicated in the neurobiology of depression and may be a viable target for novel antidepressants., 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.)

Objective: The objective of this study was to evaluate the psychometric properties of the EQ-5D (3L and 5L) and SF-6Dv2 in a group of Chinese patients with late-on Pompe disease (PD), and compare their performance in this patient group., Methods: The data used in this study were obtained from a web-based and cross-sectional survey conducted in China. All participants completed the 3L, 5L, and SF-6Dv2. Information about their sociodemographic status and health conditions was also collected. The measurement properties were assessed by examining ceiling and floor effects, evaluating convergent validity, known-group validity, and test-retest reliability (Intraclass correlation coefficient [ICC] and Gwet's AC)., Results: A total of 117 PD patients completed the questionnaire. All dimensions of the 3L showed strong ceiling effects, ranging between 17.1 and 42.7%. All three measures showed good test-retest reliability, with ICC values ranging from 0.85 to 0.87. The Gwet's AC values showed that four out of five dimensions of the 3L showed very good agreement. All hypothesized correlations between the 3L, 5L, SF-6Dv2, and items of WHODAS were supported, indicating satisfactory convergent validity. The 5L showed stronger correlations (|r|= 0.53-0.84) with WHODAS than the other two measures. The outcomes of ANOVA indicated that the 5L had higher F-statistics than the 3L and SF-6Dv2, indicating a stronger discriminant ability to differentiate most condition groups., Conclusion: The 5L demonstrates lower ceiling and floor effects, higher discriminant ability, and better convergent validity than the SF-6Dv2 and 3L in patients with PD. In addition, the 5L may generate a larger utility gain compared to the other two instruments when conducting cost-effectiveness analysis., (© 2024. The Author(s).)

Obsessive-compulsive disorder (OCD) is a chronic, severe psychiatric disorder that has been ranked by the World Health Organization as one of the leading causes of illness-related disability, and first-line interventions are limited in efficacy and have side-effect issues. However, the exact pathophysiology underlying this complex, heterogeneous disorder remains unknown. This scenario is now rapidly changing due to the advancement of powerful technologies that can be used to verify the function of the specific gene and dissect the neural circuits underlying the neurobiology of OCD in rodents. Genetic and circuit-specific manipulation in rodents has provided important insights into the neurobiology of OCD by identifying the molecular, cellular, and circuit events that induce OCD-like behaviors. This review will highlight recent progress specifically toward classic genetic animal models and advanced neural circuit findings, which provide theoretical evidence for targeted intervention on specific molecular, cellular, and neural circuit events., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (© 2024. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Mitochondrial dysfunction is one of the hallmarks in the pathophysiology of prion disease and other neurodegenerative diseases. Various metabolic dysfunctions are identified and considered to contribute to the progression of some types of neurodegenerative diseases. In this study, we evaluated the status of glycolysis pathway in prion-infected rodent and cell models. The levels of the key enzymes, hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) were significantly increased, accompanying with markedly downregulated mitochondrial complexes. Double-stained IFAs revealed that the increased HK2 and PFK distributed widely in GFAP-, Iba1-, and NeuN-positive cells. We also identified increased levels of AMP-activated protein kinase (AMPK) and the downstream signaling. Changes of AMPK activity in prion-infected cells by the AMPK-specific inhibitor or activator induced the corresponding alterations not only in the downstream signaling, but also the expressions of three key kinases in glycolysis pathway and the mitochondrial complexes. Transient removal or complete clearance of prion propagation in the prion-infected cells partially but significantly reversed the increases of the key enzymes in glycolysis, the upregulation of AMPK signaling pathway, and the decreases of the mitochondrial complexes. Measurements of the cellular oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) showed lower OCR and higher ECAR in prion-infected cell line, which were sufficiently reversed by clearance of prion propagation. Those data indicate a metabolic reprogramming from oxidative phosphorylation to glycolysis in the brains during the progression of prion disease. Accumulation of PrP Sc is critical for the switch to glycolysis, largely via activating AMPK pathway., Competing Interests: Declarations. Ethics Approval: This study was performed in line with the principles of the Chinese Laboratory Animal Management. Approval was granted by the Research Ethics Committee of the National Institute for Viral Disease Control and Prevention, China CDC. Consent to Participate: Informed consent was obtained from all individual participants included in the study. Consent for Publication: The authors affirm that human research participants provided informed consent for publication of the images in figures. Competing Interests: The authors declare no competing interests., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Long non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of skeletal muscle development through multiple mechanisms. The present study revealed that the lncRNA SOX6 AU (SRY-box transcription factor 6 antisense upstream) is reverse transcribed from upstream of the bovine sex-determining region Y (SRY)-related high-mobility-group box 6 ( SOX6 ) gene. SOX6 AU was significantly differentially expressed in muscle tissue among different developmental stages in Xianan cattle. Subsequently, knockdown and overexpression experiments discovered that SOX6 AU promoted primary skeletal muscle cells proliferation, apoptosis, and differentiation in bovine. The overexpression of SOX6 AU in bovine primary skeletal muscle cells resulted in 483 differentially expressed genes (DEGs), including 224 upregulated DEGs and 259 downregulated DEGs. GO functional annotation analysis showed that muscle development-related biological processes such as muscle structure development and muscle cell proliferation were significantly enriched. KEGG pathway analysis revealed that the PI3K/AKT and MAPK signaling pathways were important pathways for DEG enrichment. Notably, we found that SOX6 AU inhibited the mRNA and protein expression levels of the SOX6 gene. Moreover, knockdown of the SOX6 gene promoted the proliferation and apoptosis of bovine primary skeletal muscle cells. Finally, we showed that SOX6 AU promoted the proliferation and apoptosis of bovine primary skeletal muscle cells by cis-modulation of SOX6 in cattle. This work illustrates our discovery of the molecular mechanisms underlying the regulation of SOX6 AU in the development of beef.

Significant progress has been made in the pathogenesis of chronic rhinosinusitis (CRS). However, the relationship between chronic rhinosinusitis with nasal polyps (CRSwNP) and ferroptosis, as well as its underlying molecular mechanism, remains unclear. This study aimed to investigate the correlation between CRSwNP and ferroptosis and identify key gene associated with ferroptosis that could impact the diagnosis and treatment of CRS. To achieve this, gene expression profiles containing CRSwNP and CRSsNP samples were obtained from the GEO database. In addition, from the FerrDb V2 database, we acquired 2 sets of genes that are connected with ferroptosis, giving us a combined number of 260 genes associated with this particular biological process. Differential analysis and weighted gene co-expression network analysis (WGCNA) were performed on nasal tissue samples from GSE36830, leading to the identification of 1 key gene related to ferroptosis and CRS. Using stepwise regression and logistic regression analysis, we constructed a diagnostic model for CRS using ALOX15. The AUC value demonstrates that the model exhibits a strong diagnostic performance. Furthermore, the connection between immune cell infiltration in the samples and hub gene was explored, suggesting the potential significance of the hub gene in the immune response to CRS. Finally, Five drugs targeting a central gene were identified from the DrugBank database, and a few of them have exhibited efficacy in the treatment of CRS or associated ailments. In conclusion, this model holds potential for supporting the diagnosis of CRS patients, while the central gene identified may contribute to a better understanding of CRS development and drug treatment., Competing Interests: The authors have on conflict of Interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The contrast-enhanced US (CEUS) Bosniak classification, proposed by the European Federation for Ultrasound in Medicine and Biology (EFSUMB) in 2020, predicts malignancy in cystic renal masses (CRMs). However, intra- and inter-rater reproducibility for CEUS features has not been well investigated., Purpose: To explore intra- and inter-rater agreement for US features, identify confounding features, and assess the diagnostic performance of CEUS Bosniak classification., Materials and Methods: This retrospective study included patients with complex CRMs who underwent CEUS examination from January 2013 to August 2023. Radiologists (3 experts and 3 novices) evaluated calcification, echogenic content, wall, septa, and internal nodules of CRMs using CEUS Bosniak classification. Intra- and inter-rater agreements were assessed using the Gwet agreement coefficient (Gwet's AC). Linear regression identified features associated with discrepancies in Bosniak category assignment. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC)., Results: A total of 103 complex CRMs were analyzed in 103 patients (mean age, 50 ± 15 years; 66 males). Intra-rater agreement for the Bosniak category was substantial to almost perfect (Gwet's AC 0.73-0.87). Inter-rater agreement was substantial for the Bosniak category (Gwet's AC 0.75) and moderate to almost perfect for US features (Gwet's AC 0.44-0.94). Nodule variation (i.e., absence vs. obtuse margin vs. acute margin) explained 84% of the variability in the Bosniak category assignment. CEUS Bosniak classification showed good diagnostic performance, with AUCs ranging from 0.78 to 0.90 for each rater., Conclusions: CEUS Bosniak classification demonstrated substantial intra- and inter-rater reproducibility and good diagnostic performance in predicting the malignancy potential of CRMs. Nodule variations significantly predicted differences in Bosniak category assignments., Critical Relevance Statement: Contrast-enhanced US Bosniak classification reliably predicts malignancy in cystic renal masses, demonstrating substantial reproducibility and diagnostic accuracy. This improves clinical decision-making and patient management., Key Points: Intra- and inter-rater reproducibility for contrast-enhance US features for Bosniak classification have not been well investigated. Substantial inter-rater agreements for the Bosniak category and variable agreements for determining imaging features were found. Contrast-enhanced US Bosniak classification is reproducible and has good diagnostic performance for predicting malignancy in cystic renal masses., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the ethics committees of The First Affiliated Hospital of Sun Yat-Sen University. Written informed consent was waived by the Institutional Review Board. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Numerous prospective cohort studies have investigated the influence of dietary patterns on the risks of various cancers, although the findings differed., Objective: To evaluate the associations of dietary patterns with risks of various cancers and assess the strength and validity of the evidence., Methods: Relevant articles were retrieved from the PubMed, EMBASE, Web of Science, and Cochrane library databases from inception to February 22, 2024. The included systematic reviews were meta-analyses of prospective cohort studies that reported an effect size to calculate the association between dietary patterns and cancer risk. The quality of the included studies was evaluated using a measurement tool to assess systematic reviews and the certainty of evidence was assessed using credibility assessment of evidence. Outcomes of interest included any incident cancers. This study was registered with PROSPERO (CRD42023425237)., Results: Overall, 74 meta-analyses from 30 articles were identified. Three meta-analyses (4.1%) were graded as convincing evidence and included associations between adherence to the 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) dietary recommendations (per 1-unit score increase) and lower risk of all cancers (relative risk [RR] = 0.93, 95% confidence interval [CI]: 0.92-0.95), while negative associations were found comparing the highest vs. lowest categories for a prudent diet (RR = 0.89, 95% CI: 0.85-0.93) and vegetable-fruit-soybean diet (RR = 0.87, 95% CI: 0.83-0.92) in relation to breast cancer. After credibility assessment of evidence by Grading of Recommendations, Assessment, Development, and Evaluation, four (5.4%) meta-analyses were classified as high, including adherence to the 2007 WCRF/AICR dietary recommendations and decreased risks of all cancers, breast cancer, colorectal cancer, and prostate cancer., Conclusion: These findings suggest that adherence to certain healthy dietary patterns is associated with lower risk of all cancers and certain individual cancers., Register: This study was registered with PROSPERO (CRD42023425237). crd.york.ac.uk/PROSPERO/display&#95;record.php?RecordID=425237., 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 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Objective: Although quetiapine has been approved for use in schizophrenic patients, its individualized dosage regimen remains unclear, especially with respect to drug-drug interactions (DDIs). Thus, we investigated the potential DDIs and optimal initial dosage of quetiapine in schizophrenic patients based on population pharmacokinetics (PPK)., Methods: Ninety-six schizophrenic patients treated with quetiapine were included to establish the PPK model, which also includes coadministration of multiple drugs., Results: It was found that the patient weights and fluvoxamine or duloxetine coadministration affected quetiapine clearance in schizophrenic patients. Without fluvoxamine or duloxetine coadministration, 16 and 12 mg/kg/day of quetiapine were recommended to schizophrenic patients whose weights were in the ranges of 40-50 and 50-120 kg, respectively. With fluvoxamine coadministration, 8 mg/kg/day of quetiapine was recommended to patients with weights in the range of 40-120 kg. With duloxetine coadministration, 8 mg/kg/day of quetiapine was recommended to patients with weights in the 40-120 kg range. With simultaneous coadministration of fluvoxamine and duloxetine, 4 mg/kg/day of quetiapine was recommended to patients with weights in the 40-120 kg range., Conclusion: The present study was a pilot effort at investigating the potential DDIs and optimal initial dosage of quetiapine in schizophrenic patients based on PPK. The initial dosages of quetiapine administered to the patients were optimized according to the coadministration of fluvoxamine or duloxetine., 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 Chen, Zhang, Yin, Jin, He, Liu, Zhang and Wang.)

The family Clausiliidae was proposed as a model for studying the diversity of breeding biology in land snails. This study assembled a nearly complete mitogenome (15,417 bp) for the clausiliid snail Euphaedusa aculus . The mitogenome includes 13 protein-coding genes (PCGs), two ribosomal RNAs, and 22 transfer RNAs, with a gene order consistent with other clausiliids. Most PCGs use ATN start codons and complete stop codons, except for atp6, nad4 , and nad5 , which start with TTG, and atp6, cox3 , and nad3 , which have incomplete stop codons. Phylogenetic analyses revealed that E. aculus is closely related to E. planostriata . This mitogenome provides a valuable molecular resource for future evolutionary research on land snails., Competing Interests: The authors report there are no competing interests to declare., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Amid growing concerns regarding gout and hyperuricemia associated with high-protein and purine-rich diets, the need for effective prevention and management strategies with minimal side effects has become increasingly critical. This study evaluates the potential of three commonly consumed plant-based functional foods, Chrysanthemum morifolium , Perilla frutescens , and Sophora japonica , inhibiting xanthine oxidase (XO) and adenosine deaminase (ADA), key enzymes in uric acid metabolism. Results from hyperuricemia model mice indicate that this blend significantly reduces serum uric acid levels, mirroring the efficacy of conventional prevention and management strategies such as allopurinol but with fewer adverse effects. Liquid chromatography-mass spectrometry (LC-MS) analysis confirms that flavonoids are the primary bioactive agents, exhibiting a strong affinity for XO. These findings highlight the viability of integrating plant-based functional foods into comprehensive gout management strategies, underscoring their role in enhancing patient health through dietary innovation.

Background: The novel nanomaterials PNA-TN (PN) and PNA-TN-Dox (PND) have been shown to have strong inhibitory effects on breast cancer; however, it is unclear whether PN and PND have anti-head and neck squamous cell carcinoma (HNSCC) activity, and their potential mechanisms of activity are unknown. So, our study aims to explore the therapeutic effects of PN and PND on HNSCC and their possible mechanisms., Methods: We used a series of phenotypic research to evaluate the effects of PN + Laser (L) and PND + L on the biological function of HNSCC cells in vitro and in vivo. We subsequently used mechanism research to examine changes in mRNA and protein expression related to apoptosis, epithelial‒mesenchymal transition (EMT), and the JNK signalling pathway., Results: Our study revealed that PN and PND have strong inhibitory effects on HNSCC cells both in vitro and in vivo. In vitro, PN and PND significantly inhibited the proliferation, migration, invasion and EMT ability of HNSCC cells and promoted apoptosis; the inhibitory effect in the PND + L group was significantly greater than that in the PN + L group. In vivo, both treatments led to significant reductions in tumour volume and weight. Notably, the tumour volume and weight in the PND + L group were significantly lower than those in the PN + L group. Mechanism research confirmed that PN + L activated the expression of apoptosis-related proteins and inhibited the expression of EMT-related proteins via the JNK pathway. Furthermore, the anti-HNSCC effect of PN + L was blocked after the use of a JNK pathway inhibitor., Conclusion: Treatment with PN + L or PND + L significantly inhibited the malignant progress of HNSCC cells, and the therapeutic effect of PND + L was significantly stronger than that of PN + L. The JNK signalling pathway is a key mechanism by which PN exerts its anti-HNSCC activity., Competing Interests: Declarations Ethics approval and consent to participate The Laboratory Animal Welfare and Ethics Committee of Renmin Hospital of Wuhan University reviewed and approved the animal procedures (Approval No: WDRM20240704B). All animal experiments were conducted following the NIH Guide for the Care and Use of Laboratory Animals (NIH Publication No. 80 − 23; revised 1978). Consent for publication All authors have confirmed that all data from this study is publishable and have seen the final version of the article for publication. Written informed consent for publication was obtained from all participants. Competing interests The authors report no conflicts of interest in this work., (© 2024. The Author(s).)

Background: Stair climbing test (SCT) and gait speed test (GST) are two physical performance measures, both of which are associated with postoperative outcomes. However, few studies have compared these two tests for the prognostic value., Methods: A prospective study was conducted in patients undergoing radical gastrectomy for gastric cancer. Handgrip strength (HGS) test, 7-steps SCT and 6-m GST were performed before surgery. Body compositions were analyzed using abdominal computed tomography (CT). Sarcopenia was diagnosed by low HGS plus either low muscle mass or quality., Results: A total of 548 patients were included in this study. Time of GST and SCT were both significantly correlated with HGS, skeletal muscle index and skeletal muscle density, but not with subcutaneous or visceral fat area. Low SCT performance (SCT time ≥12.65s) was associated with higher incidence of postoperative complications and longer postoperative length of stay, whereas low GST performance (GST time ≥5.45s) did not. Low performance in SCT and GST were both associated with worse overall survival (OS) and disease-free survival (DFS) after surgery. Low SCT performance was an independent predictor for postoperative complications, OS, and DFS, whereas low GST performance was not significant in multivariate analyses adjusting for the same covariates. The combination of sarcopenia with low SCT performance showed higher accuracy in predicting postoperative complications and mortality compared with sarcopenia combined with low GST performance., Conclusion: SCT outperformed GST in predicting outcomes after radical gastrectomy for gastric cancer, either as a singular indicator or in combination with sarcopenia assessments., 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, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Fermented fruit drinks (FFDs) are gaining popularity among consumers for their unique flavors and potential health benefits. This review provides a systematic assessment of the flavor components in FFDs and explores the metabolic pathways for their formation. We examine the interactions between the structure of microbial communities and the development of these flavor components, highlighting the role of microorganisms in shaping the unique taste of FFDs. Additionally, we discuss the potential health benefits associated with FFDs, focusing on their relationship with microbial communities as supported by existing literature. The review also addresses future prospects and challenges in the field. Our findings indicate key fermenting microorganisms, such as lactic acid bacteria, yeast and acetic acid bacteria, are responsible for producing the distinctive flavor components in FFDs, including alcohols, ketones, aldehydes, esters, and fatty acids. These microorganisms also generate organic acids, amino acids, and carbohydrates, contributing to the drink's complex taste. Furthermore, this fermentation process enhances the bioactivity of FFDs, offering potential health benefits like antioxidant, anti-obesity, anti-diabetic, and anti-cancer properties. These insights are crucial for advancing fermentation technology and developing guidelines for producing nutrient-rich, flavorful FFDs., 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.)

Objectives: The purposes of this study were to (i) verify the role of CXCR2 in tacrolimus-induced nephrotoxicity, (ii) explore the specific mechanism of CXCR2-mediated tacrolimus nephrotoxicity, and (iii) target the antagonism of CXCR2 and provide a potential target for the treatment of tacrolimus-induced nephrotoxicity in children., Methods: CXCR2 knockout (CXCR2-KO) mice were used to evaluate the role of CXCR2 in tacrolimus-induced nephrotoxicity. Wistar rats were used to explore the underlying mechanism., Results: In the knockout mice, compared with N-WT group, the renal function index was deteriorative (P < 0.01), the degree of renal fibrosis was aggravated (P < 0.01), the pathological expression of E-cadherin (P < 0.01) and α-SMA (P < 0.01) were occurred in T-WT group. Inversely, compared with T-WT group, the above indicators were improved in T-KO group (P < 0.01). In wistar rats, compared with N group, the renal function index was deteriorative (P < 0.05 or P < 0.01), fibrosis and calcium overload occurred (P < 0.01), CXCL2-CXCR2 was activated (P < 0.05), and meanwhile PI3K/AKT/mTOR pathway was activated (P < 0.05 or P < 0.01) in T group. Inversely, compared with T group, the above indicators were reversed in C group (P < 0.05 or P < 0.01)., Conclusion: The present study was firstly to report that CXCL2-CXCR2 activated PI3K/AKT/mTOR pathway and calcium overload in tacrolimus-induced nephrotoxicity, and targeting CXCR2 could inhibit the progression of tacrolimus-induced nephrotoxicity., 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 Masson SAS.. All rights reserved.)

The mutual regulation between hydrogen sulfide (H 2 S) and microRNA (miRNA) is involved in the development of many diseases, including cancer, cardiovascular disease, inflammatory disease, and high-risk pregnancy. Abnormal expressions of endogenous H 2 S-producing enzyme and miRNA in tissues and cells often indicate the occurrence of diseases, so the maintenance of their normal levels in the body can mitigate damages caused by various factors. Many studies have found that H 2 S can promote the migration, invasion, and proliferation of cancer cells by regulating the expression of miRNA, while many H 2 S donors can inhibit cancer progression by interfering with the proliferation, apoptosis, cell cycle, metastasis, and angiogenesis of cancer cells. Furthermore, the mutual regulation between H 2 S and miRNA can also prevent cell injury in cardiovascular disease and inflammatory disease through anti-inflammation, anti-oxidation, anti-apoptosis, and pro-autophagy. In addition, H 2 S can promote angiogenesis and relieve vasoconstriction by regulating the expression of miRNA, thereby improving fetal growth in high-risk pregnancy. In this review, we discuss the mechanism of mutual regulation between H 2 S and miRNA in various diseases, which may provide reliable therapeutic targets for these diseases., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hydrogen sulfide (H 2 S), an endogenous gasotransmitter, plays a key role in several critical physiological and pathological processes in vivo, including vasodilation, anti-infection, anti-tumor, anti-inflammation, and angiogenesis. In colorectal cancer (CRC), aberrant overexpression of H 2 S-producing enzymes has been observed. Due to the important role of H 2 S in the proliferation, growth, and death of cancer cells, H 2 S can serve as a potential target for cancer therapy. In this review, we thoroughly analyzed the underlying mechanism of action of H 2 S in CRC from the following aspects: the synthesis and catabolism of H 2 S in CRC cells and its effect on cell signal transduction pathways; the inhibition effects of exogenous H 2 S donors with different concentrations on the growth of CRC cells and the underlying mechanism of H 2 S in garlic and other natural products. Furthermore, we elucidate the expression characteristics of H 2 S in CRC and construct a comprehensive H 2 S-related signaling pathway network, which has important basic and practical significance for promoting the clinical research of H 2 S-related drugs., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The genus Neocaridina , originating from East Asia and representing a small-size landlocked shrimp group of the family Atyidae, is an important group of ornamental shrimps and plays significant ecological roles in their natural habitats. Owing to the considerable variability of the taxonomic characters it employed, Neocaridina is constantly under revision, and the validation of several species is currently questionable. In the present study, several Neocaridina shrimps were collected from the Baiyangdian drainage area. Through morphological examination, they exhibited delicately diagnostical differences in the dactyli of the third pereiopod and the endopod of the first and second pleopod and were classified into morph A, morph B and morph C. According to the literature description, morph A and morph C were identified as N. denticulata denticulata and N. denticulata sinensis , respectively. Among them, morph B presents an intermediate state between morph A and morph C. Subsequently, we determined the mitogenomes of morph A, morph B and morph C. Based on the morphological characteristics, genetic variation and phylogenetic tree, we contend that N. davidi , N. d. denticulata , N. d. sinensis and N. heteropoda should belong to the same species, and we propose retaining the name N. denticulata . The reconstructed mitogenomic phylogeny indicated that the monophyly of several genera within Atyidae has been challenged, suggesting that the established classification of Atyidae requires substantial taxonomic revision at all taxonomic levels. Furthermore, the tree's topologies supported Atyidae at a deeper base within Caridea. More comprehensive taxon sampling is still needed to resolve the explicit internal relationships among Caridea.

Background: Retronychia, a condition marked by abnormal nail growth, is frequently underdiagnosed and misinterpreted, with a few reported cases in the literature., Objective: To investigate the pathophysiology, identify contributing factors, and assess the outcomes of surgical and nonsurgical treatments for retronychia., Methods and Materials: A retrospective review of 107 retronychia cases diagnosed at the center between January 2021 and July 2022 was conducted., Results: Predisposing factors were identified in 93.46% of cases, with 88.79% of patients reporting a habit of wearing socks during sleep before symptom onset. Noninvasive treatments targeting these factors led to full recovery in 79.55% of cases, while 13.64% experienced partial improvement, inducing reduced proximal nail fold inflammation. Nail avulsion, which involves removing the entire nail, achieved a relapse-free cure rate of 90.91%. When the innermost nail plate was preserved, the cure rate rose to 96.67%., Conclusion: Chronic mechanical forces, frequently overlooked, play a pivotal role in retronychia onset and progression. Conservative management targeting these mechanical factors is recommended for patients with mild cases., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Within long-term care facilities, paraprofessional nursing assistants account for the largest proportion of the health care workforce and provide essential direct care to older people with complex care needs. There is a gap in developing a theory-driven, systematic synthesis of the job characteristics and well-being outcomes specific to this occupational group, as most existing studies evaluate either professional health care workers or both professional and nursing assistants., Aim: Develop an occupation-specific conceptual model on the job characteristics and well-being of nursing assistants in long-term care facilities drawing upon the job demands-resources model., Design: Mixed methods systematic review following the Joanna Briggs Institute approach. The review protocol was registered on PROSPERO (2023 CRD42023403654)., Methods: The review included qualitative, quantitative, and mixed-method studies meeting these inclusion criteria: (1) peer-reviewed empirical research; (2) involved paraprofessional nursing assistants in long-term care facilities; (3) addressed well-being outcomes; (4) addressed occupation-specific job characteristics. Studies that are (1) not written in English, or (2) published before 1 January 2000 were excluded. A convergent synthesis approach was conducted using the content analysis method., Data Sources: Database searches (i.e., MEDLINE, PsycINFO, Embase, CINAHL, Web of Science, Scopus, and Google Scholar) and manual searches were conducted. The last search was conducted on July 31st, 2024., Results: A Nursing Assistants Job Demands-Resources Model was developed based on 21 studies included. Nursing assistants are particularly vulnerable to burnout and mental health conditions, as well as occupational hazards, because of their job characteristics. Working time demands, physical care task stressors, and emotional demands are occupation-relevant job demands, while financial rewards, professional development resources, work environment, and emotional resources are motivational job resources. Strain-related personal characteristics are also relevant to nursing assistants. Findings indicated a spiral of vulnerabilities characterized by the vicious cycle of individual vulnerabilities, poor quality job, and health inequalities among nursing assistants in long-term care facilities., Conclusion: This study finds that empirical evidence on nursing assistants' job characteristics and well-being is underdeveloped compared to research focusing on professional and all health care workers. We adapt a conceptual model and identify job and personal characteristics specific to the occupation group. Occupational-specific macro, meso, and micro-level strategies that mitigate job demands and nurture job resources should be developed to tackle the occupational health disparities that nursing assistants face in long-term care facilities., Registration: The protocol of this study was registered on PROSPERO (2023 CRD42023403654)., Competing Interests: Declaration of competing interest This work was supported by Hong Kong Research Grant Council General Research Fund (grant number 13604323)., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Streptococcus agalactiae (S. agalactiae) is a highly pathogenic bacterial pathogen in aquatic animals. Our previous study has demonstrated the significant inhibitory effect of baicalin on β-hemolytic/cytolytic activity, which is a key virulence factor of S. agalactiae. In this study, we aimed to elucidate the mechanism underlying baicalin's inhibition of S. agalactiae β-hemolytic/cytolytic activity by transcriptomic analysis. Bacteria were exposed to 39.06 µg/mL baicalin for 6 h, and their β-hemolytic/cytolytic activities were assessed using blood plates. Then, the differentially expressed genes (DEGs) were identified and characterized by RNA sequencing (RNA-Seq), and further confirmed using the qRT-PCR. A total of 10 DEGs with 7 significantly up-regulated and 3 significantly down-regulated, were found to be affected significantly under baicalin treatment. These DEGs were associated with 5 biological processes, 5 cellular components, and 3 molecular functions. They were primarily enriched in 3 pathways: lacD and lacC in galactose metabolism, lrgA and lrgB in the two-component system, and ribH/rib4 in riboflavin metabolism. These suggested that baicalin might inhibit the conversion of pyruvate to acetyl-CoA and malonyl-CoA, which are crucial precursors for β-hemolysin/cytolysin synthesis, and result in the accumulation of pyruvate, suppress the expressions of pyruvate cell membrane channel protein genes lrgA and lrgB. Baicalin could compensatory up-regulate the expressions of tryptophan/tyrosine ABC transporter family genes, ABC.X4.A, ABC.X4.P, and ABC.X4.S by inhibiting the expression of cyl A/B in cyl operons. Moreover, it hinders the conversion of D-glucose 1-phosphate to the dTDP-L-rhamnose pathway and leads to a deficiency of L-rhamnose, an important precursor for β-hemolysin/cytolysin synthesis., (© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Objective: This study aimed to evaluate the measurement properties of EQ-5D-5 L, SF-6Dv2, QLU-C10D, and FACT-8D in survivors of Classical Hodgkin's Lymphoma (CHL)., Methods: A cross-sectional, web-based survey was conducted from May to August 2022 to collect data. Chinese value sets were used to estimate the utility scores for EQ-5D-5 L, SF-6Dv2, and QLU-C10D, while the Australian value set was used for FACT-8D. The measurement properties assessed included ceiling and floor effects, convergent validity (assessing associations between similar dimensions/utility scores using Spearman's rank correlation and intraclass correlation coefficient), and known-group validity (measures could differentiate health-related quality of life (HRQoL) between risk groups)., Results: A total of 534 CHL survivors participated in the survey and completed the questionnaire. All dimensions of EQ-5D-5 L, SF-6D (except for vitality), QLU-C10D, and FACT-8D showed ceiling effects, ranging from 18 to 91.6%. The EQ-5D-5 L demonstrated the higher ceiling effects compared to other measures, with 33% of patients reporting full health on this scale. All 30 pairs of associations between similar dimensions from the four measures were statistically significant, with correlation coefficients ranging from 0.29 to 0.77. Regarding utility scores, the EQ-5D-5 L utility score showed a stronger correlation with SF-6Dv2 than with the other two measures. Statistically significant correlations of utility scores between the four measures were observed. EQ-5D-5 L can significantly differentiate HRQoL among all known-groups, while SF-6Dv2, QLU-C10D, and FACT-8D showed a less strong discriminant ability., Conclusions: EQ-5D-5 L outperformed SF-6Dv2 in terms of agreement with cancer-specific PRMs and discriminant ability. However, SF-6Dv2 showed stronger associations with similar dimensions of QLU-C10D and FACT-8D, indicating high convergent validity. The generic PBMs are sensitive enough to measure HRQoL in survivors of CHL., (© 2024. The Author(s).)

Atherosclerosis (AS) and its related cardiovascular diseases (CVDs) remain the most frequent cause of morbidity and mortality worldwide. Researches showed that bisphenol A (BPA) exposure might exacerbate AS progression. However, as an analogue of BPA, little is known about the cardiovascular toxicity of bisphenol S (BPS), especially whether BPS exposure has the pro-atherogenic effects in mammals is still unknown. Here, we firstly constructed an apolipoprotein E knockout (ApoE -/- ) mouse model and cultured cells to investigate the risk of BPS on AS and explore the underlying mechanisms. Results showed that prolonged exposure to 50 μg/kg body weight (bw)/day BPS indeed aggravated AS lesions both in the en face aortas and aortic sinuses of ApoE -/- mice. Moreover, BPS were found to be implicated in the AS pathological process: 1) stimulates adhesion molecule expression to promote monocyte-endothelial cells (ECs) adhesion with 3.6 times more than the control group in vivo; 2) increases the distribution of vascular smooth muscle cells (VSMCs) with 9.3 times more than the control group in vivo, possibly through the migration of VSMCs; and 3) induces an inflammatory response by increasing the number of macrophages (MACs), with 3.7 times more than the control group in vivo, and the release of inflammatory mediators. Furthermore, we have identified eight significant AS-related genes induced by BPS, including angiopoietin-like protein 7 (Angptl17) and lipocalin-2 (Lcn2) in ECs; matrix metalloproteinase 9 (Mmp13), secreted phosphoprotein 1 (Spp1), and collagen type II alpha 1 (Col2a1) in VSMCs; and kininogen 1 (Kng1), integrin alpha X (Itgax), and MAC-expressed gene 1 (Mpeg1) in MACs. Overall, this study firstly found BPS exposure could exacerbate mammalian AS and might also provide a theoretical basis for elucidating BPS and its analogues induced AS and related CVDs., 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: Right ventricular (RV) fibrosis is an important pathological change that occurs during the development of right heart failure (RHF) induced by pulmonary hypertension (PH). Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has been shown to play a major role in left heart failure, but it is unclear whether it has a positive effect on RHF. This study aimed to clarify the effect of DAPA on PH-induced RHF and investigate the underlying mechanisms., Methods: We conducted experiments on two rat models with PH-induced RHF and cardiac fibroblasts (CFs) exposed to pathological mechanical stretch or transforming growth factor-beta (TGF-β) to investigate the effect of DAPA., Results: In vivo, DAPA could improve pulmonary hemodynamics and RV function. It also attenuated right heart hypertrophy and RV fibrosis. In vitro, DAPA reduced collagen expression by increasing the production of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9). Additionally, DAPA was found to reduce reactive oxygen species (ROS) levels in CFs and the right heart in rats. Similar to DAPA, the ROS scavenger N-acetylcysteine (NAC) exerted antifibrotic effects on CFs. Therefore, we further investigated the mechanism by which DAPA promoted collagen degradation by reducing ROS levels., Conclusions: In summary, we concluded that DAPA ameliorated PH-induced structural and functional changes in the right heart by increasing collagen degradation. Our study provides new ideas for the possibility of using DAPA to treat RHF., 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.)

Significance: Musculoskeletal diseases seriously affect global health, but their importance is greatly underestimated. These diseases often afflict the elderly, leading to disability, paralysis, and other complications. Hydrogen sulfide (H 2 S) plays an important role in the occurrence and development of musculoskeletal diseases, which may have potential therapeutic significance for these diseases. Recent Advances: Recently, it has been found that many musculoskeletal diseases, such as osteoporosis, periodontitis, muscle atrophy, muscle ischemia-reperfusion injury, muscle contraction under high fever, arthritis, and disc herniation, can be alleviated by treatment with H 2 S. H 2 S may be conducive to the development of multiple myeloma. The mechanism of action of H 2 S in the musculoskeletal system has been partly elucidated. A variety of H 2 S donors and nano-delivery systems provide promising prospects for H 2 S-based therapies. Critical Issues: Related research remains at the level of cell or animal experiments, but clinical research is lacking. The roles of H 2 S in more musculoskeletal disorders remain largely unknown. The serious consequences of musculoskeletal diseases have not been widely concerned. Targeted delivery of H 2 S remains a challenging task in musculoskeletal diseases. Future Directions: Develop therapeutic drugs for musculoskeletal diseases based on H 2 S and test their safety, efficacy, and tolerance. Explore the combination of current drugs for musculoskeletal diseases with H 2 S-releasing components to improve the therapeutic efficacy and avoid side effects. Carry out relevant clinical trials to verify the possibility of its widespread use. Antioxid. Redox Signal. 00, 000-000.

Background: Recurrent pregnancy loss (RPL) affects women's reproductive health seriously, with immune dysfunction playing a key role in its cause, yet the exact mechanisms remain elusive. We aim to investigate potential mechanisms and identify biomarkers linked to RPL., Methods: Immune cytokine testing and metabolomic profiling were conducted on the serum of 34 RPL patients and 30 healthy individuals. The metabolic pathways of the differential metabolites were analyzed, and specific metabolites were validated through targeted profiling. Potential biomarkers were identified, and the relationships between immune cytokines and differential metabolites were explored., Results: In the RPL group, serum interleukin-6 and interleukin-10 levels were significantly higher, while interleukin-2 and interferon-γ were significantly lower. A total of 296 differential metabolites were detected by untargeted metabolomic profiling between the RPL and control groups, with most linked to amino acid metabolism. Targeted metabolomic profiling of amino acid metabolism revealed upregulation of indole-3-acetic acid, tyrosine, glycine, isoleucine, tryptophan, lysine, aspartic acid, arginine, leucine, threonine, glutamic acid, cystine, and phenylpyruvic acid (PPA) in the RPL group. Moreover, PPA and 5-hydroxy-L-tryptophan showed great potential in predicting RPL in a diagnostic model. Cystine and tyrosine were associated with immune cytokines in correlation analysis., Conclusion: The study highlights the role of amino acid metabolism in RPL pathogenesis, suggesting that PPA and 5-HTP may be potential predictive indicators, while cystine and tyrosine may potentially regulate immune responses related to RPL. Further investigation into the molecular mechanisms underlying these findings could potentially result in the creation of novel diagnostic and therapeutic approaches for RPL., 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 Ye, Ma, Guo, Guo, Li, Zhou, Hu, Hong, Xie and Wang.)

Fatigue is one of the common symptoms in individuals with diseases or disorders, significantly affecting quality of life (QoL) and the prognosis of diseases. This study aimed to comprehensively compare the features of fatigue across a wide range of diseases. We systematically searched the PubMed and Cochrane Library databases from inception to March 31st, 2021, and conducted a meta-analysis to generate precise estimates. The analyses were stratified by classification of diseases, gender, and severity of fatigue (moderate and severe), and study quality was assessed using the Newcastle-Ottawa Scale (NOS). In total, 214 articles (233 prevalence data) met our eligibility criteria, covering 102,024 participants (mean 438 ± 1,421) across 88 diseases. Among these, seventy-eight data sets (52,082 participants) and thirty-nine data sets (10,389 participants) reported gender- and severity-related fatigue prevalence. The overall prevalence among subjects with 88 diseases was 49.4% [95% CI 46.9-52.1]. According to the International Classification of Diseases-10 (ICD-10) classification, the highest prevalence of fatigue (65.9% [95% CI 54.9-79.6]) was observed in patients with mental/behavioral diseases, whereas the lowest prevalence (34.7% [95% CI 24.5-49.2]) was found among those with circulatory system diseases. A slight female dominance (43.5% vs. 49.8%) was observed in the total data, with the most notable female predominance (1.8-fold) seen in patients with low back pain. The top disease groups with a moderate to severe level of fatigue included gastroparesis (92.3%), pulmonary hypertension (90.0%), chronic obstructive pulmonary disease (COPD, 83.2%), and multiple sclerosis (80.0%). These results are the first to comprehensively show the comparative features of fatigue prevalence among subjects across 88 diseases. Our findings provide valuable reference data for future research on fatigue and for the management of patients with fatigue.Prospero registration number: CRD42021270494., (© 2024. The Author(s).)

Changes in mechanosensitive ion channels following radiation have seldom been linked to therapeutic sensitivity or specific factors involved in antitumor immunity. Here, in this study, we found that the mechanical force sensor, Piezo2, was significantly upregulated in tumor cells after radiation, and Piezo2 knockout in tumor cells enhanced tumor growth suppression by radiotherapy. Specifically, loss of Piezo2 in tumor cells induced their IL-15 expression via unleashing JAK2/STAT1/IRF-1 axis after radiation. This increase in IL-15 activates IL-15Rα on tumor-infiltrating CD8+ T cells, thereby leading to their augmented effector and stem cell-like properties, along with reduced terminal exhausted feature. Importantly, Piezo2 expression was negatively correlated with CD8 infiltration, as well as with radiosensitivity of patients with rectum adenocarcinoma receiving radiotherapy treatment. Together, our findings reveal that tumor cell-intrinsic Piezo2 induces radioresistance by dampening the IRF-1/IL-15 axis, thus leading to impaired CD8+ T cell-dependent antitumor responses, providing insights into the further development of combination strategies to treat radioresistant cancers., (© 2024 Miao et al.)

Gasotransmitters are endogenous gaseous signaling molecules that can freely pass through cell membranes and transmit signals between cells, playing multiple roles in cell signal transduction. Due to extensive and ongoing research in this field, we have successfully identified many gasotransmitters so far, among which nitric oxide, carbon monoxide, and hydrogen sulfide are best studied. Gasotransmitters are implicated in various diseases related to necroptosis, such as cardiovascular diseases, inflammation, ischemia-reperfusion, infectious diseases, and neurological diseases. However, the mechanisms of their effects on necroptosis are not fully understood. This review focuses on endogenous gasotransmitter synthesis and metabolism and discusses their roles in necroptosis, aiming to offer new insights for the therapeutic approaches to necroptosis-associated diseases., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure. We administered hydroxylamine hydrochloride (HA), a cystathionine-β-synthase inhibitor, into the PVN to suppress endogenous hydrogen sulfide and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt (HS)-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the normal salt (NS) + PVN vehicle group, the NS + PVN HA group, the HS + PVN vehicle group, and the HS + PVN HA group, with 10 rats in each group. The rats in the NS groups were fed a NS diet containing 0.3% NaCl, while the HS groups were fed a HS diet containing 8% NaCl. The mean arterial pressure was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H 2 S in the PVN and plasma norepinephrine using enzyme linked immunosorbent assay. In addition, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time polymerase chain reaction. In this study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of HS-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Four new diterpenoid tropolones, salvirrddones A-D (1-4), and four new icetexanes, salvirrddices A-D (9-12), along with thirteen new 11,12-seco-norabietane diterpenoids, salvirrddnor A-M (14-24, 31, 32) and sixteen known compounds (5-8, 13, 25-30, 33-37), were isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Their structures were elucidated by comprehensive spectroscopic analyses, quantum chemical calculations, and X-ray crystallography. Structurally, compounds 1-8 represent a class of rare natural products featuring a unique cyclohepta-2,4,6-trienone moiety with diterpenoid skeletons. Bioassays showed that only diterpenoid tropolones 3, 5, 6, and 7 exhibited significant activity against several human cancer cell lines with IC 50 values ranging from 3.01 to 11.63 μM. Additionally, 3 was shown to inhibit Hep3B cell proliferation, block the G0/G1 phase of the cell cycle, induce mitochondrial dysfunction and oxidative stress, promote apoptosis, as well as inhibit migration and invasion in vitro. Meanwhile, 3 demonstrated anti-proliferative, pro-apoptotic, and migration-inhibitory effects in the Hep3B xenograft zebrafish model in vivo. Network pharmacological analysis and molecular docking results suggested that 3 may treat hepatocellular carcinoma (HCC) through the PI3K-Akt signaling pathway, as well as by binding PARP1 and CDK2 targets. Overall, the present results extremely expand the repertoire of diterpenoids from natural products and may provide a novel chemical scaffold for the discovery of new antitumor drugs., 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 Inc. All rights reserved.)

Constructing local microenvironments is one of the important strategies to improve the electrocatalytic performances, such as in electrochemical CO 2 reduction (ECR). However, effectively customizing these microenvironments remains a significant challenge. Herein, utilizing carbon nanotube (CNT) heterostructured semi-open Co-N 2 O 2 catalytic configurations (Co-salophen), we have demonstrated the role of the local microenvironment on promoting ECR through regulating the location of hydroxyl groups. Concretely, compared with the maximum Faradaic efficiency (FE) of 62% for carbon monoxide (CO) presented by Co-salophen/CNT without a hydroxyl microenvironment, the designed Co-salophen-OH 3 /CNT, featuring hydroxyl groups at the Co-N 2 O 2 structural opening, shows remarkable CO 2 -to-CO electroreduction activity across a wide potential window, with the FE of CO up to 95%. In particular, through the deuterium kinetic isotope experiments and theoretical calculations, we decoded that the hydroxyl groups act as a proton relay station, promoting the efficient transfer of protons to the Co-N 2 O 2 active sites. The finding demonstrates a promising molecular design strategy for enhancing electrocatalysis., 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 Inc. All rights reserved.)

Background: Primary lung cancer is the leading cause of cancer-related death worldwide. Common metastatic sites include the brain, liver, bones, and adrenal glands. However, gastric metastases from lung cancer are rare. This case may be the first report of a combined gastroscopic and laparoscopic resection for gastric metastatic adenosquamous carcinoma (ASC)., Case Summary: We report a case of gastric metastasis from lung cancer. The patient was a 61-year-old Han Chinese female who first attended our hospital complaining of a persistent cough, leading to the diagnosis of advanced-stage lung adenocarcinoma. After more than four years of chemotherapy, the patient began to experience epigastric pain. Endoscopy was performed, and pathological examination of biopsy specimens confirmed that the gastric lesion was a metastasis from lung cancer. The lesion was successfully resected by combined gastroscopy and laparoscopy. Histopathological examination of the resected gastric specimen revealed ASC., Conclusion: Gastric metastases from lung cancer are rare. Endoscopy, histological and immunohistochemical staining are useful for diagnosing metastatic lesions. Surgical management may provide extended survival in appropriately selected patients., Competing Interests: Conflict-of-interest statement: All authors declare no competing financial interests for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Different initial manifestations of peritoneal dialysis-associated peritonitis (PDAP) may depend on the type of pathogenic organism. We investigated the association between the clinical characteristics of PDAP and susceptibility to vancomycin and investigated the possibility of using vancomycin monotherapy alone as an initial treatment regimen for some PDAP patients to avoid unnecessary antibiotic exposure and secondary infection., Methods: Patients with culture-positive PDAP were retrospectively analyzed and divided into two groups: peritonitis with only cloudy effluent (PDAP-cloudy) or with cloudy effluent, abdominal pain and/or fever (PDAP-multi). The bacterial culture of PD effluent and antibiotic sensitivity test results were compared between groups. Logistic regression was used to investigate factors predicting susceptibility to vancomycin., Results: Of 162 episodes of peritonitis which had a positive bacterial culture of PD fluid, 30 peritonitis were in the PDAP-cloudy group, and 132 peritonitis were in the PDAP-multi group. Thirty (100%) peritonitis in the PDAP-cloudy group had gram-positive bacterial infections, which was significantly greater than that in the PDAP-multi group (51.5%) (P < 0.001). Twenty-nine (96.7%) peritonitis in the PDAP-cloudy group were susceptible to vancomycin, compared to 67 (50.8%) in the PDAP-multi group (P < 0.001). The specificity of PDAP-cloudy for vancomycin-sensitive peritonitis was 98.48%. Only one patient (3.3%) in the PDAP-cloudy group experienced vancomycin-resistant peritonitis caused by Enterococcus gallinarum, which could neither be covered by vancomycin nor by the initial antibiotic regimen recommended by the current ISPD guidelines. The presence of only cloudy effluent was an independent predictor of susceptibility to vancomycin according to multivariate analysis (OR = 27.678, 95% CI 3.191-240.103, p = 0.003), in addition to PD effluent WBC counts (OR = 0.988, 95% CI 0.980-0.996, p = 0.004), diabetes mellitus (OR = 3.646, 95% CI 1.580-8.416, p = 0.002), first episode peritonitis (OR = 0.447, 95% CI 0.207-0.962, p = 0.039) and residual renal creatinine clearance (OR = 0.956, 95% CI 0.918-0.995, p = 0.027). Addition of these characteristics increased the AUC to 0.813 (95% CI 0.0.749-0.878, P < 0.001). The specificity of presenting with only cloudy effluent for vancomycin-sensitive peritonitis was 98.48%., Conclusions: Cloudy dialysate, as the only symptom at PDAP onset, was an independent predictor of vancomycin-sensitive PDAP, which is an important new insight that may guide the choice of initial antibiotic treatment., (© 2024. The Author(s).)

Objectives: To explore the risk factors of early postoperative taste disturbance (EPTD) after type I endoscopic tympanoplasty and operative modification strategies to improve taste disturbance. Methods: This was a controlled study. One hundred and twenty-four patients who underwent type I endoscopic tympanoplasty with tragal cartilage graft were separated evenly into control and modified groups. The full-thickness tragus cartilage graft was placed close to the bony annulus to ensure drum integrity in the control group, and in the modified group, the cartilage graft was not in contact with the posterior-superior bony annulus, and the inferior-posterior of the scutum. Univariate and multivariate models were used to analyze the possible factors affecting EPTD and the prognosis of taste recovery. Results: The incidence of EPTD was significantly lower in the modification group (24.19%) than in the control group (56.45%) (OR: 4.24, 95% CI: 1.93-9.33, P < .001). Surgical manipulation of the chorda tympani nerve resulted in a higher incidence of EPTD (OR: 2.43; 95% CI: 1.06-5.57, P = .035). The size of the graft did not affect taste disturbance. No difference in the taste recovery rate was observed between the control and test groups ( Z = -1.57, P = .116) after 3 months. The recovery rate of patients with manipulated chorda tympani nerves was still lower than that of patients without at 3 months ( Z = -2.74, P = .006). Conclusion: Modified surgery and reduced manipulation of the chorda tympani nerve effectively reduce EPTD. Manipulated chorda tympani nerves may have a persistent effect on taste recovery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Endoscopic nasopharyngectomy represents a significant intervention for recurrent nasopharyngeal carcinoma (NPC). Various surgical techniques, including transnasal and transoral approaches, are employed. However, the impact of these procedures on nasal airflow dynamics is not well understood. This computational fluid dynamics (CFD) study aimed to investigate alterations in nasal airflow and air conditioning following endoscopic nasopharyngectomy. A 55-year-old male patient with recurrent NPC was selected, whose CT data were utilized for image reconstruction. A preoperative model and two postoperative models, including the transnasal and transoral approach models, were established. The airflow patterns and various CFD parameters were analyzed. In the postoperative models, the high-speed airflow went along the soft palate and into the nasopharyngeal outlet, and there was the low-speed turbulence in the expanded nasopharyngeal cavity. Compared to the preoperative model, the postoperative models exhibited reductions in surface-to-volume ratio, nasal resistance, airflow velocity and proportion of high wall shear stress regions in nasopharynx. The changing trends of nasopharyngeal air temperature and humidity in the preoperative and transoral models were consistent. The heating and humidification efficiency decreased in the transnasal model compared to the transoral model. The endoscopic nasopharyngectomy for recurrent NPC affects the nasal airflow and warming and humidification function. The transoral approach has less influence on aerodynamics of the upper airway compared to the transnasal approach. From a CFD perspective, the endoscopic nasopharyngectomy does not increase the risk of postoperative complications, including the empty nose syndrome and the carotid blowout syndrome.

There is a resurgence of research interest in inherently chiral calixarenes and heteracalixaromatics. However, the examples of macrocyclic ring-expanded homocalixarenes and heterocalixaromatics of inherent chirality are not known. Here we report an efficient method to construct inherently chiral N 2 ,O 2 -linked homo-heteracalixaromatics from reductive amination reactions between bis-aldehydes and aliphatic diamines. Examples of post-macrocyclization derivatization were also demonstrated. Enantiomers were obtained from resolution and did not undergo racemization at an elevated temperature. This study provides a new strategy to design novel and functional inherently chiral macrocycles that have potential applications in supramolecular chemistry.

(±)-Salvicatone A ( 1 ), a C 27 -meroterpenoid featuring a unique 6/6/6/6/6-pentacyclic carbon skeleton with a 7,8,8a,9,10,10a-hexahydropyren-1 ( 6H )-one motif, was isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Its structure was characterized by comprehensive spectroscopic analyses along with computer-assisted structure elucidation, including ACD/structure elucidator and quantum chemical calculations with 1 H/ 13 C NMR and electronic circular dichroism. Biogenetically, compound 1 was constructed from decarboxylation following [4 + 2] Diels-Alder cycloaddition reaction between caffeic acid and miltirone analogue. Bioassays showed that (-)- 1 and (+)- 1 inhibited nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophage cells with an IC 50 value of 6.48 ± 1.25 and 15.76 ± 5.55 μM, respectively. The structure-based virtual screening based on the pharmacophores in ePharmaLib, as well as the molecular docking and molecular dynamics simulations study, implied that (-)- 1 and (+)- 1 may potentially bind to retinoic acid receptor-related orphan receptor C to exert anti-inflammatory activities.