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Background: Central venous catheterization, crucial for device insertion, monitoring, medication, and fluid resuscitation, commonly uses the subclavian, internal jugular, and femoral veins. Despite its general safety, complications like arterial puncture can be life-threatening, requiring rapid diagnosis and treatment., Case Presentation: A 74-year-old woman in the recovery phase of cerebral infarction underwent right subclavian vein catheterization. The catheter was mistakenly placed in the brachiocephalic trunk, with its tip in the ascending aorta, as confirmed by computed tomography (CT) and digital subtraction angiography (DSA). With the high surgical risk and the complexity of endovascular treatment, catheter replacement was chosen. One month after the initial placement, the catheter was replaced with a smaller one, and another month later, it was retracted without complications. Follow-up CT and DSA revealed no leakage, with the patient's vitals remaining stable. A three-month post-discharge phone follow-up confirmed the patient's continued stability., Conclusion: This case demonstrates the effective use of a catheter replacement technique as a minimally invasive repair method when other options are impractical. Ultrasound guidance is also recommended to improve the procedure's accuracy and safety., (© 2024. The Author(s).)

Background: Identification of active components of traditional Chinese Medicine (TCM) and their respective targets is important for understanding the mechanisms underlying TCM efficacy. However, there are still no effective technical methods to achieve this., Methods: Herein, we have established a method for rapidly identifying targets of a specific TCM and interrogating the targets with their corresponding active components based on Isothermal Shift Assay (iTSA) and database interrogation., Results: We optimized iTSA workflow and identified 110 targets for Danhong injection (DHI) which is used as an effective remedy for cardiovascular and cerebrovascular diseases. Moreover, we identified the targets of the nine major ingredients found in DHI. Database interrogation found that the potential targets for DHI, in which we verified that ADK as the target for salvianolic acid A and ALDH1B1 as the target for protocatechualdehyde in DHI, respectively., Conclusion: Overall, we established a novel paradigm model for the identification of targets and their respective ingredients in DHI, which facilitates the discovery of drug candidates and targets for improving disease management and contributes to revealing the underlying mechanisms of TCM and fostering TCM development and modernization., (© 2024. The Author(s).)

Background: The triglyceride-glucose (TyG) index is identified as an alternative indicator of insulin resistance (IR) and is associated with macro- and micro-vascular diseases among patients with type 2 diabetes mellitus. The relationship between the TyG index and IR and its impact on diabetic kidney disease (DKD) remains unclear among adults with type 1 diabetes mellitus(T1DM)., Methods: This study comprised a cross-sectional analysis using data from the Guangdong T1DM Translational Medicine Study (GTT) and a longitudinal analysis using data from the type 1 diabetes (T1D) Exchange registry study. Correlation analysis was used to investigate the association between the TyG index and IR. Logistic regression and Cox proportional hazards regression were performed to explore the impact of the TyG index on DKD risk., Results: The GTT Study included 836 adults (216 with DKD and 620 without DKD). A significant correlation existed between the TyG index and the estimated glucose disposal rate (r=-0.64, p < 0.01). The TyG index was a risk factor for DKD after confounder adjustment (OR = 1.34, 95% CI:1.03-1.74). The T1D Exchange registry study included 8,771 adults (2,050 with DKD and 6,721 without DKD). After adjusting confounding factors, the TyG index was identified as an independent risk factor for DKD at enrollment, with the highest risk of DKD incidence observed in the highest TyG tertile group (OR = 1.92, 95%CI:1.67-2.20). During a median follow-up of 44.58(21.84, 67.09) months, the risk of developing DKD was increased by 32% at every 1 SD increase of the TyG index over time among participants without DKD at enrollment., Conclusions: The TyG index could be used to assess IR and was identified as an independent risk factor of DKD among adults with T1DM., (© 2024. The Author(s).)

Background: Platycodon grandiflorum (P. grandiflorum) is a commonly used medicinal plant in China. Transcriptome sequencing studies of different tissues of P. grandiflorum have been widely conducted. However, studies on transcriptome sequencing and expression patterns of key genes in the saponin synthesis pathway of Tongcheng P. grandiflorum, a high-quality medicinal resource of different years, are relatively limited., Results: This study involved transcriptome sequencing and bioinformatics analysis of the roots from annual, biennial, and triennial P. grandiflorum in the Tongcheng area. After data filtering and assembly, we obtained 111.44 Gb of clean base data, including 742,880616 clean reads. We identified 5,156 differential expression unigenes between at least two sample groups, with differences noted among annual, biennial, and triennial P. grandiflorum plants. GO enrichment analysis annotated 3509, 1819, and 1393 DEGs in comparison TC1vsTC2, TC1vsTC3, and TC2vsTC3, respectively. Furthermore, KEGG enrichment analysis identified 16 genes encoding key enzymes in the terpene skeleton biosynthesis, sesquiterpene and triterpene biosynthesis pathways, including SE, AACT, FPPS, DXR, HMGR, HMGS, and DXS. The results of qRT-PCR experiments showed that most of the genes were most highly expressed in annual P. grandiflorum., Conclusions: The present study provided transcriptomic data from the roots of Tongcheng P. grandiflorum of different years, which provides critical bioinformatics data on the growth and development of P. grandiflorum, laying a foundation for further research on saponins and identifying key enzymes involved in this process across different growth stages., (© 2024. The Author(s).)

Background: Immunoglobulin light-chain amyloidosis is a relatively rare condition with a worldwide incidence of 5.1-12.8 cases per million person-years (Baker, 2022). It is characterized by a clonal population of immunoglobulin-secreting cells that produce a monoclonal light chain of κ or λ type as either an intact molecule or a fragment., Case Presentation: A 69-year-old East Asian (Chinese) male patient who presented with progressive dysphagia visited multiple hospitals repeatedly for more than 2 years and was finally diagnosed with immunoglobulin light-chain amyloidosis., Conclusions: Otolaryngologists should consider immunoglobulin light-chain amyloidosis when encountering suspicious clinical manifestations and intervene early to avoid misdiagnosis., (© 2024. The Author(s).)

Background: Radiation-induced skin injury is a significant adverse reaction to radiotherapy. However, there is a lack of effective prevention and treatment methods for this complication. Ferulic acid (FA) has been identified as an effective anti-radiation agent. Conventional administrations of FA limit the reaching of it on skin. We aimed to develop a novel FA hydrogel to facilitate the use of FA in radiation-induced skin injury., Methods: We cross-linked carbomer 940, a commonly used adjuvant, with FA at concentrations of 5%, 10%, and 15%. Sweep source optical coherence tomography system, a novel skin structure evaluation method, was applied to investigate the influence of FA on radiation-induced skin injury. Calcein-AM/PI staining, CCK8 assay, hemolysis test and scratch test were performed to investigate the biocompatibility of FA hydrogel. The reducibility of DPPH and ABTS radicals by FA hydrogel was also performed. HE staining, Masson staining, laser Doppler blood flow monitor, and OCT imaging system are used to evaluate the degree of skin tissue damage. Potential differentially expressed genes were screened via transcriptome analysis., Results: Good biocompatibility and in vitro antioxidant ability of the FA hydrogels were observed. 10% FA hydrogel presented a better mechanical stability than 5% and 15% FA hydrogel. All three concentrations of FA remarkably promoted the recovery of radiation-induced skin injury by reducing inflammation, oxidative conidiation, skin blood flow, and accelerating skin tissue reconstruction, collagen deposition. FA hydrogel greatly inhibiting the levels of NLRP3, caspase-1, IL-18, pro-IL-1β and IL-1β in vivo and vitro levels through restraining the activation of NLRP3 inflammasome. Transcriptome analysis indicated that FA might regulate wound healing via targeting immune response, inflammatory response, cell migration, angiogenesis, hypoxia response, and cell matrix adhesion., Conclusions: These findings suggest that the novel FA hydrogel is a promising therapeutic method for the prevention and treatment of radiation-induced skin injury patients., (© 2024. The Author(s).)

Background: Vasculogenic mimicry (VM) is a potential cause of resistance to antiangiogenic therapy and is closely related to the malignant progression of tumors. It has been shown that noncoding RNAs play an important role in the formation of VM in malignant tumors. However, the role of circRNAs in VM of bladder cancer and the regulatory mechanisms are unclear., Methods: Firstly, hsa&#95;circ&#95;0000520 was identified to have circular character by Sanger sequencing and Rnase R assays. Secondly, the potential clinical value of hsa&#95;circ&#95;0000520 was explored by quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) of clinical specimens. Thirdly, the role of hsa&#95;circ&#95;0000520 in bladder cancer invasion, migration, and VM formation was examined by in vivo and in vitro experiments. Finally, the regulatory mechanisms of hsa&#95;circ&#95;0000520 in the malignant progression of bladder cancer were elucidated by RNA binding protein immunoprecipitation (RIP), RNA pulldown, co-immunoprecipitation (co-IP), qRT-PCR, Western blot (WB), and fluorescence co-localization., Results: Hsa&#95;circ&#95;0000520 was characterized as a circular RNA and was lowly expressed in bladder cancer compared with the paracancer. Bladder cancer patients with high expression of hsa&#95;circ&#95;0000520 had better survival prognosis. Functionally, hsa&#95;circ&#95;0000520 inhibited bladder cancer invasion, migration, and VM formation. Mechanistically, hsa&#95;circ&#95;0000520 acted as a scaffold to promote binding of UBE2V1/UBC13 to Lin28a, further promoting the ubiquitous degradation of Lin28a, improving PTEN mRNA stability, and inhibiting the phosphorylation of the PI3K/AKT pathway. The formation of hsa&#95;circ&#95;0000520 in bladder cancer was regulated by RNA binding protein QKI., Conclusions: Hsa&#95;circ&#95;0000520 inhibits metastasis and VM formation in bladder cancer and is a potential target for bladder cancer diagnosis and treatment., (© 2024. The Author(s).)

Background: Primary human hepatocytes (PHHs) are highly valuable for drug-metabolism evaluation, liver disease modeling and hepatocyte transplantation. However, their availability is significantly restricted due to limited donor sources, alongside their constrained proliferation capabilities and reduced functionality when cultured in vitro. To address this challenge, we aimed to develop a novel method to efficiently expand PHHs in vitro without a loss of function., Methods: By mimicking the in vivo liver regeneration route, we developed a two-step strategy involving the de-differentiation/expansion and subsequent maturation of PHHs to generate abundant functional hepatocytes in vitro. Initially, we applied SiPer, a prediction algorithm, to identify candidate small molecules capable of activating liver regenerative transcription factors, thereby formulating a novel hepatic expansion medium to de-differentiate PHHs into proliferative human hepatic progenitor-like cells (ProHPLCs). These ProHPLCs were then re-differentiated into functionally mature hepatocytes using a new hepatocyte maturation condition. Additionally, we investigated the underlying mechanism of PHHs expansion under our new conditions., Results: The novel hepatic expansion medium containing hydrocortisone facilitated the de-differentiation of PHHs into ProHPLCs, which exhibited key hepatic progenitor characteristics and demonstrated a marked increase in proliferation capacity compared to cells cultivated in previously established expansion conditions. Remarkably, these subsequent matured hepatocytes rivaled PHHs in terms of transcriptome profiles, drug metabolizing activities and in vivo engraftment capabilities. Importantly, our findings suggest that the enhanced expansion of PHHs by hydrocortisone may be mediated through the PPARα signaling pathway and regenerative transcription factors., Conclusions: This study presents a two-step strategy that initially induces PHHs into a proliferative state (ProHPLCs) to ensure sufficient cell quantity, followed by the maturation of ProHPLCs into fully functional hepatocytes to guarantee optimal cell quality. This approach offers a promising means of producing large numbers of seeding cells for hepatocyte-based applications., (© 2024. The Author(s).)

Objective: To investigate in vivo 6-degree-of-freedom (DOF) vertebral motion in patients with isthmic spondylolisthesis (IS) during various functional weight-bearing activities., Methods: Fifteen asymptomatic volunteers (mean age 54.8 years) and fourteen patients with IS at L4-5 (mean age 53.4 years) were recruited. The positions of the vertebrae (L4-L5) in the supine, standing, flexion-extension, left-right twisting and left-right bending positions were determined using previously described CT-based models and dual fluoroscopic imaging techniques. Local coordinate systems were established at the center of the anterior vertebra of L4 isthmic spondylolisthesis (AIS), the posterior lamina of L4 isthmic spondylolisthesis (PIS) and the center of the L5 vertebra to obtain the 6DOF range of motion (ROM) at L4-L5 and the range of motion (ROM) between the AIS and the PIS., Results: The translation along the anteroposterior axis at L4-L5 during flexion-extension, left-right bending and left-right twisting was significantly greater than that of the healthy participants. However, the translation along the mediolateral axis at L4-L5 presented paradoxical motion under different positions: the ROM increased in the supine-standing and flexion-extension positions but decreased in the left-right bending and left-right twisting positions. The separation along the anteroposterior axis during flexion was significantly greater than that during standing, on average, reaching more than 1 mm. The separation along the mediolateral axis during standing, flexion and extension was significantly greater than that in the supine position., Conclusions: This study revealed the occurrence of displacement between the AIS and PIS, primarily in the form of separation during flexion. Symptomatic patients with isthmic spondylolisthesis exhibit intervertebral instability, which might be underestimated by flexion-extension radiographs., (© 2024. The Author(s).)

Hepatocellular carcinoma (HCC) is the primary malignant tumor of the liver. c-Myc is one of the most common oncogenes in clinical settings, and amplified levels of c-Myc are frequently found in HCC. Histone deacetylase inhibitors (HDACi), such as Trichostatin A (TSA), hold enormous promise for the treatment of HCC. However, the potential and mechanism of TSA in the treatment of c-Myc-induced HCC are unclear. In this study, we investigated the effects of TSA treatment on a c-Myc-induced HCC model in mice. TSA treatment delayed the development of HCC, and liver function indicators such as ALT, AST, liver weight ratio, and spleen weight ratio demonstrated the effectiveness of TSA treatment. Oil red staining further demonstrated that TSA attenuated lipid accumulation in the HCC tissues of mice. Through mRNA sequencing, we identified that TSA mainly affected cell cycle and fatty acid degradation genes, with alcohol dehydrogenase 4 (ADH4) potentially being the core molecular downstream target. QPCR, immunohistochemistry, and western blot analysis revealed that ADH4 expression was repressed by c-Myc and restored after TSA treatment both in vitro and in vivo. Furthermore, we observed that the levels of total NAD + and NADH, NAD + , NAD + /NADH, and ATP concentration increased after c-Myc transfection in liver cells but decreased after TSA intervention. The levels of phosphorylated protein kinase B (p-AKT) and p-mTOR were identified as targets regulated by TSA, and they governed the ADH4 expression and the downstream regulation of total NAD + and NADH, NAD + , NAD + /NADH, and ATP concentration. Overall, our study suggests that TSA has a therapeutic effect on c-Myc-induced HCC through the AKT-mTOR-ADH4 pathway. These findings provide valuable insights into the potential treatment of HCC using TSA and shed light on the underlying molecular mechanisms involved., (© 2024. The Author(s).)

Objective: To explore the distribution and differences in the intestinal microbiota in girls with obesity-related precocious puberty and the relationship between intestinal microbiota and obesity-related precocious puberty., Methods: 16 S rRNA gene amplicons from fecal samples from girls with precocious puberty and obesity-complicated precocious puberty and healthy children were sequenced to define microbial taxa., Results: The α- and β-diversity indices of the microbiome significantly differed among the three groups. At the phylum level, the proportions of Firmicutes, Actinobacteriota, Bacteroidota, Bacteria, Campylobacterota, and Acidobacteriota were different. At the genus level, there were differences in Bifidobacterium, Bacteroides, Anaerostipes, Fusicatenibacter, Klebsiella, Lachnospiraceae, ErysipelotrichaceaeUCG-003, Prevotella9, Ruminococcus gnavus group, and Lachnoclostridium. Additionally, Bifidobacterium, Anaerostipes, Bacteroides, Candidatus Microthrix, Eubacterium hallii group, Klebsiella, and Erysipelotrichaceae UCG-003 were identified as bacterial biomarkers by LEfSe. Furthermore, Sellimonas, Intestinibacter, Anaerostipes, Ruminococcus gnavus group, and Oscillibacter were identified as the differential biomarkers by random forest. A receiver operating characteristic (ROC) curve was used to evaluate the biomarkers with high predictive value for obesity-related precocious puberty. Spearman correlation analysis confirmed that Anaerostipes levels were negatively correlated with body weight, body mass index (BMI), bone age, luteinizing hormone, follicle-stimulating hormone, and estradiol., Conclusions: There was a significant correlation between obesity-associated precocious puberty and gut microbiota, especially the functional characteristics of the microbiome and its interactions, which can provide a theoretical basis for the clinical intervention of obesity and precocious puberty through the microbiome., (© 2024. The Author(s).)

Background: Leukemia inhibitory factor (LIF) is a multifunctional member of the IL-6 cytokine family that activates downstream signaling pathways by binding to the heterodimer consisting of LIFR and gp130 on the cell surface. Previous research has shown that LIF is highly expressed in various tumor tissues (e.g. pancreatic cancer, breast cancer, prostate cancer, and colorectal cancer) and promotes cancer cell proliferation, migration, invasion, and differentiation. Moreover, the overexpression of LIF correlates with poor clinicopathological characteristics. Therefore, we hypothesized that LIF could be a promising target for the treatment of cancer. In this work, we developed the antagonist antibody 1G11 against LIF and investigated its anti-tumor mechanism and its therapeutic efficacy in mouse models., Results: A series of single-chain variable fragments (scFvs) targeting LIF were screened from a naive human scFv phage library. These scFvs were reconstructed in complete IgG form and produced by the mammalian transient expression system. Among the antibodies, 1G11 exhibited the excellent binding activity to human, cynomolgus monkey and mouse LIF. Functional analysis demonstrated 1G11 could block LIF binding to LIFR and inhibit the intracellular STAT3 phosphorylation signal. Interestingly, 1G11 did not block LIF binding to gp130, another LIF receptor that is involved in forming the receptor complex together with LIFR. In vivo, intraperitoneal administration of 1G11 inhibited tumor growth in CT26 and MC38 models of colorectal cancer. IHC analysis demonstrated that p-STAT3 and Ki67 were decreased in tumor tissue, while c-caspase 3 was increased. Furthermore, 1G11 treatment improves CD3+, CD4 + and CD8 + T cell infiltration in tumor tissue., Conclusions: We developed antagonist antibodies targeting LIF/LIFR signaling pathway from a naive human scFv phage library. Antagonist anti-LIF antibody exerts antitumor effects by specifically reducing p-STAT3. Further studies revealed that anti-LIF antibody 1G11 increased immune cell infiltration in tumor tissues., (© 2024. The Author(s).)

Background: Treatment of gliomas, the most prevalent primary malignant neoplasm of the central nervous system, is challenging. Arachidonate 5-lipoxygenase activating protein (ALOX5AP) is crucial for converting arachidonic acid into leukotrienes and is associated with poor prognosis in multiple cancers. Nevertheless, its relationship with the prognosis and the immune microenvironment of gliomas remains incompletely understood., Methods: The differential expression of ALOX5AP was evaluated based on public Databases. Kaplan-Meier, multivariate Cox proportional hazards regression analysis, time-dependent receiver operating characteristic, and nomogram were used to estimate the prognostic value of ALOX5AP. The relationship between ALOX5AP and immune infiltration was calculated using ESTIMATE and CIBERSORT algorithms. Relationships between ALOX5AP and human leukocyte antigen molecules, immune checkpoints, tumor mutation burden, TIDE score, and immunophenoscore were calculated to evaluate glioma immunotherapy response. Single gene GSEA and co-expression network-based GO and KEGG enrichment analysis were performed to explore the potential function of ALOX5AP. ALOX5AP expression was verified using multiplex immunofluorescence staining and its prognostic effects were confirmed using a glioma tissue microarray., Result: ALOX5AP was highly expressed in gliomas, and the expression level was related to World Health Organization (WHO) grade, age, sex, IDH mutation status, 1p19q co-deletion status, MGMTp methylation status, and poor prognosis. Single-cell RNA sequencing showed that ALOX5AP was expressed in macrophages, monocytes, and T cells but not in tumor cells. ALOX5AP expression positively correlated with M2 macrophage infiltration and poor immunotherapy response. Immunofluorescence staining demonstrated that ALOX5AP was upregulated in WHO higher-grade gliomas, localizing to M2 macrophages. Glioma tissue microarray confirmed the adverse effect of ALOX5AP in the prognosis of glioma., Conclusion: ALOX5AP is highly expressed in M2 macrophages and may act as a potential biomarker for predicting prognosis and immunotherapy response in patients with glioma., (© 2024. The Author(s).)

Backgroup: The pathogenesis of shoulder impingement syndrome (SIS) is still unclear, and its questionable causal relationship with rotator cuff (RC) injury has led to confusion in treatment. The purpose of this study was to explore the bidirectional causal relationship between SIS and RC injury., Methods: SIS and RC injury datasets downloaded from the IEU Open GWAS project and GWAS catalog databases. Inverse variance weighted (IVW), MR Egger, Weighted median, and Weighted mode were used in this Mendelian randomization (MR) analysis. Cochran's Q test, leave-one-out, and funnel plot method were used to evaluate heterogeneity between single nucleotide polymorphisms (SNPs). MR-Egger regression was used to test the horizontal pleiotropy of this study., Results: The IVW method (OR = 1.189, P = 0.0059) suggest the putative causal effect of RC injury on SIS. The results of MR Egger method (OR = 1.236, P = 0.2013), weighted median method (OR = 1.097, P = 0.2428) and weighted mode method (OR = 1.013, P = 0.930) showed no statistically significant (OR = 1.069071, P = 0.6173). Heterogeneity test and horizontal pleiotropy analysis suggested that there was no significant heterogeneity and horizontal pleiotropy in the results of this MR analysis. The reverse MR analysis showed heterogeneity, and the conclusion needs to be further explored., Conclusions: The results of MR analysis support that RC injury may be causally associated with SIS., (© 2024. The Author(s).)

Introduction: Survival comparisons among patients with liver metastases from pancreatic and rectal neuroendocrine tumors (NETs) were limited, and the efficacy of observation rules in patients undergoing hepatectomy for neuroendocrine liver metastases (NELMs) was unknown. This study aims to distinguish these characteristics and clarify the effects of the observation rules on NELMs., Methods: Clinical data were separately collected from patients with pancreatic and rectal NELMs at medical centers in both Japan and China. The Japanese cohort followed the observation rules for the resection of NELMs. A comparative analysis was conducted on clinical characteristics and prognosis features such as overall survival time (OS) and disease-free survival interval (DFS-I)., Results: Enrollment included 47 and 34 patients from Japan and China, respectively. Of these, 69 and 12 patients had tumors originating from the pancreas and rectum, respectively. The OS time in patients undergoing primary tumor resection was significantly longer; however, the OS time between the patients undergoing and not undergoing radical resection of liver metastasis was the same. In asynchronous NELMs, patients with rectal (R)-NELMs showed a significantly higher proportion of type III NELMs. Additionally, the median DFS-I of asynchronous R-NELMs was longer than the recommended follow-up time, with 71.4% of them classified as G2. In the Japanese cohort, patients who adhered to the observation rules exhibited a longer median DFS after hepatectomy for NELMs compared with their counterparts., Conclusion: Although curative surgery is crucial for primary lesions, personalized approaches are required to manage NELMs. Extended overall follow-ups and shortened follow-up intervals are recommended for G2 stage rectal NETs. The observation rules for NELMs require further validation with a larger sample size., (© 2024. The Author(s).)

Background: Hepatoid adenocarcinoma of the lung (HAL) is a distinctly uncommon subtype of lung adenocarcinoma (LAC), characterized by hepatoid features and an alarmingly low 5-year survival rate of approximately 8%. The scarcity of information on this condition has contributed to the absence of standardized treatment protocols, and the molecular underpinnings of its pathogenesis remain largely unexplored. To bridge these gaps, this study compiled data from 191 primary HAL patients to delineate treatment patterns, prognostic factors, and potential pathogenic mechanisms., Methods: This study was divided into two cohorts: cohort 1, comprising 110 patients extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and cohort 2, consisting of 70 patients identified through a comprehensive literature review via the PubMed, Web of Science, and Scopus databases, in addition to 11 patients from Tongji Hospital. The Cox proportional hazards regression model was employed to identify independent prognostic factors. Kaplan-Meier survival curves were generated to assess the impact of treatment modalities centered around surgery and chemotherapy. Moreover, this study evaluated the efficacy of first-line treatment regimens and conducted Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses on identified mutated genes., Results: The demographic and clinical profile of HAL patients typically comprises older individuals who are smokers, with a predisposition for diagnosis at advanced disease stages, culminating in a high mortality rate. Key prognostic indicators identified included disease stage, chemotherapy and surgical interventions. The study suggests a treatment strategy that advocates chemotherapy for patients with stage IV HAL and surgery for those with non-stage IV disease. The combination of paclitaxel and platinum-based chemotherapy emerged as an efficacious first-line treatment, with the integration of immunotherapy and targeted therapies showing potential benefits. Genetic analysis underscored similarities between HAL and LAC, particularly highlighting aberrant kinase activity (serine, threonine, and tyrosine) and the activation of PI3K-Akt and MAPK signaling pathways as contributing factors to HAL pathogenesis., Conclusion: Despite its relatively rare occurrence, this study underscores the significance of treatment strategies and concludes probable prognostic factors. Due to limited reports, a deeper understanding of the molecular mechanisms driving tumorigenesis and progression in HAL is needed., (© 2024. The Author(s).)

Background: Anemia represents a well-established risk factor for patients diagnosed with gastric cancer, and is often associated with an unfavorable prognosis. In this context, the timely prediction of distant metastasis risk in patients with anemic gastric cancer assumes paramount importance., Methods: Information of gastric cancer patients complicated with preoperative anemia in the First Affiliated Hospital of Sun Yat-sen University was collected. The cohort from the First Affiliated Hospital of Guangxi Medical University was used as an external validation set. A Nomogram was established based on the risk factors screened by univariate and multivariate logistic regression analyses., Results: A total of 848 gastric cancer patients with preoperative anemia were enrolled. Pyloric obstruction, carcinoma antigen 125, T stage, N stage, tumor size, and preoperative weight loss were independent predictors of distant metastasis in gastric cancer patients with anemia (p < 0.05), based on which a nomogram was constructed. The accuracy, reliability and clinical value of the nomogram were evaluated by concordance index, receiver operating characteristic curve, decision curve analysis, calibration curve and showed good stability and clinical predictive value., Conclusions: Preoperative anemic gastric cancer patients, complicated with pyloric obstruction, elevated CA125, advanced T and N stage, larger tumor size, and preoperative weight loss, should be paid more attention to distant metastasis., (© 2024. The Author(s).)

Background: Ischemia-reperfusion (I/R) injury is a major factor in liver damage following hepatic resection and liver transplantation, with anesthetics demonstrating the ability to shield organs from this type of injury., Methods: Hypoxia-reoxygenation (H/R) was used to create in vitro I/R hepatocyte cell injury models. The CCK-8 assay, flow cytometer, LDH assay, and ELSIA were utilized to assess hepatocyte injury. The in vivo I/R injury rat model was then built. HE and TUNEL staining were used to assess liver tissue damage. Western-blot was applied to assess the activation of the MAPK/ERK pathway., Results: Remimazolam (RMZL) remarkably improved cell viability and decreased apoptosis in H/R-induced hepatocyte injury. RMZL reduced the release of H/R-induced inflammatory mediators (TNF-α and IL-6) as well as LDH levels. We also discovered that RMZL inhibited p38 and ERK1/2 phosphorylation in vivo and in vitro. The stimulation of MAPK/ERK, on the other hand, abolished RMZL's anti-inflammation effects in H/R-induced hepatocyte injury. Furthermore, RMZL reduced liver tissue injury in I/R rats., Conclusion: RMZL prevented hepatic I/R damage by inhibiting MAPK/ERK signaling., (© 2024. The Author(s).)

Nasopharyngeal carcinoma (NPC), primarily found in the southern region of China, is a malignant tumor known for its highly metastatic characteristics. The high mortality rates caused by the distant metastasis and disease recurrence remain unsolved clinical problems. In clinic, the berberine (BBR) compound has widely been in NPC therapy to decrease metastasis and disease recurrence, and BBR was documented as a main component with multiple anti-NPC effects. However, the mechanism by which BBR inhibits the growth and metastasis of nasopharyngeal carcinoma remains elusive. Herein, we show that BBR effectively inhibits the growth, metastasis, and invasion of NPC via inducing a specific super enhancer (SE). From a mechanistic perspective, the RNA sequencing (RNA-seq) results suggest that the RAS-RAF1-MEK1/2-ERK1/2 signaling pathway, activated by the epidermal growth factor receptor (EGFR), plays a significant role in BBR-induced autophagy in NPC. Blockading of autophagy markedly attenuated the effect of BBR-mediated NPC cell growth and metastasis inhibition. Notably, BBR increased the expression of EGFR by transcription, and knockout of EGFR significantly inhibited BBR-induced microtubule associated protein 1 light chain 3 (LC3)-II increase and p62 inhibition, proposing that EGFR plays a pivotal role in BBR-induced autophagy in NPC. Chromatin immunoprecipitation sequencing (ChIP-seq) results found that a specific SE existed only in NPC cells treated with BBR. This SE knockdown markedly repressed the expression of EGFR and phosphorylated EGFR (EGFR-p) and reversed the inhibition of BBR on NPC proliferation, metastasis, and invasion. Furthermore, BBR-specific SE may trigger autophagy by enhancing EGFR gene transcription, thereby upregulating the RAS-RAF1-MEK1/2-ERK1/2 signaling pathway. In addition, in vivo BBR effectively inhibited NPC cells growth and metastasis, following an increase LC3 and EGFR and a decrease p62. Collectively, this study identifies a novel BBR-special SE and established a new epigenetic paradigm, by which BBR regulates autophagy, inhibits proliferation, metastasis, and invasion. It provides a rationale for BBR application as the treatment regime in NPC therapy in future., (© 2024. The Author(s).)

Objectives: To develop an objective method based on texture analysis on MRI for diagnosis of congenital muscular torticollis (CMT)., Material and Methods: The T1- and T2-weighted imaging, Q-dixon, and T1-mapping MRI data of 38 children with CMT were retrospectively analyzed. The region of interest (ROI) was manually drawn at the level of the largest cross-sectional area of the SCM on the affected side. MaZda software was used to obtain the texture features of the T2WI sequences of the ROI in healthy and affected SCM. A radiomics diagnostic model based on muscle texture features was constructed using logistic regression analysis. Fatty infiltration grade was calculated by hematoxylin and eosin staining, and fibrosis ratio by Masson staining. Correlation between the MRI parameters and pathological indicators was analyzed., Results: There was positive correlation between fatty infiltration grade and mean value, standard deviation, and maximum value of the Q-dixon sequence of the affected SCM (correlation coefficients, 0.65, 0.59, and 0.58, respectively, P < 0.05).Three muscle texture features-S(2,2)SumAverg, S(3,3)SumVarnc, and T2WI extreme difference-were selected to construct the diagnostic model. The model showed significant diagnostic value for CMT (P < 0.05). The area under the curve of the multivariate conditional logistic regression model was 0.828 (95% confidence interval 0.735-0.922); the sensitivity was 0.684 and the specificity 0.868., Conclusion: The radiomics diagnostic model constructed using T2WI muscle texture features and MRI signal values appears to have good diagnostic efficiency. Q-dixon sequence can reflect the fatty infiltration grade of CMT., (© 2024. The Author(s).)

Background: The heavy metal-associated isoprenylated plant protein (HIPP) is an important regulatory element in response to abiotic stresses, especially playing a key role in low-temperature response., Results: This study investigated the potential function of PavHIPP16 up-regulated in sweet cherry under cold stress by heterologous overexpression in tobacco. The results showed that the overexpression (OE) lines' growth state was better than wild type (WT), and the germination rate, root length, and fresh weight of OE lines were significantly higher than those of WT. In addition, the relative conductivity and malondialdehyde (MDA) content of the OE of tobacco under low-temperature treatment were substantially lower than those of WT. In contrast, peroxidase (POD), superoxide dismutase (SOD), catalase (CAT) activities, hydrogen peroxide (H 2 O 2 ), proline, soluble protein, and soluble sugar contents were significantly higher than those of WT. Yeast two-hybrid assay (Y2H) and luciferase complementation assay verified the interactions between PavbHLH106 and PavHIPP16, suggesting that these two proteins co-regulated the cold tolerance mechanism in plants. The research results indicated that the transgenic lines could perform better under low-temperature stress by increasing the antioxidant enzyme activity and osmoregulatory substance content of the transgenic plants., Conclusions: This study provides genetic resources for analyzing the biological functions of PavHIPPs, which is important for elucidating the mechanisms of cold resistance in sweet cherry., (© 2024. The Author(s).)

Background: Guava is a fruit prone to rapid spoilage following harvest, attributed to continuous and swift physicochemical transformations, leading to substantial postharvest losses. This study explored the efficacy of xanthan gum (XG) coatings applied at various concentrations (0.25, 0.5, and 0.75%) on guava fruits (Gola cultivar) over a 15-day storage period., Results: The results indicated that XG coatings, particularly at 0.75%, substantially mitigated moisture loss and decay, presenting an optimal concentration. The coated fruits exhibited a modified total soluble soluble solids, an increased total titratable acidity, and an enhanced sugar-acid ratio, collectively enhancing overall quality. Furthermore, the XG coatings demonstrated the remarkable ability to preserve bioactive compounds, such as total phenolics, flavonoids, and antioxidants, while minimizing the levels of oxidative stress markers, such as electrolyte leakage, malondialdehyde, and H 2 O 2 . The coatings also influenced cell wall components, maintaining levels of hemicellulose, cellulose, and protopectin while reducing water-soluble pectin. Quantitative analysis of ROS-scavenging enzymes, including superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase, revealed significant increases in their activities in the XG-coated fruits compared to those in the control fruits. Specifically, on day 15, the 0.75% XG coating demonstrated the highest SOD and CAT activities while minimizing the reduction in APX activity. Moreover, XG coatings mitigated the activities of fruit-softening enzymes, including pectin methylesterase, polygalacturonase, and cellulase., Conclusions: This study concludes that XG coatings play a crucial role in preserving postharvest quality of guava fruits by regulating various physiological and biochemical processes. These findings offer valuable insights into the potential application of XG as a natural coating to extend the shelf life and maintain the quality of guava fruits during storage., (© 2024. The Author(s).)

Background: Tripartite motif-containing 26 (TRIM26), a member of the TRIM protein family, exerts dual function in several types of cancer. Nevertheless, the precise role of TRIM26 in clear cell renal cell carcinoma (ccRCC) has not been investigated., Methods: The expression of TRIM26 in ccRCC tissues and cell lines were examined through the use of public resources and experimental validation. The impacts of TRIM26 on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process were determined via CCK-8, colony formation, EdU incorporation, wound healing, Transwell invasion, Western blot, and Immunofluorescence assays. RNA-seq followed by bioinformatic analyses were used to identify the downstream pathway of TRIM26. The interaction between TRIM26 and ETK was assessed by co-immunoprecipitation, qRT-PCR, Western blot, cycloheximide (CHX) chase, and in vivo ubiquitination assays., Results: We have shown that TRIM26 exhibits a downregulation in both ccRCC tissues and cell lines. Furthermore, this decreased expression of TRIM26 is closely linked to unfavorable overall survival and diseases-free survival outcomes among ccRCC patients. Gain- and loss-of-function experiments demonstrated that increasing the expression of TRIM26 suppressed the proliferation, migration, invasion, and EMT process of ccRCC cells. Conversely, reducing the expression of TRIM26 had the opposite effects. RNA sequencing, coupled with bioinformatic analysis, revealed a significant enrichment of the mTOR signaling pathway in the control group compared to the group with TRIM26 overexpression. This finding was then confirmed by a western blot assay. Subsequent examination revealed that TRMI26 had a direct interaction with ETK, a non-receptor tyrosine kinase. This interaction facilitated the ubiquitination and degradation of ETK, resulting in the deactivation of the AKT/mTOR signaling pathway in ccRCC. ETK overexpression counteracted the inhibitory effects of TRIM26 overexpression on cell proliferation, migration, and invasion., Conclusion: Our results have shown a novel mechanism by which TRIM26 hinders the advancement of ccRCC by binding to and destabilizing ETK, thus leading to the deactivation of AKT/mTOR signaling. TRIM26 shows promise as both a therapeutic target and prognostic biomarker for ccRCC patients., (© 2024. The Author(s).)

Background: Colonization of carbapenem-resistant Enterobacterale (CRE) is considered as one of vital preconditions for infection, with corresponding high morbidity and mortality. It is important to construct a reliable prediction model for those CRE carriers with high risk of infection., Methods: A retrospective cohort study was conducted in two Chinese tertiary hospitals for patients with CRE colonization from 2011 to 2021. Univariable analysis and the Fine-Gray sub-distribution hazard model were utilized to identify potential predictors for CRE-colonized infection, while death was the competing event. A nomogram was established to predict 30-day and 60-day risk of CRE-colonized infection., Results: 879 eligible patients were enrolled in our study and divided into training (n = 761) and validation (n = 118) group, respectively. There were 196 (25.8%) patients suffered from subsequent CRE infection. The median duration of subsequent infection after identification of CRE colonization was 20 (interquartile range [IQR], 14-32) days. Multisite colonization, polymicrobial colonization, catheterization and receiving albumin after colonization, concomitant respiratory diseases, receiving carbapenems and antimicrobial combination therapy before CRE colonization within 90 days were included in final model. Model discrimination and calibration were acceptable for predicting the probability of 60-day CRE-colonized infection in both training (area under the curve [AUC], 74.7) and validation dataset (AUC, 81.1). Decision-curve analysis revealed a significantly better net benefit in current model. Our prediction model is freely available online at https://ken-zheng.shinyapps.io/PredictingModelofCREcolonizedInfection/ ., Conclusions: Our nomogram has a good predictive performance and could contribute to early identification of CRE carriers with a high-risk of subsequent infection, although external validation would be required., (© 2024. The Author(s).)

Background: Adamantinomatous craniopharyngiomas (ACPs) are rare benign epithelial tumours with high recurrence and poor prognosis. Biological differences between recurrent and primary ACPs that may be associated with disease recurrence and treatment have yet to be evaluated at the proteomic level. In this study, we aimed to determine the proteomic profiles of paired recurrent and primary ACP, gain biological insight into ACP recurrence, and identify potential targets for ACP treatment., Method: Patients with ACP (n = 15) or Rathke's cleft cyst (RCC; n = 7) who underwent surgery at Sanbo Brain Hospital, Capital Medical University, Beijing, China and received pathological confirmation of ACP or RCC were enrolled in this study. We conducted a proteomic analysis to investigate the characteristics of primary ACP, paired recurrent ACP, and RCC. Western blotting was used to validate our proteomic results and assess the expression of key tumour-associated proteins in recurrent and primary ACPs. Flow cytometry was performed to evaluate the exhaustion of tumour-infiltrating lymphocytes (TILs) in primary and recurrent ACP tissue samples. Immunohistochemical staining for CD3 and PD-L1 was conducted to determine differences in T-cell infiltration and the expression of immunosuppressive molecules between paired primary and recurrent ACP samples., Results: The bioinformatics analysis showed that proteins differentially expressed between recurrent and primary ACPs were significantly associated with extracellular matrix organisation and interleukin signalling. Cathepsin K, which was upregulated in recurrent ACP compared with that in primary ACP, may play a role in ACP recurrence. High infiltration of T cells and exhaustion of TILs were revealed by the flow cytometry analysis of ACP., Conclusions: This study provides a preliminary description of the proteomic differences between primary ACP, recurrent ACP, and RCC. Our findings serve as a resource for craniopharyngioma researchers and may ultimately expand existing knowledge of recurrent ACP and benefit clinical practice., (© 2024. The Author(s).)

Background: Fractures of hands and feet are common in children, but relevant epidemiological studies are currently lacking. We aim to study the epidemiological characteristics of hand and foot fractures and growth plate injuries in children and provide a theoretical basis for their prevention, diagnosis, and treatment., Methods: We retrospectively analyzed the data of children with hand and foot fractures who were hospitalized at Shenzhen Children's Hospital between July 2015 and December 2020. Data on demographic characteristics, fracture site, treatment method, etiology of injury, and accompanying injuries were collected. The children were divided into four age groups: infants, preschool children, school children, and adolescents. The fracture sites were classified as first-level (the first-fifth finger/toe, metacarpal, metatarsal, carpal, and tarsal) and second-level (the first-fifth: proximal phalanx, middle phalanx, distal phalanx, metacarpal, and metatarsal) sites. The changing trends in fracture locations and injury causes among children in each age group were analyzed., Results: Overall, 1301 children (1561 fractures; 835 boys and 466 girls) were included. The largest number of fractures occurred in preschool children (n = 549, 42.20%), with the distal phalanx of the third finger being the most common site (n = 73, 15.57%). The number of fractures in adolescents was the lowest (n = 158, 12.14%), and the most common fracture site was the proximal phalanx of the fifth finger (n = 45, 29.61%). Of the 1561 fractures, 1143 occurred in the hands and 418 in the feet. The most and least common first-level fracture sites among hand fractures were the fifth (n = 300, 26.25%) and first (n = 138, 12.07%) fingers, respectively. The most and least common first-level foot fracture locations were the first (n = 83, 19.86%) and fourth (n = 26, 6.22%) toes, respectively. The most common first-level and second level etiologies were life related injuries (n = 1128, 86.70%) and clipping injuries (n = 428, 32.90%), respectively. The incidence of sports injuries gradually increased with age, accounting for the highest proportion in adolescents (26.58%). Hand and foot fractures had many accompanying injuries, with the top three being nail bed injuries (570 cases, 36.52%), growth plate injuries (296 cases, 18.96%), and distal severed fracture (167 cases, 10.70%). Among the 296 growth plate injuries, 246 occurred on the hands and 50 on the feet., Conclusions: In contrast to previous epidemiological studies on pediatric hand and foot fractures, we mapped the locations of these fractures, including proximal, shaft, distal, and epiphyseal plate injuries. We analyzed the changing trends in fracture sites and injury etiologies with age. Hand and foot fractures have many accompanying injuries that require attention during diagnosis and treatment. Doctors should formulate accident protection measures for children of different ages, strengthen safety education, and reduce the occurrence of accidental injuries., (© 2024. The Author(s).)

Background: Natural tetramates are a family of hybrid polyketides bearing tetramic acid (pyrrolidine-2,4-dione) moiety exhibiting a broad range of bioactivities. Biosynthesis of tetramates in microorganisms is normally directed by hybrid polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) machineries, which form the tetramic acid ring by recruiting trans- or cis-acting thioesterase-like Dieckmann cyclase in bacteria. There are a group of tetramates with unique skeleton of 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione, which remain to be investigated for their biosynthetic logics., Results: Herein, the tetramate type compounds bripiodionen (BPD) and its new analog, featuring the rare skeleton of 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione, were discovered from the sponge symbiotic bacterial Streptomyces reniochalinae LHW50302. Gene deletion and mutant complementation revealed the production of BPDs being correlated with a PKS-NRPS biosynthetic gene cluster (BGC), in which a Dieckmann cyclase gene bpdE was identified by sit-directed mutations. According to bioinformatic analysis, the tetramic acid moiety of BPDs should be formed on an atypical NRPS module constituted by two discrete proteins, including the C (condensation)-A (adenylation)-T (thiolation) domains of BpdC and the A-T domains of BpdD. Further site-directed mutagenetic analysis confirmed the natural silence of the A domain in BpdC and the functional necessities of the two T domains, therefore suggesting that an unusual aminoacyl transthiolation should occur between the T domains of two NRPS subunits. Additionally, characterization of a LuxR type regulator gene led to seven- to eight-fold increasement of BPDs production. The study presents the first biosynthesis case of the natural molecule with 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione skeleton. Genomic mining using BpdD as probe reveals that the aminoacyl transthiolation between separate NRPS subunits should occur in a certain population of NRPSs in nature., (© 2024. The Author(s).)

Background: Salmonella enterica subspecies enterica serovar abortus equi (S. abortus equi) is one of the main pathogens that causes abortion in pregnant horses and donkeys, which was highly infectious and greatly restricts the healthy development of the horse industry., Objectives: In order to investigate the prevalence and biological characteristics of S. abortus equi in different regions and breeds of horses in Xinjiang., Methods: This study conducted ELISA detection of S. abortus equi antibodies on serum samples of 971 horses collected from three large-scale horse farms and five free-range horse farms in Yili Prefecture and Bayingol Mongolian Autonomous Prefecture of Xinjiang from 2020 to 2023. On this basis, bacterial isolation, culture, identification, and drug sensitivity tests were conducted on 42 samples of aborted foal tissues and 23 mare vaginal swabs., Results: The results showed that the positive rate of S. abortus equi antibody was as high as 20.91% in 971 horse serum samples. Among them, the positive rate in the Ili region (29.09%) was significantly higher than that in the Bayingole region (11.24%), and the positive rate in mares (22.45%) was higher than that in stallions (14.05%). In terms of horse breeds, the positive rates of self-propagating thoroughbred horses, half-bred horses, Ili horses and Yanqi horses were 43.22%, 28.81%, 14.72% and 11.24% respectively. In addition, S. abortus equi was more susceptible to juvenile and elderly horses, with positive rates of 70.00%and 41.86%, respectively, both of which were significantly higher than young (10.97%) and adult (19.79%) horses. Further, 9 strains of S. abortus equi were obtained through bacterial isolation, culture and identification, which were resistant to five antibiotics (Clarithromycin, Clindamycin, penicillin, Sulfamethoxazole and Rifampicin), and sensitive to 13 antimicrobial agents (Amoxicillin, Ciprofloxacin and Gentamicin, et al.)., Conclusion: There was a high infection rate of S. abortus equi in Ili Prefecture and self-propagating thoroughbred horses, and juvenile or old mares were more susceptible, which will provide scientific basis for the prevention of S. abortus equi infection in different regions and breeds of horses in Xinjiang., (© 2024. The Author(s).)

Background: Neural Tube Defects (NTDs) are congenital malformations of the central nervous system resulting from the incomplete closure of the neural tube during early embryonic development. Neuroinflammation refers to the inflammatory response in the nervous system, typically resulting from damage to neural tissue. Immune-related processes have been identified in NTDs, however, the detailed relationship and underlying mechanisms between neuroinflammation and NTDs remain largely unclear. In this study, we utilized integrated multi-omics analysis to explore the role of neuroinflammation in NTDs and identify potential prenatal diagnostic markers using a murine model., Methods: Nine public datasets from Gene Expression Omnibus (GEO) and ArrayExpress were mined using integrated multi-omics analysis to characterize the molecular landscape associated with neuroinflammation in NTDs. Special attention was given to the involvement of macrophages in neuroinflammation within amniotic fluid, as well as the dynamics of macrophage polarization and their interactions with neural cells at single-cell resolution. We also used qPCR assay to validate the key TFs and candidate prenatal diagnostic genes identified through the integrated analysis in a retinoic acid-induced NTDs mouse model., Results: Our analysis indicated that neuroinflammation is a critical pathological feature of NTDs, regulated both transcriptionally and epigenetically within central nervous system tissues. Key alterations in gene expression and pathways highlighted the crucial role of STATs molecules in the JAK-STAT signaling pathway in regulating NTDs-associated neuroinflammation. Furthermore, single-cell resolution analysis revealed significant polarization of macrophages and their interaction with neural cells in amniotic fluid, underscoring their central role in mediating neuroinflammation associated with NTDs. Finally, we identified a set of six potential prenatal diagnostic genes, including FABP7, CRMP1, SCG3, SLC16A10, RNASE6 and RNASE1, which were subsequently validated in a murine NTDs model, indicating their promise as prospective markers for prenatal diagnosis of NTDs., Conclusions: Our study emphasizes the pivotal role of neuroinflammation in the progression of NTDs and underlines the potential of specific inflammatory and neural markers as novel prenatal diagnostic tools. These findings provide important clues for further understanding the underlying mechanisms between neuroinflammation and NTDs, and offer valuable insights for the future development of prenatal diagnostics., (© 2024. The Author(s).)

Objective: Personality, emotions, and olfaction exhibit partial anatomical overlap in the limbic system structure, establishing potential mechanisms between personality, affective disorders, and olfactory-related aspects. Thus, this study aims to investigate the associations among the Big Five personality traits, alexithymia, anxiety symptoms, and odor awareness., Methods: A total of 863 college participants were recruited for this study. All participants completed the Chinese Big Five Personality Inventory-15, the Odor Awareness Scale (OAS), the Toronto Alexithymia Scale-20, and the Generalized Anxiety Disorder Screener-7. Structural equation modeling was employed to examine the hypothesized mediated model., Results: The findings revealed the majority of significant intercorrelations among the dimensions of the Big Five personality traits, alexithymia, anxiety symptoms, and OAS (|r| = 0.072-0.567, p < 0.05). Alexithymia and anxiety symptoms exhibited a serial mediation effect between neuroticism and OAS (95%CI[0.001, 0.014]), conscientiousness and OAS (95%CI[-0.008, -0.001]), and extraversion and OAS (95%CI[-0.006, -0.001]). Anxiety symptoms mediated the relationship between agreeableness and OAS (95%CI[-0.023, -0.001]) and between openness and OAS (95%CI [0.004, 0.024])., Conclusion: The mediating roles of alexithymia and anxiety symptoms between the Big Five personality traits and odor awareness support the idea of a certain level of association among personality, emotions, and olfaction, with the underlying role of the limbic system structure. This enhances our understanding of personality, emotions, and olfaction and provides insights for future intervention measures for affective disorders and olfactory dysfunctions., (© 2024. The Author(s).)

Background: The association between the triglyceride-glucose (TyG) index and arterial stiffness in individuals with normoglycaemia remains unclear. We aimed to evaluate the relationship between the TyG index and arterial stiffness in Japanese individuals with normoglycaemia, providing additional evidence for predicting early arterial stiffness., Methods: This study included 15,453 adults who participated in the NAGALA Physical Examination Project of the Murakami Memorial Hospital in Gifu, Japan, from 2004 to 2015. Data on clinical demographic characteristics and serum biomarker levels were collected. The TyG index was calculated from the logarithmic transformation of fasting triglycerides multiplied by fasting glucose, and arterial stiffness was measured using the estimated pulse wave velocity calculated based on age and mean blood pressure. The association between the TyG index and arterial stiffness was analysed using a logistic regression model., Results: The prevalence of arterial stiffness was 3.2% (500/15,453). After adjusting for all covariates, the TyG index was positively associated with arterial stiffness as a continuous variable (adjusted odds ratio (OR) = 1.86; 95% Confidence Interval = 1.45-2.39; P<0.001). Using the quartile as the cutoff point, a regression analysis was performed for arterial stiffness when the TyG index was converted into a categorical variable. After adjusting for all covariates, the OR showed an upward trend; the trend test was P<0.001. Subgroup analysis revealed a positive association between the TyG index and arterial stiffness in Japanese individuals with normoglycaemia and different characteristics., Conclusion: The TyG index in Japanese individuals with normoglycaemia is significantly correlated with arterial stiffness, and the TyG index may be a predictor of early arterial stiffness., (© 2024. The Author(s).)

Background: Asthma is a common respiratory disease. In asthma, the small airways have more intensive inflammation and prominent airway remodelling, compared to the central airways. We aimed to investigate the predictive value of risk factors and the fractional concentration of exhaled nitric oxide (FeNO) for persistent small airway dysfunction (p-SAD), and compare the effects of different treatment modalities., Methods: This retrospective cohort study included 248 children with asthma (aged 4-11 years). Binary logistic regression was used to analyse the risk factors for p-SAD. Correlations among FEV 1 /FVC, small airway function parameters, and FeNO levels in patients with asthma were analysed using Spearman's rank correlation. The receiver operating characteristic curve and the Delong test were used to analyse the predictive value of FeNO for p-SAD. Differences in the treatment effects of inhaled corticosteroids (ICS) and ICS with a long-acting beta-agonist (ICS/LABA) on p-SAD were analysed using Fisher's exact test., Results: Asthmatic children with older age of receiving the regular treatment (OR 1.782, 95% CI 1.082-2.935), with younger age at the time of onset of suspected asthma symptoms (OR 0.602, 95% CI 0.365-0.993), with longer duration of using ICS or ICS/LABA (OR 1.642, 95% CI 1.170-2.305) and with worse asthma control (OR 3.893, 95% CI 1.699-8.922) had increased risk for p-SAD. Significant negative correlations of small airway function parameters with FeNO at a 200 mL/s flow rate (FeNO 200 ), and the concentration of nitric oxide in the alveolar or acinar region (CaNO) were observed. The areas under the curve of FeNO 200 (cut-off:10.5ppb), CaNO (cut-off:5.1ppb), and FeNO 200 combined with CaNO were 0.743, 0.697, and 0.750, respectively, for asthma with p-SAD. After using ICS or ICS/LABA, switching to ICS/LABA was easier than continuing with ICS to improve small airway dysfunction (SAD) in the 8th month., Conclusions: Paediatric asthma with p-SAD is associated with older age at receiving regular treatment, younger age at the time of onset of suspected asthma symptoms, longer duration of using ICS or ICS/LABA, worse asthma control, and higher FeNO 200 and CaNO levels, all of which can be combined with small airway function indicators to distinguish p-SAD from asthma. ICS/LABA improves SAD better than ICS alone., (© 2024. The Author(s).)

Background: The etiology of premature ovarian insufficiency, that is, the loss of ovarian activity before 40 years of age, is complex. Studies suggest that genetic factors are involved in 20-25% of cases. The aim of this study was to explore the oligogenic basis of premature ovarian insufficiency., Results: Whole-exome sequencing of 93 patients with POI and whole-genome sequencing of 465 controls were performed. In the gene-burden analysis, multiple genetic variants, including those associated with DNA damage repair and meiosis, were more common in participants with premature ovarian insufficiency than in controls. The ORVAL-platform analysis confirmed the pathogenicity of the RAD52 and MSH6 combination., Conclusions: The results of this study indicate that oligogenic inheritance is an important cause of premature ovarian insufficiency and provide insights into the biological mechanisms underlying premature ovarian insufficiency., (© 2024. The Author(s).)

Background: The design of DNA materials with specific nanostructures for biomedical tissue engineering applications remains a challenge. High-dimensional DNA nanomaterials are difficult to prepare and are unstable; moreover, their synthesis relies on heavy metal ions. Herein, we developed a bimodal DNA self-origami material with good biocompatibility and differing functions using a simple synthesis method. We simulated and characterized this material using a combination of oxDNA, freeze-fracture electron microscopy, and atomic force microscopy. Subsequently, we optimized the synthesis procedure to fix the morphology of this material., Results: Using molecular dynamics simulation, we found that the bimodal DNA self-origami material exhibited properties of spontaneous stretching and curling and could be fixed in a single morphology via synthesis control. The application of different functional nucleic acids enabled the achievement of various biological functions, and the performance of functional nucleic acids was significantly enhanced in the material. Consequently, leveraging the various functional nucleic acids enhanced by this material will facilitate the attainment of diverse biological functions., Conclusion: The developed design can comprehensively reveal the morphology and dynamics of DNA materials. We thus report a novel strategy for the construction of high-dimensional DNA materials and the application of functional nucleic acid-enhancing materials., (© 2024. The Author(s).)

With the rapid development of medical imaging technology and computer technology, the medical imaging artificial intelligence of computer-aided diagnosis based on machine learning has become an important part of modern medical diagnosis. With the application of medical image security technology, people realize that the difficulty of its development is the inherent defect of advanced image processing technology. This paper introduces the background of colorectal cancer diagnosis and monitoring, and then carries out academic research on the medical imaging artificial intelligence of colorectal cancer diagnosis and monitoring and machine learning, and finally summarizes it with the advanced computational intelligence system for the application of safe medical imaging.In the experimental part, this paper wants to carry out the staging preparation stage. It was concluded that the staging preparation stage of group Y was higher than that of group X and the difference was statistically significant. Then the overall accuracy rate of multimodal medical image fusion was 69.5% through pathological staging comparison. Finally, the diagnostic rate, the number of patients with effective treatment and satisfaction were analyzed. Finally, the average diagnostic rate of the new diagnosis method was 8.75% higher than that of the traditional diagnosis method. With the development of computer science and technology, the application field was expanding constantly. Computer aided diagnosis technology combining computer and medical images has become a research hotspot., (© 2024. The Author(s).)

Background: Partial nephrectomy (PN) is usually recommended for T1 stage clear cell renal cell carcinoma (ccRCC) regardless of the nuclear grades. However, the question remains unresolved as to whether PN is non-inferior to RN in patients with T1-ccRCC at higher risk of recurrence. In fact, we found that patients with high nuclear grades treated with PN had poorer prognosis compared with those treated with radical nephrectomy (RN). Therefore, this study was designed to evaluate the associations of PN and RN in the four nuclear grade subsets with oncologic outcomes., Methods: A retrospective study was conducted in three Chinese urological centers that included 1,714 patients who underwent PN or RN for sporadic, unilateral, pT1, N0, and M0 ccRCC without positive surgical margins and neoadjuvant therapy between 2010 and 2019. Associations of nephrectomy type with local ipsilateral recurrence, distant metastases, and all-cause mortality (ACM) were evaluated using the Kaplan-Meier method and multivariable Cox proportional hazards regression models after overlap weighting (OW)., Results: A total of 1675 patients entered the OW cohort. After OW, in comparison to PN, RN associated with a reduced risk of local ipsilateral recurrence in the G2 subset (HR = 0.148, 95% CI 0.046-0.474; p < 0.05), G3 subset (HR = 0.097, 95% CI 0.021-0.455; p < 0.05), and G4 subset (HR = 0.091, 95% CI 0.011-0.736; p < 0.05), and resulting in increased five-year local recurrence-free survival rates of 7.0%, 17.9%, and 36.2%, respectively. An association between RN and a reduced risk of distant metastases in the G4 subset (HR = 0.071, 95% CI 0.016-0.325; p < 0.05), with the five-year distant metastases-free survival rate increasing by 33.1% was also observed. No significant difference in ACM between PN and RN was identified., Conclusions: Our findings substantiate that opting for RN, as opposed to PN, is more advantageous for local recurrence-free survival and distant metastases-free survival in patients with high nuclear grade (especially G4) pT1-ccRCC. We recommend placing a heightened emphasis on enhancing preoperative nuclear grade assessment, as it can significantly influence the choice of surgical plan., Trial Registration: This study was registered at Chinese Clinical Trial Registry (ID: ChiCTR2200063333)., (© 2024. The Author(s).)

Background: Major depressive disorder (MDD) is a common psychiatric disorder worldwide. Psychotic depression has been reported to be frequently under-diagnosed due to poor recognition of psychotic features. Therefore, the purpose of this study was to reveal the rate and risk factors of psychotic symptoms in young, drug-naïve patients with major depressive disorder at the time of their first episode., Methods: A total of 917 patients were recruited and divided into psychotic and non-psychotic subgroups based on the Positive and Negative Syndrome Scale (PANSS) positive subscale score. Anxiety symptoms and depressive symptoms were measured by the Hamilton Anxiety Rating Scale (HAMA) and the 17-item Hamilton Depression Rating Scale (HAMD-17), respectively. Several biochemical indicators such as total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were also measured., Results: The rate of psychotic symptoms among young adult MDD patients was 9.1%. There were significant differences in TSH (p<0.001), FBG (p<0.001), TC (p<0.0001), TG (p = 0.001), HDL-C (p = 0.049), LDL-C (p = 0.010), diastolic blood pressure (DP) (p<0.001), systolic blood pressure (SP) (p<0.001), and HAMD total score (p<0.001) between young MDD patients with and without psychotic depression. HAMD, TSH, TC, and severe anxiety were independently associated with psychotic symptoms in young adult MDD patients. In addition, among young MDD patients, the rate of suicide attempts in the psychotic subgroup was much higher than in the non-psychotic subgroup (45.8% vs. 16.9%)., Conclusions: Our findings suggest that psychotic symptoms are common in young MDD patients. Several clinical variables and biochemical indicators are associated with the occurrence of psychotic symptoms in young MDD patients., (© 2024. The Author(s).)

Background: Rye (Secale cereale), one of the drought and cold-tolerant crops, is an important component of the Triticae Dumortier family of Gramineae plants. Basic helix-loop-helix (bHLH), an important family of transcription factors, has played pivotal roles in regulating numerous intriguing biological processes in plant development and abiotic stress responses. However, no systemic analysis of the bHLH transcription factor family has yet been reported in rye., Results: In this study, 220 bHLH genes in S. cereale (ScbHLHs) were identified and named based on the chromosomal location. The evolutionary relationships, classifications, gene structures, motif compositions, chromosome localization, and gene replication events in these ScbHLH genes are systematically analyzed. These 220 ScbHLH members are divided into 21 subfamilies and one unclassified gene. Throughout evolution, the subfamilies 5, 9, and 18 may have experienced stronger expansion. The segmental duplications may have contributed significantly to the expansion of the bHLH family. To systematically analyze the evolutionary relationships of the bHLH family in different plants, we constructed six comparative genomic maps of homologous genes between rye and different representative monocotyledonous and dicotyledonous plants. Finally, the gene expression response characteristics of 22 ScbHLH genes in various biological processes and stress responses were analyzed. Some candidate genes, such as ScbHLH11, ScbHLH48, and ScbHLH172, related to tissue developments and environmental stresses were screened., Conclusions: The results indicate that these ScbHLH genes exhibit characteristic expression in different tissues, grain development stages, and stress treatments. These findings provided a basis for a comprehensive understanding of the bHLH family in rye., (© 2023. The Author(s).)

Reactive oxygen species (ROS), such as superoxides (O 2  •-) and hydroxyl groups (OH·), are short-lived molecules containing unpaired electrons. Intracellular ROS are believed to be mainly produced by the mitochondria and NADPH oxidase (NOX) and can be associated with various physiological processes, such as proliferation, cell signaling, and oxygen homeostasis. In recent years, many studies have indicated that ROS play crucial roles in regulating ultraviolet (UV)-induced photodamage of the skin, including exogenous aging, which accounts for 80% of aging. However, to the best of our knowledge, the detailed signaling pathways, especially those related to the mechanisms underlying apoptosis in which ROS are involved have not been reviewed previously. In this review, we elaborate on the biological characteristics of ROS and its role in regulating UV-induced photodamage of the skin., (© 2024. The Author(s).)

Only few studies have investigated the prevalence of feline coronavirus (FCoV) infection in domestic cats in Fujian, China. This is the first study to report the prevalence rate of FCoV infection in domestic cats in Fujian, China, and to analyse the epidemiological characteristics of FCoV infection in the region. A total of 112 cat faecal samples were collected from animal hospitals and catteries in the Fujian Province. RNA was extracted from faecal material for reverse transcription polymerase chain reaction (RT-PCR). The prevalence rate of FCoV infection was determined, and its epidemiological risk factors were analysed. The overall prevalence of FCoV infection in the cats, was 67.9%. We did not observe a significant association between the age, sex, or breed of the cats included in the study and the prevalence rate of the viral infection. Phylogenetic analysis showed that the four strains from Fujian were all type I FCoV. This is the first study to analyse the prevalence and epidemiological characteristics of FCoV infection in domestic cats in Fujian, China, using faecal samples. The results of this study provide preliminary data regarding the prevalence of FCoV infection in the Fujian Province for epidemiological studies on FCoV in China and worldwide. Future studies should perform systematic and comprehensive epidemiological investigations to determine the prevalence of FCoV infection in the region., (© 2024. The Author(s).)

Background: Tumor-associated inflammation suggests that anti-inflammatory medication could be beneficial in cancer therapy. Loratadine, an antihistamine, has demonstrated improved survival in certain cancers. However, the anticancer mechanisms of loratadine in lung cancer remain unclear., Objective: This study investigates the anticancer mechanisms of loratadine in lung cancer., Methods: A retrospective cohort of 4,522 lung cancer patients from 2006 to 2018 was analyzed to identify noncancer drug exposures associated with prognosis. Cellular experiments, animal models, and RNA-seq data analysis were employed to validate the findings and explore the antitumor effects of loratadine., Results: This retrospective study revealed a positive association between loratadine administration and ameliorated survival outcomes in lung cancer patients, exhibiting dose dependency. Rigorous in vitro and in vivo assays demonstrated that apoptosis induction and epithelial-mesenchymal transition (EMT) reduction were stimulated by moderate loratadine concentrations, whereas pyroptosis was triggered by elevated dosages. Intriguingly, loratadine was found to augment PPARγ levels, which acted as a gasdermin D transcription promoter and caspase-8 activation enhancer. Consequently, loratadine might incite a sophisticated interplay between apoptosis and pyroptosis, facilitated by the pivotal role of caspase-8., Conclusion: Loratadine use is linked to enhanced survival in lung cancer patients, potentially due to its role in modulating the interplay between apoptosis and pyroptosis via caspase-8., (© 2023. The Author(s).)

Background: Cue exposure therapy is used to treat alcohol dependence. However, its effectiveness is controversial due to the limitations of the clinical treatment setting. Virtual reality technology may improve the therapeutic effect. The aim of this study is to explore whether virtual reality-based cue exposure therapy can reduce the psychological craving and physiological responses of patients with alcohol dependence., Methods: Forty-four male alcohol-dependent patients were recruited and divided into the study group (n = 23) and the control group (n = 21) according to a random number table. The control group received only conventional clinical treatment for alcohol dependence. The study group received conventional clinical treatment with the addition of VR cue exposure (treatment). The primary outcome was to assess psychological craving and physiological responses to cues of patients before and after treatment., Results: After virtual reality-based cue exposure therapy, the changes in VAS and heart rate before and after cue exposure in the study group were significantly lower than those in the control group (P < 0.05), while the changes in skin conductance and respiration between the study group and the control group were not significantly different (P > 0.05). The changes in VAS and heart rate before and after cue exposure in the study group were significantly lower than those before treatment (P < 0.05), while the changes in skin conductance and respiration were not significantly different from those before treatment (P > 0.05). The changes in VAS, heart rate, skin conductance and respiration before and after cue exposure in the control group were not significantly different from those before treatment (P > 0.05)., Conclusion: Virtual reality-based cue exposure therapy can reduce the psychological craving and part of the physiological responses of alcohol-dependent patients during cue exposure in the short term and may be helpful in the treatment of alcohol dependence., Trial Registration: The study protocol was registered at the China Clinical Trial Registry on 26/02/2021 ( www.chictr.org.cn ; ChiCTR ID: ChiCTR2100043680)., (© 2023. The Author(s).)

Background: Currently, oblique placement of long implants or the use of short implants to circumvent the maxillary sinus area and provide support for fixed prostheses are viable alternatives. The purpose of this study was to compare these two treatment concepts and ascertain which one exhibits superior biomechanical characteristics., Methods: Two different treatment concept models were constructed. The first one, LT4I, consisting of two mesial vertical implants positioned in lateral incisor regions and two distal tilted implants (45°) situated in second premolar regions of the maxilla. The second model, VS4I, includes two mesial vertical implants in lateral incisor regions and two vertically positioned short implants in second premolar regions. Numerical simulations were conducted under three loading types: firstly, oblique forces upon the molars; secondly, vertical forces upon the molars; thirdly, oblique forces upon the incisors. The maximum principal stress (σ max ) and minimum principal stress (σ min ) of the bone, as well as von Mises stress of the implants, were calcuated., Results: Under oblique loading on the molar, higher stress values in the bone were observed in LT4I group. Under vertical loading on molar, higher stress values in the bone were also observed in LT4I group. Furthermore, little difference was found between the two groups under oblique loading on the incisor., Conclusion: Both treatment concepts can be applicable for edentulous individuals with moderate atrophic maxilla. Compared to tilted implants, short implants can transmit less occlusal force to the supporting tissues., (© 2023. The Author(s).)

Mounting evidence indicates that the gut microbiota influences the neurodevelopment and behavior of insects through the gut-brain axis. However, it is currently unclear whether the gut microbiota affect the head profiles and immune pathway in pests. Here, we find that gut bacteria is essential for the immune and neural development of adult Spodoptera frugiperda, which is an extremely destructive agricultural pest worldwide. 16 S rRNA sequencing analysis showed that antibiotics exposure significantly disturbed the composition and diversity of gut bacteria. Further transcriptomic analysis revealed that the adult head transcripts were greatly affected by gut dysbacteriosis, and differently expression genes critical for brain and neural development including A4galt, Tret1, nsun4, Galt, Mitofilin, SLC2A3, snk, GABRB3, Oamb and SLC6A1 were substantially repressed. Interestingly, the dysbacteriosis caused sex-specific differences in immune response. The mRNA levels of pll (serine/threonine protein kinase Pelle), PGRP (peptidoglycan-sensing receptor), CECA (cecropin A) and CECB (cecropin B) involved in Toll and Imd signaling pathway were drastically decreased in treated male adults' heads but not in female adults; however, genes of HIVEP2, ZNF131, inducible zinc finger protein 1-like and zinc finger protein 99-like encoding zinc-finger antiviral protein (ZAP) involved in the interferon (IFNα/β) pathway were significantly inhibited in treated female adults' heads. Collectively, these results demonstrate that gut microbiota may regulate head transcription and impact the S. frugiperda adults' heads through the immune pathway in a sex-specific manner. Our finding highlights the relationship between the gut microbiota and head immune systems of S. frugiperda adults, which is an astonishing similarity with the discoveries of other animals. Therefore, this is the basis for further research to understand the interactions between hosts and microorganisms via the gut-brain axis in S. frugiperda and other insects., (© 2023. The Author(s).)

Bacterial infection in skin and soft tissue has emerged as a critical concern. Overreliance on antibiotic therapy has led to numerous challenges, including the emergence of multidrug-resistant bacteria and adverse drug reactions. It is imperative to develop non-antibiotic treatment strategies that not only exhibit potent antibacterial properties but also promote rapid wound healing and demonstrate biocompatibility. Herein, a novel multimodal synergistic antibacterial system (SNO-CS@MoS 2 ) was developed. This system employs easily surface-modified thin-layer MoS 2 as photothermal agents and loaded with S-nitrosothiol-modified chitosan (SNO-CS) via electrostatic interactions, thus realizing the combination of NO gas therapy and photothermal therapy (PTT). Furthermore, this surface modification renders SNO-CS@MoS 2 highly stable and capable of binding with bacteria. Through PTT's thermal energy, SNO-CS@MoS 2 rapidly generates massive NO, collaborating with PTT to achieve antibacterial effects. This synergistic therapy can swiftly disrupt the bacterial membrane, causing protein leakage and ATP synthesis function damage, ultimately eliminating bacteria. Notably, after effectively eliminating all bacteria, the residual SNO-CS@MoS 2 can create trace NO to promote fibroblast migration, proliferation, and vascular regeneration, thereby accelerating wound healing. This study concluded that SNO-CS@MoS 2 , a novel multifunctional nanomaterial with outstanding antibacterial characteristics and potential to promote wound healing, has promising applications in infected soft tissue wound treatment., (© 2023. The Author(s).)

Background: Head and neck squamous cell carcinoma (HNSCC) is an extremely heterogeneous and metastatic disease. Anoikis, which is a specific type of programmed apoptosis, is involved in tumor metastasis, tissue homeostasis, and development. Herein, we constructed an anoikis-related long non-coding RNA (lncRNA) signature to predict the prognosis, immune responses, and therapeutic effects in HNSCC patients., Methods: A total of 501 HNSCC samples were acquired from the TCGA database and randomly classified into the training and validation groups (1:1 ratio). Thereafter, the results derived from the training set were analyzed with the LASSO regression analysis, and a novel anoikis-related lncRNA risk model was constructed. Time-dependent ROC curves and Kaplan-Meier analysis were carried out to assess the diagnostic value and survival outcomes. A nomogram was utilized to predict the prognostic accuracy. Furthermore, we studied the tumor microenvironment, tumor mutation burden, enrichment pathways, and the response to chemotherapy and immunotherapy., Results: Seven anoikis-related lncRNAs (AC015878.1, CYTOR, EMSLR, LINC01503, LINC02084, RAB11B-AS1, Z97200.1) were screened to design a novel risk model, which was recognized as the independent prognostic factor for HNSCC patients. The findings implied that low-risk patients showed significantly longer OS, PFS, and DSS compared to those high-risk patients. The two groups that were classified using the risk model showed significant differences in their immune landscape. The risk model also predicted that low-risk HNSCC patients could attain a better response to immunotherapy, while high-risk patients would be more sensitive to gemcitabine, docetaxel, and cisplatin., Conclusions: We constructed a novel risk model that could be employed for effectively predicting patient prognosis with a good independent prognostic value for HNSCC patients. Furthermore, this model could be used for designing new immunotherapeutic and chemotherapeutic strategies, and it helps clinicians establish personalized and detailed strategies for HNSCC patients., (© 2023. The Author(s).)