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This study evaluates the pathogenesis of COVID-19 and the therapeutic efficacy of sitagliptin in diabetic and obese mice. Using a novel double-transgenic mouse model (db/db and K18-hACE2), the findings demonstrates that SARS-CoV-2 infection (Delta variant) causes severe multi-organ damage, glucose metabolism abnormalities, insulin resistance, and pancreatic islet cell damage in diabetic mice. Infected diabetic mice displayed higher mortality, inflammation (elevated TNF-α, IL-6, IL-1β), and fibrinolytic activity (PAI-1), alongside dysregulated diabetes-related hormones (GLP-1, leptin, ghrelin, resistin) compared to non-diabetic controls. Sitagliptin treatment reduced organ injury, hyperglycemia, inflammation, and fibrinolytic activity while improving insulin resistance and glucose metabolism. This was evidenced by decreased fasting blood glucose levels, improved insulin sensitivity, and elevated insulin and GLP-1 levels. These findings suggest sitagliptin is a promising therapeutic strategy to mitigate the severity of COVID-19 in experimental diabetes by modulating inflammation and improving metabolic syndrome. Further mechanistic investigations revealed that the level of hACE2 expression, along with the activation of NF-κB and IRS-1, play critical roles in the development of SARS-CoV-2-induced diabetes, the exacerbation of pre-existing diabetes, and the therapeutic efficacy of sitagliptin., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Guirong Wang reports was provided by National Institutes of Health. Reports a relationship with that includes:. Has patent pending to. If there are other authors, they 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 © 2025. Published by Elsevier B.V.)

Understanding neurobiological mechanisms underlying changes in behavior and neural activity caused by early life stress (ELS) is essential for improving these adverse outcomes in individuals. ELS incited by exposure to maternal separation (MS) can be defined as a form of social pain, but little is known about the neural mechanism in adolescents with ELS-induced pain sensitization. Employing an MS-induced ELS paradigm in mice, we reported here that both male and female MS mice aged 1-2 months exhibited mechanical and thermal hyperalgesia using paw-withdrawal and hot/cold plate tests. The increased high gamma (γ high ) oscillations accompanied by the activation of parvalbumin-positive interneurons (PVINs) in the anterior insular cortex (AIC), but not the anterior cingulate cortex (ACC), were shown in MS mice. Moreover, ACC-driven AIC connectivity was enhanced in MS mice, characterized by amplified phase coherence in the delta (δ) and theta (θ) bands and an escalation in the coupling of the ACC θ phase and AIC γ amplitude. Chemogenetic inactivation of AIC PVINs relieved hyperalgesia and altered the ACC-AIC connectivity in MS mice. The observed increase in δ-θ synchronization and PVIN activation in the ACC-AIC circuit indicates this pathway is a therapeutic target for ELS-induced hyperalgesia.

Intracerebral hemorrhage (ICH) is associated with the highest rates of mortality and residual disability. To date, effective treatments to delay or prevent ICH are still lacking. Multiple forms of neuronal cell death have been discovered following ICH, including apoptosis, necrosis, autophagy, and ferroptosis. Aldo-keto reductase family 1 member C1 (AKR1C1) has been identified to act as a protective factor in ferroptosis. However, whether AKR1C1 was involved in the development of ICH was unknown. In this study, the left cerebral striatum of the Sprague-Dawley rat was injected with collagenase type IV to induce an in vivo model. Primary rat cortical neurons treated with oxygen hemoglobin (OxyHb) were applied to as an in vitro model. AKR1C1 was found to be downregulated and immunoreactivity colocalized with NeuN-positive neurons in the perihematomal region. Rats injected with lentiviral particles overexpressing AKR1C1 showed the reduction of cerebral hematoma and the remission of blood-brain barrier disruption. Moreover, AKR1C1 upregulation repressed cell apoptosis and ferroptosis induced by ICH through downregulating the expression of pro-apoptotic factors, inhibiting iron accumulation and lipid peroxidation, along with increasing the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). The results of in vitro assays were consistent with results from the in vivo. Mechanistically, P53 overexpression augmented the cellular damage in OxyHb-stimulated neurons when AKR1C1 was overexpressed. Taken together, AKR1C1 improves ICH injury by inhibiting neuronal cell death via negatively regulating P53 expression and affecting the SLC7A11/GPX4 pathway., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Prostate cancer (PCa) is a common form of malignancy among men. The associations between socioeconomic status (SES) indicators and PCa risks remain incompletely elucidated. Through two-sample Mendelian randomization (MR), this research seeks to assess the causal links between 4 genetically predicted SES indicators-average total household income before tax, the Townsend deprivation index at recruitment, unemployed status and college or university degree in the household-and PCa. Genetic variants were extracted from publicly available genome-wide association studies (GWAS) under stringent threshold as instrumental variables (IVs). We employed the inverse variance weighted (IVW), weighted median, weighted mode and MR-Egger to estimate the causal effect, with sensitivity analyses such as Cochran's Q tests, MR-Egger, MR-PRESSO and leave-one-out performed to detect potential heterogeneity and pleiotropy. Our MR analysis revealed a causal association between unemployment and prostate cancer (OR: 3.07, 95%CI:1.12-8.42, P = 0.03). No causal associations were identified between other SES components and prostate cancer. The MR-PRESSO suggested 2 outliers in the association between college or university degree in household and prostate cancer, which rendered the association significant after outliers were removed. The heterogeneity and pleiotropy are unlikely to affect our causal estimate. Our results indicated that unemployment poses a potential risk factor for the incidence of PCa. The findings highlight the necessity for further exploration into the underlying etiology of PCa., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: This article is a Mendelian randomization study. The data for this study were obtained from publicly available databases and published literature data and does not require ethical approval and written informed consent., (© 2025. The Author(s).)

Ferroelectric materials, celebrated for their switchable polarization, have undergone significant evolution since their early discovery in Rochelle salt. Initial challenges, including water solubility and brittleness, are overcome with the development of perovskite ferroelectrics, which enable the creation of stable, high-quality thin films suitable for semiconductor applications. As the demand for miniaturization in nanoelectronics has increased, research has shifted toward low-dimensional materials. Traditional ferroelectrics often lose their properties at the nanoscale; however, 2D van der Waals (vdW) ferroelectrics, including CuInP 2 S 6 and α-In 2 Se 3 , have emerged as promising alternatives. The recent discovery of sliding ferroelectricity, where polarization is linked to the polar stacking configuration of originally non-polar monolayers, has significantly broadened the scope of 2D ferroelectrics. This review offers a comprehensive examination of stacking orders in 2D vdW materials, stacking-order-linked ferroelectric polarization structures, and their manifestations in metallic, insulating and semiconducting 2D vdW materials. Additionally, it explores the applications of 2D vdW sliding ferroelectrics, and discusses the future prospects in nanotechnology., (© 2025 Wiley‐VCH GmbH.)

Chronic itch which is primarily associated with dermatologic, systemic, or metabolic disorders is often refractory to most current antipruritic medications, thus highlighting the need for improved therapies. Oxidative damage is a novel determinant of spinal pruriceptive sensitization and synaptic plasticity. The resolution of oxidative insult by molecular hydrogen has been manifested. Herein, we strikingly report that both hydrogen gas (2 %) inhalation and hydrogen-rich saline (5 mL/kg, intraperitoneal) injection prevent and alleviate persistent dermatitis-induced itch, diabetic itch and cholestatic itch. Hydrogen therapy reverses the decrease of spinal SIRT1 expression and antioxidant enzymes (SOD, GPx and CAT) activity after dermatitis, diabetes and cholestasis. Furthermore, hydrogen reduces spinal ROS generation, oxidation products (MDA, 8-OHdG and 3-NT) accumulation, β-catenin acetylation and dendritic spine density in persistent itch models. Spinal SIRT1 inhibition eliminates antipruritic and antioxidative effects of hydrogen, while SIRT1 agonism attenuates chronic itch phenotype, spinal β-catenin acetylation and mitochondrial damage. β-catenin inhibitors are effective against chronic itch via reducing β-catenin acetylation, blocking ERK phosphorylation and elevating antioxidant enzymes activity. Hydrogen treatment suppressed dermatitis and cholestasis mediated spontaneous excitatory postsynaptic currents in vitro. Additionally, hydrogen impairs cholestasis-induced the enhancement of cerebral functional connectivity between the right primary cingulate cortex and bilateral sensorimotor cortex, as well as bilateral striatum. Taken together, this study uncovers that molecular hydrogen protects against chronic pruritus and spinal pruriceptive sensitization by reducing oxidative damage via up-regulation of SIRT1-dependent β-catenin deacetylation in mice, implying a promising strategy in translational development for itch control., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Study Question: Is there a difference in the cumulative live birth rate (CLBR) after fresh testicular sperm aspiration (TESA) compared with the use of either pre-frozen sperm or oocyte freezing for couples experiencing ejaculation failure on the day of oocyte retrieval?, Summary Answer: After adjusting for confounding factors, the use of pre-frozen sperm or the freezing and thawing of oocytes appeared to be as effective as TESA in achieving CLBRs for couples experiencing temporary ejaculation failure., What Is Known Already: Male patients may be concerned about experiencing temporary ejaculation failure on the day of their partner's oocyte retrieval, in which case they may choose surgical sperm retrieval, oocyte freezing on the day, or have their sperm frozen in advance. However, the clinical efficacy of these three options has not yet been evaluated., Study Design, Size, Duration: A retrospective data analysis was conducted on 65 178 oocyte retrieval cycles at a university-affiliated IVF center from January 2012 to May 2021., Participants/materials, Setting, Methods: The overall characteristics, completed cycle characteristics, and clinical outcomes were analyzed among couples with ejaculation failure who underwent three distinct clinical interventions, with those receiving TESA serving as the control group. The primary outcome measure was the CLBR, and the secondary outcome measures were the clinical pregnancy rate (CPR) and live birth rate (LBR) per embryo transfer. A robust (modified) Poisson regression model was used to evaluate the association between the three clinical options for ejaculation failure and CLBRs., Main Results and Role of Chance: Of the eligible oocyte retrieval cycles, 756 cycles (1.2%) experienced ejaculation failure, with 640 cycles completing treatment. These treatments included 325 cycles using TESA, 227 cycles utilizing pre-frozen sperm, and 88 cycles involving frozen-thawed oocytes. The CLBRs for the TESA, thawed-sperm and thawed-oocyte groups were 36.9%, 48.9%, and 34.1%, respectively, showing a statistically significant difference (P = 0.007). Specifically, the thawed-sperm group demonstrated a significantly higher CLBR compared to the TESA group, while no significant difference was observed between the TESA and thawed-oocyte groups. Similarly, the CPRs and LBRs per embryo transfer for the three groups were 37.4%, 50.0%, and 41.8%, respectively (P = 0.005), and 29.9%, 39.6%, and 33.0%, respectively (P = 0.030). Again, the thawed-sperm group showed a significantly higher CPR and a significantly higher LBR, but no significant differences for the thawed-oocyte group, compared to the TESA group. Notably, the significant differences in both CLBR and LBR emerged after the second embryo transfer. However, after adjusting for multiple factors, including female age at oocyte retrieval, type and duration of infertility, female body mass index, number of previous IVF cycles, ovarian stimulation protocol, endometrial thickness on the last ultrasound, insemination method, number of oocytes retrieved, number of fertilized oocytes, and number of usable embryos on Day 3, the analysis revealed no significant association between CLBR and the use of pre-frozen sperm (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.81-1.44) or thawed oocytes (RR 1.01, 95% CI 0.76-1.33), compared with TESA., Limitations, Reasons for Caution: Given that the study is retrospective and the sample size is too small, particularly concerning the use of thawed oocytes, we acknowledge that the data present here is only suggestive and refers to an association that warrants cautious interpretation. Therefore, further research in the form of prospective studies as well as randomized controlled trials is needed to provide a definitive answer to the research question., Wider Implications of the Findings: Our findings suggest that using pre-frozen sperm or frozen-thawed oocytes can offer comparable CLBRs to TESA for cases of temporary ejaculation failure, providing clinical alternatives that may reduce the logistical challenges in ART cycles., Study Funding/competing Interest(s): This study was supported by the National Nature Science Foundation of China (grant nos. 82101672, 82171589), the National Key Research and Development Program of China (grant nos. 2022YFC2702504, 2019YFE0109500), the Basic and Applied Basic Research Foundation of Guangdong Province (grant no. 2021A1515010774), and the Guangzhou Municipal Science and Technology Project (grant nos. 202102010075, 2023A4J0578). The authors declare that they have no conflict of interest in relation to the data in this paper., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: There is substantial evidence linking bullying victimization to suicidal ideation, but the mechanism behind this link is not well understood. This study investigates whether depressive symptoms mediate the relationship between bullying victimization and suicidal ideation, and whether perceived family economic strain moderates this mediation., Methods: Data were collected from 7,702 adolescents (mean age = 14.74 ± 1.69 years, 52% girls) using a self-report questionnaire that assessed bullying victimization, depressive symptoms, suicidal ideation and perceived family economic strain. Mediation and moderated mediation analyses were conducted using the PROCESS macro in SPSS., Results: Suicidal ideation was significantly associated with both bullying victimization and depressive symptoms, as determined by linear regression analysis (both p < 0.001). The relationship between bullying victimization and suicidal ideation was partially mediated by depressive symptoms, accounting for 66.74% of the effect. Additionally, perceived family economic strain could moderate the link between bullying victimization and depressive symptoms (β=-0.017, p < 0.001), indicating that increased perceived family economic strain attenuates the impact of bullying victimization on depressive symptoms., Conclusion: Our research affirms bullying victimization substantial influence on adolescent suicidal ideation, with depressive symptoms mediating this link. The study also reveals that perceived family economic strain moderates this relationship, indicating the necessity for interventions that address both psychological and economic factors to holistically support the mental health of bullied adolescents., Competing Interests: Declarations. Ethics approval and consent to participate: This study strictly follows the Declaration of Helsinki and was approved by the Ethics Committee of Guangxi Medical University (No: 20200016). In this study, we obtained informed consent from students and their parents. All procedures are carried out in accordance with the relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The study investigates the effectiveness of immersive virtual reality (VR) as a nonpharmaceutical approach to manage postoperative pain in patients following thoracoscopic surgery. In this single-center, triple-arm pilot randomized controlled trial (RCT), 61 postsurgical patients with a postoperative pain numerical rating scale (NRS) score ≥4 after receiving standard analgesia were included and assigned to either a quantum clinics-VR (QTC-VR) group, a Placebo-VR group, or a control group. The QTC-VR group engaged in a daily 10-minute interactive pain relief 3D-VR program, while the Placebo-VR group watched a daily 10-minute relaxation-based 2D film through VR headsets for three days following surgery. 61 postsurgical patients were randomized and allocated (21 in the QTC-VR group, 20 in the Placebo-VR group, and 20 in the control group) in the final intention-to-treat (ITT) analyses. Compared with patients receiving Placebo-VR intervention, patients reported significantly lower pain scores following the daily QTC-VR intervention on postoperative days 1 (mean difference, -0.889; 95% CI, -1.464 to -0.314; P < 0.001), 2 (mean difference, -0.631; 95% CI, -1.211 to -0.051; P = 0.014), and 3 (mean difference, -0.798; 95% CI, -1.345 to -0.251; P < 0.001), respectively. Additionally, patients receiving QTC-VR intervention also reported high satisfaction and tolerable adverse events with their treatment. In conclusion, this pilot RCT demonstrates that QTC-VR might be a promising intervention for pain management post-thoracoscopic surgery, warranting further validation in ongoing phase III trials., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.)

Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive malignancies. Our previous studies revealed necroptosis-related lncRNA ENSG00000253385.1 was an independent prognostic factor for ESCC. However, the specific regulatory mechanisms are unknown. This study aimed to investigate the expression of the lncRNA ENSG00000253385.1 in ESCC tissues and its relationship with clinicopathological features and patient prognosis, and to explore its potential regulatory mechanism in ESCC cells. We detected the location of the lncRNA ENSG00000253385.1 in ESCC cells by fluorescence in situ hybridization (FISH). FISH and quantitative real-time polymerase chain reaction (qRT‒PCR) were used to detect gene expression in ESCC tissues and cells. Cell proliferation, migration and apoptosis were evaluated by CCK-8 assay, wound healing, transwell cell migration, invasion and flow cytometry assay. The levels of necroptosis-related protein were detected by western blot. The binding sites between miR-16-2-3p and lncRNA ENSG00000253385.1 or voltage-dependent anion channel 1 (VDAC1) were predicted by bioinformatics database and confirmed by dual luciferase reporter gene assay. Results revealed that the lncRNA ENSG00000253385.1 expression was higher in ESCC tissues than in the adjacent tissues. High lncRNA ENSG00000253385.1 expression, positive lymph node metastasis and clinical stage III were associated with poor overall survival (OS) in patients with ESCC, and were independent risk factors for prognosis of patients with ESCC. The lncRNA ENSG00000253385.1 was located in the cytoplasm. MiR-16-2-3p had a direct targeting regulatory relation ship with lncRNA ENSG00000253385.1 and VDAC1. MiR-16-2-3p inhibitor promoted proliferation, migration and invasion, and inhibited apoptosis of ESCC cells. Knockdown of the lncRNA ENSG00000253385.1 could inhibit the proliferation, migration and invasion, promote the apoptosis, and result in increases in the necroptosis-related proteins p-receptor-interacting protein kinase 3 (RIPK3)/RIPK3 and p-mixed lineaae kinase domain-like protein (MLKL)/MLKL and a decrease in the VDAC1 protein levels in ESCC cells, whereas miR-16-2-3p inhibition rescued these effects. Therefore, The lncRNA ENSG00000253385.1/ miR-16-2-3p/VDAC1 axis may be considered as a potential predictive biomarker and target for ESCC., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study was approved by the Ethics Committee of Shanghai XinChaobiotech Co., LTD. (SHYJS-CP-1707008). All human experiments complied with the principles outlined in the Declaration of Helsinki. Informed consent was obtained from all subjects., (© 2025. The Author(s).)

Background: The Objective Structured Clinical Examination (OSCE) is a systematic and structured assessment tool that evaluates candidates' professional medical skills in a simulated environment through a series of time-limited stations. The aim of this meta-analysis was to determine the optimal station number and duration time per station of OSCE to achieve good reliability., Methods: A comprehensive search was conducted across PubMed and Embase from inception until August 2024, without language restrictions. Studies were included if they provided data on the station number and duration time of OSCE, along with Cronbach's alpha. A random-effects model was used to pool the data., Results: A total of 23 studies encompassing 26 Cronbach's alpha were finally included. Cronbach's alpha values ranged from 0.43 to 0.93, and 11 studies demonstrated good internal consistency (Cronbach's alpha ≥ 0.8). The analysis indicated that a design of 5-10 stations, with each station lasting less than 10 min, yielded the best internal consistency (Cronbach's alpha = 0.88, 95% CI: 0.86, 1.00)., Conclusions: This meta-analysis suggests that the station number of OSCE falling in between 5 and 10, with each station time lasting no more than 10 min are likely to yield good reliability and strong internal consistency., Competing Interests: Declarations. Ethics approval and consent to participate: Because no human participants were involved, this study did not require ethical approval. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Clinical trial number: Not applicable., (© 2025. The Author(s).)

The behavior of hesperidin methylchalcone (HMC) at the oil/water interface was examined through experimental and molecular simulation methods, and a nano-emulsions based on HMC was subsequently fabricated. The findings indicated that HMC spontaneously aggregated at the oil-water interface, leading to a reduction in interfacial tension and an increase in interfacial thickness. Furthermore, its glycoside and benzene ring showed tendencies to interact with water and medium-chain triglyceride, respectively. The HMC addition amount (w), homogenization times (n) and homogenization pressure (p) significantly influenced the formation of the nano-emulsions. The nano-emulsion with an oil-droplet size of 277.26 ± 13.62 nm was obtained at w = 1.0 %, p = 200 bar, and n = 6. When compared to the Tween 20 nano-emulsion, the HMC nano-emulsion demonstrated superior storage stability, antioxidant activity, and lutein bioaccessibility. It could achieve the slow release of HMC. These findings not only broaden the application range of HMC but also contribute to the advancement of functional nano-emulsions., 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.)

The in situ monitoring of quorum sensing (QS) signal molecules in bacterial biofilms is crucial for the diagnosis and treatment of bacterial biofilms. In this work, a surface-enhanced Raman scattering (SERS) chip integrated with functional units of bacterial biofilms and in situ SERS detection is proposed for the monitoring of pyocyanine, an important signal molecule and biomarker secreted by Pseudomonas aeruginosa . The SERS chip was composed of a top self-assembled nano-silver SERS substrate layer, a PDMS layer containing a micro-chamber array and bottom quartz layer. The nano-silver SERS substrate showed good homogeneity and stability with an enhancement factor of up to 1.84 × 10 8 for pyocyanine, and the design of the SERS substrate located at the top layer of the chip could effectively attenuate interference from complex matrices. Using the SERS chip, a detection limit of as low as 1 nM for pyocyanine with a wide detection range of 1 nM-100 μM was observed. The proposed SERS chip could achieve the monitoring of pyocyanine during the growth of Pseudomonas aeruginosa biofilms with and without the treatment of different types of antibacterial drugs. Furthermore, pyocyanine secreted by Pseudomonas aeruginosa was confirmed using mass spectrometry (MS), and the concentration relationship obtained via MS/MS was consistent with that obtained via SERS detection. The proposed method based on the SERS chip for monitoring QS in bacterial biofilms offers the advantages of in situ detection, flexibility and efficiency.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that gradually destroys cognitive, memory, and thinking skills. Although increasing evidence has demonstrated that Ganoderma lucidum triterpenoids (GLT) can ameliorate the motor and spatial learning disorders of AD, the underlying mechanism remains unclear. Hence, in this study, GLT were obtained by using a traditional Chinese medicine processing method, and then the effects of GLT on motor and spatial learning disorders in 5xFAD mice were investigated by using various techniques such as behavioral analysis, micro-dialysis, and neurophysiological recording. Compared with the 5xFAD group, 0.5 g/kg GLT could decrease escape latency, the total number of limb errors, and the duration of errors. This dose could also increase the number of crossing the original platform, the total movement time, and the distance in the central region of the open-field box, as well as the maximum movement speed and continuous movement time on the rotating rod. After GLT treatment, the glutamate (Glu) content and variation coefficient of a simple spike of Purkinje cells decreased compared with the 5xFAD group, thereby improving the spatial learning and memory ability. Overall, this study shows that GLT may be a potential therapeutic method for patients with AD.

Brain functional hypernetworks that can characterize the complex and multivariate interactions among multiple brain regions have been widely used in the diagnosis and prediction of brain diseases. However, there are few studies on the structure and dynamics of brain functional hypernetworks. Such studies can help to explore how the important functional features of brain functional hypernetworks characterize the working and pathological mechanisms of the human brain. Therefore, this article introduces the hypernetwork null model to analyze the dependencies between the features of interest. Specifically, first, based on the original brain functional hypernetwork, this article proposed the optimized hyper dK-series algorithm with hyperedges to construct null models that preserved the different node attributes and hyperedge attributes of the original brain functional hypernetwork, respectively. Next, based on the original hypernetwork model and the null model, multiple node attributes and hyperedge attributes were respectively introduced. Then, the level of similarity and correlation between the topological attributes of the original brain functional hypernetwork and the topological attributes of the brain functional hypernetwork null model were calculated to analyze the dependencies between the features of interest. The results showed that there were differences in the level of dependence between the features of interest. Node degree is the main dependency attribute for multiple metrics. Hyperedge degree, node degree-dependent redundancy coefficient, and hyperedge degree-dependent redundancy coefficient are partial dependency attributes for some metrics. The dependency attributes and level of dependency are the same for the hypernetwork clustering coefficients-HCC 2 and HCC 3 . This indicates that the node degree is redundant with respect to other attributes, while the hyperedge degree, node degree-dependent redundancy coefficient, and hyperedge degree-dependent redundancy coefficient perhaps contain other topology information. In addition, there is redundancy between HCC 2 and HCC 3 . Therefore, the effects of these redundant attributes need to be considered when performing network analysis., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Lower urinary tract dysfunction (LUTD) can manifest as a spectrum of voiding symptoms in childhood, including urinary urgency, frequency, hesitancy, and incontinence. In severe cases, it can lead to frequent urinary tract infections, hydronephrosis, kidney scarring, and chronic kidney disease. Non-neurogenic neurogenic bladder (NNNB) is a diagnosis of exclusion in which children develop discoordination between the detrusor smooth muscle and external urethral sphincter in the absence of neurological or obstructive lesions, resulting in severe LUTD. Historically, such disorders of voiding were thought to result from behavioral maladaptation. However, it is now increasingly recognized that some individuals may have an underlying genetic etiology for their symptoms. Here, we performed exome sequencing for five probands with NNNB or other forms of severe LUTD, and we identified two individuals with monogenic etiologies for their symptoms. One individual had a homozygous exon 9 deletion in HPSE2 and another had a homozygous single amino acid deletion (p.Gly167del) in ARL6. We performed PCR experiments to identify the breakpoints of the HPSE2 exon 9 deletion and implicate microhomology-mediated end joining as a potential mechanism by which the deletion arose. These findings suggest that genetic testing should be considered for children with severe LUTD., (© 2024 Wiley Periodicals LLC.)

In this study we evaluated the interaction of cinchonine (Cin) and immunoglobulin G (IgG). Then, Cin-IgG nanoparticles (NPs) were synthesized and characterized. Finally, the anticancer effects of free Cin and Cin-IgG NPs on MCF-7 breast cancer (BC) cells were evaluated. The results of spectroscopy measurements show that the IgG-Cin complex's quenching mechanism is static and the structure of IgG was partially changed following interaction with Cin. The prepared Cin-IgG NPs display a hydrodynamic size of 190 nm with a PDI of 0.269, a zeta potential of -38.05 mV, an EE% of 72.38 %, a LC% of 5.41 %, and a pH-sensitive drug release behavior. In the cellular assay, it was found that the calculated IC 50 concentrations of Cin, IgG NPs, and Cin-IgG NPs are 66.4 ± 5.39, >100, and 29.2 ± ± 4.11 μM, respectively, in MCF-7 BC cells. Finally, Cin-IgG NPs induce a greater effect on the overexpression of the Bax/Bcl-2 ratio and downregulation of PI3K/p-AKT compared to the free drug. In conclusion, this study shows that Cin has the potential to bind IgG as a human plasma protein, and its complexation into a NP form with IgG can boost its anti-BC effects., 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.)

Cancer continues to be a leading factor in mortality and tackling it has been made difficult by the development of immune escape. Furthermore, alternative treatments like surgery, chemotherapy, and radiation have been unsuccessful in eradicating cancer. Despite being effective, they have not succeeded in providing a full cancer treatment and exhibit several negative effects. The field of immunotherapy has been improved by utilizing cancer vaccines, immune checkpoint inhibitors (ICIs), and adoptive cell transfer to enhance immune responses to tumors. Nevertheless, cancer cells need to adapt and become immune to immune reactions, leading to the need for innovative treatment methods. Carbohydrate polymers and their nanoparticles have been beneficial in improving cancer immunotherapy by being customizable to specifically target the immune system. These nanoparticles can change the tumor microenvironment and accelerate immunotherapy by affecting immune cells such as T cells and dendritic cells. Incorporating both chemotherapy and phototherapy into nanoparticles can improve immunotherapy. Furthermore, besides controlling immune reactions, carbohydrate polymer nanoparticles can also be used for theranostic purposes, where they are used to image tumor cells and activate the immune system to eradicate cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Purpose: DT-678 is a novel antiplatelet prodrug, capable of releasing the antiplatelet active metabolite of clopidogrel (AM) upon exposure to glutathione. In this study, we investigated factors responsible for clopidogrel high on-treatment platelet reactivity (HTPR) in acute coronary syndrome (ACS) patients and evaluated the capacity of DT-678 to overcome HTPR., Experimental Approach: A total of 300 consecutive ACS patients naive to P2Y 12 receptor inhibitors were recruited and genotyped for CYP2C19 alleles. Blood samples were drawn before and after administration of 600-mg clopidogrel. Platelet reactivity index (PRI) and plasma AM concentrations were determined and grouped according to their CYP2C19 genotypes. DT-678 was applied ex vivo to whole blood samples to examine its inhibitory effects. To further examine the antiplatelet effectiveness of DT-678 in vivo, 20 healthy human subjects were recruited in a Phase I clinical trial, and each received a single dose of either 3-mg DT-678 or 75-mg clopidogrel. The pharmacokinetics and pharmacodynamics in different CYP2C19 genotype groups were compared., Key Results: Statistical analyses revealed that CYP2C19 genotype, body mass index, hyperuricaemia, and baseline PRI were significantly associated with a higher risk of clopidogrel HTPR in ACS patients. The addition of DT-678 ex vivo decreased baseline PRI regardless of CYP2C19 genotypes, overcoming clopidogrel HTPR. This observation was further confirmed in healthy volunteers receiving 3 mg of DT-678., Conclusion and Implications: These results suggest that DT-678 effectively overcomes clopidogrel HTPR resulting from genetic and/or clinical factors in Chinese ACS patients, demonstrating its potential to improve antiplatelet therapy., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Soft rot (Pectobacterium aroidearum and Dickeya) is a devastating soil-borne bacterial disease that threatens konjac production. Intercropping with false acacia has been shown to significantly reduce soft rot incidence in konjac by shifting the microbial community. However, how intercropping shapes the root bacterial community and affects soft rot incidence remains unclear. To address this, we investigated three konjac intercropping systems (false acacia, paulownia, and maize) to explore the relationships among intercropping, soft rot incidence, root bacterial community, soil enzyme activity, and soil properties., Results: Konjac intercropped with false acacia exhibited the lowest soft rot incidence and the lowest abundance of pathogenic taxa. Soft rot incidence was negatively correlated with total soil nitrogen and potassium but positively correlated with total and available soil phosphorus. The bacterial community structure and function in konjac roots differed among intercropping types, mainly driven by available soil phosphorus. Beneficial microorganisms such as Bradyrhizobium and Variovorax were enriched under a false acacia intercropping system and were negatively correlated with soil-available phosphorus. Additionally, the stable bacterial community in healthy konjac roots under false acacia may make konjac less susceptible to pathogen invasion., Conclusion: The study showed that intercropping reduced the soft rot incidence by regulating the structure and stability of the konjac root bacterial community, and soil-available phosphorus was the main factor affecting the difference in the konjac root bacterial community, which provided a basis for the management of soil fertilization in konjac cultivation. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Xanthoangelol (C 25 H 28 O 4 ), a natural flavonoid derived from chalcones, has shown potential pharmacological activities. However, its primary interaction mechanism with proteins and cells is not well understood. In the present study, we focus on the anticancer effects of xanthoangelol against hepatocellular carcinoma (HCC) as well as its binding affinity with a plasma drug carrier protein, α2-macroglobulin. The anticancer effects of xanthoangelol on human HCC cell line HepG2 cells were assayed using MTT, LDH, qPCR, and caspase activity assays. Efficient binding of the xanthoangelol with α2-macroglobulin was established by experimental and molecular docking studies. It was found that xanthoangelol significantly mitigates cell viability through upregulating intrinsic (Bax/Bcl-2, caspase-9) and extrinsic (caspase-8) apoptotic pathways. Moreover, it was detected that xanthoangelol induces ER stress through the upregulation of CHOP in HepG2 cells. Fluorescence spectra show that xanthoangelol strongly interacts with α2-macroglobulin mediated by a static quenching mechanism and Trp1237 and Tyr1323 residues were exposed to the solvent with the addition of xanthoangelol. Meanwhile, both experimental and theoretical studies display that hydrophilic forces play a key role in the formation of xanthoangelol-α2-macroglobulin complex, leading to a slight conformational change in α2-macroglobulin. In conclusion, our findings suggest that xanthoangelol, which has a high binding affinity for a plasma carrier protein, may inhibit the viability of HCC by inducing apoptosis and ER stress., 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.)

The recovery process following ischemic stroke is a complex undertaking involving intricate cellular and molecular interactions. Cellular dysfunction or aberrant pathways can lead to complications such as brain edema, hemorrhagic transformation, and glial scar hyperplasia, hindering angiogenesis and nerve regeneration. These abnormalities may contribute to long-term disability post-stroke, imposing significant burdens on both families and society. Current clinical interventions primarily focus on endovascular therapy, overlooking the protection of brain cells themselves. However, the use of bioactive materials in stroke management has shown notable safety and efficacy. By precisely targeting the ischemic site at a cellular and molecular level, this therapeutic approach mitigates ischemia-induced brain tissue damage and promotes site repair. This review examines the protective benefits of bioactive materials in reducing cell damage and facilitating nerve restoration in accordance with the pathophysiological basis of ischemic stroke. Enhanced understanding of ischemic stroke mechanisms has the potential to advance the targeted and efficient clinical use of bioactive materials., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Wang et al.)

Shift work nurses suffered great stress and emotion dysregulation during the COVID-19 pandemic. Interpersonal emotion regulation has emerged as a promising therapeutic approach, often facilitated through confiding. It has been suggested that medical staff benefit from confiding, with the act of reflecting on the social support gained from confiding being associated with higher well-being. Consequently, we hypothesized that thinking about the social support derived from confiding about work-related hassles could enhance emotion regulation and well-being in shift work nurses. This study aimed to evaluate the effects of the intervention "thinking about the social support obtained from confiding about work-related hassles" on shift work nurses' emotion regulation and self-perceived well-being. An online randomized controlled trial was conducted with 66 shift work nurses, including 34 in the experimental group and 32 in the control group, to assess the impact of an 8-week confiding intervention focused on thinking about the social support obtained from confiding. The results indicated that the intervention significantly improved the interpersonal emotion regulation of shift work nurses in the experimental group compared to the control group. In terms of intrapersonal emotion regulation, the intervention appeared to reduce the cognitive reappraisal in the intervention group; however, there was no significant difference in cognitive reappraisal or expressive inhibition between the intervention group and control group. Furthermore, self-rated general health and sleep quality showed significant improvement in the intervention group compared to pre-test levels, but no significant differences were observed between the experimental and control groups. In conclusion, the online confiding intervention effectively enhanced interpersonal emotion regulation among shift work nurses. However, its effects on intrapersonal emotion regulation were not significant. Similarly, while participants in the intervention group reported improved self-rated general health and sleep quality, these improvements did not significantly differ from those in the control group.

Breaking the balance of the tumor microenvironment and reshaping it sustainably remain major challenges in lung cancer treatment. Here, a "tumor energy homeostasis disruptor", the Cu 2 O@Au nanozyme was developed, which exhibits excellent glucose oxidase-like activity, enabling it to be used for starvation therapy and as a mimic peroxidase for chemodynamic therapy (CDT), producing • OH. Cu 2 O@Au nanozymes consume glucose at the tumor site to block the tumor's energy supply, produce H 2 O 2 continuously, and lower the pH to enhance the efficiency of CDT, initiating a cascade reaction that leads to a storm of reactive oxygen species (ROS). Furthermore, Cu 2 O@Au nanozyme consumes glutathione and reduces the expression of the SLC7A11 ( x CT) protein to decrease cancer cell uptake of cysteine, further enhancing the burst of ROS, resulting in lipid peroxidation in tumor cells and ultimately leading to ferroptosis. The excellent photothermal performance of Cu 2 O@Au can further enhance CDT. Additionally, Cu 2 O@Au nanozyme also has computed tomography (CT) and photothermal imaging capabilities. In conclusion, Cu 2 O@Au nanozymes, acting as tumor energy homeostasis disruptor, can effectively inhibit tumor growth and successfully achieve the synergistic effects of starvation therapy/CDT/photothermal therapy (PTT). This multifunctional nanozyme holds promise for providing valuable insights and therapeutic strategies for cancer treatment.

Glomus tumor is a rare neoplasm, typically found in superficial soft tissues and extremities, particularly in the subungual region. However, it can also occasionally affect deep soft tissue or viscera, such as the bladder, albeit infrequently. Our patient was a 51-year-old man presenting with recurrent hematuria of unknown etiology, accompanied by a blood clot that resolved spontaneously after 1 day. Abdominal computed tomography revealed multiple calculi in the right kidney, whereas cystoscopy showed mucosal edema on the left side of the bladder. A magnetic resonance image of the bladder identified an ovoid mass on the left side, measuring approximately 3.1 cm × 2.7 cm × 2.1 cm. This mass demonstrated a slightly increased signal intensity on T2-weighted images and an intermediate signal intensity on T1-weighted images. These findings suggested a malignant tumor in the urinary bladder with a nonfunctional right kidney. The patient underwent laparoscopic surgery to remove the right kidney and part of the bladder. Histologically, the tumor primarily consisted of round cells and abundant eosinophilic or pale cytoplasm. Immunohistochemical staining demonstrated diffuse positivity for smooth muscle actin and vimentin, and focal positivity for synaptophysin. The final pathological diagnosis was a bladder glomus tumor. At 15 months after resection, the patient was in good health with no recurrence or metastasis. The clinical manifestations and imaging features of bladder glomus tumors can pose diagnostic challenges for urologists. Therefore, it is imperative to consider this tumor in the differential diagnosis of bladder tumors and to enhance the understanding among urologists and pathologists regarding this entity., 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.

Background: BK polyomavirus (BKV) infection is a critical complication hindering graft survival after kidney transplantation. We aimed to investigate the risk factors and outcome of BKV infection in pediatric kidney transplantation., Methods: The clinical and follow-up data of pediatric kidney transplant recipients at the Children's Hospital of Fudan University from Jan 2015 to June 2023 were retrospectively analyzed., Results: A total of 217 patients were included in the study with mean follow-up time of 24.3 ± 19.9 months. The mean age at transplantation was 9.7 ± 4.2 years. The patient survival rate and graft survival rate were 98.2% and 96.8%, respectively. Twenty-nine patients (13.4%) developed BKV infection, which was detected at 5.8 ± 3.2 months after transplantation. Among these 29 patients with BKV infection, 8 patients (3.6%) developed BKV nephropathy (BKVN), which was diagnosed at 8.3 ± 2.9 months after transplantation, and 2 patients developed graft failure eventually. Compared with the non-BKV infection group (eGFR 76.7 ± 26.1 mL/min/1.73 m 2 ) and BKV infection without BKVN group (eGFR 85.2 ± 23.8 mL/min/1.73 m 2 ), BKVN group had lowest eGFR during follow-up (33.5 ± 11.0 ml/min/1.73 m 2 , P < 0.001). Younger age at transplant (OR 0.850, 95%CI 0.762-0.948, P = 0.005), CAKUT disease of primary etiology (OR 2.890, 95%CI 1.200-6.961, P = 0.018), and CMV negative recipient serostatus before transplantation (OR 3.698, 95%CI 1.583-8.640, P = 0.003) were independent risk factors for BKV infection., Conclusions: Incidence of BKV infection is quite high within 12 months after pediatric kidney transplantation and children with BKVN have poor graft function. Younger age at transplant, CAKUT disease, and CMV negative recipient serostatus before transplantation increase the risk of BKV infection after kidney transplantation., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy. Genetic defects in the alternative complement (AP) pathway have been identified in 60-70% of individuals. Eculizumab is recommended as a first-line therapy., Methods: We collected the clinical data of a pediatric patient with aHUS accompanied by protein-losing enteropathy (PLE). Genetic testing was performed. Related literature on aHUS combined with PLE was reviewed., Results: A 15-year-old Chinese girl was diagnosed with aHUS at 3.7 years of age and experienced five episodes; her symptoms completely resolved with plasma treatment. Severe gastrointestinal symptoms and hypoalbuminemia presented after the first episode, and PLE was diagnosed. A novel homozygous CD46 variant was identified, and FACS revealed significantly decreased CD46 expression. She presented at a recent relapse with persistent GI symptoms and headache and progressed to chronic kidney failure; peritoneal dialysis was initiated. Eculizumab was given 8 months after the last recurrence. Surprisingly, PLE was cured. Afterward, dialysis was discontinued, and eGFR recovered to 44.8 ml/min/1.73 m 2 . A review of the literature indicated that PLE with thrombosis was caused by CD55 variants via hyperactivation of the AP system. We report an aHUS patient with PLE caused by CD46 variants. Symptoms of both PLE and aHUS were significantly alleviated in our patient and patients with CD55 variants treated with eculizumab, indicating that PLE was a new symptom of aHUS in our patient with a CD46 variant., Conclusions: Our case expands the phenotype of aHUS caused by a CD46 mutation and provides evidence of the efficacy of eculizumab after a long phase of chronic kidney failure., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Objective: Hematuria is one of the most common conditions in children, and increase the risk of chronic kidney disease. Persistent hematuria may be the earliest manifestation of type IV collagen-related nephropathy. Early diagnosis is essential for optimized therapy. Due to the invasive nature of kidney biopsy and the high cost of whole exome sequencing, its application in the diagnosis of isolated hematuria is rare. Hence, we performed noninvasive and convenient genetic testing approaches for type IV collagen-related nephropathy., Methods: We used noninvasive oral mucosa sampling as an alternative method for DNA isolation for genetic testing and designed a panel targeting three type IV collagen nephropathy-related genes in children with hematuria. Children with persistent hematuria unaccompanied by clinically significant proteinuria or renal insufficiency who underwent genetic testing using a hematuria panel were enrolled., Results: Thirty-seven of 112 (33.0%) patients were found to have a genetic variant in COL4A3/A4/A5 . Pathogenic/likely pathogenic COL4A3/A4/A5 variants were identified in 17 of the 112 patients analyzed (15.2%), which were considered to explain their hematuria manifestations. In addition, variants of unknown significance (VUSs) were found in 17.8% (20/112) of patients. Furthermore, we observed a much greater COL4A3/A4/A5 variant detection rate in patients with a positive family history or more severe hematuria (RBC ≥ 20/HP) or with coexisting microalbuminuria (59.2% vs. 12.7%, p  < 0.001; 64.0% vs. 24.1%, p  < 0.001; 66.7% vs. 30.1%, p  = 0.025)., Conclusions: We present the high prevalence of variants in COL4A genes in a multicenter pediatric cohort with hematuria, which requires close monitoring and long-term follow-up.

Driver assistance systems play an important role in enhancing vehicle active safety. However, most of the existing driver assistance systems overlook the impact of driver characteristics on control performance, making it difficult to optimize the intervention strength of the controller for different drivers to achieve optimal performance. This paper proposed a novel vehicle active collision avoidance control strategy considering driver characteristics. By adjusting the time domain parameters of the model predictive control (MPC), collision avoidance assistance can be more effectively tailored to different types of drivers. Firstly, the collected lane-changing and collision avoidance data of 10 drivers with varying levels of experience were analyzed and preprocessed. Based on this analysis, a comprehensive index of collision avoidance characteristics was established that integrated trajectory tracking ability and driver burden, enabling the derivation of the collision avoidance characteristic curve representing the driver's preference and habit was obtained. Secondly, a sixth-order polynomial trajectory planning method considering driver characteristics was proposed. This method was optimized under vehicle stability and driver matching constraints to generate personalized collision avoidance trajectories for different drivers. The proposed comprehensive index and personalized collision avoidance trajectory were incorporated into the active collision avoidance control system, and a personalized time-variable domain MPC controller was designed. Test results based on a driver-in-the-loop bench demonstrate that the proposed personalized MPC could better match diverse driving characteristics, enhance the driver's trajectory tracking ability in the process of collision avoidance, reduce the driving workload, thereby improving overall driving safety and comfort., 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.)

Ground-based detection of spaceborne dynamic objects, such as near-Earth asteroids and space debris, is essential for ensuring the safety of space operations. This paper presents YOLO-Dynamic, a novel detection algorithm aimed at addressing the limitations of existing models, particularly in complex environments and small-object detection. The proposed algorithm introduces two newly designed modules: the SC&#95;Block&#95;C2f and the LASF&#95;Neck. SC&#95;Block&#95;C2f, developed in this study, integrates StarNet and Convolutional Gated Linear Unit (CGLU) operations, improving small-object recognition and feature extraction. Meanwhile, LASF&#95;Neck employs a lightweight multi-scale architecture for optimized feature fusion and faster detection. The YOLO-Dynamic algorithm's performance was validated on real-world images captured at Antarctic observatory sites. Compared to the baseline YOLOv8s model, YOLO-Dynamic achieved a 7% increase in mAP@0.5 and a 10.3% improvement in mAP@0.5:0.95. Additionally, the number of parameters was reduced by 1.48 M, and floating-point operations decreased by 3.8 G. These results confirm that YOLO-Dynamic not only delivers superior detection accuracy but also maintains computational efficiency, making it well suited for real-world applications requiring reliable and efficient spaceborne object detection.

In daily life, two common algorithms are used for collecting medical disease data: data integration of medical institutions and questionnaires. However, these statistical methods require collecting data from the entire research area, which consumes a significant amount of manpower and material resources. Additionally, data integration is difficult and poses privacy protection challenges, resulting in a large number of missing data in the dataset. The presence of incomplete data significantly reduces the quality of the published data, hindering the timely analysis of data and the generation of reliable knowledge by epidemiologists, public health authorities, and researchers. Consequently, this affects the downstream tasks that rely on this data. To address the issue of discrete missing data in cardiac disease, this paper proposes the AGAN (Attribute Generative Adversarial Nets) architecture for missing data filling, based on generative adversarial networks. This algorithm takes advantage of the strong learning ability of generative adversarial networks. Given the ambiguous meaning of filling data in other network structures, the attribute matrix is designed to directly convert it into the corresponding data type, making the actual meaning of the filling data more evident. Furthermore, the distribution deviation between the generated data and the real data is integrated into the loss function of the generative adversarial networks, improving their training stability and ensuring consistency between the generated data and the real data distribution. This approach establishes the missing data filling mechanism based on the generative adversarial networks, which ensures the rationality of the data distribution while filling the missing data samples. The experimental results demonstrate that compared to other filling algorithms, the data matrix filled by the proposed algorithm in this paper has more evident practical significance, fewer errors, and higher accuracy in downstream classification prediction., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The degeneration of retinal ganglion cells (RGC) due to mitochondrial dysfunctions manifests optic neuropathy. However, the molecular components of RGC linked to optic neuropathy manifestations remain largely unknown. Here, we identified a potentially novel optic atrophy-causative CRYAB gene encoding a highly conserved major lens protein acting as mitochondrial chaperone and possessing antiapoptotic activities. The heterozygous CRYAB mutation (c.313G>A, p. Glu105Lys) was cosegregated with autosomal dominant inheritance of optic atrophy in 3 Chinese families. The p.E105K mutation altered the structure and function of CRYAB, including decreased stability, reduced formation of oligomers, and decreased chaperone activity. Coimmunoprecipitation indicated that the p.E105K mutation reduced the interaction of CRYAB with apoptosis-associated cytochrome c and voltage-dependent anion channel protein. The cell lines carrying the p.E105K mutation displayed promotion of apoptosis and defective assembly, stability, and activities of oxidative phosphorylation system as well as imbalance of mitochondrial dynamics. Involvement of CRYAB in optic atrophy was confirmed by phenotypic evaluations of Cryabp.E105K-knockin mice. These mutant mice exhibited ocular lesions that included alteration of intraretinal layers, degeneration of RGCs, photoreceptor deficits, and abnormal retinal vasculature. Furthermore, Cryab-deficient mice displayed elevated apoptosis and mitochondrial dysfunctions. Our findings provide insight of pathophysiology of optic atrophy arising from RGC degeneration caused by CRYAB deficiency-induced elevated apoptosis and mitochondrial dysfunctions.

Progress has been made in generating spinal cord and trunk derivatives from neuromesodermal progenitors (NMPs). However, maintaining the self-renewal of NMPs in vitro remains a challenge. In this study, we developed a cocktail of small molecules and growth factors that induces human embryonic stem cells to produce self-renewing NMPs (srNMPs) under chemically defined conditions. These srNMPs maintain the state of neuromesodermal progenitors in prolonged culture and have the potential to generate mesodermal cells and neurons, even at the single-cell level. Additionally, suspended srNMP aggregates can spontaneously differentiate into all tissue types of early embryonic trunks. Furthermore, transplanted srNMP-derived muscle satellite cells or progenitors of motor neurons were integrated into skeletal muscle or the spinal cord, respectively, and contributed to regeneration in mouse models. In summary, srNMPs hold great promise for applications in developmental biology and as renewable cell sources for cell therapy for trunk and spinal cord injuries., Competing Interests: Declaration of interests The authors have a patent application related to this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hyperlipidemia, commonly referred to as dyslipidemia, is characterized by elevated serum cholesterol and/or triglyceride levels. This condition contributes significantly to the high mortality rates associated with cardiovascular diseases, posing a serious threat to global health. Although statins remain the predominant pharmacological treatment for hyperlipidemia, their associated side effects have led to a growing interest in alternative therapeutic approaches. Traditional Chinese Medicine (TCM) is exploring these alternatives, with the Erchen Decoction (ECD) emerging as a promising candidate. This review aims to summarize current clinical research, elucidate the mechanisms of action, and assess the compatibility of ECD in the management of hyperlipidemia. By doing so, we hope to provide valuable insights and references for clinical practice and future research., 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 Tian, Liu, Wang, Hou, Zhou, Wang and Zhang.)

Binding phospholipid is a simple, yet flexible, strategy for anchorage of bacterial effectors at cell membrane to manipulate host signaling responses. Phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-biphosphate are the only two phospholipid species known to direct bacterial effectors to establish inner leaflet localization at the plasma membrane. Here, selectivity of phosphatidic acid (PA) by bacterial effectors for the plasma membrane anchorage and its molecular entity was identified. C-terminal BID domain of Bartonella T4SS effectors (Beps) directed the plasma membrane localization of Beps in host cells through binding with PA. A hydrophobic segment of the 'HOOK' subdomain from BID is inserted into the bilayer to enhance the interaction of positively charged residues with the lipid headgroups. Mutations of a conserved arginine facilitating the electrostatic interaction, a conserved glycine maintaining the stability of the PA binding groove, and hydrophobic residues determining membrane insertion, prevented the anchorage of Beps at the plasma membrane. Disassociation from plasma membrane to cytosol attenuated the BepC capacity to induce stress fiber formation and cell fragmentation in host cells. The substitution of alanine with aspartic acid at the -1 position preceding the conserved arginine residue hindered BepD anchoring at the plasma membrane, a vital prerequisite for its ability to elicit IL-10 secretion in host macrophages. In conclusion, our findings reveal the PA-binding properties of bacterial effectors to establish plasma membrane localization and will shed light on the intricate mechanisms employed by bacterial effectors within host cells., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Three-dimensional (3D) organotypic skin in vitro has attracted increasing attention for drug development, cosmetics evaluation, and even clinical applications. However, the severe contraction of these models restricts their application, especially in the analyses based on barrier functions such as percutaneous penetration. For the full-thickness skin equivalents, the mechanical properties of the dermis scaffold plays an important role in the contraction resistance. In this investigation, we optimized a hydrogel composed of gelatine methacrylamide (GelMA), hyaluronic acid methacrylate (HAMA), and type I collagen (Col I), adjusted the elastic moduli to 2.27±0.08 kPa to fit the skin cells growth and resist contraction as well. This optimized hydrogel exhibited a swelling ratio of 23.25 ± 0.94% and demonstrated satisfactory cell viability in fibroblasts cultures. Then, we mixed this hydrogel with fibroblasts of liquid-liquid culture to construct the dermis, on which seeded keratinocytes were seeded for another 14 days of air-liquid culture to form cornified epidermis, and a commercialized hydrogel Ava-FT-Skin was used as control. This optimized skin model could maintained its integrity for a prolonged period of 28 days. Differentiated epidermis presented basal, spinous, granular, and cornified layers, meanwhile, epidermis markers like keratin-10, keratin-14, involucrin, loricrin, filaggrin, and dermis markers vimentin were expressed distinctly in the right distribution. Furthermore, penetration of a 607 Da Cascade blue-labelled dextran was calculated and compared to the Avatarget skin model, both of which could prevent more than 99% of the fluorescent molecule. We consider that this full-thickness skin model could be widely used in pharmaceutical and cosmetic industries, especially in penetration detection, contributing to the excellent contraction resistance., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) might be useful for predicting and functional outcome in ischemic stroke patients after endovascular thrombectomy (EVT), but its clinical benefit remains controversial. Thus, this study aimed to evaluate the association of FVH on prognosis in ischemic stroke patients who received EVT., Methods: PubMed, Embase, Cochrane Library, Web of Science, and Wanfang databases were searched for potentially eligible studies published up to March 2024. Pooled standard mean difference (SMD), risk ratios (RR) with 95% confidence intervals (CI) were employed to assess the association of FVH on prognosis in ischemic stroke patients who received EVT. All statistical analyses were conducted using STATA 12.0 software., Results: A total of 10 studies were included in our study. The results indicated that higher FVH score were associated with better prognosis (SMD: 0.80, 95% CI 0.63-0.97). Moreover, the presence of FVH was significant associated with better functional outcome in ischemic stroke patients who received EVT (RR: 0.68, 95% CI, 0.58-0.79)., Conclusion: The current meta-analysis suggests that FVH is related the prognosis of ischemic stroke patients after EVT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wang and Ni.)

Non-small cell lung cancer (NSCLC), including squamous cell carcinoma and adenocarcinoma, ranks among the top 10 cancers worldwide in terms of prevalence and mortality. NSCLC, a highly malignant tumor, exhibits distant invasion and migration as well as an unfavorable prognosis. As an innovative circular RNA, hsa &#95;circ&#95;0109320 (circ&#95;0109320) has been recognized as a promising cancer modulator. However, our understanding of the influence of circ&#95;0109320 in NSCLC remains insufficient. Our research explored the clinical significance and effects of circ&#95;0109320 on oncogenic non-small cell lung cancer (NSCLC) phenotypes. Microarray analysis and qPCR indicated that circ&#95;0109320 expression in NSCLC specimens increased relative to that in adjacent normal tissues and was further elevated in metastatic lymph nodes. The specimens acquired from 25 patients confirmed these findings. Additionally, circ&#95;0109320 indicated a good score (AUC = 0.688, P = 0.013) on the ROC curves, which suggests its suitability as a promising biomarker for lung cancer. Meanwhile, circ&#95;0109320 was noticeably upregulated in lung cancer (LC) cell lines compared to human bronchial epithelial cells. Next, we performed loss- and gain-of-function experiments to examine the role of circ&#95;0109320 in the tumor phenotypes of the cell lines. We observed that depletion or overexpression of circ&#95;0109320 did not alter cell viability. However, the ectopic removal of circ&#95;0109320 repressed the migration and invasion of A549 and SK-MES-1 cells, whereas circ&#95;0109320 overexpression promoted cell migration and invasion. Furthermore, the examination of epithelial-mesenchymal transition (EMT) markers indicated that circ&#95;0109320 elevates cell EMT activity. In conclusion, circ&#95;0109320 level was highly associated with increased tumor cell proliferation and metastasis. circ&#95;0109320 could be a promising predictor of clinical outcomes and a reliable target to treat NSCLC by inhibiting metastasis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To determine the level of knowledge about skin tears among geriatric ward nurses and identify associated factors., Methods: In this cross-sectional study in Southwest China, 1172 geriatric ward nurses from 10 hospitals participated. Data were collected using Sojump, a Chinese web-based platform, and the Skin Tear Knowledge Assessment Instrument was used to assess their knowledge. The analysis involved descriptive statistics, correlation analysis, and multiple linear regression., Results: The study involved participants with an average age of 36.73 (SD = 6.54) years. More than half of the participants had less than 10 years of experience in geriatric wards. 27 % specialized in wound care, and 68.1 % lacked specific training in skin tear (ST) knowledge. Additionally, 82.7 % of geriatric nurses had never been exposed to guidelines on ST prevention and management. In the geriatric ward, 36.6 % of nurses received training in ST prevention. The average knowledge score about Skin Tears (STs) was 9.52 (SD = 2.39) out of 18. 'Treatment' had the lowest mean score, while 'Specific patient groups' had the highest. The multiple linear regression analysis found that nurses' knowledge of STs was influenced by sex(β = 0.096, P < 0.001), educational level(β = 0.062, P < 0.001), participation in ST (β = -0.193, P < 0.001 and wound care training(β = -0.120, P = 0.004), and specialization as a wound care nurse(β = -0.350, P = 0.001). These factors explained 61.3 % of the variance in knowledge about STs among the participants., Conclusion: The geriatric ward had limited knowledge of STs. To improve their skills in dealing with STs, managers should provide tailored training to nurses and establish a standardized, evidence-based nursing process., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: Hepatitis E caused by the hepatitis E virus (HEV) is prevalent worldwide. In China, considerable shifts in the epidemiology of hepatitis E have been observed over the last two decades, with ongoing changes in the prevalence of HEV., Methods: This study, in conjunction with the health examinations for students and workers, aims to estimate the seroprevalence and assess the risk factors of HEV infection in general population in Hebei province, China. Epidemiological information was collected using a specific questionnaire and blood samples were collected from each participant during the process of health examination. Anti-HEV IgG and IgM in sera were tested using the Wantai ELISA assay kits. Logistic regression modelling was used to identify associated risk factors., Results: The average positive rate of anti-HEV IgG in students (6-25 years) was 3.4%. One (0.2%) student was anti-HEV IgM positive, while also testing positive for IgG. The HEV seroprevalence was not related to students' gender, school, or family residence. In occupational populations, the overall seropositivity rate was 13.3% for anti-HEV IgG and 0.67% for IgM. HEV seropositivity increased significantly with age, ranging from 3.8% to 18.6% in age groups, and differed significantly among four occupation groups: farmers (17.6%), food supply workers (18.0%), other non-farm workers (14.7%) and healthcare workers (5.9%) (p = 0.002). Multivariable logistic analysis confirmed the significant correlations of seroprevalence with age and occupation., Conclusions: The study found a low seroprevalence of HEV in children and young adults in Hebei Province, China. Advanced age correlates with higher seroprevalence in occupational populations, indicating an accumulation of HEV infection over time. Seroprevalence varied significantly among different occupation groups, suggesting the important role of occupational exposure for HEV infection., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Background: The primary goal of the intensive care unit is to the anxiety of conscious patients is often ignored in the care unit., Aim: The purpose of this study was to assess the efficacy of various non-pharmacological therapies for anxiety disorders in adult patients in the intensive care unit, in order to enhance humanistic care in the intensive care unit and to promote the patients' physical and mental recovery together., Study Design: We conducted a systematic and comprehensive search of the literature in five databases (including the Cochrane Library, PubMed, EBSCO, Web of Science, and Embase) covering nearly a decade for randomized controlled trials of non-pharmacological therapies to reduce anxiety in adult intensive care unit patients. Two researchers independently assessed the quality of the literature, collected and condensed the data, and used STATA software to perform a network meta-analysis. The ranking probabilities for each intervention were calculated using the Surface under the Cumulative Ranking (SUCRA) method. The study protocol was registered with PROSPERO., Results: This study ultimately included 26 randomized controlled trials involving 2791 adult ICU patients. Non-pharmacological interventions for anxiety in adult ICU patients included music therapy, aromatherapy, ICU diary, virtual reality, massage therapy, monitoring room diary, and health education. when compared to the control group (usual care), aromatherapy + music therapy [MD = -2.65, 95% CI (-4.76, -0.54)] (P = 0.0137) and music therapy [MD = -1.77, 95% CI (-3.40, -0.13)] (P = 0.0338) were superior in reducing anxiety in adult ICU patients. The results of the network meta-analysis showed that aromatherapy combined with music therapy significantly alleviated anxiety in adult ICU patients (SUCRA: 99.8%)., Conclusions: Music therapy combined with aromatherapy has demonstrated superior effectiveness compared to other non-pharmacological interventions for reducing anxiety in awake adults in the ICU. However, the underlying mechanisms of this combined therapy require further exploration., Relevance to Clinical Practice: Future research on the use of music therapy combined with aromatherapy in the care unit may help reduce anxiety in patients while fostering their physical and mental healing; however, individual variances and unique clinical circumstances must be considered., (© 2024 The Author(s). Nursing in Critical Care published by John Wiley & Sons Ltd on behalf of British Association of Critical Care Nurses.)

Hepatocyte transplantation (HTx) has been a novel cell-based therapy for severe liver diseases, as the donor livers for orthotopic liver transplantation are of great shortage. However, HTx has been confronted with two main hurdles: limited high-quality hepatocyte sources and low cell engraftment and repopulation rate. To cope with, researchers have investigated on various strategies, including small molecule drugs with unique advantages. Small molecules are promising chemical tools to modulate cell fate and function for generating high quality hepatocyte sources. In addition, endothelial barrier, immune responses, and low proliferative efficiency of donor hepatocytes mainly contributes to low cell engraftment and repopulation rate. Interfering these biological processes with small molecules is beneficial for improving cell engraftment and repopulation. In this review, we will discuss the applications and advances of small molecules in modulating cell differentiation and reprogramming for hepatocyte resources and in improving cell engraftment and repopulation as well as its underlying mechanisms., 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 Shi, Ding, Sun, Lv, Wang, Ma, Lu, Yu, Li and Wang.)

Background: Cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4, which has shown substantial clinical benefits in advanced cervical cancer. In the COMPASSION-16 trial, we aimed to evaluate the addition of cadonilimab to first-line standard chemotherapy in persistent, recurrent, or metastatic cervical cancer., Methods: In this randomised, double-blind, multicentre, placebo-controlled phase 3 trial, women aged 18-75 years across 59 clinical sites in China with previously untreated persistent, recurrent, or metastatic cervical cancer were randomly assigned (1:1) to receive cadonilimab (10 mg/kg) or placebo plus platinum-based chemotherapy with or without bevacizumab every 3 weeks for six cycles, followed by maintenance therapy every 3 weeks for up to 2 years. Randomisation was performed centrally through an interactive web-response system. Stratification factors were the use of bevacizumab (yes or no) and previous concurrent chemoradiotherapy (yes or no). The dual primary outcomes were progression-free survival as assessed by blinded independent central review and overall survival in the full analysis set. This study is registered with ClinicalTrials.gov, NCT04982237; the study has completed enrolment and is ongoing for treatment and follow-up., Findings: 445 eligible women were enrolled between Sept 11, 2021, and June 23, 2022. Median progression-free survival was 12·7 months (95% CI 11·6-16·1) in the cadonilimab group and 8·1 months (7·7-9·6) in the placebo group (hazard ratio 0·62 [95% CI 0·49-0·80], p<0·0001); median overall survival was not reached (27·0 months to not estimable) versus 22·8 months (17·6-29·0), respectively (hazard ratio 0·64 [0·48-0·86], p=0·0011). The most common grade 3 or higher adverse events were decreased neutrophil count, decreased white blood cell count, and anaemia., Interpretation: The addition of cadonilimab to first-line standard chemotherapy significantly improved progression-free survival and overall survival with a manageable safety profile in participants with persistent, recurrent, or metastatic cervical cancer. The data support the use of cadonilimab plus chemotherapy as an efficacious first-line therapy in persistent, recurrent, or metastatic cervical cancer., Funding: Akeso Biopharma., Competing Interests: Declaration of interests TL, DLu, MHu, ZMW, BL, and MX are employees of Akeso Biopharma. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Asthma is an airway inflammatory disease driven by multiple factors with a high incidence in children and adolescents. Environmental tobacco smoke exposure (TSE) and diet are inducing factors for asthma. The potential of omega-3 polyunsaturated fatty acids (PUFAs) to alleviate asthma symptoms by their anti-inflammatory effects has been explored. However, to date, no studies have explored the effect of dietary PUFAs intake on the asthma in children and adolescents exposed to tobacco smoke., Objective: We aimed to examine the effect of dietary PUFAs intake on the current asthma in children and adolescents exposed to tobacco smoke., Methods: Data of this cross-sectional were extracted from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Children and adolescents with serum cotinine concentration ≥ 0.05 ng/mL were defined to exposed to tobacco smoke. Dietary PUFAs intake information were obtained from 24 h recall interview. The weighted univariate and multivariate were utilized to explore the effect of PUFAs on the association of asthma and TSE, with adjusted odds ratios (AORs) and 95% confidence intervals (CIs). These moderating effects were further explored based on the age, gender and body mass index (BMI) and sedentary time., Results: Totally, 7981 eligible children and adolescents were included, with the mean age of 11.96 ± 0.06 years old. Of whom, 1.024 (12.83%) had current asthma. After adjusted all covariates, we found children and adolescents with TSE had high occurrence of current asthma (AOR = 1.2, 95% CI 1.03-1.63); We also found omega-3 PUFAs intake (P for interaction = 0.010), not omega-6 PUFAs (P for interaction = 0.546), has a moderating effect on the association of TSE and current asthma. Moreover, we further observed that children and adolescents with TSE and low omega-3 PUFAs intake had high occurrence of current asthma (AOR = 1.58, 95% CI 1.19-2.10), while no significant association was found in children and adolescents with high omega-3 PUFAs intake (all P > 0.05). This moderating effect was more prominent in children and adolescents aged ≤ 12 years old (AOR = 1.62, 95% CI 1.06-2.47), girls (AOR = 2.14, 95% CI 1.15-3.98), overweight (AOR = 1.87, 95% CI 1.01-3.47) and sedentary time > 6 h (AOR = 1.96, 95% CI 1.00-3.86)., Conclusion: We found dietary omega-3 PUFAs plays a moderating effect on the association of asthma and TSE in children and adolescents, especially in children and adolescents aged ≤ 12 years, girls, overweight or sedentary time > 6 h. This moderating effect suggested higher omega-3 intake has potential benefits in decreasing the occurrence of asthma in children and adolescents who exposed to tobacco smoke., (© 2024. The Author(s).)

Key Message: SiDVLs inhibit auxin signaling to regulate root growth by enhancing the expression of Aux/IAAs and reducing the protein accumulation of PINs. The DEVIL/ ROTUNDIFOLIA (DVL/RTFL), a small polypeptide family, is conserved in seed plants and important in regulating plant growth and development. However, the molecular mechanisms remain largely unknown. Here, 27 SiDVLs were identified in foxtail millet genome. Overexpression of three SiDVLs in Arabidopsis (Arabidopsis thaliana) strongly repressed the plant growth, especially the root growth. We demonstrate that overexpression of SiDVLs enhances Auxin/Indole-3-Acetic Acids (Aux/IAAs) transcription, thereby weakening auxin signaling in the roots. Furthermore, SiDVLs reduced the protein levels of the auxin transporters PIN-formed 1 (PIN1), PIN2, and PIN7 in the roots. The impaired auxin signaling reduces the cell division and elongation. In conclusion, SiDVLs suppress cell division and elongation in root by inhibiting auxin signaling and transport, which lead to the reduced root growth., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Childhood Emotional Abuse (CEA) is a known risk factor for Non Suicidal Self-injury (NSSI), which could have devastating repercussions. This study aimed to establish whether Parent-Child Attachment (PCA) and depressive symptoms mediated the CEA-NSSI relationship, as well as whether school connectedness moderated both the direct and indirect relationships between CEA and NSSI., Methods: Between November and December 2022, 7447 Chinese adolescents in high schools were surveyed through multi-stage cluster random sampling. The participants completed self-reported questionnaires that assessed CEA, PCA, depressive symptoms, school connectedness, and NSSI. Relationships between these variables were examined through moderated mediation analysis using SPSS macro-PROCESS., Results: After controlling for sociodemographic variables, we found that CEA correlated positively with NSSI through two different pathways: the mediating role of depressive symptoms and the chain-mediating role of both PCA and depressive symptoms. Moreover, school connectedness could moderate the direct and indirect relationships between CEA and NSSI., Limitations: The study's cross-sectional design does not allow for causal inferences., Conclusions: Overall, PCA, depressive symptoms, and school connectedness could affect the CEA-NSSI relationship., Competing Interests: Declaration of competing interest The authors(Qiaoyue wei, Jianbo Liu, Wenwen Yin, Shuibo Pan, Chenyangzi Dai, Linhua Zhou, Xiaoyu Jiang, Chunyan Wang and Junduan Wu) 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.)

Background: The co-occurrence of Lemierre's syndrome, primarily triggered by Fusobacterium necrophorum following oropharyngeal infection, with diabetic ketoacidosis (DKA) in diabetes mellitus (DM) patients, underscores a rare but life-threatening clinical scenario. Lemierre's syndrome induced DKA is extremely rare, with only one case report in adult and no case yet reported in elderly., Case Presentation: We reported a case of a 69-year-old female who presented with DKA triggered by deep neck space infection (DNSI), leading to rapid clinical deterioration within 6 h that necessitated high flow nasal cannula (HFNC) and antibiotic administration. Laboratory findings included leukocytosis, elevated serum C-reactive protein, hyperglycemia, ketonemia, and severe metabolic acidosis. Culture of the fluid from a neck mass puncture drainage and blood were positive for Klebsiella pneumoniae. The patient was further complicated by thrombosis of the left internal jugular vein with extension to the sigmoid and a neck abscess surrounding the carotid artery sheath, consistent with Lemierre's syndrome. This condition was managed aggressively with fluid resuscitation, insulin therapy, surgical drainage, antibiotics, and anticoagulation led to a significant improvement in her condition. Following a 13-day hospitalization, there was significant clinical improvement, culminating in the patient's discharge., Conclusions: The case highlights the need for greater awareness and understanding of the interrelated and mutually promoting conditions of DKA and Lemierre's syndrome among clinicians. Early recognition and treatment are crucial to prevent mortality in such complex cases., (© 2024. The Author(s).)

Purpose: This study aimed to evaluate the comparative reproductive outcomes of ovarian stimulation combined with intrauterine insemination using partner's sperm (OS-IUI) in eumenorrheic and normogonadotropic oligomenorrheic women., Method: A retrospective cohort study was conducted, including 3833 couples who underwent 5920 cycles of OS-IUI between June 2013 and March 2019. Participants were stratified into two cohorts based on menstrual regularity: eumenorrheic and normogonadotropic oligomenorrheic. The primary outcome measured was the live birth rate (LBR) per cycle and cumulative LBR per couple. Secondary outcomes encompassed the clinical pregnancy rate (CPR) per cycle, miscarriage rate, and multiple pregnancy rate. Propensity score matching (PSM) was utilized to balance maternal baseline characteristics., Results: Prior to PSM, significant differences in CPR, LBR and cumulative LBR were observed between eumenorrheic and oligomenorrheic women, favoring the latter (CPR: 11.16% vs. 18.75%; LBR: 9.02% vs. 14.96%; cumulative LBR: 13.60% vs. 24.25%, P < 0.001). These differences persisted post-PSM (CPR: 9.74% vs. 19.29%; LBR: 7.30% vs. 16.29%; cumulative LBR 7.76% vs. 19.90%, P <0.001). Multivariate regression analyses revealed that menstrual status was a significant independent predictor of both CPR (adjusted odds ratio [OR]=1.83 before PSM, 2.24 after PSM) and LBR (adjusted OR=1.90 before PSM, 2.46 after PSM). In the subgroup analysis, female age was identified as the sole predictor of reproductive outcomes in oligomenorrheic women undergoing OS-IUI. Conversely, in eumenorrheic women, factors such as age, duration of infertility, body mass index (BMI), ovarian stimulation agents, and the number of dominant follicles were significant influencers of CPR and LBR., Conclusion: Normogonadotropic oligomenorrheic women demonstrated improved reproductive outcomes with OS-IUI, suggesting that tailored treatment strategies based on menstrual regularity could optimize success rates in infertility management., 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 Li, Long, Wang, Yang, Lv, Chen, Liu, Liu and Cao.)