Anterior cingulate cortex orexin signaling mediates early-life stress-induced social impairment in females.

Early-life stress has long-term impacts on the structure and function of the anterior cingulate cortex (ACC), and raises the risk of adult neuropsychiatric disorders including social dysfunction. The underlying neural mechanisms, however, are still uncertain. Here, we show that, in female mice, maternal separation (MS) during the first three postnatal weeks results in social impairment accompanied with hypoactivity in pyramidal neurons (PNs) of the ACC. Activation of ACC PNs ameliorates MS-induced social impairment. Neuropeptide Hcrt, which encodes hypocretin (orexin), is the top down-regulated gene in the ACC of MS females. Activating ACC orexin terminals enhances the activity of ACC PNs and rescues the diminished sociability observed in MS females via an orexin receptor 2 (OxR2)-dependent mechanism. Our results suggest orexin signaling in the ACC is critical in mediating early-life stress-induced social impairment in females.

MRUNet-3D: A multi-stride residual 3D UNet for lung nodule segmentation.

Obtaining an accurate segmentation of the pulmonary nodules in computed tomography (CT) images is challenging. This is due to: (1) the heterogeneous nature of the lung nodules; (2) comparable visual characteristics between the nodules and their surroundings. A robust multi-scale feature extraction mechanism that can effectively obtain multi-scale representations at a granular level can improve segmentation accuracy. As the most commonly used network in lung nodule segmentation, UNet, its variants, and other image segmentation methods lack this robust feature extraction mechanism. In this study, we propose a multi-stride residual 3D UNet (MRUNet-3D) to improve the segmentation accuracy of lung nodules in CT images. It incorporates a multi-slide Res2Net block (MSR), which replaces the simple sequence of convolution layers in each encoder stage to effectively extract multi-scale features at a granular level from different receptive fields and resolutions while conserving the strengths of 3D UNet. The proposed method has been extensively evaluated on the publicly available LUNA16 dataset. Experimental results show that it achieves competitive segmentation performance with an average dice similarity coefficient of 83.47 % and an average surface distance of 0.35 mm on the dataset. More notably, our method has proven to be robust to the heterogeneity of lung nodules. It has also proven to perform better at segmenting small lung nodules. Ablation studies have shown that the proposed MSR and RFIA modules are fundamental to improving the performance of the proposed model.

Effects of physical activity on the levels of remnant cholesterol: A population-based study.

Physical activity (PA) has the potential to bring about favourable changes in plasma lipid profile. However, the relationship between PA and remnant cholesterol (RC) remains unclear. We aimed to study the link between PA and RC using the database of the 2007-2020 National Health and Nutrition Examination Survey (NHANES). PA was categorized based on Physical Activity Guidelines for Americans. A multivariate linear regression model was used to determine the correlations between PA and RC. The study involved a total of 18,396 participants and revealed that individuals whose PA met the guidelines by engaging in moderate-intensity PA at least 150 min per week had lower body mass index and showed decreased levels of triglyceride, TC, and haemoglobin A1c compared to those who were physically inactive, exercising <150 min per week. Participants whose intensity of PA meets PA guidelines had a lower level of RC than those who did not met PA guidelines (ß = -1.3, 95% confidence interval [CI]: -1.9 to -0.7, p < 0.001), even after adjusting for confounders. During subgroup analysis, we observed that race (pinteraction = 0.0089) emerged as a significant factor of interaction.

LINC00115 promotes chemoresistant breast cancer stem-like cell stemness and metastasis through SETDB1/PLK3/HIF1α signaling.

BACKGROUND: Cancer stem-like cell is a key barrier for therapeutic resistance and metastasis in various cancers, including breast cancer, yet the underlying mechanisms are still elusive. Through a genome-wide lncRNA expression profiling, we identified that LINC00115 is robustly upregulated in chemoresistant breast cancer stem-like cells (BCSCs). METHODS: LncRNA microarray assay was performed to document abundance changes of lncRNAs in paclitaxel (PTX)-resistant MDA-MB-231 BCSC (ALDH+) and non-BCSC (ALDH-). RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to determine the binding proteins of LINC00115. The clinical significance of the LINC00115 pathway was examined in TNBC metastatic lymph node tissues. The biological function of LINC00115 was investigated through gain- and loss-of-function studies. The molecular mechanism was explored through RNA sequencing, mass spectrometry, and the CRISPR/Cas9-knockout system. The therapeutic potential of LINC00115 was examined through xenograft animal models. RESULTS: LINC00115 functions as a scaffold lncRNA to link SETDB1 and PLK3, leading to enhanced SETDB1 methylation of PLK3 at both K106 and K200 in drug-resistant BCSC. PLK3 methylation decreases PLK3 phosphorylation of HIF1α and thereby increases HIF1α stability. HIF1α, in turn, upregulates ALKBH5 to reduce m6A modification of LINC00115, resulting in attenuated degradation of YTHDF2-dependent m6A-modified RNA and enhanced LINC00115 stability. Thus, this positive feedback loop provokes BCSC phenotypes and enhances chemoresistance and metastasis in triple-negative breast cancer. SETDB1 inhibitor TTD-IN with LINC00115 ASO sensitizes PTX-resistant cell response to chemotherapy in a xenograft animal model. Correlative expression of LINC00115, methylation PLK3, SETDB1, and HIF1α are prognostic for clinical triple-negative breast cancers. CONCLUSIONS: Our findings uncover LINC00115 as a critical regulator of BCSC and highlight targeting LINC00115 and SETDB1 as a potential therapeutic strategy for chemotherapeutic resistant breast cancer.

Scalable Dual In Situ Synthesis of Polyester Nanocomposites for High-Energy Storage.

Incorporating ultralow loading of nanoparticles into polymers has realized increases in dielectric constant and breakdown strength for excellent energy storage. However, there are still a series of tough issues to be dealt with, such as organic solvent uses, which face enormous challenges in scalable preparation. Here, a new strategy of dual in situ synthesis is proposed, namely polymerization of polyethylene terephthalate (PET) synchronizes with growth of calcium borate nanoparticles, making polyester nanocomposites from monomers directly. Importantly, this route is free of organic solvents and surface modification of nanoparticles, which is readily accessible to scalable synthesis of polyester nanocomposites. Meanwhile, uniform dispersion of as ultralow as 0.1 wt% nanoparticles and intense bonding at interfaces have been observed. Furthermore, the PET-based nanocomposite displays obvious increases in both dielectric constant and breakdown strength as compared to the neat PET. Its maximum discharged energy density reaches 15 J cm-3 at 690 MV m-1 and power density attains 218 MW cm-3 under 150 Ω resistance at 300 MV m-1, which is far superior to the current dielectric polymers that can be produced at large scales. This work presents a scalable, safe, low-cost, and environment-friendly route toward polymer nanocomposites with superior capacitive performance.

The role of amygdala-ventral pallidum pathway in depression-like behaviors in male mice.

The basolateral amygdala (BLA) appears to serve an important function in the pathophysiology of depression. Depressive symptoms, such as anhedonia are largely caused by dysfunction in the brain's reward system, in which the ventral pallidum (VP) participates in by controlling dopamine release. However, the role of the BLA-VP pathway in the development of depression remains poorly understood. To investigate this pathway, we employed the Chronic Unpredictable Mild Stress (CUMS) mouse model, in which we injected retroAAV expressing GFP-Cre into the VP and AAV expressing hM4Di-mCherry into the BLA. We then used CNO to activate the Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) for all behavioral tests. The CUMS procedure resulted in significant depression symptoms such as decreased sucrose preference, limited weight gain, decreased immobile latency, and increased immobile time in the forced swim and tail suspension tests. Inhibition of the BLA-VP glutamatergic projections reversed these depression-like behaviors. We found that suppressing the BLA-VP circuitry had beneficial effects on CUMS-induced depression-like behaviors such as anorexia, anhedonia, and despair. Specifically, upon suppression of glutamatergic projections in the BLA-VP circuitry, these depression-like behaviors were significantly alleviated, which highlights the vital role of this circuitry in the development of depression. Furthermore, the beneficial effects of suppressing this circuitry seem to be associated with the brain's reward system, warranting further investigation.

Bibliometric analysis of worldwide research on Polycythemia Vera in the 21st century.

Polycythemia vera (PV) is a myeloproliferative tumor with low incidence and complex symptoms, affecting patients' quality of life and shortening their life span. Since the beginning of the 21st century, there has been an update but a need for uniform consensus regarding diagnosing and treating PV. With the continued interest of researchers in this field, a bibliometric study of PV is necessary. This paper aims to analyze articles on PV through bibliometric software to provide collaborative information and new ideas for researchers in this field. We collected PV-related publications in the Web of Science Core Collection database from 2000 to 2023. The included literature was analyzed using Citespace (6.2.R2), VOSviewer (1.6.19), and Bibliometrix. The study included country/region, institution, authors, journals, keywords, and references, and a visual knowledge network diagram was constructed. Microsoft Excel 2013 was also used for statistical analysis. A total of 1,093 articles were eventually included. The number of PV-related publications has steadily increased from 2000 to the present, with great potential for future growth. The US and US institutions have contributed more to this field, with the US ranking first in the number of publications, total citations, and centrality. Alessandro M. Vannucchi is the most published author. Tefferi, Ayalew is the most cited author. And BLOOD has the most publications, topping the list of the eleven high-productivity core source journals. The most cited article was "Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders" (Baxter, EJ, 2005). By examining the keywords, we found that the diagnosis and typing of true erythrocytosis, the use of ruxolitinib, and the tyrosine kinase JAK2 are the research hotspots in the field; genetic and molecular research in the field of true erythrocytosis is a cutting-edge topic in the field; and risk factors for true erythrocytosis is a cutting-edge hotspot issue in the field. The fruitful research in this century has laid the foundation for developing the field of PV. The information in this article will provide researchers with current hotspots and future potential in the discipline, helping the field achieve more extraordinary breakthroughs. Currently, research should focus on increasing global multicenter collaborative research in diagnosis and treatment to develop scientifically recognized diagnostic and treatment protocols and new clinical drug research. Our proposed model of global innovation collaboration will provide strong support for future research.

Quantitative multi-parameter assessment of age- and gender-related variation of back extensor muscles in healthy adults using Dixon MR imaging.

OBJECTIVES: Investigate sex differences in age-related back extensor muscle degeneration using Dixon MRI and analyze the relationship between quantitative muscle parameters and back muscle strength in healthy adults. METHODS: 105 healthy subjects underwent lumbar Dixon MRI. Fat fraction (FF), cross-sectional area (CSA), functional CSA (FCSA), and relative FCSA (RFCSA) of multifidus muscle (MF) and erector spinae (ES) were quantified. Back extension muscle strength was measured using an external fixation dynamometer. ANOVA with post hoc Tukey correction was used for age group comparisons. Partial and Spearman's correlation analyzed relationships between age, muscle parameters, and muscle strength. RESULTS: MF and ES FF significantly increased with age in both genders (r = 0.55-0.85; p < 0.001). Muscle FF increased prominently for females (40-49 years, MF and 50-59 years, ES) and males (60-73 years, MF and ES). In females, total ES FCSA and RFCSA (r = - 0.42, - 0.37; p < 0.01) correlated with age. While in males, all MF and ES muscle size parameters, except total MF CSA, correlated with age (r = - 0.30 to - 0.58; p < 0.05). Back extension muscle strength correlated with mean FF, total CSA, and total FCAS for MF and ES individually (p < 0.001). The combined MF + ES FCSA correlation coefficient (r = 0.63) was higher than FF (r = - 0.51) and CSA (r = 0.59) (p < 0.001). CONCLUSIONS: Age-related back extensor muscle degeneration varies by muscle type and sex. FCSA has the highest association with back muscle strength compared to FF and CSA. CLINICAL RELEVANCE STATEMENT: The investigation of sex differences in age-related back extensor muscle degeneration utilizing Dixon imaging may hold significant implications for evaluating spine health and enabling earlier intervention. Muscles' FCSA could contribute to acquiring additional evidence for reflecting muscle function change. KEY POINTS: • The multifidus muscle (MF) and erector spinae (ES) fat fraction (FF) increased with age at all lumbar disc levels in females and males. • Age-related changes in muscle morphological quantitative parameters of healthy adults were specific by muscle type and gender. • The muscle functional cross-sectional area (FCSA) measured by Dixon imaging may better monitor back extensor muscle strength changes than muscle FF and cross-sectional area (CSA).

α-linolenic acid ameliorates pentylenetetrazol-induced neuron apoptosis and neurological impairment in mice with seizures via down-regulating JAK2/STAT3 pathway.

Epilepsy ranks fourth among neurological diseases, featuring spontaneous seizures and behavioral and cognitive impairments. Although anti-epileptic drugs are currently available clinically, 30% of epilepsy patients are still ineffective in treatment, and 52% of patients experience serious adverse reactions. In this work, the neuroprotective effect of α-linolenic acid (ALA, a nutrient) in mice and its potential molecular mechanisms exposed to pentylenetetrazol was assessed. The mice were injected with pentetrazol 37 mg/kg, and ALA was intra-gastrically administered for 40 days. The treatment with ALA significantly reduced the overall frequency of epileptic seizures and improved the behavior impairment and cognitive disorder caused by pentetrazol toxicity. In addition, ALA can not only reduce the apoptosis rate of brain neurons in epileptic mice, but also significantly reduce the content of brain inflammatory factors (IL-6, IL-1, and TNF-α). Furthermore, we predicted that the possible targets of ALA in the treatment of epilepsy were JAK2 and STAT3 through molecular docking. Finally, through molecular docking and Western Blot studies, we revealed the potential mechanism of ALA ameliorates pentylenetetrazol-induced neuron apoptosis and neurological impairment in mice with seizures by downregulating the JAK2/STAT3 pathway. This study aimed to investigate the antiepileptic and neuroprotective effects of ALA, as well as explore its potential mechanisms, through the construction of a chronic ignition mouse model via intraperitoneal PTZ injection. The findings of this research provide crucial scientific support for subsequent clinical application studies in this field.

Gut microbially produced tryptophan metabolite melatonin ameliorates osteoporosis via modulating SCFA and TMAO metabolism.

Osteoporosis (OP) is a severe global health issue that has significant implications for productivity and human lifespan. Gut microbiota dysbiosis has been demonstrated to be closely associated with OP progression. Melatonin (MLT) is an important endogenous hormone that modulates bone metabolism, maintains bone homeostasis, and improves OP progression. Multiple studies indicated that MLT participates in the regulation of intestinal microbiota and gut barrier function. However, the promising effects of gut microbiota-derived MLT in OP remain unclear. Here, we found that OP resulted in intestinal tryptophan disorder and decreased the production of gut microbiota-derived MLT, while administration with MLT could mitigate OP-related clinical symptoms and reverse gut microbiota dysbiosis, including the diversity of intestinal microbiota, the relative abundance of many probiotics such as Allobaculum and Parasutterella, and metabolic function of intestinal flora such as amino acid metabolism, nucleotide metabolism, and energy metabolism. Notably, MLT significantly increased the production of short-chain fatty acids and decreased trimethylamine N-oxide-related metabolites. Importantly, MLT could modulate the dynamic balance of M1/M2 macrophages, reduce the serum levels of pro-inflammatory cytokines, and restore gut-barrier function. Taken together, our results highlighted the important roles of gut microbially derived MLT in OP progression via the "gut-bone" axis associated with SCFA metabolism, which may provide novel insight into the development of MLT as a promising drug for treating OP.

Highly Emissive and Robust Cd-Based MOF with an Unprecedented Topology for Tetracycline Sensing.

Herein, an unprecedented cadmium-based metal-organic framework (JNU-106) fabricated by utilizing pyrazole-functionalized tetraphenylethylene ligands (Py-TPE) and rod-shaped secondary building units is reported, possessing a new (3,3,3,6,6,8)-connected topological network. Thanks to the ingeniously designed intramolecular charge transfer behavior, which originates from the congruent coplanarity between Py and TPE, JNU-106 exhibits intense green luminescence with a quantum yield increased by 1.5 times. The phenomenon of remarkable fluorescence quenching of JNU-106 reveals that it possesses extremely high anti-interference performance, superior sensitivity, and dedicated selectivity toward tetracycline antibiotics (TCAs) in aqueous solutions, which are comparable to those of the state-of-the-art porous sensing compounds. Taking the theoretical calculations and experimental results into account, the luminescence quenching is mainly attributed to the internal filtration effect and the static quenching effect. Considering the portable and rapid performance of JNU-106-based testing strips for sensing TCAs, the fabricated JNU-106 provides an alternative for ecological monitoring and environmental governance.

Early psychomotor development and growth hormone therapy in children with Prader-Willi syndrome: a review.

Prader-Willi syndrome (PWS) is a rare genetic disorder caused by the loss of imprinted gene expression on the paternal chromosome 15q11-q13. PWS is characterized by varying degrees of early psychomotor developmental deficits, primarily in cognition, language, and motor development. This review summarizes the early mental cognitive development, language development, and motor development in patients with PWS, compares the correlation of genotype with phenotype, and provides an update regarding the effects and concerns related to potential main side effects of treatment with recombinant human growth hormone on early psycho-cognitive and motor function development along with the linear growth and body composition of children with PWS.Conclusion: Early psychomotor development is strongly correlated with the prognosis of patients with PWS; moreover, current studies support that the initiation of interventions at an early age can exert significant beneficial effects on enhancing the cognitive and linguistic development of patients with PWS and allow them to "catch up" with motor development.  What is Known: • Prader-Willi syndrome is a rare genetic disorder characterized by multisystem damage, and children with Prader-Willi syndrome are typically characterized by early developmental delays, specifically in the areas of cognitive and motor development. • Recombinant human growth hormone therapy is the only medical treatment approved for Prader-Willi syndrome. What is New: • Extensive presentation of psycho-cognitive and motor development features and genotype-phenotype correlation in children with Prader-Willi syndrome.  • The effects of growth hormone on early psychomotor development in children with Prader-Willi syndrome were thoroughly reviewed, including their short- and long-term outcomes and any associated adverse effects.

Gold nanoparticles exhibit anti-osteoarthritic effects via modulating interaction of the "microbiota-gut-joint" axis.

Osteoarthritis (OA) is a common degenerative joint disease that can cause severe pain, motor dysfunction, and even disability. A growing body of research indicates that gut microbiota and their associated metabolites are key players in maintaining bone health and in the progression of OA. Short-chain fatty acids (SCFAs) are a series of active metabolites that widely participate in bone homeostasis. Gold nanoparticles (GNPs) with outstanding anti-bacterial and anti-inflammatory properties, have been demonstrated to ameliorate excessive bone loss during the progression of osteoporosis (OP) and rheumatoid arthritis (RA). However, the protective effects of GNPs on OA progression are not clear. Here, we observed that GNPs significantly alleviated anterior cruciate ligament transection (ACLT)-induced OA in a gut microbiota-dependent manner. 16S rDNA gene sequencing showed that GNPs changed gut microbial diversity and structure, which manifested as an increase in the abundance of Akkermansia and Lactobacillus. Additionally, GNPs increased levels of SCFAs (such as butyric acid), which could have improved bone destruction by reducing the inflammatory response. Notably, GNPs modulated the dynamic balance of M1/M2 macrophages, and increased the serum levels of anti-inflammatory cytokines such as IL-10. To sum up, our study indicated that GNPs exhibited anti-osteoarthritis effects via modulating the interaction of "microbiota-gut-joint" axis, which might provide promising therapeutic strategies for OA.

Unlocking the mysteries of VLDL: exploring its production, intracellular trafficking, and metabolism as therapeutic targets.

Reducing circulating lipid levels is the centerpiece of strategies for preventing and treating atherosclerotic cardiovascular disease (ASCVD). Despite many available lipid-lowering medications, a substantial residual cardiovascular risk remains. Current clinical guidelines focus on plasma levels of low-density lipoprotein (LDL). Recent attention has been given to very low-density lipoprotein (VLDL), the precursor to LDL, and its role in the development of coronary atherosclerosis. Preclinical investigations have revealed that interventions targeting VLDL production or promoting VLDL metabolism, independent of the LDL receptor, can potentially decrease cholesterol levels and provide therapeutic benefits. Currently, methods, such as mipomersen, lomitapide, and ANGPTL3 inhibitors, are used to reduce plasma cholesterol and triglyceride levels by regulating the lipidation, secretion, and metabolism of VLDL. Targeting VLDL represents an avenue for new lipid-lowering strategies. Interventions aimed at reducing VLDL production or enhancing VLDL metabolism, independent of the LDL receptor, hold promise for lowering cholesterol levels and providing therapeutic benefits beyond LDL in the management of ASCVD.

The serum soluble ASGR1 concentration is elevated in patients with coronary artery disease and is associated with inflammatory markers.

BACKGROUND AND AIMS: Current research has suggested that asialoglycoprotein receptor 1 (ASGR1) is involved in cholesterol metabolism and is also related to systemic inflammation. This study aimed to assess the correlation between the serum soluble ASGR1 (sASGR1) concentration and inflammatory marker levels. Moreover, the second objective of the study was to assess the association between sASGR1 levels and the presence of coronary artery disease (CAD). METHODS: The study subjects included 160 patients who underwent coronary angiography. Ninety patients were diagnosed with CAD, while seventy age- and sex-matched non-CAD patients served as controls. We measured the serum sASGR1 levels using an ELISA kit after collecting clinical baseline characteristics. RESULTS: Patients with CAD had higher serum sASGR1 levels than non-CAD patients did (P < 0.0001). sASGR1 was independently correlated with the risk of CAD after adjusting for confounding variables (OR = 1.522, P = 0.012). The receiver operating characteristic (ROC) curve showed that sASGR1 had a larger area under the curve (AUC) than did the conventional biomarkers apolipoprotein B (APO-B) and low-density lipoprotein cholesterol (LDL-C). In addition, multivariate linear regression models revealed that sASGR1 is independently and positively correlated with high-sensitivity C-reactive protein (CRP) (ß = 0.86, P < 0.001) and WBC (ß = 0.13, P = 0.004) counts even after adjusting for lipid parameters. According to our subgroup analysis, this relationship existed only for CAD patients. CONCLUSION: Our research demonstrated the link between CAD and sASGR1 levels, suggesting that sASGR1 may be an independent risk factor for CAD. In addition, this study provides a reference for revealing the potential role of sASGR1 in the inflammation of atherosclerosis.

Whether weekend warriors (WWs) achieve equivalent benefits in lipid accumulation products (LAP) reduction as other leisure-time physical activity patterns? -Results from a population-based analysis of NHANES 2007-2018.

BACKGROUND: Obesity is characterized by excessive fat accumulation in the body. Physical activity (PA) is an effective intervention to combat obesity, but the effectiveness of different PA patterns on controlling obesity is unclear. Lipid accumulation product (LAP), derived from waist circumference and triglycerides, is a novel indicator for obesity evaluation. However, the association between PA patterns (i.e., weekend warriors and regularly active) and LAP remains unexplored. This study aims to elucidate the relationship between PA patterns and LAP in US adult population. METHODS: Adult individuals with complete data on LAP, PA patterns, and other covariates from the National Health and Nutrition Examination Survey (NHANES) database (2007-2018) were included in this study. Multivariate linear regression models were utilized to explore the association between PA patterns and LAP. Subgroup analyses, interaction tests, restricted cubic spline (RCS) regression analyses, and threshold and saturation effect analyses were also performed to investigate the stability and nonlinearity of PA-LAP association, respectively. RESULTS: A total of 11,212 participants were included in this study. After adjusting for all potential covariates, being regularly active (RA) (ß=-8.85, P < 0.05) obtained significantly higher LAP reduction as opposed to being weekend warriors (WWs) (ß=-4.70, P = 0.3841). Furthermore, subgroup analyses and interaction tests indicated that the PA-LAP association was more pronounced in individuals with higher education levels (P interaction = 0.0084) and diabetes (P interaction = 0.0062). Additionally, a significant, non-linear, and negative correlation between weekly total PA and LAP in non-inactive individuals was identified by RCS analysis (P for overall < 0.001, P for nonlinearity = 0.009). A threshold of 440 min in weekly total PA was found to arouse favorable LAP reduction. CONCLUSIONS: Being regularly active obtained better LAP reduction as opposed to being WWs. For non-inactive adults, engaging in more than 440 min of PA per week helps to reduce LAP effectively.

Delayed postoperative neurological deficits from scoliosis correction: a case series and systematic review on clinical characteristics, treatment, prognosis, and recovery.

OBJECTIVE: This study was designed to investigate the clinical features, treatment modalities, and risk factors influencing neurological recovery in patients who underwent scoliosis correction with delayed postoperative neurological deficit (DPND). METHODS: Three patients with DPND were identified from 2 central databases for descriptive analysis. Furthermore, all DPND cases were retrieved from the PubMed and Embase databases. Neurological function recovery was categorized into complete and incomplete recovery groups based on the American Spinal Injury Association (ASIA) impairment scale. RESULTS: Two patients were classified as type 3, and one was classified as type 2 based on the MRI spinal cord classification. Intraoperative neurophysiological monitoring (IONM) was consistently negative throughout the corrective procedure, and intraoperative wake-up tests were normal. The average time to DPND development was 11.8 h (range, 4-18 h), and all three patients achieved complete recovery of neurological function after undergoing revision surgery. A total of 14 articles involving 31 patients were included in the literature review. The mean time to onset of DPND was found to be 25.2 h, and 85.3% (29/34) of patients experienced DPND within the first 48 h postoperatively, with the most common initial symptoms being decreased muscle strength and sensation (26 patients, 83.9%). Regarding neurological function recovery, 14 patients were able to reach ASIA grade E, while 14 patients were not able to reach ASIA grade E. Univariate analysis revealed that preoperative diagnosis (p = 0.004), operative duration (p = 0.017), intraoperative osteotomy method (p = 0.033), level of neurological deficit (p = 0.037) and deficit source (p = 0.0358) were significantly associated with neurological outcomes. Furthermore, multivariate regression analysis indicated a strong correlation between preoperative diagnosis (p = 0.003, OR, 68.633; 95% CI 4.299-1095.657) and neurological prognosis. CONCLUSION: Our findings indicate that spinal cord ischemic injury was a significant factor for patients experiencing DPND and distraction after corrective surgery may be a predisposing factor for spinal cord ischemia. Additionally, it is important to consider the possibility of DPND when limb numbness and decreased muscle strength occur within 48 h after corrective scoliosis surgery. Moreover, emergency surgical intervention is highly recommended for DPND caused by mechanical compression factors with a promising prognosis for neurological function, emphasizing the importance of taking into account preoperative orthopedic diagnoses when evaluating the potential for neurological recovery.

Epidemiological and Whole Genome Sequencing Analysis of Restaurant Salmonella Enteritidis Outbreak Associated with an Infected Food Handler in Jiangxi Province, China, 2023.

In China, Salmonella is one of the most frequent causes of bacterial gastroenteritis, and food handlers in restaurants as an important contaminated source were rarely reported. In May 2023, an outbreak of Salmonella enterica serovar Enteritidis infection in a restaurant in Jiangxi Province, China, was investigated. Cases were interviewed. Stool samples from cases, anal swabs from restaurant employees, suspicious raw food materials, and semifinished food were collected and examined. Pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS) were performed to determine the relatedness of the pathogen isolates. Antimicrobial resistance genes and virulence genes of isolates were analyzed by WGS. The antimicrobial profile of the isolates was detected by broth microdilution, which involved 20 different antibiotics. Among the 31 patrons, 26 showed gastrointestinal symptoms. Five Salmonella Enteritidis strains were isolated from patients (2), semifinished food (2), and food handler (1). The results of PFGE and single-nucleotide polymorphism showed that these five isolates were identical clones. These findings demonstrated that this outbreak was a restaurant Salmonella Enteritidis outbreak associated with an infected food handler. The rates of resistance to nalidixic acid and colistin and intermediate resistance to ciprofloxacin were 100%, 80%, and 100%, respectively. These outbreak isolates harbored point mutation gyrA p.D87G. The cause of inconsistency between the genotype and phenotype of resistance was deeply discussed. A total of 107 virulence genes were found in each isolate, with many being associated with Salmonella pathogenicity island (SPI)-1 and SPI-2. As an overlooked contamination source, infected food handlers can easily cause large-scale outbreaks. This outbreak highlighted that the government should enhance the training and supervision of food hygiene and safety for food handlers to prevent foodborne outbreaks.

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Central precocious puberty (CPP) is a developmental disorder caused by early activation of the hypothalamic-pituitary-gonadal axis. The incidence of CPP is rapidly increasing, but the underlying mechanisms are not fully understood. Previous studies have shown that gain-of-function mutations in the KISS1R and KISS1 genes and loss-of-function mutations in the MKRN3, LIN28, and DLK1 genes may lead to early initiation of pubertal development. Recent research has also revealed the significant role of epigenetic factors such as DNA methylation and microRNAs in the regulation of gonadotropin-releasing hormone neurons, as well as the modulating effect of gene networks involving multiple variant genes on pubertal initiation. This review summarizes the genetic etiology and pathogenic mechanisms underlying CPP.

A prospective prognostic signature for pancreatic adenocarcinoma based on ubiquitination-related mRNA-lncRNA with experimental validation in vitro and vivo.

Ubiquitination-related genes (URGs) exerted a crucial part in a variety of human disease disorders; however, their association with pancreatic adenocarcinoma (PAAD) had yet to be clearly described. We aimed to comprehensively characterize the contributions of URGs in PAAD through in silico analysis and experimental validation, and then identified a robust mRNA-lncRNA-based molecular prognostic panel for patients with PAAD using bulk RNA-sequencing and single-cell RNA-sequencing data. Initially, we collected the multi-omics data from TCGA platform to depict a comprehensive landscape of URGs in pan-cancer. Furthermore, we were accurate to PAAD for in-depth analysis. Significant differences of the activation of ubiquitination pathways and the expression of URGs were detected between normal and malignant cells. Unsupervised hierarchical clustering determined two PAAD subtypes with distinct clinical outcomes, ubiquitination pathway activities, immune microenvironment, and functional annotation characteristics. The expression profiles of ubiquitination-associated mRNAs and lncRNAs in the training and validation datasets were utilized to develop and verify a novel ubiquitination-related mRNA-lncRNA prognostic panel, which had a satisfied prediction efficiency. Our ubiquitination-associated model could function as an effective prognostic index and outperformed four other recognized panels in evaluating PAAD patients' survival status. Tumor immune microenvironment, mutation burden, and chemotherapy response were intensively explored to demonstrate the underlying mechanism of prognostic difference according to our panel. Our findings also revealed that FTI-277, a farnesyltransferase inhibitor, had a better curative effect in high-risk patients, while MK-2206, an Akt allosteric inhibitor, had a superior therapeutic effect in low-risk patients. The real-time PCR results uncovered the RNA expression of AC005062.1 in all the three PAAD cell lines was elevated several thousandfold. In conclusion, our URGs-based classification panel could be triumphantly served as a prediction tool for survival evaluation in patients with PAAD, and the genes in this panel could be developed as a potential target in PAAD therapy.