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Abstract Malocclusion, identified by the World Health Organization (WHO) as one of three major oral diseases, profoundly impacts the dental-maxillofacial functions, facial esthetics, and long-term development of ~260 million children in China. Beyond its physical manifestations, malocclusion also significantly influences the psycho-social well-being of these children. Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition, by mitigating the negative impact of abnormal environmental influences on the growth. Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development, ranging from fetal stages to the early permanent dentition phase. From an economic and societal standpoint, the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated, underlining its profound practical and social importance. This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children, emphasizing critical need for early treatment. It elaborates on corresponding core principles and fundamental approaches in early orthodontics, proposing comprehensive guidance for preventive and interceptive orthodontic treatment, serving as a reference for clinicians engaged in early orthodontic treatment.

Objective:: To investigate the prevalence of low body weight in Beijing pubertal girls and to establish the cut-off for body mass index (BMI) for underweight for Chinese pubertal girls. Design:: Cross-sectional study. Setting:: Three socioeconomic areas (rural, suburban and urban) in Beijing, China. Subjects:: Random sample of 1214 adolescent girls aged 12-14[??]y from 13 middle schools. Results:: Using a modified Chinese reference, the rate of low body weight (BMI [less than] 18) was 32.2% (95% CI 29.6-34.8%). Compared with desirable weight girls (BMI=18-21), girls with low body weight had a lower bone age, delayed breast and pubic hair development, a lower rate of menarche, lower distal one-third radius and ulna bone mineral content (BMC), bone mineral density and bone width. Logistic regression showed that BMI was one of the predictors of one-third ulna BMC after adjustment for confounding variables. When comparing BMI [less than] 18 vs BMI=18-21, the risk of BMC being less than the median increased by 82% (odds ratio 1.82, 95% CI 1.06-3.13). Thinness and stunting rates assessed by WHO recommended cut-offs are also reported. Conclusions:: High prevalence of low body weight (BMI [less than] 18) was found to be a major health problem among Beijing pubertal girls. BMI [less than] 18 is confirmed as the cut-off for delayed general growth and development for Chinese girls and for screening girls at risk of lower bone mineral status. Sponsorship:: The research was supported in part by the Dairy Research and Development Corporation, Australia. European Journal of Clinical Nutrition (2003) 57, 693-700. doi: 10.1038/sj.ejcn.1601599 Keywords: low body weight, BMI, pubertal girls, bone mineral content, dietary intake, China, Author(s): X Du [1]; H Greenfield [1]; D R Fraser [2]; K Ge [3]; W Zheng [4]; L Huang [5]; Z Liu [6] Introduction Adolescence, characterized by accelerated muscle and [...]

Microbial pathogenesis is mediated by the expression of virulence genes. However, as microbes with identical virulence gene content can differ in their pathogenic potential, other virulence determinants must be involved. Here, by combining comparative genomics and transcriptomics of a large collection of isolates of the model pathogen Listeria monocytogenes, time-lapse microscopy, in vitro evolution and in vivo experiments, we show that the individual stress responsiveness of L. monocytogenes isolates determines their respective levels of virulence in vivo and reflects their degree of host adaptation. The transcriptional signature that accounts for the heterogeneity in the virulence of L. monocytogenes species is mediated by the stress response regulator SigB and driven by differential stress responsiveness. The tuning of SigB pathway responsiveness is polygenic and influenced by multiple, individually rare gene variations. This study reveals an overarching determinant of microbial virulence, challenging the paradigm of accessory virulence gene content as the major determinant of intraspecies virulence heterogeneity., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Ultramicrotomy is a well-established technique that has been applied in biology and medical research to produce thin sections or a blockface of an embedded sample for microscopy. Recently, this technique has also been applied in materials science or micro- and nanotechnology as a sample preparation method for subsequent characterization. In this work, an application of ultramicrotomy for the cross-section preparation of an inkjet-printed multilayer structure is demonstrated. The investigated device is a capacitor consisting of three layers. The top and bottom electrodes are printed with silver nanoparticle ink and the dielectric layer with a ceramic nanoparticle/polymer ink. A 3D profilometer is initially used to study the surface morphology of the printed multilayer. The measurements show that both electrodes exhibit a coffee-ring effect, which results in an inhomogeneous layer structure of the device. To obtain precise 3D information on the multilayer, cross-sections must be prepared. Argon ion beam milling is the current gold standard to produce a single cross-section in good quality, however, the cross-section position within the multilayer volume is poorly defined. Moreover, the milling process requires a significant investment of time and resources. Herein, we develop an efficient method to realize repetitive cross-section preparation at well-defined positions in the multilayer volume. Repetitive cross-sections are exposed by trimming with an ultramicrotome (UM) and this blockface is subsequently transferred into a scanning electron microscope (SEM) for imaging. A combination of custom-modified UM and SEM specimen holders allows repeated transfer of the clamped multilayer sample between instruments without damage and with high positioning accuracy. This novel approach enhances the combination of an established ultramicrotome and a SEM for multilayer sample volume investigation. Thus, a comprehensive understanding of printed multilayer structures can be gained, to derive insights for optimization of device architecture and printing process., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

FAR-RED IMPAIRED RESPONSE 1 (FAR1) is a class of transposase-derived transcription factors that play a very important role in the initiation of the photosensitive pigment A (phyA) signaling pathway. Despite their importance, the understanding of the function of FAR1 genes in quinoa is still limited, especially regarding how they affect the spike sprouting response. Quinoa has gained global attention in recent years for its health benefits and potential for sustainable agriculture. In our study, the CqFAR1 gene set in quinoa was characterized using HMMER (PF03101) and BLAST analyses, and 87 genes were identified. The 87 CqFAR1 genes were systematically classified into five groups that showed a high degree of conservation in gene structure and motif composition. Tissue expression profiles of the CqFAR1 gene indicated that the CqFAR1 gene plays a key role throughout the growth and development of quinoa, especially at mid (leaf) and end (spike) stages. By RT-qPCR analysis, we observed significant differences in the expression of the CqFAR1 gene at different developmental stages. Notably, the CqFAR1 gene showed significant expression enhancement at the early stage of quinoa spike sprouting. The results are useful for understanding the role of the CqFAR1 gene in quinoa growth and development and provide theoretical support for quinoa breeding., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

With the rapid expansion of construction engineering, the demand for traditional materials, particularly natural river sand, has surged, resulting in excessive resource exploitation and significant ecological damage. In response, the use of waste oyster shells as a sustainable alternative for fine aggregates has gained attention. However, limited research has been conducted on the dynamic properties of mortar with this substitution. This study explores the potential of using crushed oyster shell sand (OSS) as fine aggregates in mortar. A series of Split Hopkinson Pressure Bar (SHPB) tests under different gas pressures (p g ) (0.2, 0.3, and 0.4 MPa) were carried out on mortar samples with five OSS replacement ratios (R r ) (0%, 20%, 50%, 80%, and 100%), using a water-to-cement ratio of 0.55. The results showed that when the OSS replacement rate (R r ) increased from 0 to 20%, there was a significant increase in peak stress (σ max ) and elastic modulus (E), attributed to the filling effect of OSS, which enhanced the absorbed energy (E ab ) and strength contribution rate (SCR). However, at R r above 20%, a sharp decline in σ max and E was observed, primarily due to porous characteristics of OSS. Correspondingly, E ab decreased, reducing the impact resistance of mortar. Moreover, the negative SCR suggests detrimental effects on mortar integrity at higher OSS R r levels. Predictive relationships for peak stress and elastic modulus across different replacement ratios were established in this study, providing a foundational reference for the design and assessment of the dynamic mechanical response of structures incorporating OSS., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Accurate differentiation and identification of flea species are essential for both basic and applied research on fleas, as well as for the diagnosis of flea-borne diseases. However, distinguishing between flea species can be challenging, especially among those with minimal morphological differences. Therefore, some scholars have suggested the necessity of comprehensive revisions to the classification of fleas, incorporating morphological, molecular, and phylogenetic data. In this study, we focused on classifying the rodents' parasitic fleas in southeastern China and provided molecular and phylogenetic data. We also described a new subspecies Ctenophthalmus breviprojiciens fujiansis n. ssp. A total of 392 fleas were collected from 8 species of rodents in 10 counties. Morphologically, they belonged to 10 species, 9 genera and 5 families. Barcode identification based on COI gene and phylogenetic analysis based on five genetic markers (18S rDNA, 28S rDNA, EF-1a, COI, COII) revealed that the molecular and morphological identification of Xenopsylla cheopis, Aviostivalius klossi bispiniformis, Leptopsylla segnis, Monopsyllus anisus and Ctenocephalides felis felis were consistent. The taxonomic status of Neopsylla specialis minpiensis and Peromyscopsylla himalaica sinica as subspecies is questionable due to significant intraspecific genetic distance, and further morphological and molecular data are required to determine if they should be elevated to species level. The molecular identification of C. breviprojiciens n. ssp., N. dispar fukienensis, and Nosopsyllus nicanus could not be completed at this time due to a lack of sequences for related species in existing GenBank databases. Additionally, phylogenetic relationships of 31 species from 9 genera and 5 families of Siphonaptera were inferred based on five molecular markers (18S rDNA, 28S rDNA, EF-1a, COI and COII) using Maximum Likelihood analyses. The analyses revealed that various taxa of Siphonaptera are monophyletic at the subspecies, species, and genus levels. However, at the family level, Leptopsyllidae, Ceratophyllidae, Pulicidae, and Pygiopsyllidae are all monophyletic, while Ctenophthalmidae is paraphyletic. we support the view of some authors that revising the catchall group Ctenophthalmidae and elevating each of its constituent subfamilies to family status., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Acute kidney injury (AKI) is a common clinical problem, and patients who survive AKI have a high risk of chronic kidney disease (CKD). The acute protective effects of Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in AKI have been examined, there is still relatively little known regarding the impact of acute CDK4/6 inhibition on the chronic sequence of AKI. Therefore, we utilized the CDK4/6 inhibitor Palbociclib to examine the long-term effects of CDK4/6 inhibition in a rodent model of ischemic AKI. Palbociclib (Palb) was administered during the acute stage or post the acute stage of AKI and mice were sacrificed 21 days post injury. We found that Palb could cause renal senescence and renal fibrosis. Furthermore, dasatinib (D) plus quercetin (Q) were used to eliminate senescent cells in ischemic AKI murine model and Palb was administered post the treatment of D + Q. We found that Palb could reverse the senolytic and antifibrotic effects induced by D + Q, which indicates that the profibrotic effect of Palb could be ascribed to its pro-senescent effects. Our results demonstrate that CDK4/6 inhibitors treatment might be deleterious on the chronic sequence of AKI., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Biological invasion is a major global problem, leading to the loss of biodiversity and species extinction, and causing huge economic losses to countries. Obolodiplosis robiniae is a major invasive forest pest that has caused economic losses in Asia and Europe. Here, the chromosome- level genome of O. robiniae was assembled using the PacBio platform and Hi-C technology. A contig-level genome with a length of 199.49 Mb and a contig N50 of 4.66 Mb was assembled. Approximately 98.05% of contigs were successfully anchored to four chromosomes using Hi-C assisted genome assembly. The genome integrity was assessed to be 90.3% based on BUSCOs analysis. The high-quality genome provides valuable data for the study of invasive species, and a foundation for the understanding the biology and ecology of O. robiniae., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Current tools for predicting survival outcomes in colon cancer patients predominantly rely on clinical and pathologic characteristics. However, accumulating evidence demonstrates a significant correlation between nutritional status and patient outcomes. This study aimed to establish a new dynamic nomogram for individualized prediction of postoperative overall survival (OS). The clinicopathological and nutritional data of colon cancer patients undergoing radical resection were retrospectively collected and randomly divided into the primary and validation cohorts. Risk factors on OS rates were investigated by Cox analyses and, the nomogram was constructed using significant predictors. Among 1,024 patients, 341 deaths were observed after median follow-up of 54 months. Five independent prognostic factors, including nutritional status assessments, were incorporated into the nomogram. The C-index regarding 1-, 3-, and 5-year OS were 0.830, 0.859, and 0.757 in the primary cohort and 0.843, 0.870, and 0.773 in the validation cohort, respectively. Calibration curves for the probability of OS exhibited an optimal agreement. Decision curve analyses revealed the greater application value of the nomogram than the TNM staging system. Based on the nomogram, patients could be stratified into three scenarios with significant prognostic classification (P < 0.0001). In conclusion, we developed and validated an easy-to-use dynamic nomogram for predicting postoperative OS in colon cancer patients., Competing Interests: Competing interests The authors declare no competing interests or personal relationships that can influence the work reported in this paper., (© 2024. The Author(s).)

Background and Aims: Diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) both have microcirculation dysfunction. Urinary albumin-to-creatinine ratio (UACR) is a biomarker for DN. We aimed to explore the links between DPN and UACR in patients with type 2 diabetes mellitus (T2DM)., Methods: A total of 195 T2DM patients were defined as Control or DPN group. Clinical parameters were compared, and the association between HbA1c (or UACR) and DPN was analyzed. Risk factors for DPN were observed, and the diagnostic values of HbA1c and UACR were assessed., Results: Compared with 104 participants without DPN, 91 individuals with DPN exhibited higher HbA1c and UACR levels. In all patients, increased HbA1c and UACR were identified as risk factors for DPN in individuals with T2DM. Moreover, increased HbA1c was a risk factor for DPN in volunteers without DN, whereas elevated UACR was determined as a risk factor for DPN in participants with DN. The cut-off point for HbA1c (7.65%) in patients without DN had a sensitivity of 86.0% and specificity of 44.6%, while the cut-off point for UACR (196.081 mg/g) in patients with DN had a sensitivity of 52.9% and specificity of 76.2%., Conclusion: Elevated HbA1c and UACR levels are risk factors for DPN and may serve as potential biomarkers for DPN in T2DM patients., (© 2024. The Author(s).)

Hypertrophic scars arise from aberrant wound healing and can lead to functional and aesthetic impairments. One of the common interventions for treating hypertrophic scars is fractional carbon dioxide (CO2) laser, which employs narrow laser beams to stimulate dermal collagen deposition. Recent studies and reports have suggested that combining laser therapy with other interventions such as botulinum toxin type A (BTX-A) and topical growth factors may enhance treatment outcomes. Here, we examine the efficacy and safety of a sequential combination of BTX-A, fractional CO2 laser, and topical growth factors, referred to as combined therapy, for treating hypertrophic scars compared with only using fractional CO2 laser and topical growth factors, referred to as monotherapy. Our retrospective study includes 128 patients with hypertrophic scars (56 underwent monotherapy and 72 underwent combined therapy), which were followed-up for up to 15 months after the initiation of treatment to collect demographic and clinical data. Our analysis showed that the combined therapy significantly outperformed monotherapy in improving Vancouver scar scale scores (P < 0.05) and in the reduction of scar thickness (P < 0.05), without increasing adverse complications. Repeated treatments further augmented the efficacy of the combined therapy. Subgroup analysis revealed that combined therapy was notably more effective in reducing Vancouver scar scale scores and scar thickness in early-stage scars compared to late-stage (P = 0.023 and P = 0.045, respectively). Our study suggests that including BTX-A treatment before fractional CO2 laser and topical growth factors offers superior efficacy in reducing hypertrophic scars. We encourage early intervention and repeated treatments for optimal treatment outcomes., (© 2024. The Author(s).)

This study aimed to construct and assess a machine-learning algorithm designed to forecast survival rates and risk stratification for patients with gastric neuroendocrine neoplasms (gNENs) after diagnosis. Data on patients with gNENs were extracted and randomly divided into training and validation sets using the Surveillance, Epidemiology, and End Results database. We developed a prediction model using 10 machine learning algorithms across 101 combinations to forecast cancer-related mortality in patients with gNENs, selecting the best model using the highest mean over a sequence of time-dependent area under the receiver operating characteristic (ROC) curve (AUC). The performance of the final model was assessed through time-dependent ROC curves for discrimination and calibration curves for calibration. The maximum selection rank method was used to determine the best prognostic risk score threshold for classifying patients into high- and low-risk groups. Afterward, Kaplan-Meier analysis and log-rank test were used to compare survival rates among these groups. Our study examined 775 patients with gNENs, dividing them into training and validation sets. A training set comprised 543 patients, with a median follow-up of 42 months and cumulative mortality rates of 40.0% at 1 year, 48.6% at 3 years, and 54.0% at 5 years. A validation set comprised 232 patients, with cumulative mortality rates of 29.1% at 1 year, 43.5% at 3 years, and 53.2% at 5 years. The optimal random survival forest (RSF) model (mtry = 4, node size = 5) achieved an AUC of 0.839 for survival prediction in the training set. Comprising 11 variables such as demographics, treatment details, tumor characteristics, T staging, N staging, and M staging, the RSF model revealed high predictive accuracy with AUCs of 0.92, 0.96, and 0.96 for 1-, 3-, and 5-year survival, respectively, which was consistently reflected in the validation set with AUCs of 0.88, 0.92, and 0.89, respectively. Moreover, patients were risk-stratified. Although our RSF model effectively stratified patients into different prognostic groups, it needs external validation to confirm its utility for noninvasive prognostic prediction and risk stratification in gNENs. Further research is required to verify its broader clinical applicability., (© 2024. The Author(s).)

The balance between T helper type 1 (T H 1) cells and other T H cells is critical for antiviral and anti-tumour responses 1-3 , but how this balance is achieved remains poorly understood. Here we dissected the dynamic regulation of T H 1 cell differentiation during in vitro polarization, and during in vivo differentiation after acute viral infection. We identified regulators modulating T helper cell differentiation using a unique T H 1-T H 2 cell dichotomous culture system and systematically validated their regulatory functions through multiple in vitro and in vivo CRISPR screens. We found that RAMP3, a component of the receptor for the neuropeptide CGRP (calcitonin gene-related peptide), has a cell-intrinsic role in T H 1 cell fate determination. Extracellular CGRP signalling through the receptor RAMP3-CALCRL restricted the differentiation of T H 2 cells, but promoted T H 1 cell differentiation through the activation of downstream cAMP response element-binding protein (CREB) and activating transcription factor 3 (ATF3). ATF3 promoted T H 1 cell differentiation by inducing the expression of Stat1, a key regulator of T H 1 cell differentiation. After viral infection, an interaction between CGRP produced by neurons and RAMP3 expressed on T cells enhanced the anti-viral IFNγ-producing T H 1 and CD8 + T cell response, and timely control of acute viral infection. Our research identifies a neuroimmune circuit in which neurons participate in T cell fate determination by producing the neuropeptide CGRP during acute viral infection, which acts on RAMP3-expressing T cells to induce an effective anti-viral T H 1 cell response., Competing Interests: Competing interests V.K.K. has an ownership interest in Tizona Therapeutics, Bicara Therapeutics, Larkspur Biosciences and Werewolf Therapeutics; financial interests in Biocon Biologics, Perkin Elmer, Elpiscience Biopharmaceutical, Equilium and Syngene. A.H.S. has patents/pending royalties on the PD-1 pathway from Roche and Novartis; is on advisory boards for Surface Oncology, SQZ Biotechnologies, Elpiscience, Selecta, Bicara Therapeutics, Monopteros, Fibrogen, Alixis, GlaxoSmithKline and Janssen; and has received research funding from Merck, Vertex, Moderna, Quark/Iome and AbbVie (unrelated to this project). A.R. is listed as a co-inventor on patent applications filed by the Broad Institute for inventions related to single-cell genomics; is an equity holder in Immunitas; and was a scientific advisory board member of Thermo Fisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics and Asimov until 31 July 2020. From 1 August 2020, A.R. is an employee of Genentech and has equity in Roche. The other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Liver X receptors (LXRs) which link lipid metabolism and inflammation, were overexpressed in experimental rheumatoid arthritis (RA) rats as observed in our previous studies, while suppression of LXRα by silybin ameliorates arthritis and abnormal lipid metabolism. However, the role of LXRs in RA remains undefined. In this study, we investigated the inhibition role of LXRs in the polarization and activation of M1 macrophage by using a special LXRs inverse agonist SR9243, which led to ameliorating the progression of adjuvant-induced arthritis (AIA) in rats. Mechanistically, SR9243 disrupted the LPS/IFN- γ -induced Warburg effect in M1 macrophages, while glycolysis inhibitor 2-DG attenuated the inhibition effect of SR9243 on M1 polarization and the cytokines expression of M1 macrophages including iNOS, TNF-α, and IL-6 in vitro. Furthermore, SR9243 downregulated key glycolytic enzymes, including LDH-A, HK2, G6PD, GLUT1, and HIF-1α in M1 macrophages, which is mediated by increased phosphorylation of AMPK (Thr172) and reduced downstream phosphorylation of mTOR (Ser2448). Importantly, gene silencing of LXRs compromises the inhibition effect of SR9243 on M1 macrophage polarization and activation. Collectively, for the first time, our findings suggest that the LXR inverse agonist SR9243 mitigates adjuvant-induced rheumatoid arthritis and protects against bone erosion by inhibiting M1 macrophage polarization and activation through modulation of glycolytic metabolism via the AMPK/mTOR/HIF-1α pathway., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

With the aging process of the global population and the development of medical technology, the cases of postoperative cognitive dysfunction (POCD) are also increasing. Due to the complexity of the pathogenesis, urgent treatment has been sought. Neuroinflammation induced by the accumulation of lipid droplets (LDs) in microglia has been closely watched in recent years and is also considered to be an important cause of nerve damage. Our study found that derived from Withania somnifera, Withaferin A (WA) could reduce the accumulation of LDs in the hippocampus of POCD mice, inhibit the expression of inflammatory factor interleukin-1β (IL-1β), and improve the cognitive ability of mice. Further in vitro experimental studies showed that WA increased the autophagy level of microglia, promoted the degradation of LDs, and reduced the production of inflammatory factors. In this regard, our comprehensive research endeavor holds the potential to furnish novel insights into therapeutic strategies aimed at addressing POCD and its associated neural impairments., (© 2024. The Author(s).)

Cardiac arrest (CA) is a serious health concern that often results in mortality or severe neurological dysfunction in the case of survival. Our aim was to explore the neurological prognostic factors in patients with CA. This retrospective observational study included adult patients with CA. We investigated serum neuron-specific enolase (NSE), S100 calcium-binding protein β (S100β), and indices and parameters at 1, 3, 5, 7 and intensive care unit (ICU) discharge days after CA. The primary study endpoint was the Cerebral Performance Category (CPC) scale score at ICU discharge, which was dichotomized as good neurological outcome (CPC 1-2: full recovery or moderate disability) and poor neurological outcome (CPC 3-5: severe disability, vegetative state, or death). Of the 191 adult patients with CA, 42 (22%) had good neurological outcomes, and 149 (78%) had poor neurological outcomes. NSE at 1,3,5,7 and ICU discharge days showed excellent predictive accuracy for neurological outcomes (area under the curve [AUC]: 0.666, 0.716, 0.870, 0.739, and 0.901, respectively). However, S100β exhibited general predictive power (AUC: 0.666, 0.573, 0.607, 0.594, 0.727). Finally, the early warning model, which combined day 1 NSE, day 1 S100β, cardiac arrest time, SOFA scores, APACHE II scores, and age, was used to screen CA patients with poor neurological prognosis at early stages and had an AUC of 0.792. Serum concentrations of NSE and S100β were significantly elevated in CA patients and could be prognostic biomarkers to predict neurological outcomes. Day 1 NSE and S100β combined with multiple indicators could be a decent early warning model for poor neurological prognosis in patients with CA., (© 2024. The Author(s).)

Objective To evaluate the effectiveness of preemptive multimodal analgesiain elderly patients undergoing laparoscopic colorectal surgery. Methods A prospective randomized controlled study was conducted in the Department of Gastrointestinal Surgery of the Second Hospital of Hebei Medical University from January 2022 to December 2022. A total of 133 patients were included according to the criteria and randomly divided into preemptive analgesia (PRA) group (test group, 67patients) and postoperative analgesia (POA) group (control group, 66patients). Results The Visual Analog Scale (VAS)scores of PRA group 24 h, 48 h, and 72 h after operation were lower than those of POA group, and the difference was statistically significant, P < 0.001.The incidences of postoperative gastrointestinal dysfunction (POGD) and postoperative delirium (POD)in PRA group were 13.43% and 8.98%, respectively, which were significantly lower than those in POA group (31.82% and 24.24%), P < 0.05. The levels of IL-6 and IL-10 in PRA group after the operation were 17.54 ± 2.13 ng/L and 15.57 ± 1.71 ng/L respectively, which were lower than those in POA group (25.45 ± 2.95 ng/L and 23.45 ± 1.88 ng/L), P < 0.05. The level of acetylcholinesterase(AchE) was 56.34 ± 5.62 nmol/L in the POA group, which was significantly higher than that in the POA group (49.59 ± 5.52 nmol/L), P < 0.001. Conclusion Preemptive multimodal analgesia can reduce the incidence of POGD and POD in elderly patients undergoing laparoscopic gastrocolic surgery, improve the recovery process of postoperative gastrointestinal function, increase the concentrations of propionic acid and butyric acid in short chain fatty acids (SCFAs) and the number of beneficial intestinal bacteria., (© 2024. The Author(s).)

The purpose of this study is to investigate the influencing factors of abnormal pulmonary ventilation function in occupational exposed populations and to establish a risk prediction model. The findings will provide a basis for formulating corresponding strategies for the prevention and treatment of occupational diseases. The study focused on workers who underwent occupational health examinations in the year 2020. Statistical analysis was conducted using methods such as t-tests, chi-square tests, and multiple logistic regression analysis. Additionally, machine learning methods were employed to establish multiple models to address classification problems. Among the 7472 workers who participated in the occupational health examination, 1681 cases of abnormal pulmonary ventilation function were detected, resulting in a detection rate of 22.6%. Based on the analysis of occupational hazard data, a risk prediction model was established. Age, work tenure, type of the employing enterprise, and type of dust exposure are all identified as driving factors for abnormal pulmonary function. These factors were used as predictive variables for establishing the risk prediction model. Among the various models evaluated, the logistic regression model was found to be the optimal model for predicting abnormal pulmonary ventilation function., (© 2024. The Author(s).)

Ground settlement prediction for highway subgrades is crucial in related engineering projects. When predicting the ground settlement, sparse sample data are often encountered in practice, which greatly affects the prediction accuracy. However, this has been seldom explored in previous studies. To resolve it, this paper proposes a regression Kriging (RK)-based method for ground settlement prediction with sparse data. Under the framework of RK, the stationarity of sample residual and trend structure are key factors for prediction accuracy. It is found that the use of Box-Cox transformation, which can help to achieve stationarity of sample residual, leads to significant increase of the prediction accuracy with sparse data. Specifically, the various evaluation metrics (i.e., root mean square error (RMSE), mean absolute error (MAE), mean arctangent absolute percent error (MAAPE) and scatter index (SCI)) are significantly decreased when the Box-Cox transformation is incorporated. In addition, the first-order polynomial trend structure is found to be more appropriate than those with higher orders for predicting settlements resulting from primary consolidation. Moreover, comparative study is conducted among the proposed RK method, classical prediction methods and back propagation neural network (BPNN). It is found that the evaluation metrics obtained by the RK method are significantly smaller than those obtained by the other methods, indicating its highest accuracy. By contrast, BPNN has the worst performance among the various methods, because the sparse data are inadequate to establish a satisfactory BPNN model., (© 2024. The Author(s).)

Corticosteroids have always been recommended for severe cases of COVID-19. However, the efficacy of treatment with corticosteroids for COVID-19 during the SARS-CoV-2 omicron outbreak in China has not been reported. Clinical data from 406 patients hospitalized for severe/critical COVID-19 from December 2022 to January 2023 at six hospitals in Chongqing were retrospectively analyzed. The primary outcome was all-cause mortality at 28 days in the groups with and without corticosteroids treatment after propensity score matching (PSM). Secondary outcomes were to compare in-hospital mortality and length of survival time with corticosteroids and those without corticosteroids. This study included 406 patients with severe or critical COVID-19, divided into the corticosteroids group (231, 56.9%) and non-corticosteroids group (175, 43.1%). After PSM, the use of corticosteroids did not reduce all-cause mortality at 28 days (42.5% vs. 39.1%). Univariate analysis showed that corticosteroids were not associated with improved all-cause mortality at 28 days [hazard ratio (HR), 1.019; 95% confidence interval (CI), 0.639-1.623; p = 0.938]. Multivariate analysis showed similar results (HR, 1.047; 95% CI, 0.633-1.732; p = 0.858). Among non-survivors, the survival time was significantly larger in those who received corticosteroids compared with the non-corticosteroid users [median 13 (IQR 6.5-15.5) vs. 6 (4-11.25), p = 0.007]. The use of systemic corticosteroids in severe/critical COVID-19 may provide certain potential survival benefits but does not improve prognosis., (© 2024. The Author(s).)

Salmonella enterica serovar Gallinarum (S. Gallinarum) is an avian-specific pathogen responsible for fowl typhoid, a severe systemic disease with high mortality in chickens. This disease poses a substantial burden to the poultry industry, particularly in developing countries like China. However, comprehensive genome datasets on S. Gallinarum are lacking. Here, we present the most extensive S. Gallinarum genome dataset, comprising 574 well-collated samples. This dataset consists of 366 genomes sequenced in our laboratory and 208 publicly available genomes, collected from various continents over the past century. Using in silico prediction, we categorized S. Gallinarum into three distinct biovars. Regarding antimicrobial resistance, 238 strains (41.5%) carried antimicrobial resistance genes (ARGs) with a total of 635 records, while 232 strains (40.4%) exhibited multi-drug resistance. Mobile genomic elements (MGEs) serve as critical drivers for ARGs. Our dataset includes 5,636 MGEs records, with most MGEs belonging to prophages and plasmids. This dataset expands our understanding of the genomic characteristics of S. Gallinarum, providing valuable resources for future genomic studies to improve disease management., (© 2024. The Author(s).)

Frailty is a state that is closely associated with adverse health outcomes in the aging process. The frailty index (FI), which measures frailty in terms of cumulative deficits, has been widely used for frailty assessment in elderly people, and its advantage of self-reported information collection makes it applicable to a broader group of elderly people. Our study aims to simplify the Frailty Index Assessment Scale, while maintaining its reliability and accuracy, to easily and quickly assess frailty in elderly people. In this study, participants (age ≥ 65 years) from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which had 13,339, 372 and 1214 participants in 2008, 2011, and 2014, respectively, were used. The 2008 dataset was split into 80% for training and 20% for internal validation, and the data from 2011 to 2014 as external validation. In order to obtain effective predictors, we used Lasso regression, Boruta algorithm and random forest classifier score for feature selection. We used six models for predictive model construction and evaluated the models in the validation dataset. Model performance was measured by area under the curve (AUC), accuracy and F1 score. Logistic regression was found to be the best performing and most interpretable algorithm with AUC, accuracy and F1 of 0.974, 0.932 and 0.880 for the validation dataset, respectively. The AUCs for the external independent validation dataset were 0.963 and 0.977, respectively. Subgroup analysis showed that the model had good predictive power in both males and females. The predictive power was stronger among the elderly people over 80 years old, with AUC, accuracy and F1 of 0.973,0.914, and 0.893, respectively. The model also obtained good predictive power in the case of FI measured by different indicators. The model showed good robustness in the follow-up assessment of frailty status in elderly people, with the AUC remaining above 0.95 and accuracy above 0.9 over the long-term follow-up. Using machine learning techniques, we have successfully developed a simple frailty assessment prediction model based on 10 key features to shorten the frailty assessment scale with near full-scale accuracy. A user-friendly website was created to facilitate the application of this prediction model ( https://healthy-aging.shinyapps.io/Frailty&#95;Assessment/ )., (© 2024. The Author(s).)

This systematic review and network meta-analysis evaluates first-line treatment options for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases. We analyzed 24 randomized controlled trials (RCTs) involving 2,682 patients, comparing various EGFR tyrosine kinase inhibitors (TKIs) and combination therapies. Direct comparisons showed that the addition of bevacizumab or chemotherapy to first-generation (1G) EGFR-TKIs improved overall survival (OS) compared to 1G TKIs alone, with HRs of 0.704 (95% CI: 0.433-0.973) and 0.682 (95% CI: 0.464-0.899), respectively. However, third-generation (3G) TKI monotherapy did not significantly improve OS compared with 1G TKIs, with an HR of 0.855 (95% CI: 0.511-1.198). Indirect comparisons suggested that the combination of 3G TKIs with chemotherapy provided the most significant improvements in OS and progression-free survival (PFS), significantly outperforming 3G TKIs, with HRs of OS 1.69 (95% CI: 1.14-3.4) and PFS 2.13 (95% CI: 1.28-3.54). Intracranial PFS was best with 1G TKIs plus bevacizumab. Our findings suggest that 3G EGFR-TKIs in combination with chemotherapy may be the most effective strategy for patients with EGFR-mutant NSCLC and brain metastases, though further head-to-head trials are needed for validation., (© 2024. The Author(s).)

In mice, intestinal tuft cells have been described as a long-lived, postmitotic cell type. Two distinct subsets have been identified: tuft-1 and tuft-2 (ref. 1 ). By combining analysis of primary human intestinal resection material and intestinal organoids, we identify four distinct human tuft cell states, two of which overlap with their murine counterparts. We show that tuft cell development depends on the presence of Wnt ligands, and that tuft cell numbers rapidly increase on interleukin-4 (IL-4) and IL-13 exposure, as reported previously in mice 2-4 . This occurs through proliferation of pre-existing tuft cells, rather than through increased de novo generation from stem cells. Indeed, proliferative tuft cells occur in vivo both in fetal and in adult human intestine. Single mature proliferating tuft cells can form organoids that contain all intestinal epithelial cell types. Unlike stem and progenitor cells, human tuft cells survive irradiation damage and retain the ability to generate all other epithelial cell types. Accordingly, organoids engineered to lack tuft cells fail to recover from radiation-induced damage. Thus, tuft cells represent a damage-induced reserve intestinal stem cell pool in humans., (© 2024. The Author(s).)

The impact of the ketogenic diet (KD) on overall mortality and cardiovascular disease (CVD) mortality remains inconclusive.This study enrolled a total of 43,776 adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2018 to investigate the potential association between dietary ketogenic ratio (DKR) and both all-cause mortality as well as cardiovascular disease(CVD) mortality.Three models were established, and Cox proportional hazards regression analysis was employed to examine the correlation. Furthermore, a restricted cubic spline function was utilized to assess the non-linear relationship. In addition, subgroup analysis and sensitivity analysis were performed.In the adjusted Cox proportional hazards regression model, a significant inverse association was observed between DKR and all-cause mortality (HR = 0.76, 95% CI = 0.63-0.9, P = 0.003). However, no significant association with cardiovascular mortality was found (HR = 1.13; CI = 0.79-1.6; P = 0.504). Additionally, a restricted cubic spline(RCS) analysis demonstrated a linear relationship between DKR and all-cause mortality risk. In the adult population of the United States, adherence to a KD exhibits potential in reducing all-cause mortality risk while not posing an increased threat of CVD-related fatalities., (© 2024. The Author(s).)

Programmed death 1 blockade (tislelizumab) has been approved for metastatic urothelial carcinoma but not as part of neoadjuvant therapy for muscle-invasive bladder cancer (MIBC). In this multicenter single-arm trial (ChiCTR2000037670), 65 participants with cT2-4aN0M0 MIBC received neoadjuvant gemcitabine-cisplatin plus tislelizumab; 57 of them underwent radical cystectomy (RC). The primary endpoint of pathologic complete response (pCR) rate was 50.9% (29/57, 95% confidence interval (CI) 37.3-64.4%) and the pathologic downstaging (secondary endpoint) rate was 75.4% (43/57, 95% CI 62.2-85.9%) in participants undergoing RC. Genomic and transcriptomic analyses revealed three MIBC molecular subtypes (S): S1 (immune-desert) with activated cell-cycle pathway, S2 (immune-excluded) with activated transforming growth factor-β pathway and S3 (immune-inflamed) with upregulated interferon-α and interferon-γ response. Post hoc analysis showed pCR rates of 16% (3/19, S1), 77% (10/13, S2) and 80% (12/15, S3) (P = 0.006). In conclusion, neoadjuvant gemcitabine-cisplatin plus tislelizumab for MIBC was compatible with an enhanced pCR rate., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

This study aims to objectively assess the effect of three surgical approaches for posterior uterine fibroid resection: transumbilical laparoendoscopic single-site surgery (LESS), vaginal natural orifice transluminal endoscopic surgery (vNOTES) in prone position (vNOTES-P), and vNOTES in the lithotomy position (vNOTES-L). A retrospective analysis was conducted on data pertaining to all patients who underwent vNOTES and LESS for single posterior fibroids at our institution from January 2023 to July 2023. Patients were categorized into three groups based on the surgical approach: vNOTES-P group (n = 30), vNOTES-L group (n = 17), and LESS group (n = 32). Comparative analysis was performed on the demographic characteristics and perioperative outcomes among the three groups of patients. All 79 patients underwent surgery without the need for conversion to laparotomy. There were no statistically significant differences among the LESS group, vNOTES-P group, and vNOTES-L group in terms of operative time, intraoperative blood loss, and perioperative complication rates. In the vNOTES-L group, two patients required conversion to LESS during surgery. Patients had faster return of bowel function (less time to flatus) in the vNOTES group compared to the LESS group (P < 0.05). However, three cases of postoperative infection occurred in the vNOTES group, while none were reported in the LESS group. Compared to LESS, vNOTES demonstrates significant advantages in alleviating postoperative pain, shortening time to passage of flatus, speeding recovery and enhancing cosmetic outcomes. Particularly, vNOTES-P for posterior uterine fibroid resection, as an emerging surgical approach, offers certain advantages in facilitating surgical maneuverability and reducing operative time, rendering it more suitable for posterior uterine fibroid resection., (© 2024. The Author(s).)

It is crucial to precisely calculate temperature utilizing thermal models, which require the determination of thermal parameters that optimally align model outcomes with experimental data. In many instances, the refinement of these models is undertaken within space instruments. This paper introduces an optimization methodology for thermal network models, with the objective of enhancing the accuracy of temperature predictions for aerial cameras. The investigation of internal convective heat transfer coefficients for both cylindrical and planar structures provides an estimation of convective thermal parameters. Based on the identification of thermally sensitive parameters and the reliability evaluation of transient temperature data through the Monte-Carlo simulation, the genetic algorithm is employed to search for global optimal parameter values that minimize the root mean square error (RMSE) between calculated and measured node temperatures. As a result, the optimized model shows significantly improved accuracy in temperature prediction, attaining an RMSE of 1.07 ℃ and reducing the maximum relative error between predicted and experimental results from 33.8 to 3.1%. Furthermore, the flight simulation and thermal control experiments validate the robustness of the optimized model, demonstrating that discrepancies between the observed and predicted temperatures are within 2 °C after re-correcting the external convection heat transfer coefficient value., (© 2024. The Author(s).)

Background: The close relationship between bile acid (BA) metabolism and sepsis has been investigated in recent years, as knowledge of the role of the gut microbiome and metabolomics in sepsis has grown and become more comprehensive., Methods: Patients with sepsis who were admitted to the PICU of the Children's Hospital, Zhejiang University School of Medicine from January 2016 to December 2021 were enrolled in this study. Preoperative non-infectious pediatric patients undergoing elective surgeries in our hospital's department of surgery were recruited as controls during the same period. Clinical data were collected and analyzed., Results: 702 children were enrolled, comprising 538 sepsis survivors, 164 sepsis fatalities, and 269 non-infected controls. Statistical analysis revealed that total BA (TBA) increased in both the early and severe stages of pediatric sepsis. In the severe stage, TBA (OR = 2.898, 95% CI 1.946-4.315, p < 0.05) was identified as a risk factor for sepsis. A clinical model identified TBA (the cut-off value is >17.95 µmol/L) as an independent predictor of sepsis mortality with an AUC of 0.842 (95% CI 0.800-0.883), sensitivity of 54.9%, specificity of 96.6%, and HR = 7.658 (95% CI 5.575-10.520)., Conclusions: The study showed that elevated TBA was associated with a heightened risk of mortality in pediatric sepsis., Impact: Many clinical indicators show differences between children with sepsis and the control group, among which the difference in serum total bile acid levels is the most significant. During the hospitalization of the patients, the overall bile acid levels in the sepsis death group were higher and exhibited greater fluctuations compared to the survival group, with significant differences. Serum total bile acid levels can serve as effective biomarker for predicting the prognosis of children with sepsis., (© 2024. The Author(s).)

Selenium, a crucial antioxidant in the body, has been linked to all-cause and cause-specific mortality. However, the relationship between selenium and mortality in the general population remains unclear. A total of 5449 participants in the National Health and Nutrition Examination Survey (NHANES) (2003-2004, 2011-2016) were analyzed to track participant mortality until December 31, 2019. The COX proportional hazard model, Kaplan‒Meier survival analysis and restricted cubic spline regression analysis were used to investigate the associations. Subgroup analysis was conducted on the basis of age (≤ 60, > 60), sex (male, female), and smoking status (nonsmoker, former smoker, and current smoker). The second quartile was associated with lower all-cause mortality and noncardiovascular mortality (HR and 95% CI 0.61,0.45-0.83;0.59,0.42-0.83, respectively). The third quartile was associated with lower cardiovascular-related mortality (HR and 95% CI 0.49, 0.32-0.76). Elevated serum selenium concentrations were associated with lower all-cause mortality, noncardiovascular mortality (range ≤ 129.82 μg/L), and cardiovascular mortality (range ≤ 129.08 μg/L). Subgroup analysis revealed a positive correlation between the serum selenium concentration (range ≥ 129.82 μg/L) and all-cause mortality among the subgroup of current smokers (p < 0.001). This study indicates that the protective effect of the serum selenium concentration on cause-specific mortality decreases beyond a certain range in the general population, potentially increasing the risk of death among current smokers., (© 2024. The Author(s).)

Insole blanking production technology plays a vital role in contemporary machining and manufacturing industries. Existing insole blanking production models have limitations because most robots are required to accurately position the workpiece to a predetermined location, and special auxiliary equipment is usually required to ensure the precise positioning of the robot. In this paper, we present an adaptive blanking robotic system for different lighting environments, which consists of an industrial robot arm, an RGB-D camera configuration, and a customized insole blanking table and mold. We introduce an innovative edge detection framework that utilizes color features and morphological parameters optimized through particle swarm optimization (PSO) techniques to Adaptive recognition of insole edge contours. A path planning framework based on FSPS-BIT* is also introduced, which integrates the BIT* algorithm with the FSPS algorithm for efficient path planning of the robotic arm., (© 2024. The Author(s).)

Although there is an association between income status and concentration of perfluoroalkyl and polyfluoroalkyl substance (PFAS), the association remains uncertain in patients with hypertension, hyperlipidemia, and comorbidities. Data from the 2013-2016 National Health and Nutrition Examination Survey were analyzed. A total of 2665 adults were included, and the data included participants' serum PFAS (perfluorooctanoic acid [PFOA], perfluorononaic acid, perfluorodecanoic acid, perfluoroundecanoic acid, perfluorohexane sulfonic acid, and perfluorooctane sulfonic acid) levels and selected covariates. Multivariate linear regression models were used to examine the association between the ratio of family income to poverty (PIR) and individual serum PFAS concentrations in the hypertensive and/or hyperlipidemia groups after adjusting for covariates. The potential effects of sex and age on the results were explored using stratified analysis. A mediating effect model was used to explore the mediating effects of body mass index (BMI) and waist circumference on the association results. After adjusting for potential confounders, for hyperlipidemia and comorbidities (hypertension and hyperlipidemia), serum levels of multiple common PFAS increased by 0.09% (95%Confidence interval [CI] 0.02-0.15%) to 0.13% (95%CI 0.08-0.19%) and 0.10% (95%CI 0.02-0.17%) to 0.12% (95%CI 0.06-0.18%), respectively, with each 1% increase in PIR. The covariate model and stratified analyses results suggested the potential effects of different covariates such as age and sex, leading to changes in the statistical significance of the association results. BMI significantly mediated the effect of PIR on PFOA in hyperlipidemia (13%, P < 0.001). Household income in adults with hyperlipidemia and comorbidities positively correlated with serum PFAS concentration in the United States. Obesity played an indispensable mediating role in the association between economic income and PFAS concentration., (© 2024. The Author(s).)

Obesity arises from an imbalance between energy consumption and energy expenditure, and thyroid hormone levels serve as a determinant of energy expenditure. We conducted experiments at the animal and cellular levels and combined those findings with clinical data to elucidate the role of triiodothyronine (T3) in facilitating the browning of white adipose tissue (WAT) and its underlying mechanism. The results showed (i) the impaired metabolic function of local WAT and the compensatory elevation of systemic thermogenesis in obesity; (ii) T3 treatment of white adipocytes in vitro and local WAT in vivo induced a shift towards a morphologically "brown" phenotype, accompanied by upregulation of mRNA and protein expression of browning-related and mitochondrial function markers, which suggest that T3 intervention promotes the browning of WAT; and (iii) the aforementioned processes could be modulated through inhibition of the PI3K/AKT signalling pathway; however, whether T3 affects the PI3K/AKT signalling pathway by affecting insulin signalling remains to be studied and clarified. The results of our study indicate that T3 treatment promotes browning of WAT through inhibition of the PI3K/AKT signalling pathway; these findings offer novel perspectives regarding the potential of localised therapies for addressing WAT volume in individuals with obesity., (© 2024. The Author(s).)

The past two decades has witnessed a remarkable increase in the number of microbial genomes retrieved from marine systems 1,2 . However, it has remained challenging to translate this marine genomic diversity into biotechnological and biomedical applications 3,4 . Here we recovered 43,191 bacterial and archaeal genomes from publicly available marine metagenomes, encompassing a wide range of diversity with 138 distinct phyla, redefining the upper limit of marine bacterial genome size and revealing complex trade-offs between the occurrence of CRISPR-Cas systems and antibiotic resistance genes. In silico bioprospecting of these marine genomes led to the discovery of a novel CRISPR-Cas9 system, ten antimicrobial peptides, and three enzymes that degrade polyethylene terephthalate. In vitro experiments confirmed their effectiveness and efficacy. This work provides evidence that global-scale sequencing initiatives advance our understanding of how microbial diversity has evolved in the oceans and is maintained, and demonstrates how such initiatives can be sustainably exploited to advance biotechnology and biomedicine., (© 2024. The Author(s).)

Alzheimer's disease is the predominant form of dementia, and disulfidptosis is the latest reported mode of cell death that impacts various disease processes. This study used bioinformatics to analyze genes associated with disulfidptosis in Alzheimer's disease comprehensively. Based on the public datasets, the differentially expressed genes associated with disulfidptosis were identified, and immune cell infiltration was investigated through correlation analysis. Subsequently, hub genes were determined by a randomforest model. A prediction model was constructed using logistic regression. In addition, the drug-target affinity was predicted by a graph neural network model, and the results were validated by molecular docking. Five hub genes (PPEF1, NEUROD6, VIP, NUPR1, and GEM) were identified. The gene set showed significant enrichment for AD-related pathways. The logistic regression model demonstrated an AUC of 0.952, with AUC values of 0.916 and 0.864 in validated datasets. The immune infiltration analysis revealed significant heterogeneity between the Alzheimer's disease and control groups. High-affinity drugs for hub genes were identified. Through our study, a disease prediction model was constructed using potential biomarkers, and drugs targeting the genes were predicted. These results contribute to further understanding of the molecular mechanisms underlying Alzheimer's disease., (© 2024. The Author(s).)

Accurate prediction of the recovery of Disorders of Consciousness (DoC) is of paramount significance for clinicians and families. Serum total bilirubin (TBIL) formed by activation of heme oxygenase 2, is associated with incidence and prognosis of cardiovascular and cerebrovascular diseases. However, studies that based TBIL and DoC are limited. The study attempted to examine the association between serum TBIL levels and prognosis in patients with DoC. One hundred and sixty-eight patients with DoC in the Second hospital of Shandong University from June 2021 to June 2023 were recruited. The clinical characteristics and venous blood samples were collected within 24 h after admission. The diagnosis of DoC was determined by two skilled investigators employing various behavioral evaluations along the coma recovery scale-revised (CRS-R) and the investigators conducted follow-up assessments of diagnosis at 1, 3, and 6 months after admission. For statistical analysis, we categorized patients with an improvement in clinical diagnosis from study entry as having a "good outcome". In total, 139 individuals enrolled in the study. The median TBIL level was 8.2 μmol/L. Good recovery of DoC at 1, 3, and 6 months occurred in 25 (18.0%), 41 (29.5%), and 56 (40.3%) patients, respectively. After full adjustment, a significant association was found between TBIL levels and the prognosis of DoC at 1, 3, and 6 months. When TBIL levels were analyzed as categorical variables, an increasing trend in the tertiles of TBIL levels demonstrated a significant positive association with the recovery of DoC at 1, 3, and 6 months. Stratified analysis revealed that the association between serum TBIL levels and the recovery of DoC remained consistent across different sub-populations. A high serum TBIL level is associated with an improved likelihood of recovery of DoC. Additional research is required to elucidate the underlying pathophysiological causal association between TBIL levels and DoC., (© 2024. The Author(s).)

Osteosarcoma is the most common primary bone malignancy in children and young adults, and it has few treatment options. As a result, there has been little improvement in survival outcomes in the past few decades. The need for models to test novel therapies is especially great in this disease since it is both rare and does not respond to most therapies. To address this, an NCI-funded consortium has characterized and utilized a panel of patient-derived xenograft models of osteosarcoma for drug testing. The exomes, transcriptomes, and copy number landscapes of these models have been presented previously. This study now adds whole genome sequencing and reverse-phase protein array profiling data, which can be correlated with drug testing results. In addition, four additional osteosarcoma models are described for use in the research community., (© 2024. The Author(s).)

Circular RNAs (circRNAs) in controlling gene expression have been highlighted by increasing evidence, and their dysregulation has been linked to various diseases. However, the limited role of circRNAs in the adipogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) has been explored. High-throughput sequencing of circRNA was carried out on BMSCs and AD induction 7d BMSCs. Then a substantial upregulation of circNDUFA13 was detected among circRNAs in AD induction 7d BMSCs. We found that the adipogenic differentiation of BMSCs was positively linked with circNDUFA13 expression levels. Adipogenesis in BMSCs was effectively inhibited by circNDUFA13 knockdown, whereas overexpression of circNDUFA13 promoted adipogenesis. It was noted that circNDUFA13 regulated the adipogenic differentiation of BMSCs by directly interacting with the signal transducer and activator of transcription 3 (STAT3), which activates CEBPβ transcription. The in vitro model also validated the in vivo findings. our results suggest that circNDUFA13 controlled the adipogenic differentiation of BMSCs by targeting STAT3 and CEBPβ activation., (© 2024. The Author(s).)

Glioblastoma (GBM) is associated with a median survival rate of less than 15 months, necessitating innovative treatment approaches. This study investigates the safety and efficacy of the low-frequency magnetic field (LFMF) OM-100 instrument in GBM therapy. In vitro experiments utilized normal astrocyte and GBM cell lines, determining that OM-100 at 100 kHz for 72 h selectively targeted GBM cells without harming normal cells. Subsequent analyses revealed OM-100's impact on cell viability, apoptosis, migration, invasion, reactive oxide species levels, and PD-L1 expression. In vivo studies on mice with U87-induced GBM demonstrated OM-100's synergy with anti-PD-1 therapy, leading to significant tumor volume reduction and increased apoptosis. Notably, OM-100 exhibited safety in healthy mice. Overall, OM-100 could enhance anti-PD-1 immunotherapy effectiveness probably by directly inhibiting tumor proliferation and migration as well as promoting PD-L1 expression, offering a promising therapeutic strategy for GBM treatment., (© 2024. The Author(s).)

Epistasis is one of important genetic components for a quantitative trait in plant. Eshed and Zamir found negative epistatic interactions of quantitative trait loci in Tomato first. We detected that positive (negative) QTLs generated mostly negative (positive) epistatic interactions on heading date in rice, and then proposed the hypothese that QTL epistasis plays a role of homeostasis in one of our recent papers. In order to further provide additional evidence, the effects of QTLs and their epistatic effects on two quantitative traits of plant height (ph) and thousand kernel weight (tkw) were analyzed in this study. The same regularity was verified again. We detected that positive ph QTLs and negative tkw QTLs always generated reverse epistatic effects, respectively. Moreover, high-order epistatic effects were estimated on these two traits. The sum of all epistatic effects would partially neutralize the additive of constitutive QTL effects. This feature of epistsis would be the mechanism for bionts to maintain homeostasis while the obstacle for human to achieve the pyramiding breeding objectives. More evidences are still being collected to support our assumption., (© 2024. The Author(s).)

Prostate cancer, one of the most prevalent malignancies among men worldwide, is intricately linked with androgen signaling, a key driver of its pathogenesis and progression. Understanding the diverse expression patterns of androgen-responsive genes holds paramount importance in unraveling the biological intricacies of this disease and prognosticating patient outcomes. In this study, utilizing consensus clustering analysis based on the expression profiles of androgen-responsive genes, prostate cancer patients from the TCGA database were stratified into two distinct subtypes, denoted as C1 and C2. Notably, the C1 subtype demonstrates a significant upregulation of certain genes, such as CGA and HSD17B12, along with a shorter progression-free survival duration, indicating a potentially unfavorable prognosis. Further analyses elucidated the immune infiltration disparities, mutation landscapes, and gene functional pathways characteristic of each subtype. Through integrated bioinformatics approaches and machine learning techniques, key genes such as BIRC5, CENPA, and MMP11 were identified as potential therapeutic targets, providing novel insights into tailored treatment strategies. Additionally, single-cell transcriptome analysis shed light on the heterogeneous expression patterns of these genes across different cell types within the tumor microenvironment. Furthermore, virtual screening identified candidate drugs targeting the BIRC5 receptor, offering promising avenues for drug development. Collectively, these findings deepen our understanding of prostate cancer biology, paving the way for personalized therapeutic interventions and advancing the quest for more effective treatments in prostate cancer management., (© 2024. The Author(s).)

The human vagina harbours diverse microorganisms-bacteria, viruses and fungi-with profound implications for women's health. Genome-level analysis of the vaginal microbiome across multiple kingdoms remains limited. Here we utilize metagenomic sequencing data and fungal cultivation to establish the Vaginal Microbial Genome Collection (VMGC), comprising 33,804 microbial genomes spanning 786 prokaryotic species, 11 fungal species and 4,263 viral operational taxonomic units. Notably, over 25% of prokaryotic species and 85% of viral operational taxonomic units remain uncultured. This collection significantly enriches genomic diversity, especially for prevalent vaginal pathogens such as BVAB1 (an uncultured bacterial vaginosis-associated bacterium) and Amygdalobacter spp. (BVAB2 and related species). Leveraging VMGC, we characterize functional traits of prokaryotes, notably Saccharofermentanales (an underexplored yet prevalent order), along with prokaryotic and eukaryotic viruses, offering insights into their niche adaptation and potential roles in the vagina. VMGC serves as a valuable resource for studying vaginal microbiota and its impact on vaginal health., (© 2024. The Author(s).)

Tumours can obtain nutrients and oxygen required to progress and metastasize through the blood supply 1 . Inducing angiogenesis involves the sprouting of established vessel beds and their maturation into an organized network 2,3 . Here we generate a comprehensive atlas of tumour vasculature at single-cell resolution, encompassing approximately 200,000 cells from 372 donors representing 31 cancer types. Trajectory inference suggested that tumour angiogenesis was initiated from venous endothelial cells and extended towards arterial endothelial cells. As neovascularization elongates (through angiogenic stages SI, SII and SIII), APLN + tip cells at the SI stage (APLN + Tip SI ) advanced to Tip SIII cells with increased Notch signalling. Meanwhile, stalk cells, following tip cells, transitioned from high chemokine expression to elevated TEK (also known as Tie2) expression. Moreover, APLN + Tip SI cells not only were associated with disease progression and poor prognosis but also hold promise for predicting response to anti-VEGF therapy. Lymphatic endothelial cells demonstrated two distinct differentiation lineages: one responsible for lymphangiogenesis and the other involved in antigen presentation. In pericytes, endoplasmic reticulum stress was associated with the proangiogenic BASP1 + matrix-producing pericytes. Furthermore, intercellular communication analysis showed that neovascular endothelial cells could shape an immunosuppressive microenvironment conducive to angiogenesis. This study depicts the complexity of tumour vasculature and has potential clinical significance for anti-angiogenic therapy., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The medial prefrontal cortex (mPFC) sends projections to numerous brain regions and is believed to play a significant role in depression and anxiety. One of the key downstream targets of the mPFC, the lateral habenula (LHb), is essential for chronic stress (CS)-induced depressive and anxiety-like behaviors. Nevertheless, whether the mPFC-LHb pathway mediates the co-occurrence of depression and anxiety and the underlying mechanism remain incompletely understood. Here, using chemogenetics, we first determined that activation of LHb-projecting mPFC neurons is essential for the development of depressive and anxiety-like behaviors induced by CS. Subsequently, we identify the extent and distribution of LHb-projecting neurons originating from the mPFC subregion. Through circuit-specific in vivo fiber photometry, we found that Ca 2+ activity in dorsal mPFC (dmPFC) axon terminals within the LHb was increased during exposure to stressful and anxiety-related stimuli, highlighting the potential role of LHb-projecting dmPFC neurons in conveying stressful and anxiety-related information to the LHb. Finally, we observed that activation of both LHb-projecting dmPFC neurons and their postsynaptic counterparts in the LHb was necessary for CS-induced depressive and anxiety-like behaviors. Overall, this study provides multiple lines of evidence demonstrating that activation of the dmPFC-LHb pathway is a crucial neural circuitry for CS-induced depressive and anxiety-like behaviors., (© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Different delivery methods can cause variations in the composition and structure of intestinal microbiota in neonates. However, the impact of the microecological environment on host immune function requires further investigation. In this study, 75 healthy neonates were divided into two groups: vaginal delivery group (n = 36) and cesarean section group (n = 39). Fecal and peripheral blood samples were collected from the 7th to the 10th day. 16S rRNA sequencing technique was performed to investigate the gut microbiota on fecal samples. Levels of immunoglobulins and Th1 and Th2 cells in the peripheral blood of neonates were measured. The abundance of Escherichia, Bifidobacterium, and Bacteroides in neonates in the cesarean section group was significantly lower than that in the vaginal delivery group. Metabolic pathway analysis showed three significantly up-regulated metabolic pathways in the intestinal microbiota of neonates in the cesarean section group. The levels of serum IgG and IL-12p70 in the cesarean section group were lower than those in the vaginal delivery group, and the proportion of IFN-γ/IL-4 was significantly lower in the cesarean section group compared to the vaginal delivery group. The mode of delivery has potential impact on the intestinal microbiota and immune functions of neonates, potentially leading to an imbalance of Th1/Th2 cells in neonates delivered by cesarean section., (© 2024. The Author(s).)