The emerging roles of glutamine amidotransferases in metabolism and immune defense.

Glutamine amidotransferases (GATs) catalyze the synthesis of nucleotides, amino acids, glycoproteins and an enzyme cofactor, thus serving as key metabolic enzymes for cell proliferation. Carbamoyl-phosphate synthetase, Aspartate transcarbamoylase, and Dihydroorotase (CAD) is a multifunctional enzyme of the GAT family and catalyzes the first three steps of the de novo pyrimidine synthesis. Following our findings that cellular GATs are involved in immune evasion during herpesvirus infection, we discovered that CAD reprograms cellular metabolism to fuel aerobic glycolysis and nucleotide synthesis via deamidating RelA. Deamidated RelA activates the expression of key glycolytic enzymes, rather than that of the inflammatory NF-κB-responsive genes. As such, cancer cells prime RelA for deamidation via up-regulating CAD activity or accumulating RelA mutations. Interestingly, the recently emerged SARS-CoV-2 also activates CAD to couple evasion of inflammatory response to activated nucleotide synthesis. A small molecule inhibitor of CAD depletes nucleotide supply and boosts antiviral inflammatory response, thus greatly reducing SARS-CoV-2 replication. Additionally, we also found that CTP synthase 1 (CTPS1) deamidates interferon (IFN) regulatory factor 3 (IRF3) to mute IFN induction. Our previous studies have implicated phosphoribosyl formylglycinamidine synthase (PFAS) and phosphoribosyl pyrophosphate amidotransferase (PPAT) in deamidating retinoic acid-inducible gene I (RIG-I) and evading dsRNA-induced innate immune defense in herpesvirus infection. Overall, these studies have uncovered an unconventional enzymatic activity of cellular GATs in metabolism and immune defense, offering a molecular link intimately coupling these fundamental biological processes.

Tumors cells with mismatch repair deficiency induce hyperactivation of pyroptosis resistant to cell membrane damage but are more sensitive to co-treatment of IFN-γ and TNF-α to PANoptosis.

Hypermutated neoantigens in cancers with DNA mismatch repair deficiency (dMMR) are prerequisites for favorable clinical responses to immune-checkpoint blockade (ICB) therapy. However, TMB is not significantly associated with favorable prognosis from Preclinical and clinical studies. It implies that except for TMB, other mechanisms should be needed to contribute to successful cancer immunotherapy. We found that the hyperactivation of PANoptotic effective molecules in dMMR tumor cells caused cell membrane damage, induced ESCRT-mediated membrane repair, and protected tumor cells from the damage caused by Triton X-100, while DNA mismatch repair proficient (pMMR) tumor cells were sensitive to Triton X-100 mediating cell membrane damage due to the lack of ESCRT-mediated membrane repair. There was hyperactivation of GSDMD, GSDME, and p-MLKL in dMMR tumor cells. Co-treatment of IFN-γ and TNF-α induced rapid death of dMMR tumor cells by inducing PANoptosis including pyroptosis, apoptosis, and no necrosis. pMMR tumor cells had defects in the PANoptosis pathway and were resistant to co-treatment of IFN-γ and TNF-α. In conclusion, we can activate immune cells to release IFN-γ and TNF-α to overcome resistance to ICB treatment.

Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract: a randomized clinical trial.

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

AKR1C2 genetic variants mediate tobacco carcinogens metabolism involving bladder cancer susceptibility.

Tobacco carcinogens metabolism-related genes (TCMGs) could generate reactive metabolites of tobacco carcinogens, which subsequently contributed to multiple diseases. However, the association between genetic variants in TCMGs and bladder cancer susceptibility remains unclear. In this study, we derived TCMGs from metabolic pathways of polycyclic aromatic hydrocarbons and tobacco-specific nitrosamines, and then explored genetic associations between TCMGs and bladder cancer risk in two populations: a Chinese population of 580 cases and 1101 controls, and a European population of 5930 cases and 5468 controls, along with interaction and joint analyses. Expression patterns of TCMGs were sourced from Nanjing Bladder Cancer (NJBC) study and publicly available datasets. Among 43 TCMGs, we observed that rs7087341 T > A in AKR1C2 was associated with a reduced risk of bladder cancer in the Chinese population [odds ratio (OR) = 0.84, 95% confidence interval (CI) = 0.72-0.97, P = 1.86 × 10-2]. Notably, AKR1C2 rs7087341 showed an interaction effect with cigarette smoking on bladder cancer risk (Pinteraction = 5.04 × 10-3), with smokers carrying the T allele increasing the risk up to an OR of 3.96 (Ptrend < 0.001). Genetically, rs7087341 showed an allele-specific transcriptional regulation as located at DNA-sensitive regions of AKR1C2 highlighted by histone markers. Mechanistically, rs7087341 A allele decreased AKR1C2 expression, which was highly expressed in bladder tumors that enhanced metabolism of tobacco carcinogens, and thereby increased DNA adducts and reactive oxygen species formation during bladder tumorigenesis. These findings provided new insights into the genetic mechanisms underlying bladder cancer.

Interaction of immune cells with renal cancer development: Mendelian randomization (MR) study.

BACKGROUND: Renal cell carcinoma (RCC) is a prevalent and extensively immune-infiltrated malignancy of the urinary system. Immune cells play a crucial role in both the progression and therapeutic interventions targeting RCC. Nevertheless, the interplay between RCC and immune cells remains understudied, lacking substantial evidence supporting their causal relationship. METHODS: For the purpose of investigating the causal connection between RCC and immune cell characteristics, a two-way two-sample Mendelian randomization (MR) analysis was carried out in this study. The aim was to determine whether specific immune cell traits have a causal impact on the risk of RCC. In order to achieve this, publicly accessible genetic data was utilized to examine and establish the potential relationship between 731 immune cell characteristics and the likelihood of developing RCC. Additionally, various techniques were applied to verify the reliability, variability, and presence of horizontal pleiotropy in the outcomes. RESULTS: We found a bidirectional causal relationship between RCC and immune cells according to the MR analysis results. It should be noted that CD4-CD8-T cells (OR = 1.61, 95%CI = 1.02-2.55, P = 4.07 × 10-2) pose a risk for RCC, whereas BAFF-R (OR = 0.69, 95%CI = 0.53-0.89, P = 5.74 × 10-3) and CD19 (OR = 0.59, 95%CI = 1.02-2.55, P = 4.07 × 10-2) on B cells act as protective factors. Furthermore, the presence of RCC reduces the levels of B cells (OR = 1.05, 95%CI = 1.01-1.09, P = 1.19 × 10-2) and CD8 + T cells (OR = 1.04, 95%CI = 1.00-1.08, P = 2.83 × 10-2). CONCLUSIONS: Our research illustrates the intricate correlation between immune cells and RCC, presenting novel insights for the prospective safeguarding against RCC risk and the exploration of fresh therapeutic targets.

Degradation of the emerging brominated flame retardant tetrabromobisphenol S using organo-montmorillonite supported nanoscale zero-valent iron.

The widespread occurrence of emerging brominated flame retardant tetrabromobisphenol S (TBBPS) has become a major environmental concern. In this study, a nanoscale zero-valent iron (nZVI) impregnated organic montmorillonite composite (nZVI-OMT) was successfully prepared and utilized to degrade TBBPS in aqueous solution. The results show that the nZVI-OMT composite was very stable and reusable as the nZVI was well dispersed on the organic montmorillonite. Organic montmorillonite clay layers provide a strong support, facilitate well dispersion of the nZVI chains, and accelerate the overall TBBPS transformation with a degradation rate constant 5.5 times higher than that of the original nZVI. Four major intermediates, including tribromobisphenol S (tri-BBPS), dibromobisphenol S (di-BBPS), bromobisphenol S (BBPS), and bisphenol S (BPS), were detected by high-resolution mass spectrometry (HRMS), indicating sequential reductive debromination of TBBPS mediated by nZVI-OMT. The effective elimination of acute ecotoxicity predicted by toxicity analysis also suggests that the debromination process is a safe and viable option for the treatment of TBBPS. Our results have shown for the first time that TBBPS can be rapidly degraded by an nZVI-OMT composite, expanding the potential use of clay-supported nZVI composites as an environmentally friendly material for wastewater treatment and groundwater remediation.

The effects of exercise on epigenetic modifications: focus on DNA methylation, histone modifications and non-coding RNAs.

Physical activity on a regular basis has been shown to bolster the overall wellness of an individual; research is now revealing that these changes are accompanied by epigenetic modifications. Regular exercise has been proven to make intervention plans more successful and prolong adherence to them. When it comes to epigenetic changes, there are four primary components. This includes changes to the DNA, histones, expression of particular non-coding RNAs and DNA methylation. External triggers, such as physical activity, can lead to modifications in the epigenetic components, resulting in changes in the transcription process. This report pays attention to the current knowledge that pertains to the epigenetic alterations that occur after exercise, the genes affected and the resulting characteristics.

Comparison of Laminectomy with Fusion and Laminoplasty Treating Multilevel Cervical Spondylotic Myelopathy: A Single-Center Retrospective Study.

OBJECTIVE: Comparing laminectomy with fusion (LF) and laminoplasty (LP) for treating multilevel cervical spondylotic myelopathy (MCSM) and comparative analysis of neck pain and sagittal cervical parameters. METHODS: This single-center study retrospectively analyzed MCSM patients treated with LF or LP in our department between June 2018 and January 2023, with at least a 12-month follow-up. T-tests were used to identify operation time, hemoglobin, hospital stay, modified Japanese Orthopaedic Association (mJOA) score, C2-C7 Cobb angle, C2-C7 sagittal vertical axis, T1 slope, cervical range of motion (cROM), and C4/5 anterior and posterior spinal canal diameter (A-P diameter) and area. Nonparametric tests were used to identify visual analog scale (VAS) score (assessing neck pain). Pearson correlation analyses were used to identify the neck pain. RESULTS: Of all 67 patients (LF: 24, LP: 43), both groups' mJOA scores significantly improved (P < 0.001). The VAS scores had both significantly decreased, with the LF group exhibiting a more marked reduction (LF: P < 0.001, LP: P = 0.037). Both groups' C4/5 A-P diameters and areas increased significantly (P < 0.001). The cROM had both significantly decreased, with the LF group exhibiting a greater reduction. At the last follow-up, the LF group's T1 slope and C2-C7 Cobb angle considerably increased, and pain VAS scores substantially correlated with the C2-C7 Cobb angle (R = -0.451, P < 0.001). CONCLUSIONS: LF and LP were efficacious for MCSM. LF relieved neck pain better but caused greater reduction in cervical mobility. Cervical lordosis improvement was significantly correlated with neck pain alleviation.

ZmSMR10 Increases the Level of Endoreplication of Plants through Its Interactions with ZmPCNA2 and ZmCSN5B.

As a plant-specific endoreplication regulator, the SIAMESE-RELATED (SMR) family (a cyclin-dependent kinase inhibitor) plays an important role in plant growth and development and resistance to stress. Although the genes of the maize (Zea mays) SMR family have been studied extensively, the ZmSMR10 (Zm00001eb231280) gene has not been reported. In this study, the function of this gene was characterized by overexpression and silencing. Compared with the control, the transgenic plants exhibited the phenotypes of early maturation, dwarfing, and drought resistance. Expression of the protein in prokaryotes demonstrates that ZmSMR10 is a small protein, and the results of subcellular localization suggest that it travels functionally in the nucleus. Unlike ZmSMR4, yeast two-hybrid experiments demonstrated that ZmSMR10 does not interact strongly with with some cell cycle protein-dependent protein kinase (CDK) family members ZmCDKA;1/ZmCDKA;3/ZmCDKB1;1. Instead, it interacts strongly with ZmPCNA2 and ZmCSN5B. Based on these results, we concluded that ZmSMR10 is involved in the regulation of endoreplication through the interaction of ZmPCNA2 and ZmCSN5B. These findings provide a theoretical basis to understand the mechanism of the regulation of endoreplication and improve the yield of maize through the use of molecular techniques.

Evaluation of antioxidant, antidiabetic and antiobesity potential of phenylpropanoids (PPs): Structure-activity relationship and insight into action mechanisms against dual digestive enzymes by comprehensive technologies.

Phenylpropanoids (PPs), a group of natural compounds characterized by one or more C6-C3 units, have exhibited considerable potential in addressing metabolic disease. However, the comprehensive investigation on the relationship of compound structures and involved activity, along with the action mechanisms on the drug target is absent. This study aimed to evaluate the antioxidant and inhibitory activities of 16 PPs against two digestive enzymes, including α-glucosidase and pancreatic lipase, explore the structure-activity relationships and elucidate the mechanisms underlying enzyme inhibition. The findings revealed the similarities in the rules governing antioxidant and enzyme inhibitory activities of PPs. Specifically, the introduction of hydroxyl groups generally exerted positive effects on the activities, while the further methoxylation and glycosylation were observed to be unfavorable. Among the studied PPs, esculetin exhibited the most potent antioxidant activity and dual enzymes inhibition potential, displaying IC50 values of 0.017 and 0.0428 mM for DPPH and ABTS radicals scavenging, as well as 1.36 and 6.67 mM for α-glucosidase and lipase inhibition, respectively. Quantification analysis indicated esculetin bound on both α-glucosidase and lipase successfully by a mixed-type mode. Further analyses by UV-Vis, FT-IR, fluorescence spectra, surface hydrophobicity, SEM, and molecular docking elucidated that esculetin could bind on the catalytic or non-catalytic sites of enzymes to form complex, impacting the normal spatial conformation for hydrolyzing the substrate, thus exhibiting the weakened activity. These results may shed light on the utilization value of natural PPs for the management of hyperglycemia and hyperlipemia, and afford the theoretical basis for designing drugs with stronger inhibition against the dual digestive enzymes based on esculetin.

Bioresponsive nanocomplex integrating cancer-associated fibroblast deactivation and immunogenic chemotherapy for rebuilding immune-excluded tumors.

Cancer-associated fibroblasts (CAFs) play a crucial role in creating an immunosuppressive environment and remodeling the extracellular matrix within tumors, leading to chemotherapy resistance and limited immune cell infiltration. To address these challenges, integrating CAFs deactivation into immunogenic chemotherapy may represent a promising approach to the reversal of immune-excluded tumor. We developed a tumor-targeted nanomedicine called the glutathione-responsive nanocomplex (GNC). The GNC co-loaded dasatinib, a CAF inhibitor, and paclitaxel, a chemotherapeutic agent, to deactivate CAFs and enhance the effects of immunogenic chemotherapy. Due to the modification with hyaluronic acid, the GNC preferentially accumulated in the tumor periphery and responsively released cargos, mitigating the tumor stroma as well as overcoming chemoresistance. Moreover, GNC treatment exhibited remarkable immunostimulatory efficacy, including CD8+ T cell expansion and PD-L1 downregulation, facilitating immune checkpoint blockade therapy. In summary, the integration of CAF deactivation and immunogenic chemotherapy using the GNC nanoplatform holds promise for rebuilding immune-excluded tumors.

Revealing Novel Genes Related to Parkinson's Disease Pathogenesis and Establishing an associated Model.

Parkinson's disease (PD) represents a multifaceted neurological disorder whose genetic underpinnings warrant comprehensive investigation. This study focuses on identifying genes integral to PD pathogenesis and evaluating their diagnostic potential. Initially, we screened for differentially expressed genes (DEGs) between PD and control brain tissues within a dataset comprising larger number of specimens. Subsequently, these DEGs were subjected to weighted gene co-expression network analysis (WGCNA) to discern relevant gene modules. Notably, the yellow module exhibited a significant correlation with PD pathogenesis. Hence, we conducted a detailed examination of the yellow module genes using a cytoscope-based approach to construct a protein-protein interaction (PPI) network, which facilitated the identification of central hub genes implicated in PD pathogenesis. Employing two machine learning techniques, including XGBoost and LASSO algorithms, along with logistic regression analysis, we refined our search to three pertinent hub genes: FOXO3, HIST2H2BE, and HDAC1, all of which demonstrated a substantial association with PD pathogenesis. To corroborate our findings, we analyzed two PD blood datasets and clinical plasma samples, confirming the elevated expression levels of these genes in PD patients. The association of the genes with PD, as reflected by the area under the curve (AUC) values for FOXO3, HIST2H2BE, and HDAC1, were moderate for each gene. Collectively, this research substantiates the heightened expression of FOXO3, HIST2H2BE, and HDAC1 in both PD brain and blood samples, underscoring their pivotal contribution to the pathogenesis of PD.

Exploring the potential of the sit-to-stand test for self-assessment of physical condition in advanced knee osteoarthritis patients using computer vision.

Introduction: Knee osteoarthritis (KOA) is a prevalent condition often associated with a decline in patients' physical function. Objective self-assessment of physical conditions poses challenges for many advanced KOA patients. To address this, we explored the potential of a computer vision method to facilitate home-based physical function self-assessments. Methods: We developed and validated a simple at-home artificial intelligence approach to recognize joint stiffness levels and physical function in individuals with advanced KOA. One hundred and four knee osteoarthritis (KOA) patients were enrolled, and we employed the WOMAC score to evaluate their physical function and joint stiffness. Subsequently, patients independently recorded videos of five sit-to-stand tests in a home setting. Leveraging the AlphaPose and VideoPose algorithms, we extracted time-series data from these videos, capturing three-dimensional spatiotemporal information reflecting changes in key joint angles over time. To deepen our study, we conducted a quantitative analysis using the discrete wavelet transform (DWT), resulting in two wavelet coefficients: the approximation coefficients (cA) and the detail coefficients (cD). Results: Our analysis specifically focused on four crucial joint angles: "the right hip," "right knee," "left hip," and "left knee." Qualitative analysis revealed distinctions in the time-series data related to functional limitations and stiffness among patients with varying levels of KOA. In quantitative analysis, we observed variations in the cA among advanced KOA patients with different levels of physical function and joint stiffness. Furthermore, there were no significant differences in the cD between advanced KOA patients, demonstrating different levels of physical function and joint stiffness. It suggests that the primary difference in overall movement patterns lies in the varying degrees of joint stiffness and physical function among advanced KOA patients. Discussion: Our method, designed to be low-cost and user-friendly, effectively captures spatiotemporal information distinctions among advanced KOA patients with varying stiffness levels and functional limitations utilizing smartphones. This study provides compelling evidence for the potential of our approach in enabling self-assessment of physical condition in individuals with advanced knee osteoarthritis.

Polyvinylpyrrolidone-Coated Cubic Hollow Nanocages of PdPt3 and PdIr3 as Highly Efficient Self-Cascade Uricase/Peroxidase Mimics.

Uricase-catalyzed uric acid (UA) degradation has been applied for hyperuricemia therapy, but this medication is limited by H2O2 accumulation, which can cause oxidative stress of cells, resulting in many other health issues. Herein, we report a robust cubic hollow nanocage (HNC) system based on polyvinylpyrrolidone-coated PdPt3 and PdIr3 to serve as highly efficient self-cascade uricase/peroxidase mimics to achieve the desired dual catalysis for both UA degradation and H2O2 elimination. These HNCs have hollow cubic shape with average wall thickness of 1.5 nm, providing desired synergy to enhance catalyst's activity and stability. Density functional theory calculations suggest the PdIr3 HNC surface tend to promote OH*/O* desorption for better peroxidase-like catalysis, while the PdPt3 HNC surface accelerates the UA oxidation by facilitating O2-to-H2O2 conversion. The dual catalysis power demonstrated by these HNCs in cell studies suggests their great potential as a new type of nanozyme for treating hyperuricemia.

Influence of Imbibition Fracturing Fluid on the Original Water and Methane Occurrence in Actual Coalbed Methane Reservoirs Using the Integrated Device of Displacement and Low-Field Nuclear Magnetic Resonance.

The original water in the coal rock pores plays a controlling role in the occurrence of gas. Furthermore, during the hydraulic fracturing process, pressurized fracturing fluid with a higher pressure than the original pore pressure in the fractures drives the fracturing fluid to infiltrate into the coal rock pores, thereby altering the occurrence pattern of gas and water in the original pores. However, due to the limitations of the indoor simulation device, a systematic conclusion on the impact of the original pore water and imbibition fracturing fluid on coalbed methane reservoirs has not yet been formed. In this paper, an integrated device combining displacement and low-field nuclear magnetic resonance was employed using underground cylindrical coal rock samples as experimental subjects. Experimental conditions were maintained at a temperature of 30 °C, a confining pressure of 23 MPa, and an approximate reservoir pressure of 15 MPa. The initial water saturation levels were altered to 0, 27.88, and 42.18% to replicate the conditions of a coalbed methane reservoir at a depth of approximately 1200 m. Fracturing fluid with a pressure of 18 MPa was injected into the experimental samples to simulate the impact of the fracturing fluid on the original reservoir during hydraulic fracturing. This allowed for a realistic assessment of the influence of initial water saturation and fracturing fluid absorption on the coalbed methane recovery rate in the reservoir. The experimental results indicate that the imbibition process promotes the desorption of adsorbed gas, and the desorption amount of adsorbed gas increases with the increase in the original water saturation. This will result in an increase in the gas pressure within the pore system. The conditions of this experiment, in comparison to the previous ones, more closely resemble real reservoir conditions. This enables a realistic assessment of how the presence of the original water content and the absorption of the fracturing fluid affect gas occurrence within the reservoir.

ADORA3: A Key Player in the Pathogenesis of Intracranial Aneurysms and a Potential Diagnostic Biomarker.

BACKGROUND: The effects of genes on the development of intracranial aneurysms (IAs) remain to be elucidated, and reliable blood biomarkers for diagnosing IAs are yet to be established. This study aimed to identify genes associated with IAs pathogenesis and explore their diagnostic value by analyzing IAs datasets, conducting vascular smooth muscle cells (VSMC) experiments, and performing blood detection. METHODS: IAs datasets were collected and the differentially expressed genes were analyzed. The selected genes were validated in external datasets. Autophagy was induced in VSMC and the effect of selected genes was determined. The diagnostic value of selected gene on the IAs were explored using area under curve (AUC) analysis using IAs plasma samples. RESULTS: Analysis of 61 samples (32 controls and 29 IAs tissues) revealed a significant increase in expression of ADORA3 compared with normal tissues using empirical Bayes methods of "limma" package; this was further validated by two external datasets. Additionally, induction of autophagy in VSMC lead to upregulation of ADORA3. Conversely, silencing ADORA3 suppressed VSMC proliferation and autophagy. Furthermore, analysis of an IAs blood sample dataset and clinical plasma samples demonstrated increased ADORA3 expression in patients with IA compared with normal subjects. The diagnostic value of blood ADORA3 expression in IAs was moderate when analyzing clinical samples (AUC: 0.756). Combining ADORA3 with IL2RB or CCR7 further enhanced the diagnostic ability for IAs, with the AUC value over 0.83. CONCLUSIONS: High expression of ADORA3 is associated with IAs pathogenesis, likely through its promotion of VSMC autophagy. Furthermore, blood ADORA3 levels have the potential to serve as an auxiliary diagnostic biomarker for IAs.

De novo Phased Genome Assembly, Annotation and Population Genotyping of Alectoris Chukar.

The Alectoris Chukar (chukar) is the most geographically widespread partridge species in the world, demonstrating exceptional adaptability to diverse ecological environments. However, the scarcity of genetic resources for chukar has hindered research into its adaptive evolution and molecular breeding. In this study, we have sequenced and assembled a high-quality, phased chukar genome that consists of 31 pairs of relatively complete diploid chromosomes. Our BUSCO analysis reported a high completeness score of 96.8% and 96.5%, with respect to universal single-copy orthologs and a low duplication rate (0.3% and 0.5%) for two assemblies. Through resequencing and population genomic analyses of six subspecies, we have curated invaluable genotype data that underscores the adaptive evolution of chukar in response to both arid and high-altitude environments. These data will significantly contribute to research on how chukars adaptively evolve to cope with desertification and alpine climates.

Comparison of anterior cervical diskectomy with fusion (ACDF) and laminoplasty treating multilevel cervical spondylotic myelopathy with developmental canal stenosis: a retrospective study.

PURPOSE: To evaluate clinical effectiveness and radiologic results of anterior cervical diskectomy with fusion (ACDF) comparing with laminoplasty (LP) in treating multilevel cervical spondylotic myelopathy (MCSM) with developmental canal stenosis (DCS). METHODS: This was a retrospective analysis of 41 patients who had MCSM with DCS treated with ACDF or LP from December 2018 to April 2023. Patients were split into ACDF and LP groups for comparison, and patients were further separated into subgroups based on whether or not a reserving canal space was present. The operation time, hemoglobin, hospital stay, modified Japanese Orthopaedic Association (mJOA) score, and visual analog scale (VAS) score were used to assess clinical efficacy. The C2-C7 Cobb angle, C2-C7 sagittal vertical axis, T1 slope, and cervical range of motion were applied to evaluate imaging changes. RESULTS: Of the 41 patients, 19 received ACDF, and 22 received LP. At the final follow-up, both groups' mJOA scores significantly improved, and the intercomparison showed no differences; the VAS score was much lower in the ACDF group but remained unchanged in the LP group. At the final follow-up, the C2-C7 Cobb angle and T1 slope had significantly increased in the ACDF group, while the LP group showed no change; the cervical range of motion had significantly decreased in both groups, with the ACDF group exhibiting a more marked reduction. Within the ACDF subgroup, there was no postoperative symptom improvement for those with reserving space, whereas there was postoperative symptom resolution for those with non-reserving space; however, postoperative symptom in the LP subgroup was resolved. CONCLUSIONS: Both ACDF and LP were efficacious for MCSM patients with DCS. While ACDF could improve cervical lordosis and alleviate neck pain more effectively, it can also result in cervical sagittal imbalance and decreased mobility. Furthermore, the recovery from LP was superior to that from ACDF for patients with reserving space. In contrast, the recovery from both decompression techniques was comparable for individuals in non-reserving space.

An analysis of differences in Carbapenem-resistant Enterobacterales in different regions: a multicenter cross-sectional study.

OBJECTIVE: This study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE. METHODS: This was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis. RESULTS: This study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P < 0.05). However, there was no significant difference in the distribution of carbapenemase strains or enzymes between the two groups. CONCLUSIONS: The detection rate of CRE was significantly greater in provincial capital hospitals than in nonprovincial capital hospitals. The source of the patients, invasive procedures, and use of advanced antibiotics may account for the differences. Carbapenem-resistant Klebsiella pneumoniae (CR-KPN) was the most prevalent strain. Klebsiella pneumoniae carbapenemase (KPC) was the predominant carbapenemase enzyme. The distributions of carbapenemase strains and enzymes were similar in different regions.

Advances and challenges of first-line immunotherapy for non-small cell lung cancer: A review.

The current use of immune checkpoint inhibitors (ICIs) for the treatment of lung cancer has dramatically changed the clinical strategy for metastatic non-small cell lung cancer (mNSCLC). As a result of great achievements in clinical trials, 6 programmed death-1 inhibitors (sintilimab, camrelizumab, tislelizumab, pembrolizumab, cemiplimab, and nivolumab), 2 programmed death-ligand 1 inhibitors (sugemalimab and atezolizumab), and 1 cytotoxic T lymphocyte-associated antigen-4 inhibitor (ipilimumab) have been approved as first-line treatment for mNSCLC by the US Food and Drug Administration. Recently, research on ICIs has shifted from a large number of second-line to first-line settings in clinical trials. Results from first-line trials have shown that almost all driver-negative mNSCLC are treated with ICIs and significantly prolong patient survival; however, the low response rate and adverse reactions to immunotherapy remain to be addressed. Here, we summarize the use of ICIs, including monotherapy and combination therapy, in the first-line treatment of mNSCLC in recent years and discuss the low response rate and adverse reactions of ICIs as well as the challenges and expectations for the first-line treatment of mNSCLC in the future.