Dissecting the dynamic cellular transcriptional atlas of adult teleost testis development throughout the annual reproductive cycle.

Teleost testis development during the annual cycle involves dramatic changes in cellular compositions and molecular events. In this study, the testicular cells derived from adult black rockfish at distinct stages - regressed, regenerating and differentiating - were meticulously dissected via single-cell transcriptome sequencing. A continuous developmental trajectory of spermatogenic cells, from spermatogonia to spermatids, was delineated, elucidating the molecular events involved in spermatogenesis. Subsequently, the dynamic regulation of gene expression associated with spermatogonia proliferation and differentiation was observed across spermatogonia subgroups and developmental stages. A bioenergetic transition from glycolysis to mitochondrial respiration of spermatogonia during the annual developmental cycle was demonstrated, and a deeper level of heterogeneity and molecular characteristics was revealed by re-clustering analysis. Additionally, the developmental trajectory of Sertoli cells was delineated, alongside the divergence of Leydig cells and macrophages. Moreover, the interaction network between testicular micro-environment somatic cells and spermatogenic cells was established. Overall, our study provides detailed information on both germ and somatic cells within teleost testes during the annual reproductive cycle, which lays the foundation for spermatogenesis regulation and germplasm preservation of endangered species.

Deciphering dynamic interactions between spermatozoa and the ovarian microenvironment through integrated multi-omics approaches in viviparous Sebastes schlegelii.

The ovarian microenvironment plays a crucial role in ensuring the reproductive success of viviparous teleosts. However, the molecular mechanism underlying the interaction between spermatozoa and the ovarian microenvironment has remained elusive. This study aimed to contribute to a better understanding of this process in black rockfish (Sebastes schlegelii) using integrated multi-omics approaches. The results demonstrated significant upregulation of ovarian complement-related proteins and pattern recognition receptors, along with remodeling of glycans on the surface of spermatozoa at the early spermatozoa-storage stage (1 month after mating). As spermatozoa were stored over time, ovarian complement proteins were progressively repressed by tryptophan and hippurate, indicating a remarkable adaptation of spermatozoa to the ovarian microenvironment. Before fertilization, a notable upregulation of cellular junction proteins was observed. The study revealed that spermatozoa bind to ZPB2a protein through GSTM3 and that ZPB2a promotes spermatozoa survival and movement in a GSTM3-dependent manner. These findings shed light on a key mechanism that influences the dynamics of spermatozoa in the female reproductive tract, providing valuable insights into the molecular networks regulating spermatozoa adaptation and survival in species with internal fertilization.

Superresolution imaging of antibiotic-induced structural disruption of bacteria enabled by photochromic glycomicelles.

Bacterial evolution, particularly in hospital settings, is leading to an increase in multidrug resistance. Understanding the basis for this resistance is critical as it can drive discovery of new antibiotics while allowing the clinical use of known antibiotics to be optimized. Here, we report a photoactive chemical probe for superresolution microscopy that allows for the in situ probing of antibiotic-induced structural disruption of bacteria. Conjugation between a spiropyran (SP) and galactose via click chemistry produces an amphiphilic photochromic glycoprobe, which self-assembles into glycomicelles in water. The hydrophobic inner core of the glycomicelles allows encapsulation of antibiotics. Photoirradiation then serves to convert the SP to the corresponding merocyanine (MR) form. This results in micellar disassembly allowing for release of the antibiotic in an on-demand fashion. The glycomicelles of this study adhere selectively to the surface of a Gram-negative bacterium through multivalent sugar-lectin interaction. Antibiotic release from the glycomicelles then induces membrane collapse. This dynamic process can be imaged in situ by superresolution spectroscopy owing to the "fluorescence blinking" of the SP/MR photochromic pair. This research provides a high-precision imaging tool that may be used to visualize how antibiotics disrupt the structural integrity of bacteria in real time.

Exercise and osteoimmunology in bone remodeling.

Bones can form the scaffolding of the body, support the organism, coordinate somatic movements, and control mineral homeostasis and hematopoiesis. The immune system plays immune supervisory, defensive, and regulatory roles in the organism, which mainly consists of immune organs (spleen, bone marrow, tonsils, lymph nodes, etc.), immune cells (granulocytes, platelets, lymphocytes, etc.), and immune molecules (immune factors, interferons, interleukins, tumor necrosis factors, etc.). Bone and the immune system have long been considered two distinct fields of study, and the bone marrow, as a shared microenvironment between the bone and the immune system, closely links the two. Osteoimmunology organically combines bone and the immune system, elucidates the role of the immune system in bone, and creatively emphasizes its interdisciplinary characteristics and the function of immune cells and factors in maintaining bone homeostasis, providing new perspectives for skeletal-related field research. In recent years, bone immunology has gradually become a hot spot in the study of bone-related diseases. As a new branch of immunology, bone immunology emphasizes that the immune system can directly or indirectly affect bones through the RANKL/RANK/OPG signaling pathway, IL family, TNF-α, TGF-ß, and IFN-γ. These effects are of great significance for understanding inflammatory bone loss caused by various autoimmune or infectious diseases. In addition, as an external environment that plays an important role in immunity and bone, this study pays attention to the role of exercise-mediated bone immunity in bone reconstruction.

Fluorescent probes for targeting the Golgi apparatus: design strategies and applications.

The Golgi apparatus is an essential organelle constructed by the stacking of flattened vesicles, that is widely distributed in eukaryotic cells and is dynamically regulated during cell cycles. It is a central station which is responsible for collecting, processing, sorting, transporting, and secreting some important proteins/enzymes from the endoplasmic reticulum to intra- and extra-cellular destinations. Golgi-specific fluorescent probes provide powerful non-invasive tools for the real-time and in situ visualization of the temporal and spatial fluctuations of bioactive species. Over recent years, more and more Golgi-targeting probes have been developed, which are essential for the evaluation of diseases including cancer. However, when compared with systems that target other important organelles (e.g. lysosomes and mitochondria), Golgi-targeting strategies are still in their infancy, therefore it is important to develop more Golgi-targeting probes. This review systematically summarizes the currently reported Golgi-specific fluorescent probes, and highlights the design strategies, mechanisms, and biological uses of these probes, we have structured the review based on the different targeting groups. In addition, we highlight the future challenges and opportunities in the development of Golgi-specific imaging agents and therapeutic systems.

Biomimetic Design of 3D Fe3O4/V-EVOH Fiber-Based Self-Floating Composite Aerogel to Enhance Solar Steam Generation Performance.

An interfacial solar steam generation evaporator for seawater desalination has attracted extensive interest in recent years. Nevertheless, challenges still remain in relatively low evaporation rate, unsatisfactory energy conversion efficiency, and salt accumulation. Herein, we have demonstrated a biomimetic bilayer composite aerogel consisting of bottom hydrophilic and vertically aligned EVOH channels and an upper hydrophobic conical Fe3O4 array. Thanks to the design merits, the 3D Fe3O4/V-EVOH evaporator exhibits a high evaporation rate of ∼2.446 kg m-2 h-1 and an impressive solar energy conversion efficiency of ∼165.5% under 1 sun illumination, which is superior to those of state-of-the-art evaporators reported so far. Moreover, the asymmetrical wettability not only allows the evaporator to self-float on the water but also facilitates the salt ion diffusion in the channels; thus, the evaporator shows no salt crystals on its surface and only a 6% decrease in evaporation performance even after the salt concentration increases from 0 to 10.0 wt %.

Targeting OXCT1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via CD8+ T cells in hepatocellular carcinoma.

BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme 3-oxoacid CoA-transferase 1 (OXCT1). We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in HCC in vivo, we conducted multiplex immunohistochemistry experiments on human HCC specimens. To explore the role of OXCT1 in mouse HCC tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4me3 level in the Arg1 promoter. In addition, pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreased CD8+ T-cell exhaustion and slower tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in patients with HCC. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping hepatocellular carcinoma progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for hepatocellular carcinoma treatment. Herein, we found that the ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages (TAMs) and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. Pharmacological targeting or genetic downregulation of OXCT1 in TAMs enhances antitumor immunity and slows tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer.

In Situ Photogenerated Radicals of Hydroxyl Substituted Pyrene-Based Triphenylamines with Enhanced Transport and Free Doping/Post-Oxidation for Efficient Perovskite Solar Cells.

The high-performance hole transporting material (HTM) is one of the most important components for the perovskite solar cells (PSCs) in promoting power conversion efficiency (PCE). However, the low conductivity of HTMs and their additional requirements for doping and post-oxidation greatly limits the device performance. In this work, three novel pyrene-based derivatives containing methoxy-substituted triphenylamines units (PyTPA, PyTPA-OH and PyTPA-2OH) are designed and synthesized, where different numbers of hydroxyl groups are connected at the 2- or 2,7-positions of the pyrene core. These hydroxyl groups at the 2- or 2,7-positions of pyrene play a significantly role to enhance the intermolecular interactions that are able to generate in situ radicals with the assistance of visible light irradiation, resulting in enhanced hole transferring ability, as well as an enhanced conductivity and suppressed recombination. These pyrene-core based HTMs exhibit excellent performance in PSCs, which possess a higher PCE than those control devices using the traditional spiro-OMeTAD as the HTM. The best performance can be found in the devices with PyTPA-2OH. It has an average PCE of 23.44% (PCEmax = 23.50%), which is the highest PCE among the reported PSCs with the pyrene-core based HTMs up to date. This research offers a novel avenue to design a dopant-free HTM by the combination of the pyrene core, methoxy triphenylamines, and hydroxy groups.

A leaf age-dependent light use efficiency model for remote sensing the gross primary productivity seasonality over pantropical evergreen broadleaved forests.

Tropical and subtropical evergreen broadleaved forests (TEFs) contribute more than one-third of terrestrial gross primary productivity (GPP). However, the continental-scale leaf phenology-photosynthesis nexus over TEFs is still poorly understood to date. This knowledge gap hinders most light use efficiency (LUE) models from accurately simulating the GPP seasonality in TEFs. Leaf age is the crucial plant trait to link the dynamics of leaf phenology with GPP seasonality. Thus, here we incorporated the seasonal leaf area index of different leaf age cohorts into a widely used LUE model (i.e., EC-LUE) and proposed a novel leaf age-dependent LUE model (denoted as LA-LUE model). At the site level, the LA-LUE model (average R2 = .59, average root-mean-square error [RMSE] = 1.23 gC m-2 day-1) performs better than the EC-LUE model in simulating the GPP seasonality across the nine TEFs sites (average R2 = .18; average RMSE = 1.87 gC m-2 day-1). At the continental scale, the monthly GPP estimates from the LA-LUE model are consistent with FLUXCOM GPP data (R2 = .80; average RMSE = 1.74 gC m-2 day-1), and satellite-based GPP data retrieved from the global Orbiting Carbon Observatory-2 (OCO-2) based solar-induced chlorophyll fluorescence (SIF) product (GOSIF) (R2 = .64; average RMSE = 1.90 gC m-2 day-1) and the reconstructed TROPOspheric Monitoring Instrument SIF dataset using machine learning algorithms (RTSIF) (R2 = .78; average RMSE = 1.88 gC m-2 day-1). Typically, the estimated monthly GPP not only successfully represents the unimodal GPP seasonality near the Tropics of Cancer and Capricorn, but also captures well the bimodal GPP seasonality near the Equator. Overall, this study for the first time integrates the leaf age information into the satellite-based LUE model and provides a feasible implementation for mapping the continental-scale GPP seasonality over the entire TEFs.

Synthesis of 2,3-Dialkyl-5-hydroxybenzofurans via a One-pot, Three-step Reaction Sequence of 2-Monosubstituted 1,3-Diketones and 1,4-Benzoquinones.

An economical one-pot, three-step reaction sequence of readily available 2-monosubstituted 1,3-diketones and 1,4-benzoquinones has been explored for the facile access of 2,3-dialkyl-5-hydroxybenzofurans. By using cheap K2CO3 and conc. HCl as the reaction promoters, the reaction occurs smoothly via sequential Michael addition, aromatization, retro-Claisen, deacylation, hemiketalization, and dehydration processes under mild conditions in a practical manner. Additionally, an interesting phenomenon was observed during the derivatization studies, where the dihydroquinoline was converted into tetrahydroquinoline and quinoline products, respectively, via a disproportionation process.

Development and external validation of MRI-based RAS mutation status prediction model for liver metastases of colorectal cancer.

BACKGROUND: The mutation status of rat sarcoma viral oncogene homolog (RAS) has prognostic significance and serves as a key predictive biomarker for the effectiveness of antiepidermal growth factor receptor (EGFR) therapy. However, there remains a lack of effective models for predicting RAS mutation status in colorectal liver metastases (CRLMs). This study aimed to construct and validate a diagnostic model for predicting RAS mutation status among patients undergoing hepatic resection for CRLMs. METHODS: A diagnostic multivariate prediction model was developed and validated in patients with CRLMs who had undergone hepatectomy between 2014 and 2020. Patients from Institution A were assigned to the model development group (i.e., Development Cohort), while patients from Institutions B and C were assigned to the external validation groups (i.e., Validation Cohort_1 and Validation Cohort_2). The presence of CRLMs was determined by examination of surgical specimens. RAS mutation status was determined by genetic testing. The final predictors, identified by a group of oncologists and radiologists, included several key clinical, demographic, and radiographic characteristics derived from magnetic resonance images. Multiple imputation was performed to estimate the values of missing non-outcome data. A penalized logistic regression model using the adaptive least absolute shrinkage and selection operator penalty was implemented to select appropriate variables for the development of the model. A single nomogram was constructed from the model. The performance of the prediction model, discrimination, and calibration were estimated and reported by the area under the receiver operating characteristic curve (AUC) and calibration plots. Internal validation with a bootstrapping procedure and external validation of the nomogram were assessed. Finally, decision curve analyses were used to characterize the clinical outcomes of the Development and Validation Cohorts. RESULTS: A total of 173 patients were enrolled in this study between January 2014 and May 2020. Of the 173 patients, 117 patients from Institution A were assigned to the Model Development group, while 56 patients (33 from Institution B and 23 from Institution C) were assigned to the Model Validation groups. Forty-six (39.3%) patients harbored RAS mutations in the Development Cohort compared to 14 (42.4%) in Validation Cohort_1 and 8 (34.8%) in Validation Cohort_2. The final model contained the following predictor variables: time of occurrence of CRLMs, location of primary lesion, type of intratumoral necrosis, and early enhancement of liver parenchyma. The diagnostic model based on clinical and MRI data demonstrated satisfactory predictive performance in distinguishing between mutated and wild-type RAS, with AUCs of 0.742 (95% confidence interval [CI]: 0.651─0.834), 0.741 (95% CI: 0.649─0.836), 0.703 (95% CI: 0.514─0.892), and 0.708 (95% CI: 0.452─0.964) in the Development Cohort, bootstrapping internal validation, external Validation Cohort_1 and Validation Cohort_2, respectively. The Hosmer-Lemeshow goodness-of-fit values for the Development Cohort, Validation Cohort_1 and Validation Cohort_2 were 2.868 (p = 0.942), 4.616 (p = 0.465), and 6.297 (p = 0.391), respectively. CONCLUSIONS: Integrating clinical, demographic, and radiographic modalities with a magnetic resonance imaging-based approach may accurately predict the RAS mutation status of CRLMs, thereby aiding in triage and possibly reducing the time taken to perform diagnostic and life-saving procedures. Our diagnostic multivariate prediction model may serve as a foundation for prognostic stratification and therapeutic decision-making.

Biological Utility of Fluorinated Compounds: from Materials Design to Molecular Imaging, Therapeutics and Environmental Remediation.

The applications of fluorinated molecules in bioengineering and nanotechnology are expanding rapidly with the controlled introduction of fluorine being broadly studied due to the unique properties of C-F bonds. This review will focus on the design and utility of C-F containing materials in imaging, therapeutics, and environmental applications with a central theme being the importance of controlling fluorine-fluorine interactions and understanding how such interactions impact biological behavior. Low natural abundance of fluorine is shown to provide sensitivity and background advantages for imaging and detection of a variety of diseases with 19F magnetic resonance imaging, 18F positron emission tomography and ultrasound discussed as illustrative examples. The presence of C-F bonds can also be used to tailor membrane permeability and pharmacokinetic properties of drugs and delivery agents for enhanced cell uptake and therapeutics. A key message of this review is that while the promise of C-F containing materials is significant, a subset of highly fluorinated compounds such as per- and polyfluoroalkyl substances (PFAS), have been identified as posing a potential risk to human health. The unique properties of the C-F bond and the significant potential for fluorine-fluorine interactions in PFAS structures necessitate the development of new strategies for facile and efficient environmental removal and remediation. Recent progress in the development of fluorine-containing compounds as molecular imaging and therapeutic agents will be reviewed and their design features contrasted with environmental and health risks for PFAS systems. Finally, present challenges and future directions in the exploitation of the biological aspects of fluorinated systems will be described.

The characteristics of the novel bacterial strain Pseudomonas mendocina isolated from freshwater aquaculture farm.

Plastic contamination can cause damage to the water quality of fish farm ponds, and also affect the quality of the final product. Pseudomonas mendocina was found to biodegrade plastics. Our study aimed to investigate the physicochemical properties and drug resistance of P. mendocina isolated from local freshwater aquaculture farms. Firstly, the strain was isolated from aquaculture water and then identified by matrix-assisted flight mass spectrometry and 16S rDNA sequencing. Then, biochemical and antibiotic resistance analyses were performed, and a microbial high-throughput growth detector was used to assess the growth of the strain. Finally, PCR and proteomics analyses were conducted to determine drug-resistance-related genes/proteins. According to the results of the spectrum diagram and sequencing, the isolated bacteria were identified as P. mendocina, and were positive for reactions of ADH, MTE, LAC, MNE, FRU, CIT, MLT, ONPG, and ACE. P. mendocina was sensitive to most of the antibiotics, and its resistance to CHL, MIN, and TIC/CLA was intermediate. Additionally, gyrB was the resistance gene, and mdtA2, mdtA3, mdaB, and emrK1 were closely related to the drug resistance of P. mendocina. Our results show the biochemical properties of P. mendocina in isolated aquaculture water, and provide a new perspective for P. mendocina involved in the biological removal of plastics or microplastics in freshwater aquaculture farms.

A nomogram model for predicting intramyocardial hemorrhage post-PCI based on SYNTAX score and clinical features.

OBJECTIVE: The aim of this study is to develop a nomogram model for predicting the occurrence of intramyocardial hemorrhage (IMH) in patients with Acute Myocardial Infarction (AMI) following Percutaneous Coronary Intervention (PCI). The model is constructed utilizing clinical data and the SYNTAX Score (SS), and its predictive value is thoroughly evaluated. METHODS: A retrospective study was conducted, including 216 patients with AMI who underwent Cardiac Magnetic Resonance (CMR) within a week post-PCI. Clinical data were collected for all patients, and their SS were calculated based on coronary angiography results. Based on the presence or absence of IMH as indicated by CMR, patients were categorized into two groups: the IMH group (109 patients) and the non-IMH group (107 patients). The patients were randomly divided in a 7:3 ratio into a training set (151 patients) and a validation set (65 patients). A nomogram model was constructed using univariate and multivariate logistic regression analyses. The predictive capability of the model was assessed using Receiver Operating Characteristic (ROC) curve analysis, comparing the predictive value based on the area under the ROC curve (AUC). RESULTS: In the training set, IMH post-PCI was observed in 78 AMI patients on CMR, while 73 did not show IMH. Variables with a significance level of P < 0.05 were screened using univariate logistic regression analysis. Twelve indicators were selected for multivariate logistic regression analysis: heart rate, diastolic blood pressure, ST segment elevation on electrocardiogram, culprit vessel, symptom onset to reperfusion time, C-reactive protein, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, creatine kinase-MB, high-sensitivity troponin T (HS-TnT), and SYNTAX Score. Based on multivariate logistic regression results, two independent predictive factors were identified: HS-TnT (Odds Ratio [OR] = 1.61, 95% Confidence Interval [CI]: 1.21-2.25, P = 0.003) and SS (OR = 2.54, 95% CI: 1.42-4.90, P = 0.003). Consequently, a nomogram model was constructed based on these findings. The AUC of the nomogram model in the training set was 0.893 (95% CI: 0.840-0.946), and in the validation set, it was 0.910 (95% CI: 0.823-0.970). Good consistency and accuracy of the model were demonstrated by calibration and decision curve analysis. CONCLUSION: The nomogram model, constructed utilizing HS-TnT and SS, demonstrates accurate predictive capability for the risk of IMH post-PCI in patients with AMI. This model offers significant guidance and theoretical support for the clinical diagnosis and treatment of these patients.

A chromosome-level genome assembly for the desert scorpion Mesobuthus przewalskii from Asian drylands.

Scorpions are an ancient and charismatic group of arthropods with medical importance, but a high-quality reference genome for this group is still lacking. Here we perform whole-genome sequencing of Mesobuthus przewalskii, a desert scorpion endemic to the Taklimakan Desert. We combine PacBio HiFi sequencing and Hi-C chromosome conformation capturing to generate chromosomal-level, haplotype-resolved, and fully annotated genome assembly for this medically important scorpion. The assembly consists of two haplotypes (1052.01 Mbp and 1055.19 Mbp, respectively) reaching chromosome-level contiguity and >98% BUSCO completeness. Sequences were anchored in 13 chromosomes with a contig N50 of 34.44 Mbp and scaffold N50 of 81.43 Mbp. Several key genome features and the mitochondrial genome assembly were also provided. This genome represents the fifth but the most complete assembly for the order Scorpiones.

Genetic architecture in neonatal intensive care unit patients with congenital heart defects: a retrospective study from the China Neonatal Genomes Project.

BACKGROUND: Congenital heart defects (CHDs) are the most common type of birth defects. The genetic aetiology of CHD is complex and incompletely understood. The overall distribution of genetic causes in patients with CHD from neonatal intensive care units (NICUs) needs to be studied. METHODS: CHD cases were extracted from the China Neonatal Genomes Project (2016-2021). Next-generation sequencing results and medical records were retrospectively evaluated to note the frequency of genetic diagnosis and the respective patient outcomes. RESULTS: In total, 1795 patients were included. The human phenotype ontology term of atrial septal defect, patent ductus arteriosus and ventricular septal defect account for a large portion of the CHD subtype. Co-occurring extracardiac anomalies were observed in 35.1% of patients. 269 of the cases received genetic diagnoses that could explain the phenotype of CHDs, including 172 copy number variations and 97 pathogenic variants. The detection rate of trio-whole-exome sequencing was higher than clinical exome sequencing (21.8% vs 14.5%, p<0.05). Further follow-up analysis showed the genetic diagnostic rate was higher in the deceased group than in the surviving group (29.0% vs 11.9%, p<0.05). CONCLUSION: This is the largest cohort study to explore the genetic spectrum of patients with CHD in the NICU in China. Our findings may benefit future work on improving genetic screening and counselling for NICU patients with CHD.

Exploration of Diagnostic Deubiquitinating Enzymes in Endometriosis and Its Immune Infiltration.

The mechanism involved in the pathogenesis of endometriosis is poorly understood. The purpose of this study is to identify key deubiquitinating enzymes (DUBs) for endometriosis diagnosis and elucidate the possible mechanism, offering novel insights for noninvasive early diagnosis and treatment. Four gene expression datasets were employed from the Gene Expression Omnibus to identify differentially expressed genes (DEGs) between endometriosis and normal controls. GO and KEGG pathways were performed for enrichment analysis. Calibration curves, ROC, DCA, and clinical impact curves verified the clinical usefulness of the nomogram model. In addition, the ssGSEA method was conducted to estimate 23 types of immune cells. A specific DUB gene signature was constructed with Lasso regression, univariate logistic regression, and SVM analysis. RT-qPCR validated the expression of biomarkers. A total of 85 endometriosis-related DUBs were identified in the eutopic endometrium. Among them, 20 DUBs were found to be correlated with the severity of endometriosis. A diagnostic risk model based on five DUB-related genes (USP21, USP48, ZRANB1, COPS5, and EIF3F) was developed using lasso-cox regression analysis. The nomogram model exhibited a strong predictive ability to diagnose endometriosis. KEGG analysis revealed that ubiquitin-mediated proteolysis was activated in patients suffering from severe symptoms. Analysis of immune cell infiltration revealed a positive correlation between USP21 and multiple immune cells in the eutopic endometrium. However, EIF3F showed an opposite relationship. Dysregulation of DUBs was related to the immune microenvironment in endometriosis. Results from RT-qPCR confirmed the expression of DEGs in clinical samples. In summary, the diagnostic model for endometriosis constructed using five differentially expressed DUB genes demonstrates strong diagnostic capability, suggesting that these genes could serve as potential candidate biomarkers and therapeutic targets.

Comparison of the Effects of Ureteroscopy with Holmium Laser Lithotripsy and Extracorporeal Shock Wave Lithotripsy in the Treatment of Ureteral Calculi.

Objective: This study aims to compare the efficacy of ureteroscopy with holmium laser lithotripsy and extracorporeal shock wave lithotripsy (ESWL) in treating ureteral calculus (UC). Methods: We enrolled 86 patients with UC treated in our urology department from November 2020 to November 2022. Group A (n=43) underwent ureteroscopic holmium laser lithotripsy, while Group B (n=43) received ESWL. We recorded treatment duration, post-treatment hematuria duration, and post-treatment stone clearance rates. Renal function and stress response were assessed before and 3 days after treatment. Post-treatment complications were documented, and patient quality of life was evaluated using the SF-36 health questionnaire. Results: Group A exhibited significantly shorter treatment and post-treatment hematuria durations compared to Group B (P < .05). In stones >1 cm, group A demonstrated a higher clearance rate (P < .05). Post-treatment, Group A showed improved renal function and lower stress response (P < .05). The incidence of post-treatment complications did not differ significantly between groups (P > .05), but SF-36 scores were higher in Group A (P < .05). Conclusions: Ureteroscopy with holmium laser lithotripsy proves effective in UC treatment, contributing to a shortened recovery period and enhanced patient quality of life.

Assessment of HMGB1 and NLRP3 in Determining Efficacy and Prognosis in Hemodialysis Patients with Chronic Renal Failure.

Background: In chronic renal failure (CRF), evaluating treatment efficacy and predicting prognosis is crucial. High Mobility Group Protein B1 (HMGB1) and Nod-like Receptor Protein 3 (NLRP3) were chosen as key markers in chronic renal failure to elucidate their roles in treatment response and prognosis, offering potential insights for enhancing patient care strategies. Objective: This study aims to analyze the clinical impact of HMGB1 and NLRP3 in patients with CRF undergoing hemodialysis. We investigated the relationship between HMGB1 and NLRP3 levels, the efficacy of hemodialysis treatment, and the prognosis for one-year survival. Methods: An observational study was conducted. The study included 62 CRF patients (Group A) admitted to our hospital from May 2020 to August 2022, and 40 healthy individuals undergoing routine medical check-ups during the same period (Group B). We compared the levels of HMGB1 and NLRP3 in the peripheral blood of Group A and Group B. Furthermore, we assessed changes in HMGB1 and NLRP3 before and after hemodialysis in CRF patients to evaluate treatment efficacy and prognostic indicators for one-year survival. Results: Group A exhibited significantly lower HMGB1 expression and higher NLRP3 expression compared to Group B. ROC curve analysis demonstrated that the areas under the curve (AUCs) for HMGB1 and NLRP3 in predicting effective hemodialysis for CRF were 0.884 (95% CI: 0.800-0.968) and 0.721 (95% CI: 0.594-0.848), respectively. The AUCs for HMGB1 and NLRP3 in predicting death from CRF were 0.885 (95% CI: 0.804-0.967) and 0.935 (95% CI: 0.875-0.995), respectively. Conclusions: Both HMGB1 and NLRP3 levels serve as valuable indicators for assessing the efficacy and prognosis of CRF patients undergoing hemodialysis.

Effect of multimodal opioid-sparing anesthesia on intestinal function and prognosis of elderly patients with hypertension after colorectal cancer surgery.

PURPOSE: Colorectal cancer (CRC) surgery in elderly patients with hypertension poses challenges due to potential complications and prolonged recovery. This study aimed to assess the impact of multimodal opioid-sparing anesthesia on intestinal function and prognosis of elderly hypertension patients undergoing CRC surgery. METHODS: A total of 80 elderly hypertension patients who underwent open surgery for CRC in the People's Hospital of Xinjiang Uygur Autonomous Region from October 2020 to October 2022 were selected and randomly divided into two group (A and B, n = 40) through the random number table method. Group A received multimodal opioid-sparing anesthesia, defined as low-dose opioid general anesthesia combined with a transversus abdominis plane block, incision infiltration with local anesthetics, and postoperative analgesia via a patient-controlled analgesia (PCA) pump, with the remifentanil dose set at one-third (± 10%) of the conventional group's dose. Group B received conventional opioid anesthesia, involving standard general anesthesia maintained with remifentanil at 0.4-0.5 µg/(kg·min), incision infiltration with local anesthetics, and postoperative PCA. Primary outcomes included mean arterial pressure (MAP) and heart rate (HR), changes in albumin, C-reactive protein (CRP) and white blood cell (WBC), indicators of intestinal function recovery (the recovery time of bowel sounds, the first exhaust time, the first defecation time and the feeding recovery time), and visual analogue scale (VAS) pain scores. Second outcomes included postoperative complications and total hospital stays. RESULTS: After excluding 8 patients, 72 were included in the final analysis. Compared with patients in the B group, patients in the A group exhibited shorter recovery time of bowel sounds, first exhaust time and feeding recovery time (P < 0.05), higher levels of postoperative albumin, and lower levels of CRP and WBC (P < 0.05). Moreover, the incidence of nausea and vomiting was lower and the total hospital stays were fewer in the A group than in the B group (P < 0.05). CONCLUSION: Multimodal opioid-sparing anesthesia contributes to rapid recovery of postoperative intestinal function and reduction of postoperative adverse reactions. Therefore, it is safe and feasible to apply multimodal opioid-sparing anesthesia to elderly hypertension patients receiving open surgery for CRC.