Development and validation of a nomogram for predicting pulmonary complications in elderly patients undergoing thoracic surgery.

BACKGROUND: Postoperative pulmonary complications (PPCs) remain a prevalent concern among elderly patients undergoing surgery, with a notably higher incidence observed in elderly patients undergoing thoracic surgery. This study aimed to develop a nomogram to predict the risk of PPCs in this population. METHODS: A total of 2963 elderly patients who underwent thoracic surgery were enrolled and randomly divided into a training cohort (80%, n = 2369) or a validation cohort (20%, n = 593). Univariate and multivariate logistic regression analyses were conducted to identify risk factors for PPCs, and a nomogram was developed based on the findings from the training cohort. The validation cohort was used to validate the model. The predictive accuracy of the model was evaluated by receiver operating characteristic (ROC) curve, area under ROC (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: A total of 918 (31.0%) patients reported PPCs. Nine independent risk factors for PPCs were identified: preoperative presence of chronic obstructive pulmonary disease (COPD), elevated leukocyte count, higher partial pressure of arterial carbon dioxide (PaCO2) level, surgical site, thoracotomy, intraoperative hypotension, blood loss > 100 mL, surgery duration > 180 min, and malignant tumor. The AUC value for the training cohort was 0.739 (95% CI: 0.719-0.762), and it was 0.703 for the validation cohort (95% CI: 0.657-0.749). The P-values for the Hosmer-Lemeshow test were 0.633 and 0.144 for the training and validation cohorts, respectively, indicating a notable calibration curve fit. The DCA curve indicated that the nomogram could be applied clinically if the risk threshold was between 12% and 84%, which was found to be between 8% and 82% in the validation cohort. CONCLUSION: This study highlighted the pressing need for early detection of PPCs in elderly patients undergoing thoracic surgery. The nomogram exhibited promising predictive efficacy for PPCs in elderly patients undergoing thoracic surgery, enabling the identification of high-risk patients and consequently aiding in the implementation of preventive interventions.

The Values of PDK1 and LDH Levels in Patients with Sepsis and Septic Shock: A Prospective Observational Study.

Background: Metabolic changing is the significant host stress response during sepsis, but there is increasing evidence that uncontrolled metabolic reprogramming is a contributing factor to sepsis. Nevertheless, its association with outcome in patients with sepsis has been poorly investigated. As the key enzyme of metabolic reprogramming, the clinical value of PDK1 and LDH in patients with sepsis will be investigated in this study. Methods: We collected serum from 167 ICU patients within 24 hours of admission for a single-center prospective observational study. The levels of PDK1 and LDH were detected by enzyme-linked adsorption method. Pearson or Spearman coefficient for correlation analysis between PDK1, LDH and clinical indicators. Areas under the ROC curves for evaluation of mortality prediction. Kaplan-Meier survival curve analysis was performed, and Cox proportional hazards model was performed to determine the risk factors for 28-day mortality. Results: The PDK1/LDH in the septic shock group was statistically different between both the sepsis group and ICU control group, and had good correlation with ScvO2 and lactate. In predicting 28-day mortality in patients with sepsis, the best AUC was observed for PDK1/LDH, and was higher than the AUC for PDK1, lactate, and SOFA. Additionally, patients with lower PDK1/LDH had markerablely higher 28-day mortality. The multivariate Cox proportional hazards model revealed that PDK1/LDH < 0.1808 were the independent risk factors for 28-day mortality in sepsis. Conclusion: The level of PDK1/LDH at admission was markedly decreased in patients with septic shock, which can serve as a novel independent prognostic biomarker for predicting mortality.

Multi-omics integration analysis reveals the role of N6-methyladenosine in lncRNA translation during glioma stem cell differentiation.

Glioblastoma is one of the most lethal brain diseases in humans. Although recent studies have shown reciprocal interactions between N6-methyladenosine (m6A) modifications and long noncoding RNAs (lncRNAs) in gliomagenesis and malignant progression, the mechanism of m6A-mediated lncRNA translational regulation in glioblastoma remains unclear. Herein, we profiled the transcriptomes, translatomes, and epitranscriptomics of glioma stem cells and differentiated glioma cells to investigate the role of m6A in lncRNA translation comprehensively. We found that lncRNAs with numerous m6A peaks exhibit reduced translation efficiency. Transcript-level expression analysis demonstrates an enrichment of m6A around short open reading frames (sORFs) of translatable lncRNA transcripts. Further comparison analysis of m6A modifications in different RNA regions indicates that m6A peaks downstream of sORFs inhibit lncRNA translation more than those upstream. Observations in glioma-associated lncRNAs H19, LINC00467, and GAS5 further confirm the negative effect of m6A methylation on lncRNA translation. Overall, these findings elucidate the dynamic profiles of the m6A methylome and enhance the understanding of the complexity of lncRNA translational regulation.

Temporal and spatial convergence: the major depressive disorder burden attributed to intimate partner violence against women.

Background: There is a strong causal relationship between intimate partner violence and major depressive disorder, which partly endangers women's safety across the life course and potentially affects the development of future generations. The international community has placed a high priority on addressing the intimate partner violence and the resulting burden of mental illness. Data collection needs to be captured across the temporal trend and spatial distribution for major depressive disorder attributed to intimate partner violence, to reflect the priorities and expectations of survivors.Method: This research obtained raw disability-adjusted life years (DALYs) information for major depressive disorder attributed to intimate partner violence from the Global Burden of Disease 2019. Using estimated annual percentage change and two-way fixed effects models, a secondary spatio-temporal analysis of the age-standardized DALYs rate from 1990 to 2019 was performed.Results: In 2019, DALYs lost among women experiencing major depressive disorder (3.16 million) accounted for 37.18% of the DALYs lost worldwide due to intimate partner violence. The age-standardized DALYs rate of major depressive disorder attributed to intimate partner violence was 108.57 per 100,000. The highest was concentrated in the menopausal transition (45-55), with 133.61 per 100,000, and particularly distributed in Uganda (429.31 per 100,000). The early reproductive period (15-19) showed the increasing age-standardized DALYs rate from 1990 to 2019, which was mainly driven by Malaysia (3.73% per year). Furthermore, countries with higher initial levels of the age-standardized DALYs rate were growing faster than those with lower levels.Conclusions: The burden of major depressive disorder attributed to intimate partner violence showed biological and spatial inequality, prioritized intervention should be targeted at vulnerable stage women in their early reproductive period and menopausal transition. Combined political, socio-cultural as well as medical measures to prevent violence and treat major depressive disorder should be implemented and developed.

Vulnerability to different biological stages of the burden of experiencing intimate partner violence leading to major depressive disorder in women. Women in their reproductive years and during the menopausal transition were more vulnerable.Intimate partner violence-induced depressive disorder is trending younger, with an increasing burden on girls aged 15­19 over the past 30 years.The burden of major depressive disorder attributed to intimate partner violence varies increasingly across countries.

Herbal medicines for SOD1G93A mice of amyotrophic lateral sclerosis: preclinical evidence and possible immunologic mechanism.

Currently, there is no cure or effective treatment for Amyotrophic Lateral Sclerosis (ALS). The mechanisms underlying ALS remain unclear, with immunological factors potentially playing a significant role. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), a systematic review of preclinical studies was conducted, searching seven databases including PubMed, covering literature from the inception of the databases to April 10, 2024. Methodological quality of the included literature was assessed using CAMARADES, while the risk of bias in the included studies was evaluated using SYRCLE's ROB tool. Review Manager 5.4.1 statistical software was used for meta-analysis of the outcomes. The scoping review followed the Joanna Briggs Institute Methodological Guidelines and reporting of this review followed the PRISMA-extension for Scoping Reviews (PRISMA -ScR) checklist to explore the immunological mechanisms of Herbal Medicine (HM) in treating ALS. This systematic review and meta-analysis involved 18 studies with a total of 443 animals. The studies scored between 4 to 8 for methodological quality and 3 to 7 for risk of bias, both summing up to 10.A remarkable effects of HM in ALS mice, including onset time(Standardized Mean Difference(SMD): 1.75, 95% Confidence Interval(CI) (1.14 ~ 2.36), Z = 5.60, P < 0.01), survival time(SMD = 1.42, 95% CI (0.79 ~ 2.04), Z = 4.44, P < 0.01), stride length(SMD=1.90, 95% CI (1.21 to 2.59), Z = 5.39, P < 0.01) and duration time (Mean Difference(MD)=6.79, 95% CI [-0.28, 13.87], Z=1.88, P =0.06), showing HM's certain efficiency in treating ALS mice. The scoping review ultimately included 35 articles for review. HMs may treat ALS through mechanisms such as combating oxidative stress, excitatory amino acid toxicity, and calcium cytotoxicity, understanding and exploring the mechanisms will bring hope to patients. Individual herbs and their formulations within HM address ALS through a variety of immune pathways, including safeguarding the blood-brain barrier, countering neuroinflammation, impeding complement system activation, mitigating natural killer cell toxicity, and regulating T cell-mediated immune pathways. The preclinical evidence supports the utilization of HM as a conventional treatment for ALS mice. Growing evidence indicates that HM may potentially delay neurological degeneration in ALS by activating diverse signaling pathways, especially immune pathways.

In Situ Forming Asymmetric Gel Polymer Electrolyte Enhances the Performance of High-Voltage Lithium Metal Batteries.

With the rapid evolution of electric vehicle technology, concerns regarding range anxiety and safety have become increasingly pronounced. Battery systems with high specific energy and enhanced security, featuring ternary cathodes paired with lithium (Li) metal anodes, are poised to emerge as next-generation electrochemical devices. However, the asymmetric configuration of the battery structure, characterized by the robust oxidative behavior of the ternary cathodes juxtaposed with the vigorous reductive activity of the Li metal anodes, imposes elevated requisites for the electrolytes. Herein, a well-designed gel polymer electrolyte with asymmetric structure was successfully prepared based on the Ritter reaction of cyanoethyl poly(vinyl alcohol) (PVA-CN) and cationic ring-opening polymerization of s-Trioxane. With the aid of the sieving effect of separator, the in situ asymmetric gel polymer electrolyte has good compatibility with both the high-voltage cathodes and Li anodes. The amide groups generated by PVA-CN after the Ritter reaction and additional cyano groups can tolerate high voltages up to 5.1 V, matching with ternary cathodes without any challenges. The functional amide and cyano groups participate in the formation of the cathode electrolyte interface and stabilize the cathode structure. Meanwhile, the in situ formed ether-based polyformaldehyde electrolyte is beneficial for promoting uniform Li deposition on anode surfaces. Li-Li symmetric cells demonstrate sustained stability over 2000 h of cycling at a current density of 1 mA cm-2 for 1 mAh cm-2. Furthermore, the capacity retention rate of Li(Ni0.6Mn0.2Co0.2)O2-Li cells with 0.5 C cycling after 300 cycles is 92.2%, demonstrating excellent cycle stability. The electrolyte preparation strategy provides a strategy for the progress of high-performance electrolytes and promotes the rapid development of high-energy-density Li metal batteries.

Protective Effects and Mechanisms of HuDiChangRong Capsule on TNBS-Induced Ulcerative Colitis in Mice.

ETHNOPHARMACOLOGICAL RELEVANCE: UC, characterized by chronic inflammation primarily affecting the colon and rectum, follows a protracted relapsing course marked by inflammation and an abundance of free radicals at the onset. Hudichangrong Capsule (HDCRC), a traditional Chinese medicinal formula, has long been employed in the treatment of UC and chronic bacillary dysentery, exhibiting positive therapeutic outcomes and a high rate of cure in clinical practice. AIM OF THE STUDY: The precise mechanism underlying its efficacy for UC remains elusive. Our objective was to investigate the anti-inflammatory effect and underlying mechanisms of HDCRC on TNBS-induced UC. MATERIALS AND METHODS: Here, we introduced HDCRC and induced UC using TNBS. SPF BALB/c mice were divided into 6 groups as follows: control group, colitis model group, colitis treated with sulfasalazine (400mg/kg) group, and colitis treated with HDCRC (156, 312, and 624mg/kg) groups. To assess the effects of HDCRC on colitis, we measured body weight loss, disease activity index (DAI), colon length, tissue damage, degree of inflammation, immune capacity, and oxidative stress. Additionally, we evaluated the TLR-4/MyD88 pathway and its downstream signaling using immunohistochemistry, real-time qPCR, and Western blot. Network pharmacology was used for main target prediction. 16s rRNA was employed for gut microbiota detechtion and UPLC-QTOF-MS was used for its and its metabonomics. RESULTS: HDCRC significantly slowed weight loss, ameliorated DAI, restored colon length, alleviated TNBS-induced tissue damage. It exerted the therapeutic effects via reducing oxidative stress, restoring immune balance, normalizing the inflammatory mediator levels and restoring intestinal barrier integrity. Furthermore, HDCRC mainly alleviate UC via suppressing the TLR-4/MyD88 pathway and its downstream signaling. The key components of the downstream pathway, including TLR-4, MyD88, NF-κB p65, ERK, p-JNK, p38, p-JAK1, JAK1, p-STAT3, and STAT3, were improved, thereby ameliorating the TNBS-induced injury. In addition, HDCRC could regulate gut microbiota (eg. Erysipelaloclostridium,etc.) and its metabonomics (eg. Vitamin B6 metabolism) in UC mice. CONCLUSIONS: In conclusion, HDCRC exerts a protective effect against TNBS-induced UC in mice by inhibiting the TLR-4/MyD88 pathway and its downstream signaling, and partially JAK1/STAT3, suppressing oxidative stress, regulating immunity, restoring intestinal barrier integrity, and regulating gut microbiota and its metabonomics.

Analysis of factors related to radiation-induced oral mucositis in patients with head and neck tumors undergoing radiotherapy.

OBJECTIVE: To explore the risk factors of radiation-induced oral mucositis (RIOM) in patients with head and neck tumors undergoing radiotherapy. METHODS: A retrospective collection was conducted on patients with head and neck tumors who underwent radiotherapy and chemotherapy in our hospital from April 1, 2015 to April 1, 2019. They were divided into an incidence group (n = 48) and a non-incidence group (n = 76) based on whether RIOM occurred, and relevant data was collected for comparison. RESULTS: There were statistically significant differences between the two groups of patients in terms of tumor type, smoking percentage, education level percentage, tumor stage, oral mucosal inflammation stage, radiotherapy dose, mucosal protectants, and oral hygiene condition(P < 0.05); The regression analysis results showed that smoking (OR=1.274, 95 % CI: 1.095-2.007), high-dose radiotherapy (OR=1.223, 95 % CI: 1.098-2.077), and poor oral hygiene (OR=1.367, 95 % CI: 1.024-2.890) were risk factors for RIOM. CONCLUSION: Smoking, high-dose radiotherapy, and poor oral hygiene were risk factors for RIOM in head and neck patients after radiotherapy and chemotherapy.

CircJPH1 regulates the NF-κB/HERC5 axis to promote the malignant progression of esophageal squamous cell carcinoma through binding to XRCC6.

Esophageal squamous cell carcinoma (ESCC) is a prevalent and malignant cancer with an unknown pathogenesis and a poor prognosis; therefore, the identification of effective biomarkers and targets is crucial for its diagnosis and treatment. Circular (circ)RNAs are prominent functional biomarkers and therapeutic targets in various diseases, particularly cancer, due to their widespread expression and regulatory mechanisms. Our study aimed to investigate the therapeutic potential of circRNA for ESCC. We identified Hsa_circ_0137111 for the first time as one of the most significantly up-regulated genes in ESCC sequencing and named it circJPH1. The results of the present study demonstrated an enhanced expression of circJPH1 in ESCC tissues. Moreover, circJPH1-knockdown could significantly inhibit the proliferation, migration, and invasion of ESCC cells, while its overexpression promoted these characteristics. In addition, circJPH1 promoted ESCC cell tumor growth in vivo. For the first time, mass spectrometry and RNA pull-down analysis revealed the interaction of X-ray repair cross-complementary 6 (XRCC6) protein with circJPH1, thereby promoting its nuclear translocation. Consequently, the nuclear factor kappa-B (NF-κB) signaling pathway was activated, leading to an up-regulation of HECT and RLD domain containing E3 ubiquitin protein ligase 5 (HERC5), thereby promoting ESCC progression. In summary, the present study elucidated the regulatory impact of circJPH1 on ESCC progression in vitro and in vivo, thereby indicating its potential role in ESCC treatment.

Helicobacter pylori induces GBA1 demethylation to inhibit ferroptosis in gastric cancer.

This research investigates potential therapeutic targets for gastric cancer, focusing on ferroptosis-related genes. Gastric cancer is known for its lower survival rates, necessitating new treatment strategies. This study employed Mendelian randomization to identify ferroptosis-related genes and methylation sites in gastric cancer, examining correlations between Helicobacter pylori infection, GBA1 gene expression, and promoter methylation with single-cell datasets and the TCGA-STAD database. We used Helicobacter pylori-infected gastric cancer cell models and used next-generation sequencing to monitor methylation changes pre- and post-infection. GBA1 expression levels were assessed via qRT-PCR and Western blot both before and after infection. The effect of Helicobacter pylori on GC cell proliferation was analyzed using CCK-8 and EdU assays after knocking down the GBA1 gene. The association between Helicobacter pylori infection and ferroptosis, including its reversibility after GBA1 knockdown, was evaluated using FerrOrange, GSH, MDA, and C11-BODIPY assays. Mass spectrometry measured the impact of Helicobacter pylori and GBA1 knockdown on lipid metabolism. An in vivo subcutaneous tumor-bearing model was also established to confirm these findings. Mendelian randomization analysis revealed that high GBA1 expression and reduced methylation levels of its promoter are risk factors for gastric cancer. Single-cell sequencing and TCGA-STAD datasets indicated a positive correlation between Helicobacter pylori infection and GBA1 expression, with a concurrent negative correlation between GBA1 promoter methylation and GBA1 expression. In gastric cancer cell lines, Helicobacter pylori infection was observed to enhance GBA1 expression and decrease methylation levels at its promoter. Additionally, Helicobacter pylori promoted GC cell proliferation, an effect mitigated by knocking down GBA1. Infection also reduced lipid peroxidation, increased glutathione levels, and impeded ferroptosis in GC cells; however, these effects were reversed following GBA1 knockdown. Changes in sphingolipid metabolism induced by I were detected in GC cell lines. In vivo experiments using a subcutaneous tumor-bearing model demonstrated that Helicobacter pylori infection fosters tumorigenesis in GC cells. Our study demonstrates that Helicobacter pylori infection triggers demethylation and upregulation of GBA1, subsequently inhibiting ferroptosis in gastric cancer cells. These findings suggest that targeting the GBA1 pathway may offer a novel therapeutic approach for managing gastric cancer.

Refining the Rab7-V1G1 axis to mitigate iron deposition: Protective effects of quercetin in alcoholic liver disease.

Iron overload is a common feature of alcoholic liver disease (ALD) and contributes significantly to disease progression. Quercetin, a flavonoid known for its iron-chelating properties, has emerged as a potential protective compound against ALD. However, research on quercetin's regulatory effects on iron levels in ALD is limited. To address this, we conducted a study using male C57BL/6J mice were subjected to a Lieber De Carli liquid diet containing ethanol (28% energy replacement) with or without quercetin supplementation (100 mg/kg.BW) for 12 weeks. Additionally, HepG2 cells, after transfection with the CYP2E1 plasmid, were incubated with ethanol and/or quercetin. Our findings revealed that ethanol consumption led to iron overload in both hepatocytes and lysosomes. Interestingly, despite the increase in iron levels, cells exhibited impaired iron utilization, disrupting normal iron metabolism. Further analysis identified a potential mechanism involving the Rab7-V1G1 (V-ATPase subunit) axis. Inhibition of V-ATPase by Concanamycin A caused elevated ROS levels, impaired lysosomal and mitochondria function, and increased expression of HIF1α and IRP2. Ultimately, this disruption in cellular processes led to iron overload and mitochondrial iron deficiency. Quercetin supplementation mitigated ethanol-induced hepatocyte damage by reversing iron overload through modulation of the Rab7-V1G1 axis and improving the interaction between lysosomes and mitochondria. In conclusion, this study elucidates a novel pathophysiological mechanism by which quercetin protects against ALD through its regulation of iron homeostasis.

Association of hidradenitis suppurativa (HS) with waist circumference: A bidirectional two-sample Mendelian randomization study of HS with metabolic syndrome.

Observational studies have suggested an associations between hidradenitis suppurativa (HS) and metabolic syndrome (MetS) and its components. However, it remains unclear whether the relationship is causal or not. Our study aimed to investigate the causal association of HS with MetS and its components. We performed a bidirectional, two-sample Mendelian randomization study using summary-level data from the most comprehensive genome-wide association studies of HS (n = 362 071), MetS (n = 291 107), waist circumference (n = 462 166), hypertension (n = 463 010) fasting blood glucose (FBG, n = 200 622), triglycerides (n = 441 016), and high-density lipoprotein cholesterol (HDL-C, n = 403 943). Genetic instrumental variables were constructed by identifying single nucleotide polymorphisms associated with the corresponding factors. The random-effects inverse-variance weighted method was applied as the primary method. The results showed that genetically predicted HS was positively associated with waist circumference risk in both directions. High waist circumference increased the risk of HS (odds ratio [OR] 4.147; 95% confidence interval [CI] 2.610-6.590; p = 1.746 × 10-9). In addition, HS was also affected by waist circumference (OR 1.009; 95% CI 1.006-1.012; p = 3.08 × 10-7). No causal relationships were found between HS and MetS or its components other than waist circumference. The findings highlight the importance of early intervention for obesity in HS patients. Further studies are needed to determine the pathophysiology of HS associated with MetS and its components.

Analysis of human ambulation as a chaotic time-series: with nonlinear dynamics tools.

The aim of the present study is to investigate the complexity and stability of human ambulation and the implications on robotic prostheses control systems. Fourteen healthy individuals participate in two experiments, the first group run at three different speeds. The second group ascended and descended stairs of a five-level building block at a self-selected speed. All participants completed the experiment with seven inertial measurement units wrapped around the lower body segments and waist. The data were analyzed to determine the fractal dimension, spectral entropy, and the Lyapunov exponent (LyE). Two methods were used to calculate the long-term LyE, first LyE calculated using the full size of data sets. And the embedding dimensions were calculated using Average Mutual Information (AMI) and the False Nearest Neighbor (FNN) algorithm was used to find the time delay. Besides, a second approach was developed to find long-term LyE where the time delay was based on the average period of the gait cycle using adaptive event-based window. The average values of spectral entropy are 0.538 and 0.575 for stairs ambulation and running, respectively. The degree of uncertainty and complexity increases with the ambulation speed. The short term LyEs for tibia orientation have the minimum range of variation when it comes to stairs ascent and descent. Using two-way analysis of variance we demonstrated the effect of the ambulation speed and type of ambulation on spectral entropy. Moreover, it was shown that the fractal dimension only changed significantly with ambulation speed.

Controlling charge migration and CO2 conversion through surface decoration of 2D-hydrotalcite on bismuth oxybromide for enhanced artificial photosynthesis.

Photocatalytic reduction of CO2 in pure H2O media to produce chemicals presents an appealing avenue for simultaneously alleviating energy and environmental crises. However, the rapid recombination of photogenerated charge carriers presents a significant challenge in this promising field. Heterojunction engineering has emerged as an effective approach to address this dilemma. Here, by decorating 2D NiAl-layered double hydroxides (NAL) onto bismuth oxybromide (BOB), we have created a S-scheme heterojunction (N1B1 composite). This catalyst affords CO2-to-CO yields of 102.30 µmol g-1 with a selectivity of 100 %. Ultraviolet photoelectron spectroscopy (UPS) and in-situ irradiated X-ray photoelectron spectroscopy (ISI-XPS) reveal that charge transfer occurs efficiently from BOB to 2D-NAL upon light irradiation. The designed N1B1 heterojunction achieves 7.3-fold and 2.1-fold increase in the internal electric field strength compared to bare 2D-NAL and BOB, respectively, which should be accountable for the improved charge migration. Additionally, pulsed chemisorption and in-situ Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) show the presence of multiple carbonate intermediates with activated OCO bonds upon N1B1 composite, with *CO2- being identified as the most crucial species for CO production.

BCAT1 is a NOTCH1 target and sustains the oncogenic function of NOTCH1.

High levels of branched-chain amino acid (BCAA) transaminase 1 (BCAT1) have been associated with tumor aggressiveness and drug resistance in several cancer types. Nevertheless, the mechanistic role of BCAT1 in T-cell acute lymphoblastic leukemia (T-ALL) remains uncertain. We provide evidence that Bcat1 was over-expressed following NOTCH1-induced transformation of leukemic progenitors and that NOTCH1 directly controlled BCAT1 expression by binding to a BCAT1 promoter. Further, using a NOTCH1 gain-of-function retroviral model of T-ALL, mouse cells genetically deficient for Bcat1 showed defects in developing leukemia. In murine T-ALL cells, Bcat1 depletion or inhibition redirected leucine metabolism towards production of 3-hydroxy butyrate (3-HB), an endogenous histone deacetylase inhibitor. Consistently, BCAT1 depleted cells showed altered protein acetylation levels which correlated with a pronounced sensitivity to DNA damaging agents. In human NOTCH1-dependent leukemias, high expression levels of BCAT1 may predispose to worse prognosis. Therapeutically, BCAT1 inhibition specifically synergized with etoposide to eliminate tumors in patient-derived xenograft models suggesting that BCAT1 inhibitors may have a part to play in salvage protocols for refractory T-ALL.

DeepIRES: a hybrid deep learning model for accurate identification of internal ribosome entry sites in cellular and viral mRNAs.

The internal ribosome entry site (IRES) is a cis-regulatory element that can initiate translation in a cap-independent manner. It is often related to cellular processes and many diseases. Thus, identifying the IRES is important for understanding its mechanism and finding potential therapeutic strategies for relevant diseases since identifying IRES elements by experimental method is time-consuming and laborious. Many bioinformatics tools have been developed to predict IRES, but all these tools are based on structure similarity or machine learning algorithms. Here, we introduced a deep learning model named DeepIRES for precisely identifying IRES elements in messenger RNA (mRNA) sequences. DeepIRES is a hybrid model incorporating dilated 1D convolutional neural network blocks, bidirectional gated recurrent units, and self-attention module. Tenfold cross-validation results suggest that DeepIRES can capture deeper relationships between sequence features and prediction results than other baseline models. Further comparison on independent test sets illustrates that DeepIRES has superior and robust prediction capability than other existing methods. Moreover, DeepIRES achieves high accuracy in predicting experimental validated IRESs that are collected in recent studies. With the application of a deep learning interpretable analysis, we discover some potential consensus motifs that are related to IRES activities. In summary, DeepIRES is a reliable tool for IRES prediction and gives insights into the mechanism of IRES elements.

Severe novel coronavirus infection in late pregnancy: a case report.

This study reported the diagnosis, treatment and perinatal outcome of a novel coronavirus infection patient at 29+6 weeks pregnancy. The patient case came to the hospital with persistent fever and cough for 6 days. Patient's chest CT diagnosis showed double pneumonia, and viral infection was considered. Blood gas analysis revealed type I respiratory failure, and a throat swab nucleic acid test confirmed the novel coronavirus infection (critical type). After 13 days of isolation and supportive treatment, the patient recovered and was discharged from hospital after two consecutive negative nucleic acid tests. After discharge, the patient delivered a baby girl successfully by cesarean section on March 16, 2023. The newborn weighing 2050 g, with an Apgar score of 9-10 points /1-5 minutes. The newborn was transferred to the neonatology department for hospitalization and discharged 10 days later. The patient and her baby were followed up for nearly 1 year. Both mother and daughter were in good health.

Effects of FGF21 overexpression in osteoporosis and bone mineral density: a two-sample, mediating Mendelian analysis.

Objective: Fibroblast growth factor 21 (FGF21) is a secreted protein that regulates body metabolism. In recent years, many observational studies have found that FGF21 is closely related to bone mineral density and osteoporosis, but the causal relationship between them is still unclear. Therefore, this study used two-sample, mediated Mendelian randomization (MR) analysis to explore the causal relationship between FGF21 and osteoporosis and bone mineral density. Methods: We conducted a two-sample, mediator MR Analysis using genetic data from publicly available genome-wide association studies (GWAS) that included genetic variants in the inflammatory cytokine FGF21, and Total body bone mineral density, Heel bone mineral density, Forearm bone mineral density, Femoral neck bone mineral density, osteoporosis. The main analysis method used was inverse variance weighting (IVW) to investigate the causal relationship between exposure and outcome. In addition, weighted median, simple median method, weighted median method and MR-Egger regression were used to supplement the explanation, and sensitivity analysis was performed to evaluate the reliability of the results. Results: MR Results showed that FGF21 overexpression reduced bone mineral density: Total body bone mineral density (OR=0.920, 95%CI: 0.876-0.966), P=0.001), Heel bone mineral density (OR=0.971, 95%CI (0.949-0.993); P=0.01), Forearm bone mineral density (OR=0.882, 95%CI(0.799-0.973); P=0.012), Femoral neck bone mineral density (OR=0.952, 95%CI(0.908-0.998), P=0.039); In addition, it also increased the risk of osteoporosis (OR=1.003, 95%CI (1.001-1.005), P=0.004). Sensitivity analysis supported the reliability of these results. The effect of FGF21 overexpression on osteoporosis may be mediated by type 2 diabetes mellitus and basal metabolic rate, with mediating effects of 14.96% and 12.21%, respectively. Conclusions: Our study suggests that the overexpression of FGF21 may lead to a decrease in bone mineral density and increase the risk of osteoporosis, and the effect of FGF21 on osteoporosis may be mediated through type 2 diabetes and basal metabolic rate. This study can provide a reference for analyzing the potential mechanism of osteoporosis and is of great significance for the prevention and treatment of osteoporosis.

Inhibiting the Formation of Toxic HCN Induced by C3H6 Coexistence and Enhancing C3H6 Resistance of Cu-Zeolite in the NH3-SCR Reaction.

The presence of light hydrocarbons (HCs) in diesel exhaust, specifically C3H6, significantly affects the performance of the state-of-the-art Cu-SSZ-13 zeolite NH3-SCR catalysts. It also leads to the formation of highly toxic HCN, posing risks to the environment and human health. In this work, the highly toxic HCN formation is inhibited, and the C3H6 resistance of Cu-SSZ-13 is improved by secondary metal modification via doping with rare earth/transition metal elements. Upon introduction of C3H6, the activity of Cu-SSZ-13 significantly decreases at medium-high temperatures. This is primarily due to the competitive reaction between C3H6 and NH3, which compete for the NH3 reductant required in the NH3-SCR reaction, resulting in the production of HCN. The unfavorable effect is alleviated on the modified catalysts due to their enhanced oxidation capabilities toward C3H6 and the HCHO intermediate, facilitating the complete oxidation of C3H6 to COx. This inhibits the undesirable partial oxidation reaction between C3H6 and NH3, thereby improving the activity of Cu-SSZ-13 at medium to high temperatures and significantly reducing the formation of highly toxic HCN.

Comparison of lidocaine bicarbonate with fentanyl and chloroprocaine for epidural anesthesia during cesarean section: a randomized, controlled, double-blind clinical trial.

Chloroprocaine and lidocaine bicarbonate are commonly used for epidural anesthesia because of their rapid onset, particularly in the case of conversion from epidural labor analgesia to emergency cesarean section. However, it is unclear whether lidocaine bicarbonate combined with fentanyl has an advantage over chloroprocaine alone in emergency cesarean section. In this study, 102 women who underwent elective cesarean section received 15 mL 3% chloroprocaine and 1 mL saline (CP group) or 15 mL 1.73% lidocaine bicarbonate and 1 mL fentanyl 50 µg (LF group) for epidural anesthesia. Nociceptive block level was assessed by pinprick and recorded every minute. The primary outcome was the onset time to T6 block. The median onset time to T6 analgesia was 10 [10, 10] min in the CP group and 10 [7, 10] min in the LF group (COX model for CP versus LF, HR 0.47, 95% CI 0.23-0.95, p = 0.035). The median onset time to T8 analgesia was 7 [5, 9] min in CP group and 5 [4, 7] min in LF group (COX model for CP versus LF, HR 0.61, 95% CI 0.39-0.95, p = 0.027). The proportion of hypotension episodes occurring before delivery in LF group was lower than that in CP group (p = 0.011). The incidence of block level ≥ T4 after supplemental dosing in the LF group was lower than that in the CP group (p = 0.031). Compared with 3% chloroprocaine, 1.73% lidocaine bicarbonate combined with fentanyl 50 µg has a slightly faster onset time and less hypotension in epidural anesthesia for cesarean section. Clinical Trial Registration: http://www.chictr.org.cn/index.html, identifier ChiCTR2200056180.