IL-4-induced SOX9 confers lineage plasticity to aged adult lung stem cells.

Wound healing in response to acute injury is mediated by the coordinated and transient activation of parenchymal, stromal, and immune cells that resolves to homeostasis. Environmental, genetic, and epigenetic factors associated with inflammation and aging can lead to persistent activation of the microenvironment and fibrosis. Here, we identify opposing roles of interleukin-4 (IL-4) cytokine signaling in interstitial macrophages and type II alveolar epithelial cells (ATIIs). We show that IL4Ra signaling in macrophages promotes regeneration of the alveolar epithelium after bleomycin-induced lung injury. Using organoids and mouse models, we show that IL-4 directly acts on a subset of ATIIs to induce the expression of the transcription factor SOX9 and reprograms them toward a progenitor-like state with both airway and alveolar lineage potential. In the contexts of aging and bleomycin-induced lung injury, this leads to aberrant epithelial cell differentiation and bronchiolization, consistent with cellular and histological changes observed in interstitial lung disease.

Machine learning-enabled prediction of prolonged length of stay in hospital after surgery for tuberculosis spondylitis patients with unbalanced data: a novel approach using explainable artificial intelligence (XAI).

BACKGROUND: Tuberculosis spondylitis (TS), commonly known as Pott's disease, is a severe type of skeletal tuberculosis that typically requires surgical treatment. However, this treatment option has led to an increase in healthcare costs due to prolonged hospital stays (PLOS). Therefore, identifying risk factors associated with extended PLOS is necessary. In this research, we intended to develop an interpretable machine learning model that could predict extended PLOS, which can provide valuable insights for treatments and a web-based application was implemented. METHODS: We obtained patient data from the spine surgery department at our hospital. Extended postoperative length of stay (PLOS) refers to a hospitalization duration equal to or exceeding the 75th percentile following spine surgery. To identify relevant variables, we employed several approaches, such as the least absolute shrinkage and selection operator (LASSO), recursive feature elimination (RFE) based on support vector machine classification (SVC), correlation analysis, and permutation importance value. Several models using implemented and some of them are ensembled using soft voting techniques. Models were constructed using grid search with nested cross-validation. The performance of each algorithm was assessed through various metrics, including the AUC value (area under the curve of receiver operating characteristics) and the Brier Score. Model interpretation involved utilizing methods such as Shapley additive explanations (SHAP), the Gini Impurity Index, permutation importance, and local interpretable model-agnostic explanations (LIME). Furthermore, to facilitate the practical application of the model, a web-based interface was developed and deployed. RESULTS: The study included a cohort of 580 patients and 11 features include (CRP, transfusions, infusion volume, blood loss, X-ray bone bridge, X-ray osteophyte, CT-vertebral destruction, CT-paravertebral abscess, MRI-paravertebral abscess, MRI-epidural abscess, postoperative drainage) were selected. Most of the classifiers showed better performance, where the XGBoost model has a higher AUC value (0.86) and lower Brier Score (0.126). The XGBoost model was chosen as the optimal model. The results obtained from the calibration and decision curve analysis (DCA) plots demonstrate that XGBoost has achieved promising performance. After conducting tenfold cross-validation, the XGBoost model demonstrated a mean AUC of 0.85 ± 0.09. SHAP and LIME were used to display the variables' contributions to the predicted value. The stacked bar plots indicated that infusion volume was the primary contributor, as determined by Gini, permutation importance (PFI), and the LIME algorithm. CONCLUSIONS: Our methods not only effectively predicted extended PLOS but also identified risk factors that can be utilized for future treatments. The XGBoost model developed in this study is easily accessible through the deployed web application and can aid in clinical research.

Microbiome and antibiotic resistome in bioelectrochemical toilets for onsite treatment of fecal sludge.

Effective management of fecal sludge (FS) is essential for preventing environmental and public health risks. Developing safe and efficient FS treatment technology is crucial for reducing the health risks of onsite sanitation systems. In this study, bioelectrochemical toilets (BETs) were developed to treat FS onsite. Compared with the open-circuit BETs (OC-BETs), BETs exhibited higher removal efficiencies for total organic carbon, total nitrogen, and total phosphorus. Specifically, the enhancements in removal efficiencies were 18.82 ± 1.73 %, 7.28 ± 0.32 %, and 11.41 ± 0.05 % for urine, and 19.28 ± 4.08 %, 21.65 ± 1.23 %, and 24.68 ± 0.95 % for feces, respectively. Microbiome analysis indicated that the dominant populations were affiliated with electroactive bacteria (Desulfuromonas and Pseudomonas) in the electrode biofilm of BETs. The species co-occurrence network showed that the electrode biofilm microbiome in BETs had more complex correlations than that in OC-BETs, suggesting that a weak electrical current enhanced the microbiome stability. The relative abundance of antibiotic resistance genes in BETs and OC-BETs reduced by 59.85 ± 1.32 % and 53.01 ± 2.81 % compared with the initial FS, respectively. These findings indicate that BETs are an alternative system for enhancing onsite treatment of fecal sludge and provide a theoretical foundation for the implementation of BETs.

Ultrasonic vibration assisted gas tungsten arc welding of Inconel 690 alloy: Ultrasonic effect to refine grains and improve mechanical properties.

The Inconel 690 alloy is widely used in the manufacturing of nuclear equipment, such as pipe welding for steam generators (SG) and pressure vessels, due to its excellent high-temperature strength, corrosion resistance, and thermal stability. However, coarse grains have been observed in the welded joint of Inconel 690. Considering its crucial role as a structural material under high pressure, temperature, and corrosive conditions, improvements should be made to the microstructure of the welded joint. The ultrasonic-assisted gas tungsten arc welding (UA-GTAW) was used in Inconel 690 welding. The influence of ultrasonic vibration on the microstructure and mechanical properties of welded joints was studied. The results show that the ultrasonic refined the microstructure further to improve the mechanical properties. The UA-GTAW sample performed superiorities over regular GTAW joint in multi perspective including refined solidification grains, less element segregation, higher tensile strength and hardness. The Yield strength, ultimate tensile strength, and elongation increased from 320 MPa, 591 MPa, and 25.1 % to 387 MPa, 672 MPa, and 31.6 %, respectively.

CRISPR activation screens identify the SWI/SNF ATPases as suppressors of ferroptosis.

Ferroptosis is an iron-dependent cell death mechanism characterized by the accumulation of toxic lipid peroxides and cell membrane rupture. GPX4 (glutathione peroxidase 4) prevents ferroptosis by reducing these lipid peroxides into lipid alcohols. Ferroptosis induction by GPX4 inhibition has emerged as a vulnerability of cancer cells, highlighting the need to identify ferroptosis regulators that may be exploited therapeutically. Through genome-wide CRISPR activation screens, we identify the SWI/SNF (switch/sucrose non-fermentable) ATPases BRM (SMARCA2) and BRG1 (SMARCA4) as ferroptosis suppressors. Mechanistically, they bind to and increase chromatin accessibility at NRF2 target loci, thus boosting NRF2 transcriptional output to counter lipid peroxidation and confer resistance to GPX4 inhibition. We further demonstrate that the BRM/BRG1 ferroptosis connection can be leveraged to enhance the paralog dependency of BRG1 mutant cancer cells on BRM. Our data reveal ferroptosis induction as a potential avenue for broadening the efficacy of BRM degraders/inhibitors and define a specific genetic context for exploiting GPX4 dependency.

Levels, Distribution and Ecological Risk Assessment of PBDEs in Soils and Plants Around the Engineering Plastics Factory.

This study systematically investigated the pollution levels and migration trends of PBDEs in soils and plants around engineering plastics factory, and identified the ecological risks of PBDEs in the environment around typical pollution sources.The results showed that 13 kinds of PBDEs were widely detected in the surrounding areas, and the concentration level was higher than the general environmental pollution level. The total PBDE concentrations (∑13PBDEs) in soils ranged from 14.6 to 278.4 ng/g dry weight (dw), and in plants ranged from 11.5 to 176 ng/g dw. Both soil and plant samples showed that BDE-209 was the most important congener, the pollution level in soil and plant was similar, and the composition of PBDEs congener was similar. In the soil column (50 cm), the radial migration of PBDEs was mainly concentrated in the 0-30 cm section. Except for BDE-66, which was mainly located in the 20-30 cm soil layer, the concentration of PBDEs was the highest in the 0-10 cm region. Furthermore, the environmental risks of PBDEs in soil and plants were evaluated by hazard quotient method, and the HQ values were all < 1, which did not exhibit any ecological risk. The evaluation results also showed that the ecological risk of PBDEs in soil was higher than that of plants, especially penta-BDE, which should be paid more attention.

Peripheral Neuropathy Associated with Higher Mortality in Population with Chronic Kidney Disease: National Health and Nutrition Examination Surveys.

Introduction: Peripheral neuropathy (PN), one of the commonest neurological complications of chronic kidney disease (CKD), was associated with physical limitation. Studies showed that a decrease in physical capability in patients with CKD is related with an increased risk of mortality. The objective of our research was to directly explore the relationship between PN and risk of mortality in patients with CKD. Method: 1,836 participants with CKD and 6,036 participants without CKD, which were classified by PN based on monofilament examination in National Health and Nutrition Examination Survey (NHANES), were collected from the 1999 to 2004 National Health and Nutrition Examination Surveys. Multivariable Cox proportional hazard models were conducted to assess the relationships of PN and deaths in patients with CKD and non-CKD. Results: During 14 years of a median follow-up from 1999 to 2015 and 2004 to 2015, 1,072 (58.4%) and 1,389 (23.0%) deaths were recorded in participants with CKD and without CKD, respectively. PN was related with increased all-cause mortality even after adjusting possible confounding factors in population with CKD (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.17-1.53) and without CKD (HR 1.27, 95% CI 1.12-1.43). And the adjusted HRs (95% CI) for cardiovascular mortality of the people with CKD and without CKD who suffered from PN were 1.42 (1.07, 1.90) and 1.23 (0.91, 1.67), respectively, versus those without PN. Conclusion: PN was related with a higher risk of all-cause and cardiovascular death in people with CKD, which clinically suggests that the adverse prognostic impact of PN in the CKD population deserves attention and is an important target for intervention.

Maternal-fetal immunity and recurrent spontaneous abortion.

Recurrent Spontaneous Abortion (RSA) is a common pregnancy complication, that has multifactorial causes, and currently, 40%-50% of cases remain unexplained, referred to as Unexplained RSA (URSA). Due to the elusive etiology and mechanisms, clinical management is exceedingly challenging. In recent years, with the progress in reproductive immunology, a growing body of evidence suggests a relationship between URSA and maternal-fetal immunology, offering hope for the development of tailored treatment strategies. This article provides an immunological perspective on the pathogenesis, diagnosis, and treatment of RSA. On one hand, it comprehensively reviews the immunological mechanisms underlying RSA, including abnormalities in maternal-fetal interface immune tolerance, maternal-fetal interface immune cell function, gut microbiota-mediated immune dysregulation, and vaginal microbiota-mediated immune anomalies. On the other hand, it presents the diagnosis and existing treatment modalities for RSA. This article offers a clear knowledge framework for understanding RSA from an immunological standpoint. In conclusion, while the "layers of the veil" regarding immunological factors in RSA are gradually being unveiled, our current research may only scratch the surface. In terms of immunological etiology, effective diagnostic tools for RSA are currently lacking, and the efficacy and safety of immunotherapies, primarily based on lymphocyte immunotherapy and intravenous immunoglobulin, remain contentious.

circTldc1 increases Tldc1 expression by targeting miR-485-5p to promote fibroblast-like synoviocytes proliferation in collagen-induced arthritis.

Abnormalities in the function of fibroblast-like synoviocytes (FLSs) are crucial factors leading to joint damage of rheumatoid arthritis. In recent years, the role of circular RNA (circRNA) in RA has gradually been revealed. However, the functional regulation of FLSs mediated by circRNA and its potential mechanisms remain unclear. In this study, we elucidated the expression profile of circRNA in FLSs, as well as the role and molecular mechanisms of circTldc1. Through sequencing and validation experiments on primary FLSs derived from collagen-induced arthritis (CIA) rats, we found that circTldc1 can promote FLSs proliferation and exacerbate CIA-induced joint damage. The data revealed that circTldc1's parent gene, Tldc1, is homologous to human Tldc1, and circTldc1 is located in the cytoplasm of FLSs, belonging to the exonic circRNA category. The results from bioinformatics analysis, molecular experiments on FLSs (manipulating circTldc1 expression in vitro), and animal experiments (local regulation of circTldc1 expression in vivo) collectively confirmed that circTldc1 promotes Tldc1 expression by targeting miR-485-5p. High expression of Tldc1 further enhances FLSs proliferation and inflammatory responses, thereby worsening joint damage in CIA rats. High expression of circTldc1 and its parent gene Tldc1 may serve as biomarkers for RA. Local regulation of circTldc1 and Tldc1 gene levels in the joint cavity may represent a potential strategy to improve joint damage and inflammation in RA.

MRI-based interpretable radiomics nomogram for discrimination between Brucella spondylitis and Pyogenic spondylitis.

Background: Pyogenic spondylitis (PS) and Brucella spondylitis (BS) are commonly seen spinal infectious diseases. Both types can lead to vertebral destruction, kyphosis, and long-term neurological deficits if not promptly diagnosed and treated. Therefore, accurately diagnosis is crucial for personalized therapy. Distinguishing between PS and BS in everyday clinical settings is challenging due to the similarity of their clinical symptoms and imaging features. Hence, this study aims to evaluate the effectiveness of a radiomics nomogram using magnetic resonance imaging (MRI) to accurately differentiate between the two types of spondylitis. Methods: Clinical and MRI data from 133 patients (2017-2022) with pathologically confirmed PS and BS (68 and 65 patients, respectively) were collected. We have divided patients into training and testing cohorts. In order to develop a clinical diagnostic model, logistic regression was utilized to fit a conventional clinical model (M1). Radiomics features were extracted from sagittal fat-suppressed T2-weighted imaging (FS-T2WI) sequence. The radiomics features were preprocessed, including scaling using Z-score and undergoing univariate analysis to eliminate redundant features. Furthermore, the Least Absolute Shrinkage and Selection Operator (LASSO) was employed to develop a radiomics score (M2). A composite model (M3) was created by combining M1 and M2. Subsequently, calibration and decision curves were generated to evaluate the nomogram's performance in both training and testing groups. The diagnostic performance of each model and the indication was assessed using the receiver operating curve (ROC) with its area under the curve (AUC). Finally, we used the SHapley Additive exPlanations (SHAP) model explanations technique to interpret the model result. Results: We have finally selected 9 significant features from sagittal FS-T2WI sequences. In the differential diagnosis of PS and BS, the AUC values of M1, M2, and M3 in the testing set were 0.795, 0.859, and 0.868. The composite model exhibited a high degree of concurrence with the ideal outcomes, as evidenced by the calibration curves. The nomogram's possible clinical application values were indicated by the decision curve analysis. By using SHAP values to represent prediction outcomes, our model's prediction results are more understandable. Conclusions: The implementation of a nomogram that integrates MRI and clinical data has the potential to significantly enhance the accuracy of discriminating between PS and BS within clinical settings.

In vitro dissolution profile comparison using bootstrap bias corrected similarity factor, f2.

In vitro dissolution profile has been shown to be correlated with the drug absorption and has often been considered as a metric for assessing in vitro bioequivalence between a test product and corresponding reference one. Various methods have been developed to assess the similarity between two dissolution profiles. In particular, similarity factor f2 has been reviewed and discussed extensively in many statistical articles. Although the f2 lacks inferential statistical properties, the estimation of f2 and its various modified versions were the most widely used metric for comparing dissolution profiles. In this paper, we investigated performances of the naive f2 estimate method, bootstrap f2 confidence interval method and bias corrected-accelerated (BCa) bootstrap f2 confidence interval method for comparing dissolution profiles. Our studies show that naive f2 estimate method and BCa bootstrap f2 confidence interval method are unable to control the type I error rate. The bootstrap f2 confidence interval method can control the type I error rate under a specific level. However, it will cause great conservatism on the power of the test. To solve the potential issues of the previous methods, we recommended a bootstrap bias corrected (BC) f2 confidence interval method in this paper. The type I error rate, power and sensitivity among different f2 methods were compared based on simulations. The recommended bootstrap BC f2 confidence interval method shows better control of type I error than the naive f2 estimate method and BCa bootstrap f2 confidence interval method. It also provides better power than the bootstrap f2 confidence interval method.

Glycolithocholic acid increases the frequency of circulating Tregs through constitutive androstane receptor to alleviate postmenopausal osteoporosis.

BACKGROUND AND PURPOSE: Gut microbiota and their metabolic activity are important regulators of host immunity. However, the role of gut microbiota and their metabolic activity-mediated osteoimmunity in postmenopausal osteoporosis (PMO) remains unknown. This study aimed to explore the role of gut microbiota and their metabolic activity in PMO. EXPERIMENTAL APPROACH: 16S rDNA sequencing was used for analyzing the gut microbiota diversity of patients with PMO and rat models, and a targeted metabolism study was performed for analyzing metabolite levels. Flow cytometry was used for analyzing the frequency of immune cells. Micro-CT was used for analyzing bone damage in rat models. Fecal microbiota transplantation was performed for exploring the therapeutic effect of the gut microbiota on PMO. CD4+ T cells were co-cultured with bone marrow mesenchymal stem cells for evaluating their molecular mechanisms. KEY RESULTS: Patients with PMO exhibited reduced gut microbiota diversity, and fecal glycolithocholic acid (GLCA) levels correlated with the degree of osteoporosis. GLCA levels in the gut were positively correlated with the frequency of circulating Tregs in ovariectomized rats. Restoration of the gut microbiota alleviated osteoporosis in ovariectomized rats. Circulating GLCA augmented CD4+ T cell differentiation into Tregs via constitutive androstane receptors. The increased frequency of Tregs further promoted the osteogenic differentiation of bone marrow mesenchymal stem cells to alleviate osteoporosis. CONCLUSION AND IMPLICATIONS: GLCA alleviated PMO by increasing the frequency of circulating Tregs, acting via the constitutive androstane receptor. This study reveals a new strategy for the treatment of PMO, with GLCA as a potential drug candidate.

Clinical Outcomes of 27-Gauge Pars Plana Vitrectomy for Diabetic Tractional Retinal Detachment Repair.

Purpose: To analyze the clinical outcomes of 27-gauge pars plana vitrectomy (PPV) repair of diabetic tractional retinal detachment (TRD) of various severities. Methods: This retrospective case series examined the outcomes of 27-gauge PPV to repair diabetic TRD from 2016 to 2020. The effect of medical and ophthalmologic history parameters and baseline detachment characteristics on visual acuity (VA) and retinal reattachment was analyzed. A grading system was established to stage the severity of the baseline vitreoretinal traction or detachment and compare the visual and anatomic outcomes between stages. Results: The study comprised 79 eyes (79 patients). The overall redetachment rate was 10.1% (8/79). The proportion of eyes with severe visual impairment (worse than 20/200) decreased from 81.0% (64/79) preoperatively to 56.9% (37/65) 6 months postoperatively (P < .001). Worse preoperative logMAR VA was associated with greater odds of redetachment (P = .017) and worse postoperative VA (P < .001). Insulin dependence was associated with better VA at 6 months (P = .017). A shorter known duration of diabetes (P = .026) and evidence of neovascularization of the iris (NVI) or angle (P = .004) were associated with worse visual outcomes. Eyes with detachment involving the posterior pole extending beyond the equator had worse VA at 6 months (P = .048). Conclusions: The primary reattachment rate after 27-gauge PPV was 89.9%. There was significant VA improvement, with a roughly 40% reduction in the number of eyes with severe visual impairment by the final follow-up. Insulin dependence, duration of diabetes, presence of NVI before surgery, and baseline posterior pole detachment extending beyond the equator were predictors of visual outcomes.

Implementation of a Virtual Reality Based Digital-Twin Robotic Minimally Invasive Surgery Simulator.

The rapid development of computers and robots has seen robotic minimally invasive surgery (RMIS) gradually enter the public's vision. RMIS can effectively eliminate the hand vibrations of surgeons and further reduce wounds and bleeding. However, suitable RMIS and virtual reality-based digital-twin surgery trainers are still in the early stages of development. Extensive training is required for surgeons to adapt to different operating modes compared to traditional MIS. A virtual-reality-based digital-twin robotic minimally invasive surgery (VRDT-RMIS) simulator was developed in this study, and its effectiveness was introduced. Twenty-five volunteers were divided into two groups for the experiment, the Expert Group and the Novice Group. The use of the VRDT-RMIS simulator for face, content, and structural validation training, including the peg transfer module and the soft tissue cutting module, was evaluated. Through subjective and objective evaluations, the potential roles of vision and haptics in robot surgery training were explored. The simulator can effectively distinguish surgical skill proficiency between experts and novices.

Circ-Plod2 destabilizes Mpo mRNA by binding to IGF2BP2 to promote osteogenic differentiation of bone marrow mesenchymal stem cells.

Osteogenic differentiation, proliferation, and/or apoptosis of bone marrow mesenchymal stem cells (BMSCs) are involved in the progression of postmenopausal osteoporosis (PMO). However, circular RNA (circRNA)-mediated changes in the cellular function of BMSCs in PMO are still unclear. This study revealed the excellent ability of circ-Plod2 to promote osteogenic differentiation of BMSCs and its molecular mechanisms. In this study, ovariectomized (OVX) rats and control (Sham) rats were used to simulate PMO. Initially, we found that the expression of circ-Plod2 in OVX BMSCs is down-regulated and the expression of the Mpo gene is up-regulated by sequencing and verification. Further, we confirmed that circ-Plod2 is located in the cytoplasm and belongs to exon-type circRNA. Interestingly, circ-Plod2 promotes Mpo-dependent osteogenic differentiation of BMSCs without affecting proliferation, apoptosis, adipogenic differentiation, or chondrogenic differentiation of BMSCs. Mechanistically, we demonstrated that circ-Plod2 specifically binds IGF2BP2 to form an RNA-protein complex that destabilizes Mpo mRNA. Overexpression of circ-Plod2 in the bone marrow cavity effectively alleviated osteoporosis in OVX rats and inhibited the expression of MPO in BMSCs. Together, this study reveals that circ-Plod2 destabilizes Mpo mRNA by binding to IGF2BP2 to promote osteogenic differentiation of BMSCs to alleviate osteoporosis. The findings of this study may provide biomarkers for the diagnosis of PMO, and may also provide potential strategies for the clinical treatment of PMO.

The Potential of a CT-Based Machine Learning Radiomics Analysis to Differentiate Brucella and Pyogenic Spondylitis.

Background: Pyogenic spondylitis (PS) and Brucella spondylitis (BS) are common spinal infections with similar manifestations, making their differentiation challenging. This study aimed to explore the potential of CT-based radiomics features combined with machine learning algorithms to differentiate PS from BS. Methods: This retrospective study involved the collection of clinical and radiological information from 138 patients diagnosed with either PS or BS in our hospital between January 2017 and December 2022, based on histopathology examination and/or germ isolations. The region of interest (ROI) was defined by two radiologists using a 3D Slicer open-source platform, utilizing blind analysis of sagittal CT images against histopathological examination results. PyRadiomics, a Python package, was utilized to extract ROI features. Several methods were performed to reduce the dimensionality of the extracted features. Machine learning algorithms were trained and evaluated using techniques like the area under the receiver operating characteristic curve (AUC; confusion matrix-related metrics, calibration plot, and decision curve analysis to assess their ability to differentiate PS from BS. Additionally, permutation feature importance (PFI; local interpretable model-agnostic explanations (LIME; and Shapley additive explanation (SHAP) techniques were utilized to gain insights into the interpretabilities of the models that are otherwise considered opaque black-boxes. Results: A total of 15 radiomics features were screened during the analysis. The AUC value and Brier score of best the model were 0.88 and 0.13, respectively. The calibration plot and decision curve analysis displayed higher clinical efficiency in the differential diagnosis. According to the interpretation results, the most impactful features on the model output were wavelet LHL small dependence low gray-level emphasis (GLDN). Conclusion: The CT-based radiomics models that we developed have proven to be useful in reliably differentiating between PS and BS at an early stage and can provide a reliable explanation for the classification results.

JunB: a paradigm for Jun family in immune response and cancer.

Jun B proto-oncogene (JunB) is a crucial member of dimeric activator protein-1 (AP-1) complex, which plays a significant role in various physiological processes, such as placental formation, cardiovascular development, myelopoiesis, angiogenesis, endochondral ossification and epidermis tissue homeostasis. Additionally, it has been reported that JunB has great regulatory functions in innate and adaptive immune responses by regulating the differentiation and cytokine secretion of immune cells including T cells, dendritic cells and macrophages, while also facilitating the effector of neutrophils and natural killer cells. Furthermore, a growing body of studies have shown that JunB is involved in tumorigenesis through regulating cell proliferation, differentiation, senescence and metastasis, particularly affecting the tumor microenvironment through transcriptional promotion or suppression of oncogenes in tumor cells or immune cells. This review summarizes the physiological function of JunB, its immune regulatory function, and its contribution to tumorigenesis, especially focusing on its regulatory mechanisms within tumor-associated immune processes.

Development and validation of a novel nomogram to predict the risk of the prolonged postoperative length of stay for lumbar spinal stenosis patients.

BACKGROUND: Lumber spinal stenosis (LSS) is the increasingly reason for spine surgery for elder patients since China is facing the fastest-growing aging population. The aim of this research was to create a model to predict the probabilities of requiring a prolonged postoperative length of stay (PLOS) for lumbar spinal stenosis patients, minimizing the healthcare burden. METHODS: A total of 540 LSS patients were enrolled in this project. The outcome was a prolonged PLOS after spine surgery, defined as hospitalizations ≥ 75th percentile for PLOS, including the day of discharge. The least absolute shrinkage and selection operator (LASSO) was used to identify independent risk variables related to prolonged PLOS. Multivariable logistic regression analysis was utilized to generate a prediction model utilizing the variables employed in the LASSO approach. The receiver operating characteristic (ROC) curve's area under the curve (AUC) and the calibration curve's respective curves were used to further validate the model's calibration with predictability and discriminative capabilities. By using decision curve analysis, the resulting model's clinical effectiveness was assessed. RESULTS: Among 540 individuals, 344 had PLOS that was within the usual range of P75 (8 days), according to the interquartile range of PLOS, and 196 had PLOS that was above the normal range of P75 (prolonged PLOS). Four variables were incorporated into the predictive model, named: transfusion, operation duration, blood loss and involved spine segments. A great difference in clinical scores can be found between the two groups (P < 0.001). In the development set, the model's AUC for predicting prolonged PLOS was 0.812 (95% CI: 0.768-0.859), while in the validation set, it was 0.830 (95% CI: 0.753-0.881). The calibration plots for the probability showed coherence between the expected probability and the actual probability both in the development set and validation set respectively. When intervention was chosen at the potential threshold of 2%, analysis of the decision curve revealed that the model was more clinically effective. CONCLUSIONS: The individualized prediction nomogram incorporating five common clinical features for LSS patients undergoing surgery can be suitably used to smooth early identification and improve screening of patients at higher risk of prolonged PLOS and minimize health care.

Development of a new prognostic index PNPI for prognosis prediction of CKD patients with pneumonia at hospital admission.

Background: The aim of this study was to investigate the relationship between pneumonia and chronic kidney disease (CKD), to elucidate potential risk factors, and to develop a new predictive model for the poor prognosis of pneumonia in CKD patients. Method: We conducted a retrospective observational study of CKD patients admitted to Tongji Hospital between June 2012 and June 2022. Demographic information, comorbidities or laboratory tests were collected. Applying univariate and multivariate logistic regression analyses, independent risk factors associated with a poor prognosis (i.e., respiratory failure, shock, combined other organ failure, and/or death during hospitalization) for pneumonia in CKD patients were discovered, with nomogram model subsequently developed. Predictive model was compared with other commonly used pneumonia severity scores. Result: Of 3,193 CKD patients with pneumonia, 1,013 (31.7%) met the primary endpoint during hospitalization. Risk factors predicting poor prognosis of pneumonia in CKD patients were selected on the result of multivariate logistic regression models, including chronic cardiac disease; CKD stage; elevated neutrophil to lymphocyte ratio (NLR) and D-dimer; decreased platelets, PTA, and chloride iron; and significant symptom presence and GGO presentation on CT. The nomogram model outperformed other pneumonia severity indices with AUC of 0.82 (95% CI: 0.80, 0.84) in training set and 0.83 (95% CI: 0.80, 0.86) in testing set. In addition, calibration curve and decision curve analysis (DCA) proved its efficiency and adaptability. Conclusion: We designed a clinical prediction model PNPI (pneumonia in nephropathy patients prognostic index) to assess the risk of poor prognosis in CKD patients with pneumonia, which may be generalized after more external validation.

Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution.

Aging is characterized by a decline in tissue function, but the underlying changes at cellular resolution across the organism remain unclear. Here, we present the Aging Fly Cell Atlas, a single-nucleus transcriptomic map of the whole aging Drosophila. We characterized 163 distinct cell types and performed an in-depth analysis of changes in tissue cell composition, gene expression, and cell identities. We further developed aging clock models to predict fly age and show that ribosomal gene expression is a conserved predictive factor for age. Combining all aging features, we find distinctive cell type-specific aging patterns. This atlas provides a valuable resource for studying fundamental principles of aging in complex organisms.