Histone lysine demethylase KDM5B facilitates proliferation and suppresses apoptosis in human acute myeloid leukemia cells through the miR-140-3p/BCL2 axis.

The histone lysine demethylase KDM5B is frequently up-regulated in various human cancer cells. However, its expression and functional role in human acute myeloid leukemia (AML) cells remain unclear. Here, we found that the expression level of KDM5B is high in primary human AML cells. We have demonstrated that knocking down KDM5B leads to apoptosis and impairs proliferation in primary human AML and some human AML cell lines. We further identified miR-140-3p as a downstream target gene of KDM5B. KDM5B expression was inversely correlated with the miR-140-3p level in primary human AML cells. Molecular studies showed that silencing KDM5B enhanced H3K4 trimethylation (H3K4me3) at the promoter of miR-140-3p, leading to high expression of miR-140-3p, which in turn inhibited B-cell CLL/lymphoma 2 (BCL2) expression. Finally, we demonstrate that the defective proliferation induced by KDM5B knockdown (KD) can be rescued with the miR-140-3p inhibitor or enhanced by combining KDM5B KD with a BCL2 inhibitor. Altogether, our data support the conclusion that KDM5B promotes tumorigenesis in human AML cells through the miR-140-3p/BCL2 axis. Targeting the KDM5B/miR-140-3p/BCL2 pathway may hold therapeutic promise for treating human AML.

Racial and Ethnic Disparities in Tuberculosis Incidence, Arkansas, USA, 2010-2021.

We conducted an epidemiologic assessment of disease distribution by race/ethnicity to identify subpopulation-specific drivers of tuberculosis (TB). We used detailed racial/ethnic categorizations for the 932 TB cases diagnosed in Arkansas, USA, during 2010-2021. After adjusting for age and sex, racial/ethnic disparities persisted; the Native Hawaiian/Pacific Islander (NHPI) group had the highest risk for TB (risk ratio 173.6, 95% CI 140.6-214.2) compared with the non-Hispanic White group, followed by Asian, Hispanic, and non-Hispanic Black. Notable racial/ethnic disparities existed across all age groups; NHPI persons 0-14 years of age were at a particularly increased risk for TB (risk ratio 888, 95% CI 403-1,962). The risks for sputum smear-positive pulmonary TB and extrapulmonary TB were both significantly higher for racial/ethnic minority groups. Our findings suggest that TB control in Arkansas can benefit from a targeted focus on subpopulations at increased risk for TB.

Circ_100549 promotes tumor progression in lung adenocarcinoma through upregulation of BIRC6.

Lung adenocarcinoma (LUAD) is a subtype of lung cancer with high incidence and mortality globally. Emerging evidence suggests that circular RNAs (circRNAs) exert critical functions in human cancers, including LUAD. CircRNA_100549 (circ_100549) has been reported to be significantly upregulated in non-small cell lung cancer (NSCLC) samples, while its role in modulating LUAD progression remains to be explored. The current study aims at investigating the functional roles of circ_100549 in LUAD and its downstream molecular mechanism. First, we found that the expression of circ_100549 was higher in LUAD cell lines. Loss-of-function assays verified that depletion of circ_100549 repressed LUAD cell proliferation but accelerated cell apoptosis. Furthermore, in vivo experiments demonstrated that silencing of circ_100549 suppressed tumor growth. Subsequently, based on database analysis, we carried out a series of experiments to explore the mechanisms and effects of circ_100549 underlying LUAD progression, including RNA-binding protein immunoprecipitation (RIP), RNA/DNA pull-down, luciferase reporter, and chromatin immunoprecipitation (ChIP) assays. The results indicated that circ_100549 serves as a ceRNA by sponging miR-95-5p to upregulate BPTF expression, thus upregulating BIRC6 expression at a transcriptional level in LUAD. In summary, our study demonstrated that circ_100549 facilitates LUAD progression by upregulating BIRC6 expression.

Polyphenol Supplementation Enhances the Efficacy of PD-1/PD-L1 Inhibitors Against Cancer: A Meta-Analysis of Animal Studies.

BACKGROUND: This study performed a meta-analysis to evaluate the combined effects of polyphenols and anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors. METHODS: Relevant studies were collected from electronic databases. Standardized mean differences (SMDs) or hazard ratio (HR) was calculated by Stata 15.0 software. RESULTS: Sixteen preclinical studies were included. The overall meta-analysis showed that, compared to anti-PD-1/PD-L1 alone, polyphenol combined therapy significantly reduced the tumor volume (SMD = -3.28), weight (SMD = -2.18), number (SMD = -2.17), and prolonged the survival (HR = 0.45) of mice (all P < 0.001). Pooled analysis of mechanism studies indicated polyphenol combined therapy could increase the number of cytotoxic CD8+ T cells (SMD = 3.88; P < 0.001), IFN-γ+ CD8+ T cells (SMD = 2.38; P < 0.001), decrease the number of myeloid-derived suppressor cells (SMD = -2.52; P = 0.044) and Treg cells (SMD = -4.00; P = 0.004) and suppress PD-L1 expression in tumors (SMD = -13.41; P < 0.001). Subgroup analyses demonstrated curcuminoids, flavonoids, and stilbene changed the tumor volume, the percentage of CD8+ T cells, IFN-γ+CD8+ T cells, and PD-L1 expression. CONCLUSION: Polyphenol supplementation may be a promising combined strategy for patients with poor response to anti-PD-1/PD-L1 monotherapy.

Depression of LncRNA DANCR alleviates tubular injury in diabetic nephropathy by regulating KLF5 through sponge miR-214-5p.

OBJECTIVE: Diabetic nephropathy (DN) manifests a critical aspect in the form of renal tubular injury. The current research aimed to determine the function and mechanism of long non-coding ribonucleic acid (LncRNA) differentiation antagonising non-protein coding RNA (DANCR), with a focus on its impact on renal tubular injury. METHODS: Quantitative reverse transcription polymerase chain reaction was employed to analyze the RNA levels of DANCR in the serum of patients with DN or human proximal tubular epithelial cells (human kidney 2 [HK2]). The diagnostic significance of DANCR was assessed using a receiver operating characteristic curve. A DN model was established by inducing HK-2 cells with high glucose (HG). Cell proliferation, apoptosis, and the levels of inflammatory factors, reactive oxygen species (ROS), and malondialdehyde (MDA) were detected using the Cell Counting Kit - 8, flow cytometry, and enzyme-linked immunosorbent assay. The interaction between microRNA (miR)-214-5p and DANCR or Krüppel-like factor 5 (KLF5) was investigated using RNA immunoprecipitation and dual-luciferase reporter assays. RESULTS: Elevated levels of DANCR were observed in the serum of patients with DN and HG-inducted HK-2 cells (P < 0.05). DANCR levels effectively identified patients with DN from patients with type 2 diabetes mellitus. Silencing of DANCR protected against HG-induced tubular injury by restoring cell proliferation, inhibiting apoptosis, and reducing the secretion of inflammatory factors and oxidative stress production (P < 0.05). DANCR functions as a sponge for miR-214-5p, and the mitigation of DANCR silencing on HG-induced renal tubular injury was partially attenuated with reduced miR-214-5p (P < 0.05). Additionally, KLF5 was identified as the target of miR-214-5p. CONCLUSION: DANCR was identified as diagnostic potential for DN and the alleviation of renal tubular injury via the miR-214-5p/KLF5 axis, following DANCR silencing, introduces a novel perspective and approach to mitigating DN.

Machine learning-based prediction of in-hospital mortality for critically ill patients with sepsis-associated acute kidney injury.

OBJECTIVES: This study aims to develop and validate a prediction model in-hospital mortality in critically ill patients with sepsis-associated acute kidney injury (SA-AKI) based on machine learning algorithms. METHODS: Patients who met the criteria for inclusion were identified in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and divided according to the validation (n = 2440) and development (n = 9756, 80%) queues. Ensemble stepwise feature selection method was used to screen for effective features. The prediction models of short-term mortality were developed by seven machine learning algorithms. Ten-fold cross-validation was used to verify the performance of the algorithm in the development queue. The area under the receiver operating characteristic curve (ROC-AUC) was used to evaluate the differentiation accuracy and performance of the prediction model in the validation queue. The best-performing model was interpreted by Shapley additive explanations (SHAP). RESULTS: A total of 12,196 patients were enrolled in this study. Eleven variables were finally chosen to develop the prediction model. The AUC of the random forest (RF) model was the highest value both in the Ten-fold cross-validation and evaluation (AUC: 0.798, 95% CI: 0.774-0.821). According to the SHAP plots, old age, low Glasgow Coma Scale (GCS) score, high AKI stage, reduced urine output, high Simplified Acute Physiology Score (SAPS II), high respiratory rate, low temperature, low absolute lymphocyte count, high creatinine level, dysnatremia, and low body mass index (BMI) increased the risk of poor prognosis. CONCLUSIONS: The RF model developed in this study is a good predictor of in-hospital mortality for patients with SA-AKI in the intensive care unit (ICU), which may have potential applications in mortality prediction.

Exploring objective feature sets in constructing the evolution relationship of animal genome sequences.

BACKGROUND: Exploring evolution regularities of genome sequences and constructing more objective species evolution relationships at the genomic level are high-profile topics. Based on the evolution mechanism of genome sequences proposed in our previous research, we found that only the 8-mers containing CG or TA dinucleotides correlate directly with the evolution of genome sequences, and the relative frequency rather than the actual frequency of these 8-mers is more suitable to characterize the evolution of genome sequences. RESULT: Therefore, two types of feature sets were obtained, they are the relative frequency sets of CG1 + CG2 8-mers and TA1 + TA2 8-mers. The evolution relationships of mammals and reptiles were constructed by the relative frequency set of CG1 + CG2 8-mers, and two types of evolution relationships of insects were constructed by the relative frequency sets of CG1 + CG2 8-mers and TA1 + TA2 8-mers respectively. Through comparison and analysis, we found that evolution relationships are consistent with the known conclusions. According to the evolution mechanism, we considered that the evolution relationship constructed by CG1 + CG2 8-mers reflects the evolution state of genome sequences in current time, and the evolution relationship constructed by TA1 + TA2 8-mers reflects the evolution state in the early stage. CONCLUSION: Our study provides objective feature sets in constructing evolution relationships at the genomic level.

Rational Design of Orange-Red Emissive Carbon Dots for Tracing Lysosomal Viscosity Dynamics in Living Cells and Zebrafish.

Lysosomal viscosity is an essential microenvironment parameter in lysosomes, which is closely associated to the occurrence and development of various diseases, including cancer. Thus, accurately quantifying lysosomal viscosity changes is highly desirable for a better understanding of the dynamics and biological functions of lysosomes. In this study, lysosome self-targetable orange-red emissive carbon dots (OR-CDs) were rationally designed and developed for monitoring lysosomal viscosity fluctuations. The enhanced fluorescence of OR-CDs could be obviously observed as the viscosity increased from 1.07 to 950 cP. Moreover, the as-prepared OR-CDs could quickly enter cells for lysosome-targeting imaging and visualize viscosity variations in living cells and zebrafish. More importantly, by utilizing OR-CDs, we successfully achieved tracing the variations in lysosomal viscosity during the autophagy process. Additionally, as cancer cells possess high viscosity than normal cells, the OR-CDs have been effectively utilized for cancer imaging from cell, tissue, and organ to in vivo levels. It is expected that the developed OR-CDs not only provide a meaningful tool for visualizing investigations of lysosome viscosity-related diseases but also shed light on the development based on the nanomaterial for the clinical diagnosis of cancer.

Pre-treatment systemic immune-inflammation index as a non-invasive biomarker for predicting clinical outcomes in patients with renal cell carcinoma: a meta-analysis of 20 studies.

INTRODUCTION: To systematically assess the predictive significance of systemic immune-inflammation index (SII) in renal cell carcinoma (RCC). METHODS: Relevant studies published before November 2022 were retrieved from public databases. Hazard ratio (HR), standardised mean difference (SMD) and relative risk (RR) were calculated to estimate associations of SII with prognosis, treatment responses and clinicopathological features. RESULTS: Twenty studies involving 6887 patients were eligible. The meta-analysis results revealed a high SII level was associated with worse overall survival (HR: 1.45, p < 0.001), progression-free survival (HR: 1.63, p = 0.001), cancer-specific survival (HR: 1.86, p < 0.001), lower overall response rate (RR: 0.62, p = 0.003), disease control rate (RR: 0.69, p = 0.002), larger tumour size (SMD: 0.39, p = 0.001), poorer IMDC risk (RR: 7.09, p < 0.001), higher Fuhrman grade (RR: 1.54, p = 0.004), tumour stage (RR: 1.67, p = 0.045), the presence of distant metastasis (brain: RR, 2.04, p = 0.001; bone: RR, 1.33, p = 0.024) and tumour necrosis (RR: 1.57, p = 0.031). Subgroup analysis showed SII predicted OS and PFS for non-Asian, but CSS for both Asian and non-Asian populations. CONCLUSION: Pre-treatment SII may be a promising predictor of clinical outcomes for RCC patients.

ITGA9-AS1 up-regulates ITGA9 by targeting miR-4765 and recruiting HNRNPU to affect the proliferation and apoptosis of non-small cell lung cancer cells.

Long non-coding RNAs (lncRNAs) have been regarded as promising biomarkers in the regulation of various biological and pathological processes of non-small cell lung cancer (NSCLC). LncRNAITGA9-AS1 has been reported to be down-regulated in elderly patients with lung cancer, but how it may influence NSCLC remains to be identified. Therefore, we aim to explore the specific mechanism involving ITGA9-AS1 and ITGA9 in NSCLC. A functional assay was conducted to verify ITGA9-AS1's proliferative effects on NSCLC cells. Mechanism experiments with bioinformatics predictions were performed to explore the interaction of ITGA9-AS1 and ITGA9 in NSCLC cells. ITGA9-AS1 inhibited NSCLC cell proliferation while enhancing cell apoptosis. It up-regulated ITGA9 by competitively sponging miR-4765, and it stabilizedITGA9 mRNA by recruiting a RNA-binding protein (RBP)-HNRNPU (heterogeneous nuclear ribonucleoprotein U) in NSCLC cells. ITGA9-AS1 suppressed NSCLC progression by the up-regulation of ITGA9 via targeting miR-4765 and recruiting HNRNPU.

Analysis of the Analgesic Effect, Emotion, and Safety of Esketamine in Cesarean Section Analgesia for Puerperae.

Objective: This retrospective study aimed to evaluate the effectiveness and safety of esketamine as an analgesic during cesarean section procedures. Methods: 102 puerperae undergoing cesarean section were divided into a control group and an esketamine (SK) group. Various parameters, including HR, MAP, and postoperative pain, were analyzed. Blood gas analysis and Apgar scores were assessed in neonates. Postoperative depression and satisfaction were evaluated in puerperae. Drug concentrations were measured using liquid-phase tandem mass spectrometry. Results: No significant differences in dimension levels were observed between the two groups (P > .05). However, the SK group showed better HR and MAP indicators at various time points, less postoperative pain, and better mental well-being on postpartum days 1, 3, and 7 (P < .05). Adverse reaction rates were similar between groups (P > .05), but postoperative satisfaction was significantly different (P = .027). Neonatal outcomes did not differ significantly (P > .05). In the SK group, SK2 and SK3 groups had better results compared to SK1 (P < .05). Conclusion: Esketamine during cesarean section stabilized vital signs, reduced pain, and improved well-being in puerperae without affecting newborns. Optimal dosage: 30 µg/kg/h esketamine, 15 ng/kg/h sufentanil.

The Application Value of Esketamine and Dexmedetomidine in Preventing Postoperative Delirium and Hyperalgesia in Elderly Patients with Thoracic Anesthesia.

Objective: Our aim was to evauate the application value of esesketamine and dexmedetomidine in preventing postoperative hyperalgesia in elderly patients who received thoracic anesthesia. Methods: A total of 94 elderly patients who underwent thoracic anesthesia in Sanmen People's Hospital from January 2021 to October 2022 were selected and divided into a dexmedetomidine group (n = 47) and an esketamine group (n = 47) by the random number table method. All patients were continuously received intravenous (IV) remifentanil. In the dexmedetomidine group, dexmedetomidine 0.7 µg/kg was administered IV, followed by 0.2 to 0.5 µg/kg/h to maintain anesthesia, while in the esketamine group, esketamine 0.5 mg/kg was given IV 20 min after induction of anesthesia was completed. Results: Visual analogue scale (VAS) scores in the esketamine group were lower than in the dexmedetomidine group at 1, 6, 12 and 24 h postoperatively (P < .05), and Ramsay sedation scores were not statistically different from those in the dexmedetomidine group (P > .05). At 3 d postoperatively, the Mini-Mental State Examination (MMSE) scores in the dexmedetomidine group were lower than 1 d preoperatively; at 5 d postoperatively, the negative mood and Pittsburgh Sleep Quality Index (PSQI) scores were significantly higher in both groups than 1 d preoperatively; at 14 d postoperatively, the PSQI scores were higher in both groups than 1 d preoperatively, and there was no statistical difference between the negative mood scores at 1 d before surgery (P > .05). At 5 d postoperatively in the esketamine group, the negative mood scores were lower than in the dexmedetomidine group at 5 d postoperatively and the PSQI scores at 5 and 14 d postoperatively were lower than in the dexmedetomidine group (P < .05). Conclusion: Both esketamine and dexmedetomidine can be used to prevent postoperative delirium and nociceptive hypersensitivity after anesthesia in elderly patients with thoracic surgery. However, esketamine is superior to dexmedetomidine in analgesic effect, improvement of negative mood and sleep and stabilization of intraoperative hemodynamics, leading to better effect in preventing delirium and hyperalgesia after anesthesia.

Unveiling the Role and Mechanism of Nb Doping and In Situ Carbon Coating on Improving Lithium-Ion Storage Characteristics of Rod-Like Morphology FeF3 ·0.33H2 O.

Given the inherent characteristics of transition metal fluorides and open tunnel-type frameworks, intercalation-conversion-type FeF3 ·0.33H2 O has attracted widespread attention as a promising lithium-ion battery cathode material with high operating voltage and high energy density. However, its low electronic conductivity and poor structural stability impede its practical application in high-rate capacity and long-lifetime batteries. Herein, rod-like Nb-substituted FeF3 ·0.33H2 O (Nb-FeF3 ·0.33H2 O@C) nanocrystals with a carbon coating derived from in situ carbonization in an ionic liquid are deliberately designed and prepared. Based on first-principles calculations and electrochemical analysis, it is shown that substitution of Nb into a proportion of Fe sites can dramatically reduce the total energy of the system and the bandgap, thus boosting the structural stability and electronic conductivity of FeF3 ·0.33H2 O. Simultaneously, the combination of a surface conductive carbon coating and assembly of the nanoparticles into a rod-like mesoporous architecture can produce an omni-directional ion/electron transmission network and a robust 3D composite structure. The Nb-FeF3 ·0.33H2 O@C composite with 3% Nb-doping displays high capacity (583.2 mAh g-1 at 0.2 C), good rate capacity (187.8 mAh g-1 at a high rate of 5.0 C), and excellent long-term cycle stability (160.4 mAh g-1 after 300 long cycles).

Exploring the physicochemical role of Pd dopant in promoting Li-ion diffusion dynamics and storage performance of NbS2 at the atomic scale.

The two-dimensional layered niobium disulfide (NbS2), as a kind of anode material for Li-ion batteries, has received great attention because of its excellent electronic conductivity and structural stability. However, its ionic conductivity is far from desirable. Herein, we have proposed an effective way to acquire the rapid promotion of its Li-ion diffusion dynamics from the palladium doping effect. By first-principle calculations, we firstly investigated quantitative relations among lattice constants, mechanical properties, and Pd-doped concentration (x) for Pd doped NbS2 (PdxNbS2). It is found that the interlayer spacing of PdxNbS2 undergoes dramatic expansion, which contributes to affording its large space for Li-ion storage. And Pd0.25NbS2 has the best ductility, exhibiting its excellent destruction-resistant properties. Among PdxNbS2 (x = 0, 0.083, 0.167, 0.250, 0.333, and 0.417), it is also proved that Pd0.25NbS2 is the easiest to be prepared with the introduction of NbPd3 as the raw material for the Pd-dopant and it also exhibits excellent thermal stability at room temperature (300 K). Most importantly, by analysis with the climbing-image nudged elastic band method (CI-NEB), it is revealed that Pd0.25NbS2 shows the lowest Li-ion diffusion energy barrier of 0.26 eV, which is also much lower than that of NbS2 (0.43 eV). This is attributed to the inductive effect of the Pd-dopant in its layered structure, trying to maintain the Li-S six-coordinated structure at the initial state when Li-ions transfer to the saddle point. Accordingly, it induces a small structural difference in coordinate structures between initial states and transition states. Moreover, Pd0.25NbS2 undergoes a less obvious oxidation and reduction reaction, maintaining its excellent structural stability during Li intercalation/deintercalation. Additionally, the theoretical average voltage of Pd0.25NbS2 (1.75 V for Li0.75Pd0.25NbS2vs. Li/Li+) is also much lower than that of NbS2 (2.41 V vs. Li/Li+), implying that it can provide a higher power density. Therefore, our theoretical results pave a distinctive way to develop an ultrahigh-rate and long-life anode material for Li-ion batteries.

Resident- and Institutional-Level Factors, Frailty, and Nursing Homes Residents.

BACKGROUND: Frailty is a major cause of adverse health outcomes, such as hospitalization, falls, disability, and morbidity, among older adults; the elucidation of factors affecting frailty trends over time may facilitate the development of effective interventions. OBJECTIVES: This study aimed to examine the trend of frailty over time (at baseline, 6-month follow-up, and 12-month follow-up) among Chinese nursing home residents and identify associated resident- and institutional-level factors. METHODS: This longitudinal study included 353 residents who were admitted into 27 nursing homes in Jinan, China. Frailty was defined based on the seven self-reported components of the FRAIL-NH scale, which was designed for nursing home residents. Information was gathered using scales that assessed resident-level (sociodemographic characteristics and physical, psychological, and social factors) and institutional-level characteristics (hospital affiliation, fitness sites, green space, occupancy percentage, staff-resident ratio, and staff turnover rate). These data were subjected to a multilevel linear analysis. RESULTS: Frailty was identified in 49.7% of residents at baseline and exhibited a progressively worsening trend over 1 year. Among institutional-level characteristics, the provision of fitness sites in nursing homes was a protective factor for frailty. Among resident-level characteristics, undernutrition was a significant independent risk factor and played a key role in increasing frailty over time. Other risk factors for frailty included younger age, poorer self-rated health, lower physical function, chewing difficulty, loneliness, anxiety, and being less active in leisure activities. DISCUSSION: Frailty was highly prevalent among Chinese nursing home residents and gradually increased over time. The results of this study could be used to inform the development of interventions targeted at modifiable risk factors and shape public health policies aimed at promoting healthy aging and delaying frailty and its adverse outcomes.

Evaluation of the Load Reduction Performance Via a Suspended Backpack With Adjustable Stiffness.

Backpacks are essential for travel but carrying a load during a long journey can easily cause muscle fatigue and joint injuries. Previous studies have suggested that suspended backpacks can effectively reduce the energy cost while carrying loads. Researchers have found that adjusting the stiffness of a suspended backpack can optimize its performance. Therefore, this paper proposes a stiffness-adjustable suspended backpack; the system stiffness can be adjusted to suitable values at different speeds. The stiffness of the suspended backpack with a 5-kg load was designed to be 690 N/m for a speed of 4.5 km/h, and it was adjusted to 870 and 1050 N/m at speeds of 5.5 and 6.5 km/h, respectively. The goal of this study was to determine how carrying a stiffness-adjustable suspended backpack affected performance while carrying a load. Six healthy participants participated in experiments where they wore two backpacks under three conditions: the adjustable-stiffness suspended backpack condition (S_A), the unadjustable-stiffness suspended backpack condition (S_UA), and the ordinary backpack condition (ORB). Our results showed that the peak accelerations, muscle activities, and peak ground reaction forces in the S_A condition were reduced effectively by adjusting the stiffness to adapt to different walking speeds; this adjustment decreased the metabolic cost by 4.21 ± 1.21% and 2.68 ± 0.88% at 5.5 km/h and 4.27 ± 1.35% and 3.38 ± 1.31% at 6.5 km/h compared to the ORB and S_UA, respectively.

Coagulation parameters may predict clinical outcomes in patients with septic acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) and coagulation disorders are common complications of sepsis that affect its prognosis. However, the relationship between coagulation function and the prognosis of septic AKI has not been fully elucidated. MATERIALS AND METHODS: In this retrospective study, clinical data from patients with septic AKI admitted to the First Affiliated Hospital of Guangxi Medical University from June 2016 to March 2019 were analyzed. Based on clinical outcomes within 60 days, septic AKI patients were divided into a survival and non-survival group, and the survivors were divided into a recovered and non-recovered group depending on renal function. RESULTS: A total of 338 septic AKI patients were enrolled and followed up; 86 patients died, and 124 patients' renal function did not recover. The all-cause mortality rate in the septic AKI group was higher than in the non-AKI group by 1 : 1 propensity score matching (25.4 vs. 18.9%). The recovery rate for renal function was 50.8% (128/252), and 228 patients (67.5%) had at least one abnormal coagulation index. Logistic analysis indicated that male sex, advanced age, multiple organ dysfunction syndrome, thrombocytopenia, and an increased international standardized ratio (INR) were independent risk factors for all-cause mortality in septic AKI. Concomitant heart disease and prolonged activated partial thrombin time (APTT) were independent risk factors for renal function non-recovery among survivors. Kaplan-Meier curves showed that the cumulative survival rate was lower, and the mean survival time was shorter, in the abnormal coagulation parameter group compared to the normal coagulation parameter group (all p < 0.05). CONCLUSION: Many patients with septic AKI have a poor prognosis. Coagulation disorders, including thrombocytopenia, increased INR, and prolonged APTT might predict poor clinical outcomes in patients with septic AKI.

A chromatin perspective on metabolic and genotoxic impacts on hematopoietic stem and progenitor cells.

Fate determination in self-renewal and differentiation of hematopoietic stem and progenitor cells (HSCs and HPCs) is ultimately controlled by gene expression, which is profoundly influenced by the global and local chromatin state. Cellular metabolism directly influences the chromatin state through the dynamic regulation of the enzymatic activities that modify DNA and histones, but also generates genotoxic metabolites that can damage DNA and thus pose threat to the genome integrity. On the other hand, mechanisms modulating the chromatin state impact metabolism by regulating the expression and activities of key metabolic enzymes. Moreover, through regulating either DNA damage response directly or expression of genes involved in this process, chromatin modulators play active and crucial roles in guarding the genome integrity, breaching of which results in defective HSPC function. Therefore, HSPC function is regulated by the dynamic and two-way interactions between metabolism and chromatin. Here, we review recent advances that provide a chromatin perspective on the major impacts the metabolic and genotoxic factors can have on HSPC function and fate determination.

Patient characteristics associated with different types of prison TB: an epidemiological analysis of 921 TB cases diagnosed at an Ethiopian prison.

BACKGROUND: Despite incarcerated population being at an increased risk of tuberculosis (TB) and serving as a potential source of TB transmission for the general population, prison TB remains understudied. Given its adverse impact on progress towards TB elimination, World Health Organization (WHO) has identified prison TB research as a top priority to guide TB treatment/control interventions. METHODS: We retrospectively analyzed 921 notified TB cases that were diagnosed at Kality Federal Prison, Ethiopia during 2009-2017. To assess trends of microbiologically confirmed pulmonary TB (PTB), extra-pulmonary TB (EPTB), and TB-HIV co-infection, an ecological analysis of aggregated cases was used to report trends over time. Additionally, we used multivariable log binomial regression to identify patient characteristics associated with microbiologically confirmed PTB, EPTB, and TB-HIV co-infection. RESULTS: Microbiologically confirmed PTB proportion increased over time. Young age was identified as an important risk factor for EPTB (adjusted prevalence ratio [aPR] = 1.74, 95% CI 0.97, 3.13) while HIV coinfection was negatively associated with EPTB (aPR = 0.73, 95% CI 0.55, 0.97). While previous TB history was associated with a lower likelihood of EPTB (aPR = 0.42, 95% CI 0.25, 0.70), it was associated with an increased risk of TB-HIV coinfection (aPR = 1.37, 95% CI 1.10, 1.71). Clinically diagnosed PTB patients were more likely to have TB-HIV coinfection compared to microbiologically confirmed PTB patients (aPR = 1.32, 95% CI 1.02, 1.72). CONCLUSIONS: Increasing proportion of microbiologically confirmed PTB may suggest delayed access to treatment, severe disease and increased risk of intramural transmission. Associations with clinical/demographic factors varied for different types of TB and were not always consistent with what has been previously reported for the general population, necessitating the need to refocus prison TB control/treatment strategies based on context specific epidemiological factors.

Intrinsic laws of k-mer spectra of genome sequences and evolution mechanism of genomes.

BACKGROUND: K-mer spectra of DNA sequences contain important information about sequence composition and sequence evolution. We want to reveal the evolution rules of genome sequences by studying the k-mer spectra of genome sequences. RESULTS: The intrinsic laws of k-mer spectra of 920 genome sequences from primate to prokaryote were analyzed. We found that there are two types of evolution selection modes in genome sequences, named as CG Independent Selection and TA Independent Selection. There is a mutual inhibition relationship between CG and TA independent selections. We found that the intensity of CG and TA independent selections correlates closely with genome evolution and G + C content of genome sequences. The living habits of species are related closely to the independent selection modes adopted by species genomes. Consequently, we proposed an evolution mechanism of genomes in which the genome evolution is determined by the intensities of the CG and TA independent selections and the mutual inhibition relationship. Besides, by the evolution mechanism of genomes, we speculated the evolution modes of prokaryotes in mild and extreme environments in the anaerobic age and the evolving process of prokaryotes from anaerobic to aerobic environment on earth as well as the originations of different eukaryotes. CONCLUSION: We found that there are two independent selection modes in genome sequences. The evolution of genome sequence is determined by the two independent selection modes and the mutual inhibition relationship between them.