Perspectives of clinical research on Shen-Shuai-Ning in the treatment of diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most common chronic complications in patients with diabetes and remains a leading cause of end-stage renal disease. Despite current treatment strategies focusing primarily on blood glucose control and antihypertensive medications, their efficacy is often limited, failing to halt disease progression effectively. However, Shen-Shuai-Ning (SSN), a traditional Chinese medicine compound, has demonstrated significant clinical efficacy in DN treatment in recent years. SSN exerts multifaceted effects, including immunomodulation, attenuation of oxidative stress, and inhibition of fibrosis, leading to improvements in renal function indices and reductions in proteinuria levels, with favorable tolerability. Furthermore, when combined with conventional treatments, SSN exhibits enhanced therapeutic efficacy, providing a comprehensive and effective treatment strategy for DN patients. Future research endeavors should prioritize large-scale, multicenter clinical trials to validate its efficacy and safety across diverse populations, thereby further advancing its integration into clinical practice.

Comparative investigations on the metabolomic responses to cadmium in clams Ruditapes philippinarum from the Bohai Sea and South China Sea.

Cadmium (Cd) is a typical heavy metal contaminant along China coasts. Clams Ruditapes philippinarum are widely distributed in multiple climatic zones. However, few research has been conducted on the different responses to Cd in clams from different climatic zones. In this study, the temperate zone Bohai Sea (BS) and tropical zone South China Sea (SCS) clams exhibited distinct background metabolome profiles, characterized by different strategies of osmotic regulation, energy metabolism, and anaerobiosis tendencies, suggesting different tolerance and enrichment capacities to Cd. After Cd treatments, the BS clams demonstrated quicker and higher accumulations of Cd than the SCS clams. Despite differences in their background metabolomes, both BS and SCS clams displayed similar metabolomic responses to Cd, such as anaerobiosis inhibition and increased energy demands. Overall, these findings suggested that the inconsistency of biological responses induced by geographic conditions should be considered in ecotoxicological studies. CAPSULE ABSTRACT: This study elucidated the biological differences in clams Ruditapes philippinarum from the Bohai Sea and South China Sea, and the metabolomic responses in these two clam populations after Cd (200 µg/L) treatments.

Incidence of and risk factors for preoperative deep vein thrombosis in elderly patients with end-stage osteoarthritis following total knee arthroplasty: a retrospective cohort study.

BACKGROUND: Deep vein thrombosis (DVT) is a common and serious risk in elderly patients with knee osteoarthritis (OA), making preoperative detection crucial. Despite this, identifying OA patients at high risk for preoperative DVT and appropriately targeting them for venous ultrasound screening remains a challenge. There is limited research-based evidence on the risk factors for preoperative DVT in elderly patients with end-stage OA. We examined the incidence of and risk factors for preoperative DVT in elderly patients with end-stage OA scheduled for total knee arthroplasty. METHODS: We retrospectively analyzed the demographic data (age, sex, body mass index, current smoking, alcohol consumption, walking status, and Barthel index score), medical history, and laboratory test indices of 1411 patients with end-stage OA aged ≥ 60 years scheduled for total knee arthroplasty from January 2015 to December 2018. Risk factors for preoperative DVT were evaluated by univariate and multivariate logistic analyses. Receiver operating characteristic analysis was performed to determine optimal cut-off values. RESULTS: The incidence of preoperative DVT was 4.5% (63 of 1411 patients). Seven independent risk factors were correlated with preoperative DVT in the multivariate logistic regression: age (odds ratio [OR], 1.073; P = 0.002), D-dimer concentration (OR, 1.173; P = 0.003), hyperlipidemia (OR, 2.038; P = 0.045), atrial fibrillation (OR, 4.004; P = 0.033), chronic renal failure (OR, 6.732; P = 0.008), chronic obstructive pulmonary disease (COPD) (OR, 8.721; P = 0.001), and walking status (wheelchair) (OR, 2.697; P = 0.002). The optimal cut-off values for predicting preoperative DVT were 0.585 µg/mL for the D-dimer concentration (area under the curve [AUC], 0.769; P < 0.001) and 72.5 years for age (AUC, 0.668; P < 0.001). CONCLUSION: Among elderly patients with end-stage OA, venous ultrasonography to rule out DVT risk should be prioritized in those with a high D-dimer concentration (> 0.585 µg/mL), high age (> 72.5 years), hyperlipidemia, atrial fibrillation, chronic renal failure, COPD, and walking status (wheelchair).

Methylobacterium flocculans sp. nov., a Floc-Forming Bacterium Isolated from Aquaculture Ponds.

Strain FF17T, a Gram-negative, obligate aerobic, motile, pink-pigmented, and methylotrophic bacterium, was selected for a polyphasic taxonomic investigation due to its capacity for aggregation, or floc formation. The predominant respiratory quinone observed was Q-10, accounting for 83.36% of the total, while the major fatty acids were summed feature 8 (18:1 w6c and/or 18:1 w7c). The major polar lipids included Diphosphatidylglycerol (DPG), phosphatidylglycerol, phosphatidylethanolamine (PE), phosphatidylinositol (PI), and one unknown polar lipid. Phylogenetic analysis showed that strain FF17T was hithermost related to Methylobacterium goesingense iEII3T (99.86%), M. gossipiicola Gh-105 T (99.22%), M. adhaesivum AR27T (98.92%), and M. iners 5317S-33 T (97.27%) based on 16S rRNA gene sequence similarity. A 5,735,273-bp chromosome and six plasmids make up the genome, making it larger than the genomes of the other four Methylobacterium species described above. The digital DNA-DNA hybridization and average nucleotide identity values between strain FF17T and the reference strains were 21.90-28.70 and 77.39-85.04%, respectively. Strain FF17T had a genome DNA G + C content of 68.5 mol%. The analysis of genomes indicated that cellulose apparently plays an important character in the aggregation of Methylobacterium species. Genome annotation revealed the presence of genes involved in assimilatory/dissimilatory nitrate reduction and ammonia assimilation. In conclusion, Strain FF17T is identified as a new species in the Methylobacterium genus, based on analyses of genomics, phylogeny, biochemistry, and fatty acids, and the name Methylobacterium flocculans sp. nov. is proposed. The type strain is FF17T (= MCCC 1K08738T = KCTC 8320 T).

CD8 cell-derived granzyme B may be a predictor for Coronary artery involvement and MACE in Takayasu arteritis patients.

Coronary artery involvement (CAI) is a special but not rare manifestation of Takayasu arteritis (TAK). Granzyme B (GzmB) is a multifunctional protease associated with the immune system and coronary artery disease. However, its role in patients with TAK and CAI remains unclear. This study investigates the role of GzmB+ cell subsets in TAK. The study included 105 TAK patients and 58 healthy controls. The percentages of different GzmB+ cells in blood samples were analyzed by flow cytometry. We found that age, age at onset, BMI, disease duration month, hypertension, and hyperlipidemia were significantly different between TAK patients with and without CAI (P=0.000, P=0.038, P=0.003, P=0.031, P=0.039, P=0.000). The proportions of CD3+CD8+cells (P=0.001) and CD3+CD4+cells (P=0.000) in GzmB+ cells were significantly increased, while the proportion of CD3-CD56+cells (P=0.001) in GzmB+ cells was decreased in TAK patients. The proportions of three types of GzmB+ subsets in lymphocytes (CD3+CD4+GzmB+, CD3+CD8+GzmB+, CD3+CD56+ GzmB+) were higher in TAK patients with CAI compared to those without CAI (P=0.021, P=0.007, P=0.007). The increased proportion of CD3+CD8+GzmB+cells/lymphocytes was an independent risk factor for coronary involvement in TAK (OR=4.990 [1.766-14.098], P=0.002). Additionally, patients with a high CD3+CD8+GzmB+cells/lymphocytes ratio had a higher MACE rate than those with a low ratio in TAK (P=0.019). Our results indicate that CD8 cell-derived Gzm B may be a predictor for CAI and MACE in TAK patients. Targeting CD3+CD8+GzmB+ lymphocytes or using GzmB inhibitors could be a potential therapeutic approach for the treatment of CAI in TAK.

A multidimensional recommendation framework for identifying biological targets to aid the diagnosis and treatment of liver metastasis in patients with colorectal cancer.

The quest to understand the molecular mechanisms of tumour metastasis and identify pivotal biomarkers for cancer therapy is increasing in importance. Single-omics analyses, constrained by their focus on a single biological layer, cannot fully elucidate the complexities of tumour molecular profiles and can thus overlook crucial molecular targets. In response to this limitation, we developed a multiobjective recommendation system (RJH-Metastasis 1.0) anchored in a multiomics knowledge graph to integrate genome, transcriptome, and proteome data and corroborative literature evidence and then conducted comprehensive analyses of colorectal cancer with liver metastasis (CRCLM). A total of 25 key genes significantly associated with CRCLM were recommended by our system, and GNB1, GATAD2A, GBP2, MACROD1, and EIF5B were further highlighted. Specifically, GNB1 presented fewer mutations but elevated RNA transcription and protein expression in CRCLM patients. The role of GNB1 in promoting the malignant behaviours of colon cancer cells was demonstrated via in vitro and in vivo studies. Aberrant expression of GNB1 could be regulated by METTL1-driven m7G modification. METTL1 knockdown decreased m7G modification in the 3' UTR of GNB1, increasing its mRNA transcription and translation during liver metastasis. Furthermore, GNB1 induced the formation of an immunosuppressive microenvironment by promoting the CLEC2C-KLRB1 interaction between memory B cells and KLRB1+PD-1+CD8+ cells. GNB1 expression and the efficacy of PD-1 antibody-based treatment in CRCLM patients were significantly correlated. In summary, our recommendation system can be used for effective exploration of key molecules in colorectal cancer, among which GNB1 was identified as a critical CRCLM promoter and immunotherapy biomarker in colorectal cancer patients.

Application of bone perforation in the surgery of medication-related osteonecrosis of the jaw in stage â ¡.

OBJECTIVES: This study aimed to explore the effect of surgery combined with bone perforation for treating stage Ⅱ medication-related osteonecrosis of the jaw (MRONJ). METHODS: A total of 21 patients with stage Ⅱ mandibular MRONJ who underwent surgical treatment from June 2020 to June 2023 were included in this study. Retrospective analysis was conducted on their clinical data, including gender, age, primary disease, drug name and administration method, pre-surgery drug cessation, and prognosis. The cohort comprised 14 males and 7 females, with an average age at onset of 68.33±10.74 years. According to the guidelines of the American Association of Oral and Maxillofacial Surgeons, the included patients had stage Ⅱ mandibular MRONJ. The treatment approach consisted of partial mandibulectomy combined with bone perforation techniques, ensuring tension-free suturing of soft tissues. Follow-up was performed regularly, and the curative effect was evaluated. The SF-12 health survey was used to assess the quality of life for all patients before and after surgery. RESULTS: A total of 21 patients were followed up for 8-38 months after surgery, and the mucosal healing of 17 patients was good (80.95%). The postoperative quality of life score (83.62±5.90) was significantly higher than that before operation (63.67±4.70, P<0.05). CONCLUSIONS: Surgery combined with bone perforation te-chnique is an effective treatment method with high success rate in refractory stage Ⅱ MRONT patients.

Combined metabolomic and microbial community analyses reveal that biochar and organic manure alter soil C-N metabolism and greenhouse gas emissions.

The use of biochar to reduce the gas emissions from paddy soils is a promising approach. However, the manner in which biochar and soil microbial communities interact to affect CO2, CH4, and N2O emissions is not clearly understood, particularly when compared with other amendments. In this study, high-throughput sequencing, soil metabolomics, and quantitative real-time PCR were utilized to compare the effects of biochar (BC) and organic manure (OM) on soil microbial community structure, metabolomic profiles and functional genes, and ultimately CO2, CH4, and N2O emissions. Results indicated that BC and OM had opposite effects on soil CO2 and N2O emissions, with BC resulting in lower emissions and OM resulting in higher emissions, whereas BC, OM, and their combined amendments increased cumulative CH4 emissions by 19.5 %, 31.6 %, and 49.1 %, respectively. BC amendment increased the abundance of methanogens (Methanobacterium and Methanocella) and denitrifying bacteria (Anaerolinea and Gemmatimonas), resulting in an increase in the abundance of mcrA, amoA, amoB, and nosZ genes and the secretion of a flavonoid (chrysosplenetin), which caused the generation of CH4 and the reduction of N2O to N2, thereby accelerating CH4 emissions while reducing N2O emissions. Simultaneously, OM amendment increased the abundance of the methanogen Caldicoprobacter and denitrifying Acinetobacter, resulting in increased abundance of mcrA, amoA, amoB, nirK, and nirS genes and the catabolism of carbohydrates [maltotriose, D-(+)-melezitose, D-(+)-cellobiose, and maltotetraose], thereby enhancing CH4 and N2O emissions. Moreover, puerarin produced by Bacillus metabolism may contribute to the reduction in CO2 emissions by BC amendment, but increase in CO2 emissions by OM amendment. These findings reveal how BC and OM affect greenhouse gas emissions by modulating soil microbial communities, functional genes, and metabolomic profiles.

Artemisinin attenuates perinatal inflammation and consequent oxidative stress in oligodendrocyte precursor cells by inhibiting IRAK-4 and IRAK-1.

BACKGROUND: The main causes of abnormal white matter development (periventricular leukomalacia) in premature infants are perinatal inflammation and the consequent oxidant/antioxidant imbalance in oligodendrocyte precursor cells (OPCs); however, the underlying mechanisms remain largely unclear. In this work, a rat model of prenatal inflammation was used to examine the mechanism by which artemisinin (ART) protects against white matter dysplasia. METHODS: We established a primary OPC model and rat model of perinatal inflammation. ART was identified from the FDA-approved medicinal chemical library to be beneficial for treating OPC inflammation in model systems. Based on bioinformatics analysis of protein interactions and molecular docking analysis, we further identified the possible targets of ART and evaluated its specific effects and the underlying molecular mechanisms in vivo and in vitro. RESULTS: Following inflammatory stimulation, ART strongly promoted the maturation of OPCs and the development of white matter in the brain. A Cellular thermal shift assay (CETSA) demonstrated that interleukin-1 receptor-associated kinase-4 (IRAK-4) and interleukin-1 receptor-associated kinase-1 (IRAK-1) may be targets of ART, which was consistent with the findings from molecular modelling with Autodock software. Experiments conducted both in vivo and in vitro demonstrated the activation of the IRAK-4/IRAK-1/nuclear factor kappa-B (NF-κB) pathway and the production of inflammatory factors (IL-1ß, IL-6, and TNF-α) in OPCs were greatly suppressed in the group treated with ART compared to the lipopolysaccharide (LPS)-treated group. Moreover, ART dramatically decreased reactive oxygen species (ROS) levels in OPCs while increasing nuclear factor e2-related factor 2 (Nrf2) levels. CONCLUSION: Our findings suggest that ART can significantly reduce OPC perinatal inflammation and consequent oxidative stress. The targeted inhibition of IRAK-4 and IRAK-1 by ART may be a potential therapeutic strategy for alleviating abnormalities in white matter development in premature newborns.

Static magnetic field contributes to osteogenic differentiation of hPDLSCs through the H19/Wnt/ß-catenin axis.

BACKGROUND: Static magnetic field (SMF) as an effective physical stimulus is capable of osteogenic differentiation for multiple mesenchymal stem cells, including human periodontal ligament stem cells (hPDLSCs). However, the exact molecular mechanism is still unknown. Therefore, this study intends to excavate molecular mechanisms related to SMF in hPDLSCs using functional experiments. METHODS: hPDLSCs were treated with different intensities of SMF, H19 lentivirus, and Wnt/ß-catenin pathway inhibitor (XAV939). Changes in osteogenic markers (Runx2, Col Ⅰ, and BMP2), Wnt/ß-catenin markers (ß-catenin and GSK-3ß), and calcified nodules were examined using RT-qPCR, western blotting, and alizarin red staining in hPDLSCs. RESULTS: SMF upregulated the expression of H19, and SMF and overexpressing H19 facilitated the expression of osteogenic markers (Runx2, Col Ⅰ, and BMP2), activation of the Wnt/ß-catenin pathway, and mineralized sediment in hPDLSCs. Knockdown of H19 alleviated SMF function, and treatment with XAV939 limited SMF- and H19-mediated osteogenic differentiation of hPDLSCs. Notably, the expression of hsa-miR-532-3p, hsa-miR-370-3p, hsa-miR-18a-5p, and hsa-miR-483-3p in hPDLSCs was regulated by SMF, and may form an endogenous competitive RNA mechanism with H19 and ß-catenin. CONCLUSION: SMF contributes to the osteogenic differentiation of hPDLSCs by mediating the H19/Wnt/ß-catenin pathway, and hsa-miR-532-3p, hsa-miR-370-3p, hsa-miR-18a-5p, and hsa-miR-483-3p may be the key factors in it.

Hepatitis B virus enhancer 1 activates preS1 and preS2 promoters of integrated HBV DNA impairing HBsAg secretion.

Background & Aims: The expression of HBsAg from integrated HBV DNA limits the achievement of functional cure for chronic hepatitis B. Thus, characterising the unique expression and secretion of HBsAg derived from integrated HBV DNA is of clinical significance. Methods: A total of 563 treatment-naive patients and 62 functionally cured patients were enrolled, and HBsAg and HBcAg immunohistochemistry of their liver biopsy tissues was conducted followed by semi-quantitative analysis. Then, based on stratified analysis of HBeAg-positive and -negative patients, long-read RNA sequencing analysis, as well as an in vitro HBV integration model, we explored the HBsAg secretion characteristics of integrated HBV DNA and underlying mechanisms. Results: In contrast to the significantly lower serum HBsAg levels, no significant decrease of intrahepatic HBsAg protein was observed in HBeAg-negative patients, as compared with HBeAg-positive patients. The results of long-read RNA sequencing of liver tissues from patients with chronic HBV infection and in vitro studies using integrated HBV DNA mimicking dslDNA plasmid revealed that, the lower HBsAg secretion efficiency seen in HBeAg-negative patients might be attributed to an increased proportion of preS1 mRNA derived from integrated HBV DNA instead of covalently closed circular DNA. The latter resulted in an increased L-HBsAg proportion and impaired HBsAg secretion. Enhancer 1 (EnhI) in integrated HBV DNA could retarget preS1 (SP1) and preS2 (SP2) promoters to disrupt their transcriptional activity balance. Conclusions: The secretion of HBsAg originating from integrated HBV DNA was impaired. Mechanistically, functional deficiency of core promoter leads to retargeting of EnhI and thus uneven activation of the SP1 over the SP2 promoter, resulting in an increase in the proportion of L-HBsAg. Impact and implications: Integrated hepatitis B virus (HBV) DNA can serve as an important reservoir for HBV surface antigen (HBsAg) expression, and this limits the achievement of a functional cure. This study revealed that secretion efficiency is lower for HBsAg derived from integrated HBV DNA than HBsAg derived from covalently closed circular DNA, as determined by the unique sequence features of integrated HBV DNA. This study can broaden our understanding of the role of HBV integration and shed new light on antiviral strategies to facilitate a functional cure. We believe our results are of great general interest to a broad audience, including patients and patient organisations, the medical community, academia, the life science industry and the public.

Polyphenols in health and food processing: antibacterial, anti-inflammatory, and antioxidant insights.

Polyphenols, as subordinate metabolites of plants, have demonstrated significant antibacterial, anti-inflammatory, and antioxidant action in scientific learn. These compounds exert their effects through various mechanisms, containing interference with microbial cell structures, rule of host immune responses, and neutralization of free radicals. This multifaceted activity positions polyphenols as promising candidates for maintaining human health and treating related diseases. Notably, in the context of escalating antibiotic resistance, the antibacterial properties of polyphenols offer innovative avenues for the development of new therapeutic agents. Additionally, their anti-inflammatory and antioxidant effects hold substantial potential for treating inflammatory diseases and mitigating the aging process. This review aims to summarize the latest findings on the biological activities of polyphenols, highlighting their mechanisms of action and potential applications in health and disease management. Furthermore, optimizing polyphenol extraction methods aligns with the goals of sustainable and green processing, reducing environmental impact while enhancing food safety and extending shelf life. Employing advanced analytical techniques, such as spectroscopy and chromatography, can ensure the accurate evaluation of polyphenol content and efficacy. These efforts collectively contribute to the ongoing improvement of food processing practices and product quality, promoting a healthier and more sustainable future in the food industry.

Discovery of CYP2E1 as a novel target in rheumatoid arthritis and validation by a new specific CYP2E1 inhibitor.

Considerable evidence indicates that CYP2E1 is associated with a variety of inflammatory diseases. Here we evaluated CYP2E1 as a potential therapeutic target for rheumatoid arthritis (RA) and established the protective effect of a new CYP2E1 inhibitor. Gene-expression datasets were used to analyze the change in expression of CYP2E1 in RA patients; CYP2E1 activity in collagen-induced arthritis (CIA) rats was determined by HPLC. We further evaluated the protective effects of Cyp2e1 knockout and a CYP2E1-specific inhibitor, Q11, synthesized by our group, in CIA and adjuvant-induced arthritis (AIA) rats. The expression of CYP2E1 in synovial tissue was elevated in RA patients and in CIA rats and the activity of CYP2E1 in vivo and in vitro in CIA rats was greater than that of controls. Cyp2e1 knockout significantly reduced the incidence of CIA and alleviated the severity of symptoms. Treatment with different doses of Q11 decreased paw thickness, volume and arthritis scores and reduced the serum levels of IL-6, TNF-α, IL-1ß and MDA, and increased the level of GSH in CIA rats. A similar inhibitory effect was exhibited for Q11 in the AIA rats. Moreover, Q11 significantly impeded proliferation, migration, and invasion of human rheumatoid arthritis synovial fibroblasts cells. Q11 decreased the release of ROS and enhanced Nrf2 nuclear translocation and HO-1 expression in the cell nucleus. Overall, our results indicated that CYP2E1 may be a new target for RA and Q11 has potential protective effects against RA by reducing oxidative stress and opposing the inflammatory response via the ROS/Nrf2/HO-1 signaling pathway.

Integrated multi-omics characterization of SMAD4 mutant colorectal cancer.

Colorectal cancer is one of the most common cancers around the world, which is a severe threat to people's health. SMAD4 belongs to the dwarfin/SMAD family, which plays a crucial role in TGF-ß and BMP signal pathways. As the molecular characterization of colon cancer patients following SMAD4 mutations remains unclear, we integrated multi-omics data of SMAD4 mutant patients to reveal the profile of molecular characterization of SMAD4 mutation. A missense mutation is the most common mutant type of SMAD4. Patients with SMAD4 mutation had worse survival. Tumor tissues from patients carrying the SMAD4 mutation showed a reduction in various immune cells, such as CD4 + memory T cells and memory B cells. Many differential genes were identified compared to the SMAD4 mutation-free group and could be significantly enriched for tumor- and immune-related signaling pathways. In addition, the mutant group had different drug sensitivities than the non-mutant group.

Correlates of Frailty in Hospitalized Older Adults with Hypertension and Its Influence on Clinical Prognosis.

Objective: This study aims to explore the correlates of frailty in hospitalized elderly hypertensive patients and its impact on clinical prognosis, and to construct a predictive model for the occurrence of frailty in this population. Methods: A cross-sectional and prospective observational cohort study was conducted, involving 312 elderly hypertensive patients diagnosed at the institution from January to June 2022. Frailty was diagnosed using the Fried Frailty Phenotype (FP), while the Charlson Comorbidities Index (CCI) assessed the presence of chronic conditions. Data analysis was performed using SPSS 22.0. Binary logistic regression analysis was conducted with frailty as the dependent variable to identify risk factors. Patients were followed for one year to monitor readmission rates and all-cause mortality. Results: Multivariate logistic regression identified CCI grade (P=0.030), gender (OR=21.618, 95% CI: 4.062-115.061, P < 0.001), age (OR=1.147, 95% CI: 1.086-1.211, P < 0.001), bedridden state (OR=11.620, 95% CI: 3.282-41.140, P < 0.001), arrhythmia (OR=14.414, 95% CI: 4.558-45.585, P < 0.001), heart failure (OR=5.439, 95% CI: 1.029-28.740, P < 0.05), along with several biochemical markers, as independent predictors of frailty. A predictive model was developed, demonstrating a robust discriminative ability with an area under the receiver operating characteristic curve (AUC) of 0.915. Statistically significant differences in readmission rates and all-cause mortality were observed among the frail, pre-frail, and non-frail groups (P<0.001), with the frail group exhibiting the highest incidence of these adverse outcomes. Notably, frailty emerged as a significant predictor of readmission (P<0.05) but not of all-cause mortality in this cohort. Conclusion: This study establishes a robust frailty prediction model for elderly hypertensive patients, highlighting the influence of CCI grade, gender, age, and other clinical and biochemical factors on frailty. The model offers a valuable tool for healthcare providers to identify at-risk elderly individuals, facilitating targeted intervention strategies for cardiovascular disease management.

Nitrate transporters and mechanisms of nitrate signal transduction in Arabidopsis and rice.

Nitrate (NO3 -) is a significant inorganic nitrogen source in soil, playing a crucial role in influencing crop productivity. As sessile organisms, plants have evolved complex mechanisms for nitrate uptake and response to varying soil levels. Recent advancements have enhanced our understanding of nitrate uptake and signaling pathways. This mini-review offers a comparative analysis of nitrate uptake mechanisms in Arabidopsis and rice. It also examines nitrate signal transduction, highlighting the roles of AtNRT1.1 and AtNLP7 as nitrate receptors and elucidating the OsNRT1.1B-OsSPX4-OsNLP3 cascade. Additionally, it investigates nuclear transcriptional networks that regulate nitrate-responsive genes, controlled by various transcription factors (TFs) crucial for plant development. By integrating these findings, we highlight mechanisms that may help to enhance crop nitrogen utilization.

[A multicenter clinical study of critically ill patients with sepsis complicated with acute kidney injury in Beijing: incidence, clinical characteristics and outcomes].

OBJECTIVE: To investigate the epidemiological characteristics and prognosis of critically ill patients with sepsis combined with acute kidney injury (AKI) in intensive care unit (ICU) in Beijing, and to analyze the risk factors associated with in-hospital mortality among these critically ill patients. METHODS: Data were collected from the Beijing AKI Trial (BAKIT) database, including 9 049 patients consecutively admitted to 30 ICUs in 28 tertiary hospitals in Beijing from March 1 to August 31, 2012. Patients were divided into non-AKI and non-sepsis group, AKI and non-sepsis group, non-AKI and sepsis group, AKI and sepsis group. Clinical data recorded included demographic characteristics, primary reasons for ICU admission, comorbidities, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II(APACHE II) within 24 hours of ICU admission, physiological and laboratory indexes, treatment in the ICU, AKI staging based on the Kidney Disease: Improving Global Outcomes (KDIGO), as well as the prognostic indicators including length of stay in ICU, length of stay in hospital, ICU and in-hospital mortality. The primary endpoint was discharge or in-hospital death. Multivariate Logistic regression analysis was used to investigate the risk factors for hospital death in ICU patients. Kaplan-Meier survival curve was drawn to analyze the cumulative survival of ICU patients during hospitalization. RESULTS: A total of 3 107 critically ill patients were ultimately enrolled, including 1 259 cases in the non-AKI and non-sepsis group, 931 cases in the AKI and non-sepsis group, 264 cases in the non-AKI and sepsis groups, and 653 cases in the AKI and sepsis group. Compared with the other three group, patients in the AKI and sepsis group were the oldest, had the lowest mean arterial pressure (MAP), and the highest APACHE II score, SOFA score, blood urea nitrogen (BUN), and serum creatinine (SCr) levels, and they also had the highest proportion of receiving mechanical ventilation, requiring vasopressor support, and undergoing renal replacement therapy (RRT), all P < 0.01. Of these 3 107 patients, 1 584 (51.0%) were diagnosed with AKI, and the incidence of AKI in patients with sepsis was significantly higher than in those without sepsis [71.2% (653/917) vs. 42.5% (931/2 190), P < 0.01]. The highest proportion of KDIGO 0 stage was observed in the non-sepsis group (57.5%), while the highest proportion of KDIGO 3 stage was observed in the sepsis group (32.2%). Within the same KDIGO stage, the mortality of patients with sepsis was significantly higher than that of non-sepsis patients (0 stage: 17.8% vs. 3.1%, 1 stage: 36.3% vs. 7.4%, 2 stage: 42.7% vs. 17.1%, 3 stage: 54.6% vs. 28.6%, AKI: 46.1% vs. 14.2%). The ICU mortality (38.7%) and in-hospital mortality (46.1%) in the AKI and sepsis group were significantly higher than those in the other three groups. Kaplan-Meier survival curves further showed that the cumulative survival rate of patients with AKI and sepsis during hospitalization was significantly lower than that of the other three groups (53.9% vs. 96.9%, 85.8%, 82.2%, Log-Rank: χ 2 = 379.901, P < 0.001). Subgroup analysis showed that among surviving patients, length of ICU stay and total length of hospital stay were significantly longer in the AKI and sepsis group than those in the other three groups (both P < 0.01). Multivariate regression analysis showed that age, APACHE II score and SOFA score within 24 hours of ICU admission, coronary heart disease, AKI, sepsis, and AKI combined with sepsis were independent risk factors for ICU mortality in patients (all P < 0.05). After adjusting for covariates, AKI, sepsis, and sepsis combined with AKI were significantly associated with higher ICU and in-hospital mortality, with the highest ICU mortality [adjusted odds ratio (OR) = 14.82, 95% confidence interval (95%CI) was 8.10-27.12; Hosmer-Lemeshow test: P = 0.816] and in-hospital mortality (adjusted OR = 7.40, 95%CI was 4.94-11.08; Hosmer-Lemeshow test: P = 0.708) observed in patients with sepsis combined with AKI. CONCLUSIONS: The incidence of AKI is high in sepsis patients, and those with both AKI and sepsis have a higher disease burden, more abnormalities in physiological and laboratory indicators, and significantly increased ICU and in-hospital mortality. Among surviving patients, the length of ICU stay and total length of hospital stay are also longer in the AKI and sepsis group. Age, APACHE II score and SOFA score within 24 hours of ICU admission, coronary heart disease, AKI, and sepsis are independent risk factors for in-hospital mortality in ICU patients.

Interferon-α could induce liver steatosis to promote HBsAg loss by increasing triglyceride level.

Background: The correlation between metabolic syndrome (MetS) and hepatitis B surface antigen (HBsAg) loss remains to be further elucidated, particularly in patients receiving pegylated interferon-α (PEG-IFN) treatment. Methods: 758 patients with low HBsAg quantification who had received nucleos(t)ide analog (NUC) therapy for at least one year and subsequently switched to or add on PEG-IFN therapy over an unfixed course were enrolled. 412 patients were obtained with baseline data matched. A total of 206 patients achieved HBsAg loss (cured group) within 48 weeks. Demographic and biochemical data associated with MetS were gathered for analysis. HepG2.2.15 cell line was used in vitro experiments to validate the efficacy of interferon-α (IFN-α). Results: The proportion of patients with diabetes or hypertension in the uncured group was significantly higher than in the cured group. The levels of fasting blood glucose (FBG) and glycated albumin remained elevated in the uncured group over the 48 weeks. In contrast, the levels of blood lipids and uric acid remained higher in the cured group within 48 weeks. Triglycerides levels and liver steatosis of all patients increased after PEG-IFN therapy. Baseline elevated uric acid levels and hepatic steatosis may be beneficial for HBsAg loss. IFN-α could induce hepatic steatosis and indirectly promote HBsAg loss by increasing triglyceride level through upregulation of acyl-CoA synthetase long-chain family member 1(ACSL1). Conclusions: IFN-α could induce liver steatosis to promote HBsAg loss by increasing triglyceride level through upregulation of ACSL1. Comorbid diabetes may be detrimental to obtaining HBsAg loss with PEG-IFN therapy in CHB patients.

MICAL1 promotes the proliferation in acute myeloid leukemia and is associated with clinical prognosis and immune infiltration.

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies that has a poor prognosis and a high rate of relapse. Dysregulated metabolism plays an important role in AML progression. This study aimed to conduct a comprehensive analysis of MRGs using TCGA and GEO datasets and further explore the potential function of critical MRGs in AML progression. In this study, we identified 17 survival-related differentially expressed MRGs in AML using TCGA and GEO datasets. The 150 AML samples were divided into three molecular subtypes using 17 MRGs, and we found that three molecular subtypes exhibited a different association with ferroptosis, cuproptosis and m6A related genes. Moreover, a prognostic signature that comprised nine MRGs and had good predictive capacity was established by LASSO-Cox stepwise regression analysis. Among the 17 MRGs, our attention focused on MICAL1 which was highly expressed in many types of tumors, including AML and its overexpression was also confirmed in several AML cell lines. We also found that the expression of MICAL1 was associated with several immune cells. Moreover, functional experiments revealed that knockdown of MICAL1 distinctly suppressed the proliferation of AML cells. Overall, this study not only contributes to a deeper understanding of the molecular mechanisms underlying AML but also provides potential targets and prognostic markers for AML treatment. These findings offer robust support for further research into therapeutic strategies and mechanisms related to AML, with the potential to improve the prognosis and quality of life for AML patients. Nevertheless, further research is needed to validate these findings and explore more in-depth molecular mechanisms.