Novel Therapies for ANCA-associated Vasculitis: Apilimod Ameliorated Endothelial Cells Injury through TLR4/NF-κB Pathway and NLRP3 Inflammasome.

BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a rapidly progressive form of glomerulonephritis for which effective therapeutic drugs are currently lacking, and its underlying mechanism remains unclear. AIMS: This study aimed to investigate new treatment options for AAV through a combination of bioinformatics analysis and cell molecular experiments. METHODS: The research utilized integrated bioinformatics analysis to identify genes with differential expression, conduct enrichment analysis, and pinpoint hub genes associated with AAV. Potential therapeutic compounds for AAV were identified using Connectivity Map and molecular docking techniques. In vitro experiments were then carried out to examine the impact and mechanism of apilimod on endothelial cell injury induced by MPO-ANCA-positive IgG. RESULTS: The findings revealed a set of 374 common genes from differentially expressed genes and key modules of WGCNA, which were notably enriched in immune and inflammatory response processes. A proteinprotein interaction network was established, leading to the identification of 10 hub genes, including TYROBP, PTPRC, ITGAM, KIF20A, CD86, CCL20, GAD1, LILRB2, CD8A, and COL5A2. Analysis from Connectivity Map and molecular docking suggested that apilimod could serve as a potential therapeutic cytokine inhibitor for ANCA-GN based on the hub genes. In vitro experiments demonstrated that apilimod could mitigate tight junction disruption, endothelial cell permeability, LDH release, and endothelial activation induced by MPO-ANCA-positive IgG. Additionally, apilimod treatment led to a significant reduction in the expression of proteins involved in the TLR4/NF-κB and NLRP3 inflammasome-mediated pyroptosis pathways. CONCLUSION: This study sheds light on the potential pathogenesis of AAV and highlights the protective role of apilimod in mitigating MPO-ANCA-IgG-induced vascular endothelial cell injury by modulating the TLR4/ NF-kB and NLRP3 inflammasome-mediated pyroptosis pathway. These findings suggest that apilimod may hold promise as a treatment for AAV and warrant further investigation.

Determinants of macaques' space use: A test for the ecological constraints model using GPS collars.

As a central topic in Behavioral Ecology, animal space use involves dynamic responses to social and ecological factors. We collared 22 rhesus macaques (Macaca mulatta) from six groups on Neilingding Island, China, and collected 80,625 hourly fixes over a year. Using this high-resolution location data set, we quantified the macaques' space use at the individual level and tested the ecological constraints model while considering various environmental and human interfering factors. As predicted by the ecological constraints model, macaques in larger groups had longer daily path lengths (DPLs) and larger home ranges. We found an inverted U-shape relationship between mean daily temperatures and DPLs, indicating that macaques traveled farther on mild temperature days, while they decreased DPLs when temperatures were too high or too low. Anthropogenic food subsidies were positively correlated to DPLs, while the effect of rainfall was negative. Macaques decreased their DPLs and core areas when more flowers and less leaves were available, suggesting that macaques shifted their space use patterns to adapt to the seasonal differences in food resources. By applying GPS collars on a large number of individuals living on a small island, we gained valuable insights into within-group exploitation competition in wild rhesus macaques.

Role of gut microbiota in regulating immune checkpoint inhibitor therapy for glioblastoma.

Glioblastoma (GBM) is a highly malignant, invasive, and poorly prognosed brain tumor. Unfortunately, active comprehensive treatment does not significantly prolong patient survival. With the deepening of research, it has been found that gut microbiota plays a certain role in GBM, and can directly or indirectly affect the efficacy of immune checkpoint inhibitors (ICIs) in various ways. (1) The metabolites produced by gut microbiota directly affect the host's immune homeostasis, and these metabolites can affect the function and distribution of immune cells, promote or inhibit inflammatory responses, affect the phenotype, angiogenesis, inflammatory response, and immune cell infiltration of GBM cells, thereby affecting the effectiveness of ICIs. (2) Some members of the gut microbiota may reverse T cell function inhibition, increase T cell anti-tumor activity, and ultimately improve the efficacy of ICIs by targeting specific immunosuppressive metabolites and cytokines. (3) Some members of the gut microbiota directly participate in the metabolic process of drugs, which can degrade, transform, or produce metabolites, affecting the effective concentration and bioavailability of drugs. Optimizing the structure of the gut microbiota may help improve the efficacy of ICIs. (4) The gut microbiota can also regulate immune cell function and inflammatory status in the brain through gut brain axis communication, indirectly affecting the progression of GBM and the therapeutic response to ICIs. (5) Given the importance of gut microbiota for ICI therapy, researchers have begun exploring the use of fecal microbiota transplantation (FMT) to transplant healthy or optimized gut microbiota to GBM patients, in order to improve their immune status and enhance their response to ICI therapy. Preliminary studies suggest that FMT may enhance the efficacy of ICI therapy in some patients. In summary, gut microbiota plays a crucial role in regulating ICIs in GBM, and with a deeper understanding of the relationship between gut microbiota and tumor immunity, it is expected to develop more precise and effective personalized ICI therapy strategies for GBM, in order to improve patient prognosis.

Hybrid Microneedle-Mediated Transdermal Delivery of Atorvastatin Calcium-Loaded Polymeric Micelles for Hyperlipidemia Therapy.

Hyperlipidemia has been a huge challenge to global health, leading to the cardiovascular disease, hypertension, and diabetes. Atorvastatin calcium (AC), a widely prescribed drug for hyperlipidemia, faces huge challenges with oral administration due to poor water solubility and hepatic first-pass effects, resulting in low therapeutic efficacy. In this work, we designed and developed a hybrid microneedle (MN) patch system constructed with soluble poly(vinyl alcohol) (PVA) and AC-loaded polymeric micelles (AC@PMs) for transdermal delivery of AC to enhance the hyperlipidemia therapy. We first prepared various AC@PM formulations self-assembled from mPEG-PLA and mPEG-PLA-PEG block copolymers using a dialysis method and evaluated the physicochemical properties in combination with experiment skills and dissipative particle dynamics (DPD) simulations. Then, we encapsulated the AC@PMs into the PVA MN patch using a micromold filling method, followed by characterizing the performances, especially the structural stability, mechanical performance, and biosafety. After conducting in vivo experiments using a hyperlipidemic rat model, our findings revealed that the hybrid microneedle-mediated administration exhibited superior therapeutic efficacy when compared to oral delivery methods. In summary, we have successfully developed a hybrid microneedle (MN) patch system that holds promising potential for the efficient transdermal delivery of hydrophobic drugs.

Assessing the structural stability and drug encapsulation efficiency of poly(ethylene glycol)-poly(L-lactic acid) nanoparticles loaded with atorvastatin calcium: Based on dissipative particle dynamics.

Block polymer micelles have been proven highly biocompatible and effective in improving drug utilization for delivering atorvastatin calcium. Therefore, it is of great significance to measure the stability of drug-loading nano micelles from the perspective of block polymer molecular sequence design, which would provide theoretical guidance for subsequent clinical applications. This study aims to investigate the structural stability of drug-loading micelles formed by two diblock/triblock polymers with various block sequences through coarse-grained dissipative particle dynamics (DPD) simulations. From the perspectives of the binding strength of poly(L-lactic acid) (PLLA) and polyethylene glycol (PEG) in nanoparticles, hydrophilic bead surface coverage, and the morphological alteration of nanoparticles induced by shear force, the ratio of hydrophilic/hydrophobic sequence length has been observed to affect the stability of nanoparticles. We have found that for diblock polymers, PEG3kda-PLLA2kda has the best stability (corresponding hydrophilic coverage ratio is 0.832), while PEG4kda-PLLA5kda has the worst (coverage ratio 0.578). For triblock polymers, PEG4kda-PLLA2kda-PEG4kda has the best stability (0.838), while PEG4kda-PLLA5kda-PEG4kda possesses the worst performance (0.731), and the average performance on stability is better than nanoparticles composed of diblock polymers.

USP25 attenuates anti-GBM nephritis in mice by negative feedback regulation of Th17 cell differentiation.

PURPOSE: This study aimed to elucidate the role of USP25 in a mouse model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). METHODS: USP25-deficient anti-GBM GN mice were generated, and their nephritis progression was monitored. Naïve CD4+ T cells were isolated from spleen lymphocytes and stimulated to differentiate into Th1, Th2, and Th17 cells. This approach was used to investigate the impact of USP25 on CD4+ T lymphocyte differentiation in vitro. Furthermore, changes in USP25 expression were monitored during Th17 differentiation, both in vivo and in vitro. RESULTS: USP25-/- mice with anti-GBM GN exhibited accelerated renal function deterioration, increased infiltration of Th1 and Th17 cells, and elevated RORγt transcription. In vitro experiments demonstrated that USP25-/- CD4+ T lymphocytes had a higher proportion for Th17 cell differentiation and exhibited higher RORγt levels upon stimulation. Wild-type mice with anti-GBM GN showed higher USP25 levels compared to healthy mice, and a positive correlation was observed between USP25 levels and Th17 cell counts. Similar trends were observed in vitro. CONCLUSION: USP25 plays a crucial role in mitigating renal histopathological and functional damage during anti-GBM GN in mice. This protective effect is primarily attributed to USP25's ability to inhibit the differentiation of naïve CD4+ T cells into Th17 cells. The underlying mechanism may involve the downregulation of RORγt. Additionally, during increased inflammatory responses or Th17 cell differentiation, USP25 expression is activated, forming a negative feedback regulatory loop that attenuates immune activation.

Development of interpretable machine learning models for prediction of acute kidney injury after noncardiac surgery: a retrospective cohort study.

BACKGROUND: Early identification of patients at high-risk of postoperative acute kidney injury (AKI) can facilitate the development of preventive approaches. This study aimed to develop prediction models for postoperative AKI in noncardiac surgery using machine learning algorithms. The authors also evaluated the predictive performance of models that included only preoperative variables or only important predictors. MATERIALS AND METHODS: Adult patients undergoing noncardiac surgery were retrospectively included in the study (76 457 patients in the discovery cohort and 11 910 patients in the validation cohort). AKI was determined using the KDIGO criteria. The prediction model was developed using 87 variables (56 preoperative variables and 31 intraoperative variables). A variety of machine learning algorithms were employed to develop the model, including logistic regression, random forest, extreme gradient boosting, and gradient boosting decision trees. The performance of different models was compared using the area under the receiver operating characteristic curve (AUROC). Shapley Additive Explanations (SHAP) analysis was employed for model interpretation. RESULTS: The patients in the discovery cohort had a median age of 52 years (IQR: 42-61 years), and 1179 patients (1.5%) developed AKI after surgery. The gradient boosting decision trees algorithm showed the best predictive performance using all available variables, or only preoperative variables. The AUROCs were 0.849 (95% CI: 0.835-0.863) and 0.828 (95% CI: 0.813-0.843), respectively. The SHAP analysis showed that age, surgical duration, preoperative serum creatinine, and gamma-glutamyltransferase, as well as American Society of Anesthesiologists physical status III were the most important five features. When gradually reducing the features, the AUROCs decreased from 0.852 (including the top 40 features) to 0.839 (including the top 10 features). In the validation cohort, the authors observed a similar pattern regarding the models' predictive performance. CONCLUSIONS: The machine learning models the authors developed had satisfactory predictive performance for identifying high-risk postoperative AKI patients. Furthermore, the authors found that model performance was only slightly affected when only preoperative variables or only the most important predictive features were included.

Effects of different hot-air drying methods on the dynamic changes in color, nutrient and aroma quality of three chili pepper (Capsicum annuum L.) varieties.

The effects of constant and variable temperature hot-air drying methods on drying time, colors, nutrients, and volatile compounds of three chili pepper varieties were investigated in this study. Overall, the variable temperature drying could facilitate the removal of water, preserve surface color, and reduce the loss of total sugar, total acid, fat and capsaicin contents. Electronic-nose (E-nose) and gas chromatography-ion mobility spectroscopy (GC-IMS) analyses found that aldehydes, ketones, alcohols and esters contributed to the aroma of chili peppers. The drying process led to an increase in acids, furans and sulfides contents, while decreasing alcohols, esters and olefins levels. In addition, the three chili pepper varieties displayed distinct physical characteristics, drying times, chromatic values, nutrients levels and volatile profiles during dehydration. This study suggests variable temperature drying is a practical approach to reduce drying time, save costs, and maintain the commercial appeal of chili peppers.

The Chinese herbal prescription JZ-1 promotes extracellular vesicle production and protects against herpes simplex virus type 2 infection in vitro.

Objective: Genital herpes, primarily caused by HSV-2 infection, remains a widespread sexually transmitted ailment. Extracellular vesicles play a pivotal role in host-virus confrontation. Recent research underscores the influence of Chinese herbal prescriptions on extracellular vesicle production and composition. This study aims to probe the impact of JieZe-1 (JZ-1) on extracellular vesicle components, elucidating its mechanisms against HSV-2 infection via extracellular vesicles. Methods: The JZ-1's anti-HSV-2 effects were assessed using CCK-8 assay. Extracellular vesicles were precisely isolated utilizing ultracentrifugation and subsequently characterized through TEM, NTA, and Western Blot analyses. The anti-HSV-2 activity of extracellular vesicles was gauged using CCK-8, Western Blot, and immunofluorescence. Additionally, high-throughput sequencing was employed to detect miRNAs from extracellular vesicles, unraveling the potential antiviral mechanisms of JZ-1. Results: Antiviral efficacy of JZ-1 was shown in VK2/E6E7, HeLa, and Vero cells. The samples extracted from cell supernatant by ultracentrifugation were identified as extracellular vesicles. In VK2/E6E7 cells, extracellular vesicles from JZ-1 group enhanced cell survival rates and diminished the expression of intracellular viral protein gD, contrasting with the inert effect of control group vesicles. Extracellular vesicles from JZ-1 treated Vero cells demonstrated a weaker yet discernible anti-HSV-2 effect. Conversely, extracellular vesicles of HeLa cells exhibited no anti-HSV-2 effect from either group. High-throughput sequencing of VK2/E6E7 cell extracellular vesicles unveiled significant upregulation of miRNA-101, miRNA-29a, miRNA-29b, miRNA-29c, and miRNA-637 in JZ-1 group vesicles. KEGG pathway analysis suggested that these miRNAs may inhibit PI3K/AKT/mTOR signaling pathway and induce autophagy of host cells to protect against HSV-2. Western blot confirmed the induction of autophagy and inhibition of AKT/mTOR in VK2/E6E7 cells with JZ-1 group extracellular vesicles treatment. Conclusion: JZ-1 had an anti-HSV-2 efficacy. After JZ-1 stimulation, VK2/E6E7 cells secreted extracellular vesicles which protect host cells from HSV-2 infection. High-throughput sequencing showed that these extracellular vesicles contained a large number of miRNAs targeting PI3K/AKT/mTOR pathway. JZ-1 group extracellular vesicles could inhibit the activation of AKT/mTOR pathway and induce the host cells autophagy.

Three­dimensional finite element analysis: Anatomical splint fixation for Colles fractures.

With the rapid development of digital research in clinical orthopedics, the efficacy and safety of splint fixation can be better evaluated through biomechanical analysis based on a three-dimensional (3D) finite element model. It is essential to address the current gap in understanding the biomechanical implications of anatomical splint fixation for Colles fractures. By employing advanced 3D finite element analysis, the present study aimed to provide a comprehensive evaluation, offering valuable insights that can contribute to enhancing the effectiveness of anatomical splint fixation in the clinical management of Colles fractures. The 3D finite element models of the forearm and hand were constructed using Mimics 15.0 according to data from computed tomography of a patient with a Colles fracture. After the validity of the model was verified, the corresponding material properties of the models were adjusted to simulate a Colles fracture. Subsequently, the reduction functions, such as radial inclination and ulnar deviation, of the simulated fracture were completed and the mechanical changes of the tissues surrounding the fracture were calculated. Anatomical splints were then placed on the surfaces of the 3D finite element models of Colles fractures at various positions to analyze the changes in the stress cloud diagram, such as for the soft tissue and anatomical splints. In the present study, the constructed 3D finite element models were accurate and valid. The maximum stress of the anatomical splints and soft tissues was 2.346 and 0.106 MPa in pronation, 1.780 and 0.069 MPa in median rotation and 3.045 and 0.057 MPa in supination, respectively. Splint stress reached the highest level in supination and soft tissue stress achieved the highest level in pronation. The peak of splint stress occurred during supination, which contrasts to the peak of soft tissue stress observed in pronation, suggesting splint fixation median rotation can effectively avoid compression of the local soft tissue.

Preparation of high-performance monoazo disperse dyes bearing ester groups based on benzisothiazole and their dyeing performance on polyester fabrics.

To obtain high-performance disperse dyes, a series of azo disperse dyes containing different kinds of ester groups based on benzisothiazole were synthesized by the coupling reaction of diazotization of 3-amino-5-nitro [2,1] benzisothiazole with N-substituted aniline compounds bearing different ester moieties. The structures of the synthesized dyes were evaluated using Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance techniques (1H-NMR), and MS analysis. UV-Vis spectrophotometry methods were applied to study absorption maxima, molar extinction coefficients, and solvatochromic behaviors of the dyes, and time-dependent density functional theory (TD-DFT) simulations were applied to reveal the nature of the absorption spectrum properties. Polyester fabrics were colored using a high-temperature dyeing method under pressure, and the dyed fabrics exhibited deep and bright intense blue hues. In addition, excellent fastness properties, including washing fastness, sublimation fastness, rubbing fastness, and light fastness, were achieved.

Colour perception develops throughout childhood with increased risk of deficiencies in children born prematurely.

AIM: To quantify the impact of prematurity on chromatic discrimination throughout childhood, from 2 to 15 years of age. METHODS: We recruited two cohorts of children, as part of the TrackAI Project, an international project with seven different study sites: a control group of full-term children with normal visual development and a group of children born prematurely. All children underwent a complete ophthalmological exam and an assessment of colour discrimination along the three colour axes: deutan, protan and trytan using a DIVE device with eye tracking technology. RESULTS: We enrolled a total of 1872 children (928 females and 944 males) with a mean age of 6.64 years. Out of them, 374 were children born prematurely and 1498 were full-term controls. Using data from all the children born at term, reference normative curves were plotted for colour discrimination in every colour axis. Pre-term children presented worse colour discrimination than full-term in the three colour axes (p < 0.001). Even after removing from the comparison, all pre-term children with any visual disorder colour discrimination outcomes remained significantly worse than those from full-term children. CONCLUSION: While colour perception develops throughout the first years of life, children born pre-term face an increased risk for colour vision deficiencies.

Identification of potential biomarkers and therapeutic targets for antineutrophil cytoplasmic antibody-associated glomerulonephritis.

Exploring key genes for antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) is of great significance. Through bioinformatics analysis, 79 immune protein-differentially expressed genes (IP-DEGs) were obtained. Six hub genes (PTPRC, CD86, TLR2, IL1B, CSF-1R, and CCL2) were identified and verified to be increased in ANCA-GN patients. Random forest algorithm and ROC analysis showed that CSF-1R was a potential biomarker. Plasma CSF-1R levels increased significantly in ANCA-GN-active patients compared with remission stage and control. Correlation analysis revealed that CSF-1R levels had positive relationship with serum creatinine and Birmingham scoring, while inversely correlated with eGFR. Multivariate analysis revealed that plasma CSF-1R were an independent poor prognostic variable for end-stage renal disease or death, after adjusting for age and gender (HR = 3.05, 95% CI = 1.45-6.43, p = 0.003). Overall, we revealed that the CSF-1R is related to disease activity and might be a vital gene associated with the pathogenesis of ANCA-GN.

The association between urinary metals/metalloids and chronic kidney disease among general adults in Wuhan, China.

The relation between exposure to single metal/metalloid and the risk of chronic kidney disease (CKD) remains unclear. We aimed to determine the single and mixed associations of 21 heavy metals/metalloids exposure and the risk of CKD. We performed a cross-sectional study that recruited 4055 participants. Multivariate logistic regression, linear regression and weighted quantile sum (WQS) regression were conducted to explore the possible effects of single and mixed metals/metalloids exposure on the risk of CKD, the risk of albuminuria and changes in the estimated glomerular filtration rate (eGFR). In single-metal models, Cu, Fe, and Zn were positively associated with increased risks of CKD (P-trend < 0.05). Compared to the lowest level, the highest quartiles of Cu (OR = 2.94; 95% CI: 1.70, 5.11; P-trend < 0.05), Fe (OR = 2.39; 95% CI: 1.42, 4.02; P-trend < 0.05), and Zn (OR = 2.35; 95% CI: 1.31, 4.24; P-trend < 0.05) were associated with an increased risk of CKD. After multi-metal adjustment, the association with the risk of CKD remained robust for Cu (P < 0.05). Weighted quantile sum regression revealed a positive association between mixed metals/metalloids and the risk of CKD, and the association was largely driven by Cu (43.7%). Specifically, the mixture of urinary metals/metalloids was positively associated with the risk of albuminuria and negatively associated with eGFR.

Targeting miR-146b-5p to Regulate KDM6B Expression Aggravates Bronchopulmonary Dysplasia.

miR-146b-5p has been studied to be highly expressed in bronchopulmonary dysplasia (BPD), but whether it is involved in regulating the process of BPD in premature infants remains unclear. This study was to explore miR-146b-5p in premature BPD and reveal its molecular mechanism. BPD mouse model and high-oxygen MLE-12 cell model were established. HE staining, TUNEL staining, and IF staining were conducted to evaluate the pathological injury and protein expression in mouse lung tissue. LDH assay, MMT assay, and flow cytometry were achieved to evaluate cytotoxicity, cell viability, and apoptosis. ELISA and immunoblotting were performed to evaluate inflammatory cytokines and Wnt pathway proteins in lung tissues and cells. Dual-luciferase reporter assay and RIP assay were needed to examine the targeting relationship between miR-146b-5p and KDM6B. miR-146b-5p was abundantly expressed in BPD and KDM6B was lowly expressed. miR-146b-5p knockdown improved hyperoxia-induced lung epithelial cell inflammation and apoptosis in both models. miR-146b-6p upregulation or KDM6B downregulation aggravated hyperoxia-induced inflammation and apoptosis of lung epithelial cells. This effect of overexpressing miR-146b-5p was rescued by forcing KDM6B. MiR-146b-5p activated Wnt signaling by regulating KDM6B. miR-146b-5p activates the Wnt pathway through targeted regulation of KDM6B, thereby aggravating hyperoxia-induced inflammation and apoptosis of lung epithelial cells.

The m6 A reader MhYTP2 negatively modulates apple Glomerella leaf spot resistance by binding to and degrading MdRGA2L mRNA.

Glomerella leaf spot (GLS), caused by the fungal pathogen Colletotrichum fructicola, significantly threatens apple production. Some resistances to plant disease are mediated by the accumulation of nucleotide-binding site and leucine-rich repeat (NBS-LRR) proteins that are encoded by a major class of plant disease resistance genes (R genes). However, the R genes that confer resistance to GLS in apple remain largely unclear. Malus hupehensis YT521-B homology domain-containing protein 2 (MhYTP2) was identified as an N6 -methyladenosine RNA methylation (m6 A) modified RNA reader in our previous study. However, whether MhYTP2 binds to mRNAs without m6 A RNA modifications remains unknown. In this study, we discovered that MhYTP2 exerts both m6 A-dependent and -independent functions by analysing previously obtained RNA immunoprecipitation sequencing results. The overexpression of MhYTP2 significantly reduced the resistance of apple to GLS and down-regulated the transcript levels of some R genes whose transcripts do not contain m6 A modifications. Further analysis indicated that MhYTP2 binds to and reduces the stability of MdRGA2L mRNA. MdRGA2L positively regulates resistance to GLS by activating salicylic acid signalling. Our findings revealed that MhYTP2 plays an essential role in the regulation of resistance to GLS and identified a promising R gene, MdRGA2L, for use in developing apple cultivars with GLS resistance.

A predictive molecular signature consisting of lncRNAs associated with cellular senescence for the prognosis of lung adenocarcinoma.

The role of long noncoding RNAs (lncRNAs) has been verified by more and more researches in recent years. However, there are few reports on cellular senescence-associated lncRNAs in lung adenocarcinoma (LUAD). Therefore, to explore the prognostic effect of lncRNAs in LUAD, 279 cellular senescence-related genes, survival information and clinicopathologic parameters were derived from the CellAge database and The Cancer Genome Atlas (TCGA) database. Then, we constructed a novel cellular senescence-associated lncRNAs predictive signature (CS-ALPS) consisting of 6 lncRNAS (AC026355.1, AL365181.2, AF131215.5, C20orf197, GAS6-AS1, GSEC). According to the median of the risk score, 480 samples were divided into high-risk and low-risk groups. Furthermore, the clinicopathological and biological functions, immune characteristics and common drug sensitivity were analyzed between two risk groups. In conclusion, the CS-ALPS can independently forecast the prognosis of LUAD, which reveals the potential molecular mechanism of cellular senescence-associated lncRNAs, and provides appropriate strategies for the clinical treatment of patients with LUAD.

Enhanced vitamin K2 production by engineered Bacillus subtilis during leakage fermentation.

Menaquinone-7 (MK-7), a valuable member of the vitamin K2 series, is an essential nutrient for humans. It is used for treating coagulation disorders, and osteoporosis, promoting liver function recovery, and preventing cardiovascular diseases. In this study, to further improve the metabolic synthesis of MK-7 by the mutant strain, the effect of surfactants on the metabolic synthesis of MK-7 by the mutant strain Bacillus subtilis 168 KO-SinR (BS168 KO-SinR) was analyzed. The scanning electron microscopy and flow cytometry results showed that the addition of surfactants changed the permeability of the cell membrane of the mutant strain and the structural components of the biofilm. When 0.7% Tween-80 was added into the medium, the extracellular and intracellular synthesis of MK-7 reached 28.8 mg/L and 59.2 mg/L, respectively, increasing the total synthesis of MK-7 by 80.3%. Quantitative real-time PCR showed that the addition of surfactant significantly increased the expression level of MK-7 synthesis-related genes, and the electron microscopy results showed that the addition of surfactant changed the permeability of the cell membrane. The research results of this paper can serve as a reference for the industrial development of MK-7 prepared by fermentation.

Administration of modified Gegen Qinlian decoction for hemorrhagic chronic radiation proctitis: A case report and review of literature.

BACKGROUND: Hemorrhagic chronic radiation proctitis (CRP) is a common late complication of irradiation of the pelvis and seriously impairs life quality. There is no standard treatment for hemorrhagic CRP. Medical treatment, interventional treatment, and surgery are available, but they are limited in their applications due to nondefinite efficacy or side effects. Chinese herbal medicine (CHM), as a complementary or alternative therapy, may provide another option for hemorrhagic CRP treatment. CASE SUMMARY: A 51-year-old woman with cervical cancer received intensity-modulated radiation therapy and brachytherapy with a total dose of 93 Gy fifteen days after hysterectomy and bilateral adnexectomy. She received six additional cycles of chemotherapy with carboplatin and paclitaxel. Nine months after radiotherapy treatment, she mainly complained of 5-6 times diarrhea daily and bloody purulent stools for over 10 d. After colonoscopy examinations, she was diagnosed with hemorrhagic CRP with a giant ulcer. After assessment, she received CHM treatment. The specific regimen was 150 mL of modified Gegen Qinlian decoction (GQD) used as a retention enema for 1 mo, followed by replacement with oral administration of 150 mL of modified GQD three times per day for 5 mo. After the whole treatment, her diarrhea reduced to 1-2 times a day. Her rectal tenesmus and mild pain in lower abdomen disappeared. Both colonoscopy and magnetic resonance imaging confirmed its significant improvement. During treatment, there were no side effects, such as liver and renal function damage. CONCLUSION: Modified GQD may be another effective and safe option for hemorrhagic CRP patients with giant ulcers.