Novel Insight into Ferroptosis in Kidney Diseases.

BACKGROUND: Various kidney diseases such as acute kidney injury, chronic kidney disease, polycystic kidney disease, renal cancer, and kidney stones, are an important part of the global burden, bringing a huge economic burden to people around the world. Ferroptosis is a type of nonapoptotic iron-dependent cell death caused by the excess of iron-dependent lipid peroxides and accompanied by abnormal iron metabolism and oxidative stress. Over the past few decades, several studies have shown that ferroptosis is associated with many types of kidney diseases. Studying the mechanism of ferroptosis and related agonists and inhibitors may provide new ideas and directions for the treatment of various kidney diseases. SUMMARY: In this review, we discuss the differences between ferroptosis and other types of cell death such as apoptosis, necroptosis, pyroptosis, cuprotosis, pathophysiological features of the kidney, and ferroptosis-induced kidney injury. We also provide an overview of the molecular mechanisms involved in ferroptosis and events that lead to ferroptosis. Furthermore, we summarize the possible clinical applications of this mechanism among various kidney diseases. KEY MESSAGE: The current research suggests that future therapeutic efforts to treat kidney ailments would benefit from a focus on ferroptosis.

Effects of empowerment education on the self-management and self-efficacy of liver transplant patients: a randomized controlled trial.

BACKGROUND: Despite the increasing survival rates, liver transplant patients experience numerous postoperative complications and encounter significant challenges in long-term self-management. This study aims to examine the effectiveness of empowerment education in enhancing self-management skills and self-efficacy among liver transplant recipients. METHODS: A randomized, single-blind, single-center trial was conducted in China between August 2019 and September 2020, involving liver transplant recipients. The intervention group received 12 weeks of empowerment education, while the control group received 12 weeks of routine education. .The study assessed the patients' self-management and self-efficacy using the Liver Transplant Recipient Self-Management Questionnaire and the Self-efficacy for Managing Chronic Disease 6-Item Scale. Follow-up assessments were conducted at 1, 3, and 6 months after the intervention. RESULTS: Eighty-four patients were initially randomized to either the intervention group (n1 = 42) or the routine education group (n2 = 42). Twelve patients were excluded from the analysis due to loss of follow-up or discontinuation of the intervention, leaving 72 patients (n1 = 35, n2 = 37) for the final analysis. The scores for exercise and lifestyle management were significantly higher in the intervention group than in the control group at 1, 3, and 6 months after the intervention (t = 3.047, 5.875, 8.356, and t = 5.759, 4.681, 11.759, respectively; P < 0.05). At 3 and 6 months after the intervention, the scores for cognitive symptom management, communication with physicians, and self-efficacy were significantly higher in the intervention group than in the control group (t = 5.609, 6.416, and t = 5.576, 11.601, and t = 6.867, 15.071, respectively; P < 0.001). Within the intervention group, self-management scores increased significantly over time, while within the control group, the scores for communication with physicians, lifestyle, and self-efficacy showed a significant decline from 3 to 6 months after routine health education. CONCLUSIONS: The results of this study suggest that empowerment education is an effective means of improving the self-management and self-efficacy of liver transplant patients, with better outcomes compared to routine health education. These findings have important implications for nursing practice and provide valuable guidance for clinical education of liver transplant patients. TRIAL REGISTRATION: ChiCTR2200061561.

Prevotella as the hub of the cervicovaginal microbiota affects the occurrence of persistent human papillomavirus infection and cervical lesions in women of childbearing age via host NF-κB/C-myc.

There is evidence that coinfection of cervicovaginal high-risk human papillomavirus (HR-HPV) and bacteria is common in women of childbearing age. However, the relationship between bacterial vaginosis (BV) and persistent HR-HPV infection in women of childbearing age and the underlying mechanisms remain unclear. In this study, we determined whether BV affects persistent HR-HPV infection in women aged 20-45 years and explored the possible mechanisms of their interactions. From January 1 to April 30, 2020, we recruited women aged 20-45 years with and without BV at a ratio of 1:2 from Fujian Maternity and Child Health Hospital. All women were followed up at 0, 12, and 24 months. A BV assay, HR-HPV genotyping and cervical cytology were performed at each follow-up. At 0 months, additional vaginal secretions and cervical exfoliated cells were collected for 16S ribosomal RNA sequencing, bacterial metabolite determination, and POU5F1B, C-myc, TLR4, NF-κB, and hTERT quantification. A total of 920 women were included. The abundance of Prevotella (p = 0.016) and Gardnerella (p = 0.027) were higher, whereas the abundance of Lactobacillus was lower (p = 0.001) in women with persistent HR-HPV infection and high-grade squamous intraepithelial lesions (HSIL). The abundance of Prevotella (p = 0.025) and Gardnerella (p = 0.018) increased in the vaginas of women with persistent HPV16 infection, whereas only the abundance of Prevotella (p = 0.026) was increased in women with persistent HPV18 infection. The abundance of Prevotella in the vagina was significantly positively correlated with the expression levels of TLR4, NF-κB, C-myc, and hTERT in host cervical cells (p < 0.05). Our findings suggest that overgrowth of Prevotella in the vagina may influence the occurrence of persistent HR-HPV infection-related cervical lesions through host NF-κB and C-myc signaling.

Forming a Double-Helix Phase of Single Polymer Chains by the Cooperation between Local Structure and Nonlocal Attraction.

Double-helix structures, such as DNA, are formed in nature to realize many unique functions. Inspired by this, researchers are pursuing strategies to design such structures from polymers. A key question is whether the double helix can be formed from the self-folding of a single polymer chain without specific interactions. Here, using Langevin dynamics simulation and theoretical analysis, we find that a stable double-helix phase can be achieved by the self-folding of single semiflexible polymers as a result of the cooperation between local structure and nonlocal attraction. The critical temperature of double-helix formation approximately follows T^{cri}∼ln(k_{θ}) and T^{cri}∼ln(k_{τ}), where k_{θ} and k_{τ} are the polymer bending and torsion stiffness, respectively. Furthermore, the double helix can exhibit major and minor grooves due to symmetric break for better packing. Our results provide a novel guide to the experimental design of the double helix.

Molecular Characteristics and Risk Factors of Bloodstream Infection Caused by Escherichia coli ST131 in Southeast China.

BACKGROUND: E. coli ST131 is the predominant lineage among extraintestinal pathogenic E. coli isolates worldwide and is an important pathogen associated with all kinds of human infections. The aim of this study was to investigate the prevalence and molecular characteristics of E. coli ST131 and non-ST131 isolates that cause bloodstream infections and evaluate the risk factors for E. coli ST131. METHODS: A total of 103 E. coli isolates associated with bloodstream infection were collected between August 2014 and August 2015 at a Chinese university hospital. The isolates were classified into ST131 and non-ST131 E. coli groups by multilocus sequence typing. Phylogenetic analysis, susceptibility testing, virulence genotyping, PCR-based O typing, and pulsed-field gel electrophoresis (PFGE) were performed, and the clinical features of patients in both groups were compared. RESULTS: Overall, 12 isolates (11.7%) were identified as ST131 isolates, including 10 O25b-ST131 (83.3%) and 2 O16-ST131 (16.7%) clones. All 103 E. coli isolates were divided into four phylogenetic groups: B2 was the predominant phylogenetic group (n = 39, 37.9%), and it was followed in descending order by D (n = 33, 32.0%), A (n = 20, 19.4%), and B1 (n = 11, 10.7%). Compared with the non-ST131 isolates, the E. coli ST131 isolates harbored more virulence factors and were associated with a significantly higher incidence of urinary tract infection (p = 0.040) and a significantly greater length of hospital stay (p = 0.045). According to PFGE analysis, the molecular features of the E. coli ST131 isolates were highly diverse, and there was no dominant clone. CONCLUSIONS: The ST131 isolates collected from Southeast China in this study exhibited strong virulence and multiple drug resistance, and the main serotype was O25b-ST131. Therefore, future studies should focus on O16-ST131 subclones in order to better understand the prognosis of patients with bloodstream infection caused by E. coli ST131.

Characterization of Integrons and Antimicrobial Resistance in Escherichia coli Sequence Type 131 Isolates.

BACKGROUND: Escherichia coli sequence type 131 (ST131) is an important multidrug-resistant extraintestinal pathogen, which can cause many kinds of infections. Integrons may play a crucial role in the dissemination of antibiotic resistance genes. The purpose of this study was to characterize the prevelance of integrons among E. coli ST131 strains in China. METHODS: Eighty-three E. coli ST131 strains in China. E. coli ST131 strains in China. RESULTS: Overall, 26.5% (22/83) of the E. coli ST131 strains in China. dfrA17-aadA5 and aac(6')-Ib-cr-cmlA5. Only one type of Pc promoter variant was detected among 22 integron-positive isolates (PcW). In vivo transfer of integron was successful for 9 of integron-positive E. coli ST131 strains in China. E. coli ST131 strains in China. CONCLUSIONS: Our study showed a low prevalence of integrons was detected in E. coli ST131. Continued surveillance of this mobile genetic element should be performed to study the evolution of antibiotic resistance among E. coli ST131.E. coli ST131 strains in China. E. coli ST131 strains in China.

Antimicrobial Resistance, Genetic Diversity and Virulence Genes of Salmonella Typhimurium Isolated in Infant with Acute Diarrhea in Fuzhou, China, 2015 - 2017.

BACKGROUND: S. Typhimurium was the dominant serovar in an infant in Fuzhou, China. There have been few comprehensive studies on Salmonella typhimurium in infants in China. METHODS: We conducted a retrospective study on 30 Salmonella typhimurium from 3,200 fecal samples of infants with acute diarrhea from 2015 to 2017. Thirty S. Typhimurium strains were tested for antimicrobial susceptibility and characterized for virulence genes. Pulsed-field gel electrophoresis (PFGE) was also applied for comparison of genetic relatedness. RESULTS: All of the strains harbored misL, orfL, pipD, prgH, sifA, sopB, sitC, spiC, and invA genes. The other three gene distributions in the strains are different. Strains subtyped into 4 virulotypes (VP1-VP4), the most common virulence profile was VP3, accounting for 63.3% of the strains. The resistance to ciprofloxacin and ceftriaxone was 26.7%. The proportion of MDR isolates is approximately 90.0%. Sixteen different antimicrobial resistance patterns were observed and the most frequent resistance type was antibiotype 13 (resistance to streptomycin, tetracycline, amoxicillin), occurring in 43.3% of the isolates. Regarding PFGE, 30 isolates of S. Typhimurium showed genetic diversity, while no predominant PFGE patterns were observed in S. Typhimurium. Moreover, no correlation between virulence profiles or antibiotic patterns and PFGE clusters was observed. With one exception, VP1 which harbors pefA showed more diversity than the other virulence profiles among PFGE profiles. CONCLUSIONS: Our study provided valuable information on virulence gene content, antibiotic resistance, and genetic diversity of S. Typhimurium isolated from infant with acute diarrhea in Fuzhou, China.

Effects of transtheoretical model-based intervention on the self-management of patients with an ostomy: A randomised controlled trial.

AIMS AND OBJECTIVES: To determine the effect of a transtheoretical model (TTM)-based intervention on patients with an ostomy and provide patient-centred, accessible assistance and dynamic education to improve patient self-management. BACKGROUND: Proper self-management may promote the rehabilitation of patients with an ostomy. TTM-based interventions have resulted in positive health behavioural changes. DESIGN: Randomised controlled trial performed according to the CONSORT guidelines. SUBJECT AND SETTING: The sample comprised 55 men and 37 women (24-77 years old, mean ± SD = 52.8 ± 11.13 years). The study settings included three tertiary hospitals in Changsha, Hunan, China. METHODS: The 92 patients, recruited from August 2012 to March 2013, were randomised into a control group and an intervention group. Randomisation was done by using a block randomisation list with a block size of 4. Self-management behaviours were assessed at the baseline, 2 days before discharge and after 1, 3 and 6 months of follow-up. The chi-squared test, independent sample t test and repeated measures analysis of variance were used to analyse the data. RESULTS: Patients in the intervention group were more likely to be at the action and maintenance stages compared with those in the control group. We also observed significant improvements in the self-management ability in the process of change, the decisional balance and self-efficacy in the intervention group compared with those in the control group after four intervention sessions and up to 6 months of follow-up. No serious intervention-related adverse events were observed. CONCLUSIONS: The TTM-based intervention had positive effects on self-management behaviours of patients with an ostomy. RELEVANCE TO CLINICAL PRACTICE: The TTM-based intervention had positive effects on self-management behaviours of patients with an ostomy and may provide a reference for health providers to develop behaviour promotion programmes to improve the self-management of patients with an ostomy.

Analysis of 2 Reverse Syphilis Testing Algorithms in Diagnosis of Syphilis: A Large-Cohort Prospective Study.

Background: Two serologic syphilis screening algorithms recommended by the US Centers for Disease Control and Prevention (US CDC) and the European Centre for Disease Prevention and Control (ECDC), respectively, are commonly used for syphilis screening; however, which one is optimal remains to be determined. Methods: We conducted a prospective study of 119891 subjects to analyze the consistency of the US CDC- and ECDC-recommended algorithms. The US CDC-recommended algorithm begins with a treponemal immunoassay, followed by a rapid plasma reagin (RPR) test. RPR-nonreactive samples are confirmed by the Treponema pallidum particle agglutination assay (TPPA). The ECDC-recommended algorithm begins with a treponemal immunoassay, followed by a confirmatory treponemal test. If the confirmatory test is reactive, a quantitative nontreponemal assay is used to assess the disease activity and treatment response. In the present study, a total of 119891 serum samples from a large hospital (sixth largest in China) were included, and each sample was screened with a chemiluminescent immunoassay (CIA). CIA-reactive samples were then simultaneously tested with RPR and TPPA. The consistency of these 2 algorithms was determined by calculating the percentage of agreement and κ coefficient. Results: The overall percentage of agreement and κ value between these 2 algorithms were 99.996% and 0.999, respectively. The positivity rate for syphilis as determined by the US CDC- and ECDC-recommended algorithms was 1.43% and 1.42%, respectively. Conclusions: Our results suggest that the US CDC-recommended algorithm and the ECDC-recommended algorithm have comparable performances for syphilis screening in low-prevalence populations.

Helcococcus ovis in a patient with an artificial eye: a case report and literature review.

BACKGROUND: Helcococcus ovis, belonging to the genus of Helcococcu in Peptostreptococcaceae, is one kind of facultative anaerobic and gram-positive cocci, which was first isolated from a mixed infection in sheep in 1999. To our knowledge, it's known as an invasive pathogen in animals, and never been reported as a human pathogen in published literature. The aims of this work are to describe the first report of H. ovis which was recovered from the artificial eye of human case and perform a literature review. CASE PRESENTATION: A 26 year-old man reporting pyogenic infection with an artificial eye attended ophthalmic ward in Tongji hospital. After physical examination, clinical and laboratory investigations, the diagnosis of eye infection caused by Helcococcus ovis and Staphylococcus aureus was established. Receiving a medico-surgical approach, the patient was successfully treated. The treatment consisted in intravenous cefotaxime and ornidazole, levofloxacin eye drops during two weeks and removing of right artificial eye with debridement. CONCLUSIONS: We describe here the first known case of H. ovis which was recovered from human artificial eye. This report different from previous data found in the literature emphasizes the invasive potential of this bacterial species as a pathogen in human. Prospectively, the application of next generation sequencing tools would contribute to a more accurate classification of clinical strains.

Characteristics of diarrheagenic Escherichia coli among children under 5 years of age with acute diarrhea: a hospital based study.

BACKGROUND: Diarrhea is the leading infectious cause of childhood morbidity and mortality. Among bacterial agents, diarrheagenic Escherichia coli (DEC) is the major causal agent of childhood diarrhea in developing countries, particularly in children under the age of 5 years. Here, we performed a hospital-based prospective study to explore the pathotype distribution, epidemiological characteristics and antibiotic resistance patterns of DEC from < 5-year-old diarrheal children. METHODS: Between August 2015 and September 2016, 684 stool samples were collected from children (< 5 years old) with acute diarrhea. All samples were cultured and identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and biochemical tests. PCR was used for subtyping, and enteropathogenic E. coli (EPEC) isolates were identified simultaneously with serology. Furthermore, antimicrobial sensitivity tests and sequencing of antibiotic resistance-related genes were conducted. RESULTS: DEC strains were identified in 7.9% of the 684 stool samples. Among them, the most commonly detected pathotype was EPEC (50.0% of DEC), of which 77.8% were classified as atypical EPEC (aEPEC). Age and seasonal distribution revealed that DEC tended to infect younger children and to occur in summer/autumn periods. Multidrug-resistant DEC isolates were 66.7%; resistance rates to ampicillin, co-trimoxazole, cefazolin, cefuroxime, cefotaxime, and ciprofloxacin were ≥ 50%. Among 5 carbapenem-resistant DEC, 60.0% were positive for carbapenemase genes (2 blaNDM-1 and 1 blaKPC-2). Among 30 cephalosporin-resistant DEC, 93.3% were positive for extended-spectrum ß-lactamase (ESBL) genes, with blaTEM-1 and blaCTX-M-55 being the most common types. However, no gyrA or gyrB genes were detected in 16 quinolone-resistant isolates. Notably, aEPEC, which has not received much attention before, also exhibited high rates of drug resistance (81.0%, 66.7%, and 14.3% for ampicillin, co-trimoxazole , and carbapenem resistance, respectively). CONCLUSIONS: EPEC was the most frequent DEC pathotype in acute diarrheal children, with aEPEC emerging as a dominant diarrheal agent in central China. Most DEC strains were multidrug-resistant, making even ciprofloxacin unsuitable for empiric treatment against DEC infection. Among carbapenem-resistant DEC strains, those harboring blaNDM-1 and blaKPC-2 were the main causal agents. blaTEM-1 and blaCTX-M-55 were the major genetic determinants associated with high levels of cephalosporin resistance.

TIGIT signalling pathway negatively regulates CD4+ T-cell responses in systemic lupus erythematosus.

B-lymphocyte hyperactivity in systemic lupus erythematosus (SLE) is T-cell-dependent, and CD4+ T-cell activation is essential to SLE pathogenesis. However, the mechanism of the deregulation of CD4+ T cells in SLE is largely unknown. T-cell immunoglobulin and ITIM domain (TIGIT) is a new inhibitory receptor preferentially expressed on activated CD4+ T cells. Here, we address the role of TIGIT in the pathogenesis of SLE. Our results showed that TIGIT expression on CD4+ T cells was significantly elevated in patients with SLE and highly correlated with the activity of the disease. TIGIT+ CD4+ T cells from both healthy individuals and patients with SLE had a more activated phenotype than TIGIT- CD4+ T cells. In contrast, the activation, proliferation and cytokine production potential of TIGIT+ CD4+ T cells were significantly lower than those of TIGIT- CD4+ T cells. Furthermore, activation of the TIGIT pathway by using CD155 could substantially down-regulate the activities of CD4+ T cells from SLE patients in vitro, and in vivo administration of CD155 resulted in a delayed development of SLE in MRL/lpr mice. TIGIT is a powerful negative regulator of CD4+ T cells in SLE, which suggests that the TIGIT signalling pathway may be used as a potential therapeutic target for treating this disease.

TIGIT expression levels on human NK cells correlate with functional heterogeneity among healthy individuals.

Human NK cells display extensive phenotypic and functional heterogeneity among healthy individuals, but the mechanism responsible for this variation is still largely unknown. Here, we show that a novel immune receptor, T-cell immunoglobulin and ITIM domain (TIGIT), is expressed preferentially on human NK cells but shows wide variation in its expression levels among healthy individuals. We found that the TIGIT expression level is related to the phenotypic and functional heterogeneity of NK cells, and that NK cells from healthy individuals can be divided into three categories according to TIGIT expression. NK cells with low levels of TIGIT expression show higher cytokine secretion capability, degranulation activity, and cytotoxic potential than NK cells with high levels of TIGIT expression. Blockade of the TIGIT pathway significantly increased NK-cell function, particularly in NK cells with high levels of TIGIT expression. We further observed that the TIGIT expression level was inversely correlated with the IFN-γ secretion capability of NK cells in patients with cancers and autoimmune diseases. Importantly, we propose a novel mechanism that links TIGIT expression with NK-cell functional heterogeneity, and this mechanism might partially explain why individuals have different susceptibilities to infection, autoimmune disease, and cancer.

Tim-3 pathway affects NK cell impairment in patients with active tuberculosis.

Active tuberculosis (TB) patients show impaired NK cell function, and the underlying mechanism remains largely unknown. In this study, we confirmed the decrease in activation, cytokine secretion, and degranulation potential of NK cells in active TB patients. We further investigated whether coinhibitory receptor Tim-3 was involved with impairment of NK cells. Our results revealed that the expression of Tim-3 on NK cells was increased in active TB patients. Tim-3 expression was inversely correlated with IL-12-stimualted IFN-γ production. Moreover, blocking the Tim-3 pathway restored IFN-γ secretion and degranulation of NK cells. Blocking this pathway also increased NK cell cytotoxicity against K562 target cells, and improved the ability of NK cells to control Mtb growth in monocyte-derived macrophages. The Tim-3 expression on NK cells was also observed to be significantly decreased in TB patients post-treatment. In this study, we have identified that Tim-3 is involved with NK cell impairment in TB patients.

[Analysis of triterpenoids in Ganoderma lucidum by microwave-assisted continuous extraction].

For further improving the extraction efficiency of microwave extraction, a microwave-assisted contijuous extraction (MACE) device has been designed and utilized. By contrasting with the traditional methods, the characteristics and extraction efficiency of MACE has also been studied. The method was validated by the analysis of the triterpenoids in Ganoderma lucidum. The extraction conditions of MACE were: using 95% ethanol as solvent, microwave power 200 W and radiation time 14.5 min (5 cycles). The extraction results were subsequently compared with traditional heat reflux extraction ( HRE) , soxhlet extraction (SE), ultrasonic extraction ( UE) as well as the conventional microwave extraction (ME). For triterpenoids, the two methods based on the microwaves (ME and MACE) were in general capable of finishing the extraction in 10, 14.5 min, respectively, while other methods should consume 60 min and even more than 100 min. Additionally, ME can produce comparable extraction results as the classical HRE and higher extraction yield than both SE and UE, however, notably lower extraction yield than MASE. More importantly, the purity of the crud extract by MACE is far better than the other methods. MACE can effectively combine the advantages of microwave extraction and soxhlet extraction, thus enabling a more complete extraction of the analytes of TCMs in comparison with ME. And therefore makes the analytic result more accurate. It provides a novel, high efficient, rapid and reliable pretreatment technique for the analysis of TCMs, and it could potentially be extended to ingredient preparation or extracting techniques of TCMs.

Optical fiber axial micro-displacement sensor based on Mach-Zehnder interferometer.

A Mach-Zehnder interferometer (MZI) based fiber axial micro-displacement sensor was proposed. The MZI was constructed by a bowknot-type taper (BTT) combining with a fiber core-offset between two single mode fibers (SMFs). The axial micro-displacement of the core offset is correlated with the MZI transmission spectrum and varied with the interferometer arm length. For the arm length L of 12, 18, 24 and 30 mm, the proposed sensors showed high sensitivity of -0.362 dB/µm, -0.385 dB/µm, -0.332 dB/µm and -0.235dB/µm, and temperature errors of -0.056 dB/°C, -0.036 dB/°C, -0.044 dB/°C, -0.048 dB/°C, respectively. The theoretical simulations of the energy distributions were also given. The obtained sensitivity of -0.385 dB/µm is about 150 times high than that of the current similar existing axial micro-displacement sensor.

Fine Modeling of Multiscale Fracture Cavity Fusion in Fault Solution Reservoirs Based on Multiscale Discrete Crack Modeling Method.

Geological modeling is a three-dimensional (3D) representation of comprehensive geological research results in oil fields. In this paper, first, the comprehensive geological research results were fully applied to establish geological models such as matrix, reservoir, and fractures in the study area. Second, in response to the geological characteristics of carbonate fractured and vuggy reservoirs, various data are integrated. Finally, by collecting and organizing various basic data mentioned above, a refined geological model of the oil reservoir in the study area is established. Results show that (a) Due to the complexity of the distribution of cracks and pores, the presence of these unrelated grids also affects the observation of target cracks and pores. (b) There may be multiple adjacent nodes in the initial access node. The strategy of depth-first traversal is to first access the first adjacent node. (c) There is a significant difference between the connected units extracted solely from static data and the connected units reextracted after fine-tuning the crack position considering dynamic data.

Effects of Surface Tethering on the Thermodynamics and Kinetics of Frustrated Protein Folding.

The interaction between the protein and surface plays an important role in biology and biotechnology. To understand how surface tethering influences the folding behavior of frustrated proteins, in this work, we systematically study the thermodynamics and folding kinetics of the bacterial immunity protein Im7 and Fyn SH3 domain tethered to a surface using Langevin dynamics simulations. Upon surface tethering, the stabilization often results from the entropic effect, whereas the destabilization is usually caused by either an energetic or entropic effect. For the Fyn SH3 domain with a two-state folding manner, the influence of nonnative interactions on thermodynamic stability is not significant, while nonnative interactions can weaken the effect of surface tethering on the change in the folding rate. By contrast, for the frustrated protein Im7, depending on where the protein is tethered, the surface tethering can promote or suppress misfolding by modulating specific nonnative contacts, thereby altering the folding rate and folding mechanism. Because surface tethering can change the intrachain diffusivity of unfolding, the kinetic stability cannot be well captured by the thermodynamic stability at some tether points. This study should be helpful in general to understand how surface tethering affects the folding energy landscape of frustrated proteins.

Changes of the vaginal microbiota in HPV infection and cervical intraepithelial neoplasia: a cross-sectional analysis.

This study aimed to explore the changes of the vaginal microbiota and enzymes in the women with high-risk human papillomavirus (HR-HPV) infection and cervical lesions. A total of 448 participants were carried out HPV genotyping, cytology tests, and microecology tests, and 28 participants were treated as sub-samples, in which vaginal samples were characterized by sequencing the bacterial 16S V4 ribosomal RNA (rRNA) gene region. The study found the prevalence of HR-HPV was higher in patients with BV (P = 0.036). The HR-HPV infection rate was 72.73% in G. vaginalis women, which was significantly higher than that of women with lactobacillus as the dominant microbiota (44.72%) (P = 0.04). The positive rate of sialidase (SNA) was higher in women with HR-HPV infection (P = 0.004) and women diagnosed with cervical intraepithelial neoplasia (CIN) (P = 0.041). In HPV (+) women, the α-diversity was significantly higher than that in HPV (-) women. The 16S rRNA gene-based amplicon sequencing results showed that Lactobacillus was the dominant bacteria in the normal vaginal microbiota. However, the proportion of Gardnerella and Prevotella were markedly increased in HPV (+) patients. Gardnerella and Prevotella are the most high-risk combination for the development of HPV (+) women. The SNA secreted by Gardnerella and Prevotella may play a significant role in HPV infection progress to cervical lesions.

Regulation Networks of Non-Coding RNA-Associated ceRNAs in Cisplatin-Induced Acute Kidney Injury.

Cisplatin is widely used as a chemotherapeutic drug to treat various solid tumors. However, it often induces severe side effects, including nephrotoxicity, which limits its application in clinical settings. Furthermore, the underlying mechanisms of action are unclear. Here, we applied whole-transcriptome RNA sequencing to a cisplatin-induced acute kidney injury (CP-AKI) mouse model to evaluate competing endogenous RNA (ceRNA) networks. We found 4460 mRNAs, 1851 long non-coding RNAs, 101 circular RNAs, and 102 microRNAs significantly differentially expressed between CP-AKI and control mice. We performed gene set enrichment analysis to reveal the biological functions of the mRNAs and constructed non-coding RNA-associated ceRNA networks in CP-AKI mice. Two ceRNA regulatory pathways, Lhx1os-203/mmu-miR-21a-3p/Slc7a13 and circular RNA_3907/mmu-miR-185-3p/Ptprn, were validated using quantitative real-time PCR. The protein-protein interaction network indicated that Il6, Cxcl1, Cxcl2, and Plk1 serve as hub genes and are highly connected with the inflammatory response or DNA damage. Transcription factors, such as Stat3, Cebpb, and Foxm1, regulate gene expression levels in CP-AKI. Our study provides insight into non-coding RNA-associated ceRNA networks and mRNAs in CP-AKI and identifies potential treatment targets.