Abstract
The virulence factor database (VFDB, http://www.mgc.ac.cn/VFs/) is dedicated to presenting a comprehensive knowledge base and a versatile analysis platform for bacterial virulence factors ...(VFs). Recent developments in sequencing technologies have led to increasing demands to analyze potential VFs within microbiome data that always consist of many different bacteria. Nevertheless, the current classification of VFs from various pathogens is based on different schemes, which create a chaotic situation and form a barrier for the easy application of the VFDB dataset for future panbacterial metagenomic analyses. Therefore, based on extensive literature mining, we recently proposed a general category of bacterial VFs in the database and reorganized the VFDB dataset accordingly. Thus, all known bacterial VFs from 32 genera of common bacterial pathogens collected in the VFDB are well grouped into 14 basal categories along with over 100 subcategories in a hierarchical architecture. The new coherent and well-defined VFDB dataset will be feasible and applicable for future panbacterial analysis in terms of virulence factors. In addition, we introduced a redesigned JavaScript-independent web interface for the VFDB website to make the database readily accessible to all users with various client settings worldwide.
The virulence factor database (VFDB, http://www.mgc.ac.cn/VFs/) is dedicated to providing up-to-date knowledge of virulence factors (VFs) of various bacterial pathogens. Since its inception the VFDB ...has served as a comprehensive repository of bacterial VFs for over a decade. The exponential growth in the amount of biological data is challenging to the current database in regard to big data analysis. We recently improved two aspects of the infrastructural dataset of VFDB: (i) removed the redundancy introduced by previous releases and generated two hierarchical datasets--one core dataset of experimentally verified VFs only and another full dataset including all known and predicted VFs and (ii) refined the gene annotation of the core dataset with controlled vocabularies. Our efforts enhanced the data quality of the VFDB and promoted the usability of the database in the big data era for the bioinformatic mining of the explosively growing data regarding bacterial VFs.
Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that function as transcription factors regulating the expression of numerous target genes. PPARs play an essential ...role in various physiological and pathological processes, especially in energy metabolism. It has long been known that metabolism and circadian clocks are tightly intertwined. However, the mechanism of how they influence each other is not fully understood. Recently, all three PPAR isoforms were found to be rhythmically expressed in given mouse tissues. Among them, PPARα and PPARγ are direct regulators of core clock components, Bmal1 and Rev-erbα, and, conversely, PPARα is also a direct Bmal1 target gene. More importantly, recent studies using knockout mice revealed that all PPARs exert given functions in a circadian manner. These findings demonstrated a novel role of PPARs as regulators in correlating circadian rhythm and metabolism. In this review, we summarize advances in our understanding of PPARs in circadian regulation.
Aim: We used a dataset from a cross-sectional survey conducted in China to determine which of the anthropometric indices of obesity are important in terms of carotid atherosclerosis free of ...cardiovascular and cerebrovascular diseases.Methods: A total of 5,245 participants who were volunteering for carotid ultrasound unit in this cross-sectional survey were included in the present analysis. All subjects were free of angina, myocardial infarction, heart failure and stroke, and cancer. A low-risk subgroup was defined as people free of hypertension, diabetes, and hyperlipidemia. All analyses based on logistic regression were gender-specific.Results: The present study consisted of 2,501 males and 2,744 females, with 776 (31.03%) diagnosed as carotid artery plaque in males and 550 (20.04%) in females. Univariable analyses in unadjusted logistic model showed significant associations between disease presence and all central obesity indices. After adjusting for more variables, only a body shape index (ABSI) was associated with the presence of disease in both males and females. Moreover, stepwise regression approaches revealed that ABSI was always an independent determinant of the presence of subclinical carotid plaque. Multiple regression shows a linear and significant increase in the prevalence of atherosclerosis in males and females as ABSI decile levels increased. Similar results were obtained when the association between ABSI and carotid plaque was studied in this low-risk subgroup.Conclusions: ABSI, as a novel anthropometric indicator compared with traditional indices, was found to have a closer relationship with subclinical carotid atherosclerosis, even in populations free of hypertension, diabetes, and hyperlipidemia.
The absorption of glucose is electrogenic in the small intestinal epithelium. The major route for the transport of dietary glucose from intestinal lumen into enterocytes is the Na⁺/glucose ...cotransporter (SGLT1), although glucose transporter type 2 (GLUT2) may also play a role. The membrane potential of small intestinal epithelial cells (IEC) is important to regulate the activity of SGLT1. The maintenance of membrane potential mainly depends on the activities of cation channels and transporters. While the importance of SGLT1 in glucose absorption has been systemically studied in detail, little is currently known about the regulation of SGLT1 activity by cation channels and transporters. A growing line of evidence suggests that cytosolic calcium (Ca(2+)cyt) can regulate the absorption of glucose by adjusting GLUT2 and SGLT1. Moreover, the absorption of glucose and homeostasis of Ca(2+) in IEC are regulated by cation channels and transporters, such as Ca(2+) channels, K⁺ channels, Na⁺/Ca(2+) exchangers, and Na⁺/H⁺ exchangers. In this review, we consider the involvement of these cation channels and transporters in the regulation of glucose uptake in the small intestine. Modulation of them may be a potential strategy for the management of obesity and diabetes.
The scale of fluctuation (SOF) is used to evaluate the correlation between two locations of geotechnical parameter, which is important for mineral exploration and engineering construction. In this ...study, the performances of conventional moment methods are firstly estimated, and then the exponential autocorrelation function method that can achieve the best performance in estimating SOF is selected. After that, the Torque Penetration Index (TPI) and the Field Penetration Index (FPI) obtained from the Yinsong Water Diversion Project are used to detect the scale effect of SOF and to quantify the influences of rock types and surrounding rock mass grades on SOF. As the spatial scale increases, the SOF values increase, and the uncertainty in the SOF of the surrounding rock mass properties increases. The SOF calculated using TPI is slightly higher than using FPI. The mean values of SOF for granite, tuff, diorite, and limestone are quite close at the 50 m–200 m scales, with coefficients of variation (COVs) of SOF range from about 0.2 to 0.4. There are differences in SOF between grade III and grade IV surrounding rock masses at the 50 m–500 m scales. The mean values of SOF in grade III surrounding rock mass are about 4%–15% higher than that in grade IV surrounding rock mass, and this difference in general increases as scale increases. The rock mass with better conditions has a stronger spatial correlation. The COVs of SOF for the two rock grades reached about 0.3–0.5, owning to the inherent spatial variability.
•Exponential autocorrelation function method tends to yield accurate SOF values.•TPI and FPI could be used to calculate the SOFs of the surrounding rock masses.•The SOF and the uncertainty increase as the scale increases.•The surrounding rock mass grades play a dominant role in SOF values.
The p53 tumor suppressor is a sequence-specific DNA binding protein that activates gene transcription to regulate cell survival and proliferation. Dynamic control of p53 degradation and DNA binding ...in response to stress signals are critical for tumor suppression. The p53 N terminus (NT) contains two transactivation domains (TAD1 and TAD2), a proline-rich region (PRR), and multiple phosphorylation sites. Previous work revealed the p53 NT reduced DNA binding in vitro. Here, we show that TAD2 and the PRR inhibit DNA binding by directly interacting with the sequence-specific DNA binding domain (DBD). NMR spectroscopy revealed that TAD2 and the PRR interact with the DBD at or near the DNA binding surface, possibly acting as a nucleic acid mimetic to competitively block DNA binding. In vitro and in vivo DNA binding analyses showed that the NT reduced p53 DNA binding affinity but improved the ability of p53 to distinguish between specific and nonspecific sequences. MDMX inhibits p53 binding to specific target promoters but stimulates binding to nonspecific chromatin sites. The results suggest that the p53 NT regulates the affinity and specificity of DNA binding by the DBD. The p53 NT-interacting proteins and posttranslational modifications may regulate DNA binding, partly by modulating the NT–DBD interaction.
Bullous pemphigoid (BP) is an autoimmune blistering disorder that predominantly affects the elderly. As the main treatment for BP, systemic corticosteroids are often limited by their side effects. ...Safer treatment modalities are therefore needed. Dupilumab is a biologic agent used to treat BP in recent years.
Medical records of patients with moderate-to-severe BP were retrospectively reviewed. Twenty-four patients were included (follow-up period: 32 weeks), eight of whom received dupilumab in combination with methylprednisolone and azathioprine (dupilumab group) while the other 16 patients received methylprednisolone and azathioprine (conventional group). Response to dupilumab was evaluated by comparison of several parameters (time to stop new blister formation, time to reduce the systemic glucocorticoids to minimal dose, and total amount of methylprednisolone).
The median age of patients in the dupilumab and conventional groups were 64.50 years (range: 22-90 years) and 64.50 years (range: 17-86 years), respectively. The median duration of disease before admission in the dupilumab group was 2 months (range: 1-240 months) and 2.5 months (range: 1-60 months) in the conventional group. The median time to stop new blister formation was 8 days (range: 1-13 days) and 12 days (range: 5-21 days) in patients of the dupilumab and conventional groups, respectively (
= 0.028 by Kaplan-Meier analysis). In addition, the median time to reduce the systemic glucocorticoids to minimal dose (methylprednisolone 0.08 mg/kg/day) was 121.5 and 148.5 days for the dupilumab and conventional therapy groups, respectively (
= 0.0053 by Kaplan-Meier analysis). The median total amount of methylprednisolone (at the time of reaching the minimal dose) used in the dupilumab group was 1,898 mg (range: 1,624-2,932 mg) while the cumulative dose of conventional group was 2,344 mg (range: 1,708-4,744 mg) (
= 0.036 by Mann-Whitney
test). The median total amount of azathioprine (at the time of reaching the minimal dose) used in dupilumab group was 8,300 mg (range: 7,100-10,400 mg) while the total dose of conventional group was 10,300 mg (range: 8,900-14,400 mg) (
= 0.0048 by Mann-Whitney
test). No adverse event related to dupilumab was recorded.
Dupilumab in addition to methylprednisolone and azathioprine seems superior to methylprednisolone/azathioprine alone in controlling disease progression and accelerating the tapering of glucocorticoids.
Emerging evidence of immunological dysfunction have been described in endometriosis. Dendritic cells (DCs), one of the main antigen-presenting cells, are specialized in the initiation and modulation ...of the adaptive immune response. Emerging studies demonstrated both endometrial and circulating differences in DCs populations in women with endometriosis. However, the role and mechanism of peritoneal DCs in endometriosis is still unclear. The present study was undertaken to explore the features of peritoneal DCs in the pathogenesis of endometriosis. This study is beneficial to further clarify the cause of endometriosis and provide a new insight into the medical treatment for endometriosis.
The study included 12 women with endometriosis and 11 women without endometriosis. The C57BL6 mouse model of endometriosis was established by intraperitoneal injection of endometrial segments. The peritoneal DCs of endometriosis patients and mouse models were analyzed by fluorescence associated cell sorting (FACS) examination.
Increased cell density of peritoneal DCs were observed in endometriosis patients. Moreover, the proportion of mature DCs (mDCs, CD80
CD1a
cells) in the peritoneal DCs was lower whereas the proportion of immature DCs (iDCs, CD80
CD1a
cells) was increased in endometriosis patients. Similarly, the cell density of peritoneal DCs in murine models increased immediately after the injection of endometrial tissues and reached the highest level at 14 days. In addition, the proportion of mDCs (CD11c
CD80
cells) in the peritoneal DCs decreased immediately after the injection of endometrial tissues and then increased with the time until 42 days, but still lower than the control group. In contrast, the proportion of iDCs (CD11c
CD80
cells) in the peritoneal DCs showed the opposite dynamic changes. However, after treated with LPS, the mDCs proportion was significantly increased, leading to lower volume and weight of the endometriosis lesions.
Increased level of peritoneal DCs facilitated the pathogenesis of endometriosis lesions, especially in the early stage of the disease. Furthermore, peritoneal DCs maturation played an important role in the development of endometriosis.
Chronic wounds impose a substantial economic burden on healthcare systems and result in decreased productivity. Honey possesses diverse properties, rendering it a promising, cost-effective, and ...efficacious intervention strategy for the management of chronic wounds. However, the findings are controversial. We have presented an updated and comprehensive systematic review and meta-analysis to evaluate the efficacy and safety of honey dressings in the management of chronic wounds. Nine electronic databases were systematically searched to identify relevant studies published prior to 22 March 2024. A total of eight studies, including 906 individuals that met the inclusion criteria, were incorporated. The findings demonstrated a significant acceleration in wound healing time with honey dressings (MD = −17.13, 95% CI −26.37 to −7.89, p = 0.0003) and an increase in the percentage of wound healing (MD = 18.31, 95% CI 8.86 to 27.76, p = 0.0001). No statistically significant differences were observed in the healing rate (RR = 2.00, 95% CI 0.78 to 5.10, p = 0.15), clearance time of bacteria (MD = −11.36, 95% CI: −25.91 to 3.18, p = 0.13) and hospital stay duration. Honey may decrease the VAS score but may increase the incidence of painful discomfort during treatment. The topical application of honey is an effective therapeutic approach for managing chronic wounds, but the quality of the evidence was very low due to the quality of risk of bias, inconsistency, and publication bias, highlighting the necessity for larger-scale studies with adequately powered RCTs to ensure the safety and efficacy of honey dressings in chronic wound healing.
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