Imaging GPCR Dimerization in Living Cells with Cucurbit[7]uril and Hemicyanine as a "Turn-On" Fluorescence Probe.

Although multiple forms of dimers have been described for GPCR, their dynamics and function are still controversially discussed field. Fluorescence microscopy allows GPCR to be imaged within their native context; however, a key challenge is to site-specifically incorporate reporter moieties that can produce high-quality signals upon formation of GPCR dimers. To this end, we propose a supramolecular sensor approach to detect agonist-induced dimer formation of µ-opioid receptors (µORs) at the surface of intact cells. With the macrocyclic host cucurbit[7]uril and its guest hemicyanine dye tethered to aptamer strands directed against the histidine residues, the sensing module is assembled by host-guest complexation once the histidine-tagged µORs dimerize and bring the discrete supramolecular units into close proximity. With the enhanced sensitivity attributed by the "turn-on" fluorescence emission and high specificity afforded by the intermolecular recognition, in situ visualization of dynamic GPCR dimerization was realized with high precision, thereby validating the supramolecular sensing entity as a sophisticated and versatile strategy to investigate GPCR dimers, which represent an obvious therapeutic target.

Association between chinese visceral adiposity index and risk of kidney stones in a health screening population: an ultrasonography based cross-sectional study.

BACKGROUND: Obesity is an important risk factor for kidney stones(KS). Chinese Visceral Adiposity Index (CVAI), as a specific indicator for visceral obesity in the Chinese population, can more accurately assess the visceral fat content in Chinese individuals compared to Visceral Adiposity Index (VAI). However, the association between CVAI and risk for KS has not been studied. METHODS: A total of 97,645 participants from a health screening cohort underwent ultrasound examinations for the diagnosis of kidney stones, along with measurements of their CVAI. Logistic regressions were utilized to determine the relationship between different quartiles of CVAI and the incidence of kidney stones. Simultaneously, subgroup analysis and the computation of dose-response curves were employed to pinpoint susceptible populations. RESULTS: Among the participants, 2,888 individuals (3.0%) were diagnosed with kidney stones. The mean CVAI values ± standard deviation for the four groups were: Q1 (18.42 ± 19.64), Q2 (65.24 ± 10.39), Q3 (98.20 ± 9.11), and Q4 (140.40 ± 21.73). In the fully adjusted multivariable model, CVAI was positively correlated with urolithiasis (OR = 1.001; 95% CI = 1.000, 1.002). Compared with the first quartile of CVAI, the population in the fourth quartile of CVAI had a higher prevalence of kidney stones (OR = 1.231; 95% CI = 1.066, 1.415). Through subgroup analysis, a positive correlation between CVAI and the risk of kidney stones was found in non-smokers (OR = 1.001, 95%CI:1.000, 1.002), non-drinkers (OR = 1.001, 95%CI:1.000, 1.002), non-hypertensive subgroups (OR = 1.003, 95%CI:1.002, 1.003), and non-diabetes subgroups (OR = 1.001, 95%CI:1.000, 1.002). CONCLUSION: The findings suggest that CVAI could be a reliable and effective biomarker for assessing the potential risk of kidney stone prevalence, with significant implications for the primary prevention of kidney stones and public health.

Violent Victimization During Childhood in the United States: Associations With Revictimization and Health.

Childhood violence victimization is a serious adverse childhood experience with lasting health impacts. This study examined the prevalence and characteristics of five forms of childhood violence victimization and their association with revictimization and negative health conditions among adults. Data are from the 2010-2012 National Intimate Partner and Sexual Violence Survey. Age at first victimization and perpetrator sex were assessed; adjusted odds ratios assessed associations with revictimization and health. Ages 14-17 were the most common age at first victimization for most violence types; almost half of male (46.7%) and a quarter of female (27.0%) rape victims reported first victimization before age 10. Most victimization was associated with revictimization and negative health, controlling for adult victimization. Primary prevention of childhood violence may reduce later health risks.

Effect of major components of Tripterygium wilfordii Hook. f on the uptake function of organic anion transporting polypeptide 1B1.

Organic anion transporting polypeptide 1B1 (OATP1B1), which is specifically expressed at the basolateral membrane of human hepatocytes, is well recognized as the key determinant in the pharmacokinetics of a wide variety of drugs and considered as an important drug-drug interaction (DDI) site. Triptergium wilfordii Hook. f. (TWHF) is a traditional Chinese medicine that has a long history in treating diseases and more pharmacological effects were demonstrated recently. Components of TWHF mainly belong to the groups of alkaloids, diterpenoids, and triterpenoids. However, whether TWHF constituents are involved in herb-drug interaction (HDI) remains largely unknown. In the present study, we investigated the effect of four major components of TWHF, i.e. Triptolide (TPL), Celastrol (CL), and two alkaloids Wilforine (WFR) and Wilforgine (WFG) on the function of OATP1B1. It was found that co-incubation of these compounds greatly inhibited the uptake function of OATP1B1, with WFG (IC50 = 3.63 ± 0.61 µM) and WFR (IC50 = 3.91 ± 0.30 µM) showing higher inhibitory potency than TPL (IC50 = 184 ± 36 µM) and CL (IC50 = 448 ± 81 µM). Kinetic analysis revealed that co-incubation of WFG or WFR led to the reduction of both Km and Vmax of the DCF uptake. On the other hand, pre-incubation of WFG or WFR increased Km value of OATP1B1; while CL affected both Km and Vmax. In conclusion, co- and pre-incubation of the tested TWHF components inhibited OATP1B1 activity in different manners. Although co-incubation of WFG and WFR did not seem to directly compete with the substrates, pre-incubation of these alkaloids may alter the substrate-transporter interaction.

Input aperture restriction of the spatial spectral compressive spectral imager and a comprehensive solution for it.

Compressive spectral imaging (CSI) is an attractive spectral imaging technique since it could acquire a spectral image data cube in a single snapshot. One notable CSI scheme is the spatial spectral compressive spectral imager (SSCSI), which has low complexity and high quality of the recovering spectral image. However, the SSCSI suffers from a small input aperture, which reduces the optical efficiency and signal-to-noise ratio of the system. In this paper, the effect of the input aperture size on the SSCSI system is analyzed. It shows that with the increase of input aperture, the incident light from different spectral bands will overlap with each other on the mask, and the encoding pattern of each spectral band will be ambiguous. Thus, the reconstruction quality of the data cube will highly deteriorate. A new scheme is proposed to deal with this problem. First, the observed image is resampled and recombined into new sub-observed images to improve the frequency response of the encoding pattern. Then each sub-observed image is divided into multiple sub-sets to reduce the coherence of the sensing matrix. Compared to the original reconstruction algorithm for the SSCSI system, the peak signal-to-noise ratio (PSNR) is promoted by more than 3dB, and the spectral reconstruction accuracy and noise suppression capability are also improved.

Urea-to-Albumin Ratio and In-Hospital Mortality in Severe Pneumonia Patients.

OBJECTIVE: The urea-to-albumin ratio (UAR), as a new marker of the systemic inflammatory response, is associated with the mortality in pneumonia patients. However, the association between the UAR and in-hospital mortality in severe pneumonia (SP) has received little attention. METHODS: In this single-center retrospective cohort study, 212 SP patients in intensive care unit (ICU) from June 1, 2016, to June 1st, 2020, with baseline UAR were enrolled. The primary outcome was in-hospital mortality. The association of UAR with in-hospital mortality was assessed using a multivariable-adjusted Cox model. RESULTS: Of 212 patients, the median age was 73.0 (61.0, 82.8) years, 70.8% of patients were male, and the APACHE II score was 20.0 (16.0, 26.0). During the hospital period, 101 (47.6%) patients died. In-hospital mortality rates for the lower and higher UAR were 16 (27.6%) and 85 (55.2%), respectively (P < 0.001). Kaplan-Meier analysis revealed that survival rates were significantly different between the two groups (log rank = 13.71, P < 0.001). After adjusted for confounding factors, the higher UAR group was significantly associated with a hazard ratio (HR) for in-hospital mortality of 2.234 (95% confidence interval: 1.146-4.356, P=0.018). Besides, this pattern persisted in subgroup analyses considering sex (HR = 9.380; 95% CI: 2.248-39.138; P=0.002). CONCLUSIONS: Higher UAR levels at the commencement of admission to ICU may be independently associated with increased in-hospital mortality in SP patients.

Cabin1 involves in renal tubular epithelial cells mitochondrial dysfunction through SIRT1/p53 pathway.

Background: Angiotensin II (AngII) induced Calcineurin binding protein 1 (Cabin1) protein expression significantly increased during Renal tubular epithelial cells (RTEC) injury. However, the detailed function of Cabin1 protein in RTEC was not characterized well. In this study, we aimed to explore the downstream target of Cabin1 in vitro model.Methods: Rat kidney epithelial cells were cultured and stimulated with AngII. Electron microscopy was performed to observe mitochondrial morphology change. Immunofluorescence staining was detected to observe the distribution of cytoskeleton and Cabin1. Mitochondrial morphology change and protein expression were detected by electrical microscopy and western blot.Results: AngII induced the disruption of cytoskeleton at 24 and 48 h. Western blot analysis showed AngII significantly induced the overexpression of Cabin1. AngII induced a great deal of small, long and irregular mitochondria in RTEC, aspect ratio which reflects the length-to-width ratio of mitochondria remarkably increased at 12 and 24 h. Knocking down Cabin1 aggravated mitochondrial morphological abnormality in AngII treated RTEC. In comparison with control, Cabin1, p53 and cyto C level were significantly increased in AngII treated cells, while SIRT1 level was obviously decreased. Knocked down Cabin1 plus AngII stimulated, SIRT1 was further decreased, while p53 and cyto C were significantly increased.Conclusions: Cabin1 involves in RTEC mitochondrial dysfunction through SIRT1/p53 pathway. Cabin1 may be used as a new marker for the mechanisms of RTEC injury.

High Mean Platelet Volume Associates with In-Hospital Mortality in Severe Pneumonia Patients.

BACKGROUND: Although mean platelet volume (MPV) appears to be associated with poor outcome of pneumonia, the relationship between MPV and in-hospital mortality is unclear in severe pneumonia (SP) patients. METHODS: In this retrospective cohort study, 115 SP patients from June 1st, 2016, to September 29th, 2019, were included and divided into two groups. The primary outcome was in-hospital mortality. The receiver operating characteristic (ROC) curve was performed to assess the predictive ability for in-hospital mortality. Kaplan-Meier cumulative incidence curves were applied to observe the incidence of mortality. Multivariable Cox regression analyses were used to evaluate the hazard ratios (HRs). Besides, a formal test for interaction was investigated to analyze the relationship between MPV and sex. RESULTS: During the course of hospitalization, 63 cases of mortality were recorded. ROC analysis suggested that MPV had a modest power for predicting in-hospital mortality (AUC = 0.723, 95% CI: 0.628-0.818, P < 0.001). Yet the cutoff value of MPV was 10.5 (sensitivity = 73.02%; specificity = 73.08%). Compared to the low-MPV group, the high-MPV group had significantly increased in-hospital mortality (log-rank test = 13.501, P < 0.001), while the adjusted Cox model indicated that the high-MPV group was associated with an elevated risk of in-hospital mortality (HR: 2.267, 95% CI: 1.166-4.406, P = 0.016). Moreover, analyses of in-hospital mortality suggested a significant interaction between optimal MPV level and sex (P = 0.011). In a multivariate Cox model which included females only, a high MPV level was associated with increased risk of in-hospital mortality (HR: 11.387, 95% CI: 1.767-73.380, P = 0.011). CONCLUSION: High MPV level is an independent risk factor for in-hospital mortality in patients with SP.

Benefits of a transtheoretical model-based program on exercise adherence in older adults with knee osteoarthritis: A cluster randomized controlled trial.

AIMS: Benefits of a transtheoretical model-based exercise program on exercise adherence (primary outcome) and secondary outcomes (self-efficacy, decisional balance, knee osteoarthritis symptoms, and physical function) were assessed among older adults with knee osteoarthritis. DESIGN: A two-arm, superiority, assessor-blinded, cluster randomized trial with randomization at the community level. METHODS: Participants were recruited from 14 communities in Beijing between April - October 2018 (N = 189). The intervention was a 24-week transtheoretical model-based exercise program and the control group underwent a non-theory-based exercise program. Exercise adherence was collected every 4 weeks and secondary outcomes were measured at baseline, 12 weeks, and 24 weeks. An independent t test and repeated-measures ANOVA were the main statistical tests. RESULTS: Most participants were women (92.5%), married (81.4%), with high-school education (36.0%), with both knees affected (50.3%), and did not make use of a walker (93.8%). There were no significant differences between groups in any of the outcome measures at baseline. Repeated-measures ANOVA indicated that there was a significant difference in the trend of adherence scores between the two groups from 0-24 weeks. The independent t test showed that scores in the intervention group were significantly better than in the control group at 16, 20, and 24 weeks. Improvements in the intervention group were also significantly greater in all secondary outcomes than in the control group. CONCLUSION: A theory-based exercise program could improve exercise adherence, self-efficacy, decisional balance, knee osteoarthritis symptoms, and physical functioning in older adults with knee osteoarthritis. TRIAL REGISTRATION: Chinese Clinical Trials Registry number ChiCTR1800015458. Registered 31 March 2018. IMPACT: The 24-week theory-based exercise program could improve exercise adherence, self-efficacy, decisional balance, symptoms of knee osteoarthritis, and physical functioning in older adults with knee osteoarthritis. The theory-based exercise program could help older adults with knee osteoarthritis to improve their symptoms and knee function.

The effects of job characteristics, organizational justice and work engagement on nursing care quality in China: A mediated effects analysis.

AIM: To analyse the structural associations among job characteristics, organizational justice, work engagement and nursing care quality in Chinese nurses. BACKGROUND: Nursing care quality helps ensure patient safety, which are core concerns. The explicit relationships among the study's variables from a management perspective can help hospital managers to implement effective strategies to improve nursing care quality. METHODS: This cross-sectional study was conducted to investigate the relationships among the variables in 1,615 nurses in eight Chinese tertiary hospitals. Structural equation modelling was used to test a proposed model of these relationships. RESULTS: The scores of job characteristics, organizational justice, work engagement and nursing care quality were 3.55 ± 0.41, 3.84 ± 0.77, 4.67 ± 1.30 and 3.42 ± 0.70. Job characteristics and organizational justice had direct effects on nursing care quality. Work engagement mediated the relationship of nursing care quality with job characteristics and organizational justice. The final model explained 24% of nursing care quality. CONCLUSION: The results provide a better understanding of the associations between the study's variables. Perceived job characteristics and organizational justice can improve nursing care quality through work engagement. IMPLICATIONS FOR NURSING MANAGEMENT: Reconfiguring work design to strengthen nurses' positive perceptions of job characteristics and organizational justice can enhance nursing care quality.

Vital Signs: Estimated Proportion of Adult Health Problems Attributable to Adverse Childhood Experiences and Implications for Prevention - 25 States, 2015-2017.

INTRODUCTION: Adverse childhood experiences, such as violence victimization, substance misuse in the household, or witnessing intimate partner violence, have been linked to leading causes of adult morbidity and mortality. Therefore, reducing adverse childhood experiences is critical to avoiding multiple negative health and socioeconomic outcomes in adulthood. METHODS: Behavioral Risk Factor Surveillance System data were collected from 25 states that included state-added adverse childhood experience items during 2015-2017. Outcomes were self-reported status for coronary heart disease, stroke, asthma, chronic obstructive pulmonary disease, cancer (excluding skin cancer), kidney disease, diabetes, depression, overweight or obesity, current smoking, heavy drinking, less than high school completion, unemployment, and lack of health insurance. Logistic regression modeling adjusting for age group, race/ethnicity, and sex was used to calculate population attributable fractions representing the potential reduction in outcomes associated with preventing adverse childhood experiences. RESULTS: Nearly one in six adults in the study population (15.6%) reported four or more types of adverse childhood experiences. Adverse childhood experiences were significantly associated with poorer health outcomes, health risk behaviors, and socioeconomic challenges. Potential percentage reductions in the number of observed cases as indicated by population attributable fractions ranged from 1.7% for overweight or obesity to 23.9% for heavy drinking, 27.0% for chronic obstructive pulmonary disease, and 44.1% for depression. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Efforts that prevent adverse childhood experiences could also potentially prevent adult chronic conditions, depression, health risk behaviors, and negative socioeconomic outcomes. States can use comprehensive public health approaches derived from the best available evidence to prevent childhood adversity before it begins. By creating the conditions for healthy communities and focusing on primary prevention, it is possible to reduce risk for adverse childhood experiences while also mitigating consequences for those already affected by these experiences.

Residual Normality Assumption and the Estimation of Multiple Membership Random Effects Models.

While conventional hierarchical linear modeling is applicable to purely hierarchical data, a multiple membership random effects model (MMrem) is appropriate for nonpurely nested data wherein some lower-level units manifest mobility across higher-level units. Although a few recent studies have investigated the influence of cluster-level residual nonnormality on hierarchical linear modeling estimation for purely hierarchical data, no research has examined the statistical performance of an MMrem given residual non-normality. The purpose of the present study was to extend prior research on the influence of residual non-normality from purely nested data structures to multiple membership data structures. Employing a Monte Carlo simulation study, this research inquiry examined two-level MMrem parameter estimate biases and inferential errors. Simulation factors included the level-two residual distribution, sample sizes, intracluster correlation coefficient, and mobility rate. Results showed that estimates of fixed effect parameters and the level-one variance component were robust to level-two residual non-normality. The level-two variance component, however, was sensitive to level-two residual non-normality and sample size. Coverage rates of the 95% credible intervals deviated from the nominal value assumed when level-two residuals were non-normal. These findings can be useful in the application of an MMrem to account for the contextual effects of multiple higher-level units.

Erratum: [Corrigendum] Relationship between changes in mitochondrial function and hippocampal neuronal apoptosis after recurrent convulsion during developmental stage.

[This corrects the article DOI: 10.3892/etm.2018.6147.].

Association of Contact Sexual Violence Victimization and Health in the U.S.

INTRODUCTION: Sexual violence victimization is related to negative impacts, including chronic health conditions. Less is known about possible confounders of this relationship. This study examines the association between lifetime experience of contact sexual violence (CSV) and health conditions by sex, controlling for demographics and other victimization. METHODS: Data are from the 2016/2017 National Intimate Partner and Sexual Violence Survey, a nationally representative study of English- or Spanish-speaking adults. Ten health conditions (e.g., HIV/AIDS) and four activity limitations (e.g., difficulty dressing) were examined related to CSV victimization. Logistic regression models examined the association between CSV victimization and health controlling for demographics and other victimization experiences. Analyses were conducted in 2022 to 2023. RESULTS: For women and men, many health conditions and activity limitations were significantly associated with CSV after controlling for demographics. Accounting for other victimization, female CSV victims had higher odds of experiencing difficulty sleeping (Adjusted Odds Ratio [AOR]=1.3); difficulty concentrating, remembering, or making decisions (AOR=1.7); and difficulty doing errands alone (AOR=1.4) than nonvictims. Male victims had higher odds than nonvictims of having HIV/AIDS (AOR=5.2); frequent headaches (AOR=1.5); chronic pain (AOR=1.5); difficulty sleeping (AOR=1.4); serious difficulty hearing (AOR=1.3); and difficulty concentrating, remembering, or making decisions (AOR=1.5). CONCLUSIONS: CSV had a negative impact on health, although other types of victimization appear to also have an impact, especially for women. Demographic characteristics also aid the understanding of the relationship between CSV and health. Efforts to prevent CSV and other forms of violence can be coupled with healthcare- and population-level approaches to improve long-term health.

Rape and Sexual Coercion Related Pregnancy in the United States.

INTRODUCTION: Sexual violence is a major public health problem in the U.S. that is associated with numerous health impacts, including pregnancy. U.S. population-based estimates (2010-2012) found that three million women experienced a rape-related pregnancy during their lifetimes. The current study presents more recent estimates of rape and sexual coercion-related pregnancy and examines prevalence by demographic characteristics. METHODS: Data years 2016/2017 were pooled from the National Intimate Partner and Sexual Violence Survey, a random-digit-dial telephone survey of U.S. non-institutionalized adults 18 years and older. The analysis, conducted in 2023, examined lifetime experience of rape-related pregnancy, sexual coercion-related pregnancy, or both among U.S. women. Authors calculated prevalence estimates with 95% CIs and conducted pairwise chi-square tests (p-value<0.05) to describe experiences by current age, race/ethnicity, and region of residence among U.S. women overall and among victims. RESULTS: One in 20 women in the U.S., or over 5.9 million women, experienced a pregnancy from either rape, sexual coercion, or both during their lifetimes. Non-Hispanic Multiracial women experienced a higher prevalence of all three outcomes compared with non-Hispanic White, non-Hispanic Black, and Hispanic women. Among victims who experienced pregnancy from rape, 28% experienced a sexually transmitted disease, 66% were injured, and over 80% were fearful or concerned for their safety. CONCLUSIONS: Pregnancy as a consequence of rape or sexual coercion is experienced by an estimated six million U.S. women. Prevention efforts may include healthcare screenings to identify violence exposure and use of evidence-based prevention approaches to reduce sexual violence.

A positive correlation between serum lactate dehydrogenase level and in-hospital mortality in ICU sepsis patients: evidence from two large databases.

BACKGROUND: Sepsis presents a significant healthcare challenge, characterized by high morbidity and mortality rates. There is a scarcity of relevant studies investigating the association between serum lactate dehydrogenase level and the prognosis of sepsis in patients from intensive care unit, with smaller sample sizes compared to other studies. METHODS: A retrospective analysis was conducted utilizing data from the Second Affiliated Hospital of Guangzhou Medical University and the Medical Information Mart for Intensive Care IV (MIMIC-IV). The primary outcome was the in-hospital mortality. Multivariate Cox proportional hazards regression was adopted to assess the independent association. Receiver operator characteristic (ROC) curve was used to evaluate the predictive value. RESULTS: We included a total of 2148 patients in the Guangzhou Sepsis Cohort (GZSC) database and 5830 patients in the MIMIC-IV database. In multivariate Cox proportional hazards regression, high levels of LDH are significantly associated with higher mortality (HR = 1.21, 95% CI 1.13-1.30, p < 0.001 in the GZSC database and HR = 1.19, 95% CI 1.13-1.25, p < 0.001 in the MIMIC-IV database). The ROC curves showed that the AUC of LDH was 0.663 in the GZSC database and 0.660 in the MIMIC-IV database. CONCLUSIONS: A lower lactate dehydrogenase level is associated with reduced in-hospital mortality among patients with sepsis, suggesting its potential as a valuable marker for predicting prognosis in this patient population.

Association between albumin-bilirubin score and in-hospital mortality in patients with sepsis: Evidence from two large databases.

Background: The Albumin-Bilirubin (ALBI) score, recommended for assessing the prognosis of hepatocellular carcinoma patients, has garnered attention. The efficacy of ALBI score in forecasting the risk of death in sepsis patients remains limited. We designed two cohort studies to assess the association between ALBI score and in-hospital mortality in patients with sepsis. Methods: A retrospective analysis was conducted utilizing data from the Second Affiliated Hospital of Guangzhou Medical University and the Medical Information Mart for Intensive Care IV(MIMIC-IV). Patients diagnosed with sepsis were included in the analysis. The primary outcome was the in-hospital mortality. Multivariate Cox regression analysis was conducted to assess the independent association between the ALBI score and mortality, with adjustment for potential confounders. Subgroup analysis was conducted to assess the robustness of the findings. Results: The Guangzhou Sepsis Cohort (GZSC) of the Second Affiliated Hospital of Guangzhou Medical University comprised 2969 participants, while the MIMIC-IV database included 8841 participants. The ALBI score were categorized into < -2.60, -2.60∼-1.39, and >-1.39. After adjusting for confounders, a linear relationship was observed between ALBI score and mortality. Patients with a high ALBI grade were associated with higher in-hospital mortality in both the GZSC (HR: 1.52, 95%CI: 1.24-1.87, p < 0.001) and the MIMIC-IV database (HR: 1.57, 95%CI: 1.46-1.70, p < 0.001). Conclusions: A high ALBI score is associated with higher in-hospital mortality among sepsis patients in ICU.

The Double-Leucine Motifs Affect Internalization, Stability, and Function of Organic Anion Transporting Polypeptide 1B1.

Organic anion transporting polypeptide 1B1 (OATP1B1) is specifically expressed at the basolateral membrane of human hepatocytes and plays important roles in the uptake of various endogenous and exogenous compounds including many drugs. The proper functioning of OATP1B1, hence, is essential for the bioavailability of various therapeutic agents and needs to be tightly regulated. Dileucine-based signals are involved in lysosomal targeting, internalization, and trans-Golgi network to endosome transporting of membrane proteins. In the current study, we analyzed the 3 intracellular and 13 transmembrane dileucine motifs (DLMs) within the sequence of OATP1B1. It was found that the simultaneous replacement of I332 and L333 with alanine resulted in a significantly reduced level of the mature form of OATP1B1. The cell surface expression of I332A/L333A could be partially rescued by MG132, as well as agents that prevent clathrin-dependent protein internalization, suggesting that this dileucine motif may be involved in the endocytosis of OATP1B1. On the other hand, I376/L377 and I642/L643, which are localized at transmembrane helices (TM) 8 and 12, respectively, are involved in the interaction of the transporter with its substrates. I642A/L643A exhibited a significantly decreased protein level compared to that of the wild-type, implying that the motif is important for maintaining the stability of OATP1B1 as well.

Activation of angiotensin II type 2 receptor attenuates lung injury of collagen-induced arthritis by alleviating endothelial cell injury and promoting Ly6Clo monocyte transition.

As one of the most frequent extra-articular manifestations of rheumatoid arthritis (RA), interstitial lung disease (ILD) is still challenging due to unrevealed pathophysiological mechanism. To address this question, in the present study, we used the classical collagen-induced arthritis (CIA) mouse model to determine the related-immune mechanism of lung injury and possible pharmacological treatment for RA-ILD. At the peak of arthritis, we found CIA mice developed apparent lung injury, characterized by interstitial thickening, inflammatory cell infiltration, and lymphocyte follicle formation. Additionally, the endothelial injury occurred as the number of endothelial cells (ECs) and their CD31 expression decreased. Along with those, monocytes, predominantly Ly6Chi monocytes with pro-inflammatory phenotype, were also increased. While in the remission period of arthritis, ECs gradually increased with retrieved CD31 expression, leading to decreased infiltrating monocytes, but boosted Ly6Clo population. Ly6Clo monocytes were prone to locate around damaged ECs, promoted ECs proliferation and vascular tube formation, and lessened the expression of adhesion molecules. In addition, we evaluated angiotensin II type 2 receptor (Agtr2), which has been demonstrated to be protective against lung injury, could be beneficial in RA-ILD. We found elevated Agtr2 in CIA lung tissue, and activation of Agtr2, within its specific agonist C21, alleviated the pulmonary inflammation in vivo, reduced ECs injury, and promoted monocytes conversion from Ly6Chi to Ly6Clo monocytes in vitro. Our data reveal a potential pathological mechanism of RA-ILD that involves ECs damage and inflammatory monocytes infiltration and provide a potential drug target, Agtr2, for RA-ILD treatment.

Whole-Genome Analysis of Termite-Derived Bacillus velezensis BV-10 and Its Application in King Grass Silage.

Bacillus velezensis (B. velezensis) is a cellulose-degrading strain that has the potential as an additive in fermented feed. B. velezensis BV-10 was isolated and screened from the termite gut. We sequenced the whole genome of this new source of B. velezensis to reveal its potential for use in cellulose degradation. Whole-genome sequencing of B. velezensis BV-10 showed that it has a circular chromosome of 3929792 bp containing 3873 coding genes with a GC content of 45.51% and many genes related to cellulose, hemicellulose, and lignin degradation. King grass silage was inoculated with B. velezensis BV-10 and mixed with other feed additives to assess the effect of B. velezensis BV-10 on the fermentation quality of silage. Six treatment groups were established: the control, B. velezensis BV-10, molasses, cellulase, B. velezensis BV-10 plus molasses, and B. velezensis BV-10 plus cellulase groups. After 30 days of silage-fermentation testing, B. velezensis BV-10 was found to rapidly reduce the silage pH value and significantly reduce the acid-detergent fiber (ADF) content (p < 0.05). The addition of B. velezensis BV-10 plus molasses and cellulase in fermented feed significantly reduced the silage neutral-detergent fiber and ADF content and promoted organic-acid accumulation (p < 0.05). The above results demonstrate that B. velezensis BV-10 promotes the fermentation quality of silage and that this effect is greater when other silage-fermentation additives are included. In conclusion, genes involved in cellulose degradation in B. velezensis BV-10 were identified by whole-genome sequencing and further experiments explored the effects of B. velezensis BV-10 and different feed additives on the fermentation quality of king grass silage, revealing the potential of Bacillus velezensis as a new silage additive.