Effects of sodium tanshinone IIA sulfonate injection on inflammatory factors and vascular endothelial function in patients with acute coronary syndrome undergoing percutaneous coronary intervention: A systematic review and meta-analysis of randomized clinical trials.

Background: Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) therapy may experience further damage to the vascular endothelium, leading to increased inflammatory response and in-stent thrombosis. In many clinical studies, sodium tanshinone IIA sulfonate injection (STS) has been found to reduce inflammatory factors and enhance vascular endothelial function in patients with ACS while improving the prognosis of PCI. However, to date, there has been no systematic review assessing the effectiveness and safety of STS on inflammatory factors and vascular endothelial function. Purpose: The aim of this study is to systematically review the effects of STS on inflammatory factors and endothelial function in patients with ACS treated with PCI. Methods: Until October 2022, eight literature databases and two clinical trial registries were searched for randomized controlled trials (RCTs) investigating STS treatment for ACS patients undergoing PCI. The quality of the included studies was assessed using the Cochrane Risk Assessment Tool 2.0. Meta-analysis was performed using RevMan 5.4 software. Results: Seventeen trials met the eligibility criteria, including 1,802 ACS patients undergoing PCI. The meta-analysis showed that STS significantly reduced high-sensitivity C-reactive protein (hs-CRP) levels (mean difference [MD = -2.35, 95% CI (-3.84, -0.86), p = 0.002], tumor necrosis factor-alpha (TNF-α) levels (standard mean difference [SMD = -3.29, 95%CI (-5.15, -1.42), p = 0,006], matrix metalloproteinase-9 (MMP-9) levels [MD = -16.24, 95%CI (-17.24, -15.24), p < 0.00001], and lipid peroxidation (LPO) levels [MD = -2.32, 95%CI (-2.70, -1.93), p < 0.00001], and increased superoxide dismutase (SOD) levels [SMD = 1.46, 95%CI (0.43, 2.49), p = 0,006] in patients with ACS. In addition, STS significantly decreased the incidence of major adverse cardiovascular events (relative risk = 0.54, 95%CI [0.44, 0.66], p < 0.00001). The quality of evidence for the outcomes was assessed to be very low to medium. Conclusion: STS can safely and effectively reduce the levels of hs-CRP, TNF-α, MMP-9, and LPO and increase the level of SOD in patients with ACS treated with PCI. It can also reduce the incidence of adverse cardiovascular events. However, these findings require careful consideration due to the small number of included studies, high risk of bias, and low to moderate evidence. In the future, more large-scale and high-quality RCTs will be needed as evidence in clinical practice.

Prostate cancer bone metastases biology and clinical management (Review).

Prostate cancer (PCa) is one of the most prominent causes of cancer-related mortality in the male population. A highly impactful prognostic factor for patients diagnosed with PCa is the presence or absence of bone metastases. The formation of secondary tumours at the bone is the most commonly observed site for the establishment of PCa metastases and is associated with reduced survival of patients in addition to a cohort of life-debilitating symptoms, including mobility issues and chronic pain. Despite the prevalence of this disease presentation and the high medical relevance of bone metastases, the mechanisms underlying the formation of metastases to the bone and the understanding of what drives the osteotropism exhibited by prostate tumours remain to be fully elucidated. This lack of in-depth understanding manifests in limited effective treatment options for patients with advanced metastatic PCa and culminates in the low rate of survival observed for this sub-set of patients. The present review aims to summarise the most recent promising advances in the understanding of how and why prostate tumours metastasise to the bone, with the ultimate aim of highlighting novel treatment and prognostic targets, which may provide the opportunity to improve the diagnosis and treatment of patients with PCa with bone metastases.

His-Purkinje system pacing reduced tricuspid regurgitation in patients with persistent atrial fibrillation after left-sided valve surgery.

Background & objective: Tricuspid regurgitation after left-sided valve surgery was a common and difficult problem. Atrial fibrillation was considered to be an important etiology of tricuspid regurgitation. His-Purkinje system pacing (HPSP) was a physiological pacing method, which could prevent and treat heart failure and might reduce tricuspid regurgitation. Our study aimed to investigate the effect of HPSP on tricuspid regurgitation in patients with persistent atrial fibrillation after left-sided valve surgery. Methods: This study was a retrospective study. The 3-year patient review focused on those who underwent permanent cardiac pacemaker implantation of HPSP after mitral valve and/or aortic valve replacement from Jan 1st, 2019 to Jan 1st, 2022. HPSP included His bundle pacing (HBP) or left bundle branch pacing (LBBP). Clinical data collected included electrocardiogram, pacing parameters, ultrasonic cardiogram parameters and chest x-ray at implantation and 3-month follow up. Univariate and multivariate linear regression analysis of tricuspid regurgitation velocity were performed. Results: A total of 44 patients was retrospectively reviewed. Eight patients who had undergone implantation of HPSP after left-sided heart valve replacement were enrolled in the study. All patients had persistent atrial fibrillation. Three of them received HBP and five underwent LBBP. At 3-month follow-up, the tricuspid regurgitation grade was significantly lower than that before implantation (P = 0.007). The tricuspid regurgitation velocity significantly decreased (317 ± 74 cm/s vs. 261 ± 52 cm/s, P = 0.022) and tricuspid valve pressure gradient (PG) reduced (42 ± 21 mmHg vs. 28 ± 10 mmHg, P = 0.040). The cardiothoracic ratio of patients was significantly lower than that before implantation (0.61 ± 0.08 vs. 0.64 ± 0.09, P = 0.017). The NYHA classification of patients also improved (P = 0.013). In multivariate liner regression analysis, the pacing ratio (ß = 0.736, P = 0.037) was an independent determinant of tricuspid regurgitation velocity variation. Conclusion: HPSP might reduce tricuspid regurgitation and improve cardiac function in patients with persistent atrial fibrillation after left-sided valve surgery.

Identification and Characterization of a Novel Major Facilitator Superfamily Efflux Pump, SA09310, Mediating Tetracycline Resistance in Staphylococcus aureus.

Drug efflux systems have recently been recognized as an important mechanism of multidrug resistance in bacteria. Here, we described the identification and characterization of a novel chromosomally encoded multidrug efflux pump (SA09310) in Staphylococcus aureus. SA09310 is a 43-kDa protein with 12 transmembrane helices. The conserved amino acid sequence motifs of the major facilitator superfamily (MFS) were identified in the protein SA09310, which indicated that SA09310 belonged to the MFS transporters. Expression of the sa09310 gene was induced by different types of antibiotics, including aminoglycoside, tetracycline, macrolides, and chloramphenicol. An sa09310 gene knockout mutant (Δsa09310) was constructed, and its susceptibility to 30 different antibiotics was evaluated. The Δsa09310 mutant exhibited increased sensitivity to tetracycline and doxycycline, with 64-fold- and 8-fold-decreased MICs, respectively. The mechanism of SA09310 mediation of tetracycline resistance was demonstrated by its ability to extrude intracellular tetracycline from within the cells into the environment. The efflux activity of SA09310 was further confirmed by ethidium bromide (EtBr) accumulation and efflux assays. In addition, the efflux activity of SA09310 was observed to be blocked by the known efflux pump inhibitor carbonyl cyanide chlorophenylhydrazone (CCCP), which provided direct evidence that suggested the H+-dependent activity of the SA09310 efflux pump. The conservation of SA09310 homologs in Staphylococcus indicated the universal function of these SA09310-like protein clusters. In conclusion, the function-unknown protein SA09310 has been identified and characterized as a tetracycline efflux pump mediating tetracycline resistance in S. aureus.

The emerging landscape of microfluidic applications in DNA data storage.

DNA has been considered a promising alternative to the current solid-state devices for digital information storage. The past decade has witnessed tremendous progress in the field of DNA data storage contributed by researchers from various disciplines. However, the current development status of DNA storage is still far from practical use, mainly due to its high material cost and time consumption for data reading/writing, as well as the lack of a comprehensive, automated, and integrated system. Microfluidics, being capable of handling and processing micro-scale fluid samples in a massively paralleled and highly integrated manner, has gradually been recognized as a promising candidate for addressing the aforementioned issues. In this review, we provide a discussion on recent efforts of applying microfluidics to advance the development of DNA data storage. Moreover, to showcase the tremendous potential that microfluidics can contribute to this field, we will further highlight the recent advancements of applying microfluidics to the key functional modules within the DNA data storage workflow. Finally, we share our perspectives on future directions for how to continue the infusion of microfluidics with DNA data storage and how to advance toward a truly integrated system and reach real-life applications.

Plasma levels of bone morphogenic protein-4 are downregulated in elderly hypertensive patients with heart failure with preserved ejection fraction.

OBJECTIVE: This study aimed to evaluate the association between plasma bone morphogenic protein-4 (BMP-4) levels and heart failure (HF) with preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF) in elderly hypertensive patients. METHODS: A total of 222 hypertensive individuals meeting the inclusion criteria were enrolled from October 2021 to July 2022. Data were collected including clinical characteristics, laboratory tests and echocardiogram measurements. Plasma BMP-4 levels were tested using enzyme-linked immunosorbent assay analysis. RESULTS: Among 222 elderly hypertensive patients, 149 were without HF, 59 had HFpEF, and 14 had HFmrEF. Plasma BMP-4 levels were strikingly downregulated in hypertensive patients with HFpEF/HFmrEF [median (25th, 75th percentile): 15.89 (7.69, 23.12) pg/mL vs. 19.67 (10.60, 33.04) pg/mL; P = 0.002]. After univariate and multivariate logistic regression analysis, the risk of HFpEF/HFmrEF was declined in the 4th quartile BMP-4 group when compared with the 1st quartile BMP-4 group (odds ratio, 0.20, 95% confidence interval (CI), 0.04 to 1.00; P = 0.050, P for trend = 0.025). Receiver operating characteristic curve analysis revealed that BMP-4 ≤ 28.5 pg/mL exhibited a sensitivity of 95.9% and a specificity of 28.2% in HFpEF/HFmrEF diagnosis. Furthermore, the area under the curve (AUC) was 0.619 (95% CI:0.540-0.698, P < 0.001). The corresponding AUC for brain natriuretic peptide (BNP) was 0.781 (95% CI: 0.710-0.852), P < 0.001. Adding BMP-4 to BNP increased the AUC to 0.790 (95% CI: 0.724-0.856), vs. BMP-4, P < 0.001; vs. BNP, P = 0.730, respectively. CONCLUSIONS: Plasma BMP-4 levels are downregulated in elderly hypertensive patients with HFpEF. BMP-4 is a promising biomarker for diagnosing HFpEF/HFmrEF during hypertension.

The experience of loneliness among the Chinese bereaved parents-a qualitative study from the life course perspective.

BACKGROUND: With the implementation of the 37 years one-child policy, many couples only have one child in China. Chinese parents whose only child died and did not give birth to or adopt another child are known as "Shidu" parents or "Shiduer". Characterised by elements of childlessness, bereavement, and ageing, Shiduer are at a higher risk of experiencing loneliness. However, little is known about their loneliness experience. Adopting a life course perspective, this research aims to investigate how loneliness was experienced and coped by older Chinese Shidu parents and identify the most vulnerable groups for policy intervention. METHODS: Qualitative method was adopted for this study. Semi-structured interviews were conducted with 27 participants from urban and rural Wuhan, the capital city of Hubei province in central China, to collect data on participants' life course related resources and loneliness experience after bereavement. An abductive approach was used to analyse the data. RESULTS: The results demonstrate that the social environment (urban/rural), timing of bereavement (midlife/older age), social network (strong/weak), and coping strategies (escape-avoidance/problem-solving) differentiate the experience of loneliness among the Shiduer. Those who lived in rural communities, those bereaved in older age, those who had a weak social network, and those who adopted the escape-avoidance strategy were found vulnerable and suffered from more chronic and intensive loneliness than their counterparts without these characteristics. CONCLUSION: This study is among the first attempts to examine loneliness experience and coping among older Chinese bereaved parents from a qualitative, life course perspective. It provides insights into how loneliness has been perceived and experienced differently among the bereaved one-child parents in China. The results of the current study provide important implications for policymakers and practitioners/social workers for the intervention of loneliness.

Anterior segment measurements and determinants of angle width with short, medium, and long axial lengths in a rural Chinese population.

Purpose: To report the anterior segment measurements and investigate the determinants of angle width with short, medium, and long axial length (AL) in a rural Chinese population. Design: Observational, population-based, cross-sectional study. Methods: Subjects aged ≥35 years who underwent complete ocular examinations during the follow-up of the Handan Eye Study were included. Ocular data of the right eye were analyzed. Anterior segment parameters were obtained and stratified by age and sex. AL was categorized into short (<22.0 mm), medium (22.0-23.5 mm), and long (>23.5 mm) subgroups. Linear regression analyses were performed to identify the parameters associated with angle width (angle opening distance at 500 µm from the scleral spur (SS) [AOD500]). Results: The final analysis included 4435 subjects (58.0 [49.0, 64.0] years old, 44.1% males). Smaller AOD500 was significantly associated with female sex (P = 0.032), larger iris thickness at 750 µm from the SS (IT750) (P < 0.001), larger lens vault (LV) (P < 0.001), and smaller anterior chamber volume (ACV) (P < 0.001) in the short AL subgroup; larger sphere equivalent (SE), IT750, iris curvature (IC), and LV and smaller ACV (all P < 0.001) in the medium AL subgroup; and larger SE, IT750, IA, IC, and LV and smaller ACV (all P < 0.001) in the long AL subgroup. Conclusions: Our study provides the anterior segment parameters of a large rural Chinese population. IT750, ACV, and LV were found to be the most important factors associated with angle width.

Combined treatment with Prunella vulgaris and Radix bupleuri activated the Bax/Bcl-2 and Caspase-3 signal pathways in papillary thyroid carcinoma cells.

To explore the effect of Prunella vulgaris (PV) combined with Radix bupleuri (RB) on apoptosis of papillary thyroid carcinoma cells. Our study was divided into four groups: the control group, the PV group, the RB group, and the PV combined with the RB group. The viability of cells from different treatment groups was assessed by the CCK-8 assay. Cell migration and invasion were assessed by healing wounding and the transwell assay, respectively. Cell apoptosis rate and cell cycle arrest were detected by a flow cytometry assay. The protein expression of Bcl-2, Bax, Caspase-3, CyclinA1, CyclinB1, and CDK1 was detected using a western blot assay. Our results indicated that, compared with the control group, PV combined with RB group could significantly alter the cell morphology, inhibit cell migration and invasion, decrease the number of cells in the G0/G1 phase and increase the number of cells in the G2/M phase, and promote the cell apoptosis. Moreover, PV combined with RB treatment also obviously increased the expression of Bax/Bcl2 and caspase-3 proteins and decreased the expression of Cyclin A1, Cyclin B1, and CDK1 proteins. Overall, our results indicated that PV combined with RB could activate the Bax/Bcl-2 and Caspase-3 signal pathways to induce cell apoptosis in papillary thyroid carcinoma cells; this also provides a new way to treat thyroid cancer.

MicroRNA-142-5p promotes the proliferation and metastasis of nasopharyngeal carcinoma.

Growing pieces of evidence reported abnormal expression of microRNA in various cancer. Our research aimed to ascertain the miR-142-5p expression and its potential function in the growth and metastasis of human nasopharyngeal carcinoma (NPC). In human NPC tissues and cell lines, miR-142-5p expression was quantified via the real-time qPCR assay. Functionally, the potential effect of miR-142-5p in human CNE-1 and SUNE-1 cells through MTT assay, colony formation assay, Transwell assay, and cell cycle assay. In addition, the potential target gene of miR-142-5p was determined by the dual-luciferase reporter assay. MiR-142-5p expression was remarkably elevated in human NPC tissues, CNE-1 and SUNE-1 cells. MiR-142-5p overexpression obviously enhanced the ability of cell proliferative and colony formation, and prevented G1 phase arrest in CNE-1 and SUNE-1 cells. Further, the migration number of NPC cells was increased compared to NP69 cells. BTG3 was identified as the direct target gene of miR-142-5p. Inhibition of BTG3 expression could reverse the cell proliferation by miR-142-5p-induced. Overall, miR-142-5p could strengthen the NPC cell's proliferation and migration by directly targeting BTG3. Hence, miR-142-5p may provide a new strategy and program for future clinical treatment of NPC.

Ligand-Assistant Iced Photocatalytic Reduction to Synthesize Atomically Dispersed Cu Implanted Metal-Organic Frameworks for Photo-Enhanced Uranium Extraction from Seawater.

Uranium extraction from natural seawater is one of the most promising routes to address the shortage of uranium resources. By combination of ligand complexation and photocatalytic reduction, porous framework-based photocatalysts have been widely applied to uranium enrichment. However, their practical applicability is limited by poor photocatalytic activity and low adsorption capacity. Herein, atomically dispersed Cu implanted UiO-66-NH2 (Cu SA@UiO-66-NH2 ) photocatalysts are prepared via ligand-assistant iced photocatalytic reduction route. N-Cu-N moiety acts as an effective electron acceptor to potentially facilitate charge transfer kinetics. By contrast, there exist Cu sub-nanometer clusters by the typical liquid phase photoreduction, resulting in a relatively low photocatalytic activity. Cu SA@UiO-66-NH2 adsorbents exhibit superior antibacterial ability and improved photoreduction conversion of the adsorbed U(VI) to insoluble U(IV), leading to a high uranium sorption capacity of 9.16 mg-U/g-Ads from natural seawater. This study provides new insight for enhancing uranium uptake by designing SA-mediated MOF photocatalysts.

Glioma-associated microglia/macrophages (GAMs) in glioblastoma: Immune function in the tumor microenvironment and implications for immunotherapy.

Glioma is a mixed solid tumor composed of neoplastic and non-neoplastic components. Glioma-associated macrophages and microglia (GAMs) are crucial elements of the glioma tumor microenvironment (TME), regulating tumor growth, invasion, and recurrence. GAMs are also profoundly influenced by glioma cells. Recent studies have revealed the intricate relationship between TME and GAMs. In this updated review, we provide an overview of the interaction between glioma TME and GAMs based on previous studies. We also summarize a series of immunotherapies targeting GAMs, including clinical trials and preclinical studies. Specifically, we discuss the origin of microglia in the central nervous system and the recruitment of GAMs in the glioma background. We also cover the mechanisms through which GAMs regulate various processes associated with glioma development, such as invasiveness, angiogenesis, immunosuppression, recurrence, etc. Overall, GAMs play a significant role in the tumor biology of glioma, and a better understanding of the interaction between GAMs and glioma could catalyze the development of new and effective immunotherapies for this deadly malignancy.

Alterations in the gut microbiome and metabolome profiles of septic mice treated with Shen FuHuang formula.

Sepsis has a high mortality rate, and treating sepsis remains a significant challenge worldwide. In former studies, our group found that traditional Chinese medicine, Shen FuHuang formula (SFH), is a promising medicine in treating coronavirus disease 2019 (COVID-19) patients with the septic syndrome. However, the underlying mechanisms remain elusive. In the present study, we first investigated the therapeutic effects of SFH on septic mice. To investigate the mechanisms of SFH-treated sepsis, we identified the gut microbiome profile and exploited untargeted metabolomics analyses. The results demonstrated that SFH significantly enhanced the mice's 7-day survival rate and hindered the release of inflammatory mediators, i.e., TNF-α, IL-6, and IL-1ß. 16S rDNA sequencing further deciphered that SFH decreased the proportion of Campylobacterota and Proteobacteria at the phylum level. LEfSe analysis revealed that the treatment of SFH enriched Blautia while decreased Escherichia_Shigella. Furthermore, serum untargeted metabolomics analysis indicated that SFH could regulate the glucagon signaling pathway, PPAR signaling pathway, galactose metabolism, and pyrimidine metabolism. Finally, we found the relative abundance of Bacteroides, Lachnospiraceae_NK4A136_group, Escherichia_Shigella, Blautia, Ruminococcus, and Prevotella were closely related to the enrichment of the metabolic signaling pathways, including L-tryptophan, uracil, glucuronic acid, protocatechuic acid, and gamma-Glutamylcysteine. In conclusion, our study demonstrated that SFH alleviated sepsis by suppressing the inflammatory response and hence reduced mortality. The mechanism of SFH for treating sepsis may be ascribed to the enrichment of beneficial gut flora and modulation in glucagon signaling pathway, PPAR signaling pathway, galactose metabolism, and pyrimidine metabolism. To sum up, these findings provide a new scientific perspective for the clinical application of SFH in treating sepsis.

Mean nocturnal baseline impedance: Influencing factors and diagnostic value in gastroesophageal reflux disease.

BACKGROUND: At present, there are few studies related to mean nocturnal baseline impedance (MNBI), esophageal dynamic reflux monitoring, high-resolution esophageal manometry (HRM) parameter indexes, and its diagnostic value in gastroesophageal reflux disease (GERD). OBJECTIVE: To analyze the factors influencing MNBI and examine the diagnostic value of MNBI in GERD. METHODS: A retrospective analysis on 434 patients with typical reflux symptoms who underwent gastroscopy, 24-hour multichannel intraluminal impedance and pH monitoring (MII/pH) and HRM. They were divided into the conclusive evidence group (103 cases), borderline evidence group (229 cases), and exclusion evidence group (102 cases) according to the level of diagnostic evidence of GERD based on the Lyon Consensus. We analyzed the differences in MNBI, esophagitis grade, MII/pH and HRM index among the groups; the correlation between MNBI and the above indexes and its influence on MNBI; and to evaluate the diagnostic value of MNBI in GERD. RESULTS: There were significant differences in MNBI, Acid Exposure Time (AET) 4%, DeMeester score, and total reflux episodes among the three groups (P< 0.001). EGJ contractile integral (EGJ-CI) of the conclusive evidence group and the borderline evidence group was significantly lower than that in the exclusion evidence group (P< 0.001). MNBI was significantly and negatively correlated with age, BMI, AET 4%, DeMeester score, total reflux episodes, EGJ classification, esophageal motility abnormalities, and esophagitis grade (all P< 0.05), and significantly and positively correlated with EGJ-CI (P< 0.001). Age, BMI, AET 4%, EGJ classification, EGJ-CI, and esophagitis grade had significant effects on MNBI (P< 0.05); MNBI was used to diagnose GERD with a diagnostic cutoff of 2061 Ω, and AUC was 0.792 (sensitivity 74.9%, specificity 67.4%); MNBI was used to diagnose exclusion evidence group with a diagnostic cutoff of 2432 Ω, AUC was 0.774 (sensitivity 67.6%, specificity 72%). CONCLUSION: AET, EGJ-CI, and esophagitis grade are the most important influence factors of MNBI. MNBI has good diagnostic value in identifying conclusive GERD.

Roles of various enzymes in the biotransformation of 6:2 fluorotelomer alcohol (6:2 FTOH) by a white-rot fungus.

Six-carbon-chained polyfluoroalkyl substances, such as 6:2 fluorotelomer alcohol (6:2 FTOH), are being used to replace longer chained compounds in the manufacture of various commercial products. This study examined the effects of growth substrates and nutrients on specific intracellular and extracellular enzymes mediating 6:2 FTOH aerobic biotransformation by the white-rot fungus, Phanerochaete chrysosporium. Cellulolytic conditions with limited glucose were a suitable composition, resulting in high 5:3 FTCA yield (37 mol%), which is a key intermediate in 6:2 FTOH degradation without forming significant amounts of terminal perfluorocarboxylic acids (PFCAs). Sulfate and ethylenediaminetetraacetic acid (EDTA) were also essential for 5:3 FTCA production, but, at lower levels, resulted in the buildup of 5:2 sFTOH (52 mol%) and 6:2 FTUCA (20 mol%), respectively. In non-ligninolytic nutrient-rich medium, 45 mol% 6:2 FTOH was transformed but produced only 12.7 mol% 5:3 FTCA. Enzyme activity studies imply that cellulolytic conditions induce the intracellular cytochrome P450 system. In contrast, extracellular peroxidase synthesis is independent of 6:2 FTOH exposure. Gene expression studies further verified that peroxidases were relevant in catalyzing the downstream transformations from 5:3 FTCA. Collectively, the identification of nutrients and enzymatic systems will help elucidate underlying mechanisms and biogeochemical conditions favorable for fungal transformation of PFCA precursors in the environment.

Association between calf circumference and incontinence in Chinese elderly.

BACKGROUND: The objective of this study was to analyze the association between calf circumference and incontinence in Chinese elderly, and to find out the maximal cut-off point by gender for the use of calf circumference in screening for incontinence. METHODS: In this study, participants were from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS). The maximal calf circumference cut-off point and other incontinence-related risk factors were explored using receiver operating characteristic (ROC) curves and logistic regression analysis. RESULTS: The study included 14,989 elderly people (6,516 males and 8,473 females) over 60. The prevalence of incontinence in elderly males was 5.23% (341/6,516), significantly lower than females, which was 8.31% (704/8,473) (p < 0.001). There was no correlation between calf circumference < 34 cm in males and < 33 cm in females and incontinence after adjusting the confounders. We further stratified by gender to predict incontinence in elderly based on the Youden index of ROC curves. We found the association between calf circumference and incontinence was the strongest when the cut-off points were < 28.5 cm for males and < 26.5 cm for females, with an odds rate (OR) value of 1.620 (male, 95%CI: 1.197-2.288) and 1.292 (female, 95%CI: 1.044-1.600) after adjusting the covariates, respectively. CONCLUSIONS: Our study suggests that calf circumference < 28.5 cm in males and < 26.5 cm in females is a risk factor for incontinence in the Chinese elderly population. Calf circumference should be measured in routine physical examination, and timely interventions should be made to reduce the risk of incontinence in subjects with calf circumference less than the threshold.

New insights into the impact of microbiome on horizontal and vertical transmission of a tick-borne pathogen.

BACKGROUND: The impact of host skin microbiome on horizontal transmission of tick-borne pathogens , and of pathogen associated transstadial and transovarial changes in tick microbiome are largely unknown, but are important to control increasingly emerging tick-borne diseases worldwide. METHODS: Focusing on a rickettsiosis pathogen, Rickettsia raoultii, we used R. raoultii-positive and R. raoultii-negative Dermacentor spp. tick colonies to study the involvement of skin microbiota in cutaneous infection with rickettsiae in laboratory mice, and the function of the tick microbiome on maintenance of rickettsiae through all tick developmental stages (eggs, larvae, nymphs, adults) over two generations. RESULTS: We observed changes in the skin bacteria community, such as Chlamydia, not only associated with rickettsial colonization but also with tick feeding on skin. The diversity of skin microbiome differed between paired tick-bitten and un-bitten sites. For vertical transmission, significant differences in the tick microbiota between pathogenic rickettsia-positive and -negative tick chorts was observed across all developmental stages at least over two generations, which appeared to be a common pattern not only for R. raoultii but also for another pathogenic species, Candidatus Rickettsia tarasevichiae. More importantly, bacterial differences were complemented by functional shifts primed for genetic information processing during blood feeding. Specifically, the differences in tick microbiome gene repertoire between pathogenic Rickettsia-positive and -negative progenies were enriched in pathways associated with metabolism and hormone signals during vertical transmission. CONCLUSIONS: We demonstrate that host skin microbiome might be a new factor determining the transmission of rickettsial pathogens through ticks. While pathogenic rickettsiae infect vertebrate hosts during blood-feeding by the tick, they may also manipulate the maturation of the tick through changing the functional potential of its microbiota over the tick's life stages. The findings here might spur the development of new-generation control methods for ticks and tick-borne pathogens. Video Abstract.

Polymorphism in interferon alpha/beta receptor contributes to glucocorticoid response and outcome of ARDS and COVID-19.

BACKGROUND: The use of glucocorticoids has given contradictory results for treating acute respiratory distress syndrome (ARDS). The use of intravenous Interferon beta (IFN ß) for the treatment of ARDS was recently tested in a phase III ARDS trial (INTEREST), in which more than half of the patients simultaneously received glucocorticoids. Trial results showed deleterious effects of glucocorticoids when administered together with IFN ß, and therefore, we aimed at finding the reason behind this. METHODS: We first sequenced the genes encoding the IFN α/ß receptor of the patients, who participated in the INTEREST study (ClinicalTrials.gov Identifier:  NCT02622724 , November 24, 2015) in which the patients were randomized to receive an intravenous injection of IFN ß-1a (144 patients) or placebo (152 patients). Genetic background was analyzed against clinical outcome, concomitant medication, and pro-inflammatory cytokine levels. Thereafter, we tested the influence of the genetic background on IFN α/ß receptor expression in lung organ cultures and whether, it has any effect on transcription factors STAT1 and STAT2 involved in IFN signaling. RESULTS: We found a novel disease association of a SNP rs9984273, which is situated in the interferon α/ß receptor subunit 2 (IFNAR2) gene in an area corresponding to a binding motif of the glucocorticoid receptor (GR). The minor allele of SNP rs9984273 associates with higher IFNAR expression, more rapid decrease of IFN γ and interleukin-6 (IL-6) levels and better outcome in IFN ß treated patients with ARDS, while the major allele associates with a poor outcome especially under concomitant IFN ß and glucocorticoid treatment. Moreover, the minor allele of rs9984273 associates with a less severe form of coronavirus diseases (COVID-19) according to the COVID-19 Host Genetics Initiative database. CONCLUSIONS: The distribution of this SNP within clinical study arms may explain the contradictory results of multiple ARDS studies and outcomes in COVID-19 concerning type I IFN signaling and glucocorticoids.

Peptidoglycan-associated lipoprotein contributes to the virulence of Acinetobacter baumannii and serves as a vaccine candidate.

The role of peptidoglycan-associated lipoprotein (Pal) in A. baumannii pathogenesis remains unclear. Here, we illustrated its role by constructing a pal deficient A. baumannii mutant and its complementary strain.Transcriptome analysis of the WT and pal mutant revealed a total of 596 differentially expressed genes. Gene Ontology analysis revealed that pal deficiency caused the downregulation of genes related to material transport and metabolic processes. The pal mutant showed a slower growth and was sensitive to detergent and serum killing compared to WT strain, whereas, the complemented pal mutant showed rescued phenotype. The pal mutant caused decreased mortality in mice pneumonia infection compared to WT strain, while the complemented pal mutant showed increased mortality. Mice immunized with recombinant Pal showed 40% protection against A. baumannii-mediated pneumonia. Collectively, these data indicate Pal is a virulence factor of A. baumannii and may serve as a potential target for preventive or therapeutic interventions.

Mechanomemory in protein diffusivity of chromatin and nucleoplasm after force cessation.

It is known that external mechanical forces can regulate structures and functions of living cells and tissues in physiology and diseases. However, after cessation of the force, how structures are altered in response to the dynamics of the chromatin and molecules in the nucleoplasm remains elusive. Here, using single-molecule imaging approaches, we show that exogenous local forces via integrins applied for 2 to 10 min decondensed the chromatin and increased chromatin and nucleoplasm protein mobility inside the nucleus, leading to elevated diffusivity of single protein molecules in the nucleoplasm, tens of minutes after the cessation of force. Diffusion experiments with fluorescence correlation spectroscopy in live single cells show that the mechanomemory in chromatin and nucleoplasm protein diffusivity was regulated by nuclear pore complexes. Protein molecular dynamics simulation recapitulated the experimental findings in live cells and showed that nucleoplasm protein diffusivity was regulated by the number of nuclear pore complexes. The mechanomemory in elevated protein diffusivity of the nucleoplasm after force cessation represents a physical process that reverses protein-protein condensation in phase separation via unjamming of the chromatin. Our findings of mechanomemory in chromatin and nucleoplasm protein diffusivity suggest that the effect of force on the nucleus remains tens of minutes after force cessation and thus is more far-reaching than previously anticipated.