Dietary Selenium Insufficiency Induces Cardiac Inflammatory Injury in Chicks.

BACKGROUND: Laying hens undergo intensive metabolism and are vulnerable to cardiac insults. Previous research demonstrated overt heart disorders of broiler chickens induced by dietary Se deficiency. OBJECTIVES: This study aimed to reveal effects and mechanism of dietary Se insufficiency on cardiac injuries of egg-type chicks in their early life. METHODS: White Leghorn chicks (0-d-old, female) were fed a corn-soy, Se-insufficient basal diet (BD, 0.05 mg Se/kg; n = 11) or the BD supplemented with 0.3 mg Se/kg (as sodium selenite; n = 8) for 35 d. Cardiac tissues were collected at the end of study for histology and to determine its relationship with heart Se contents, selenoprotein expression profiles, antioxidant and inflammatory status, and the Toll-like receptor 4/extracellular signal-regulated kinases/p38 map kinase/c-Jun N-terminal kinase (TLR4/ERK/P38/JNK) pathway. RESULTS: Compared with those fed 0.35 mg Se/kg, chicks fed BD had significantly lower body weights and average daily gain, and 28% lower heart Se, and developed cardiac mononuclear inflammatory cell infiltration, along with elevated (P < 0.05) serum concentrations of creatine kinase, aldolase, and interleukin-1 (IL-1). The BD decreased (P < 0.05) body weight and heart glutathione contents and expression of selenoproteins but increased (P < 0.05) heart concentrations of malondialdehyde and reactive oxygen species. These changes were associated with increased (P < 0.05) mRNA and/or protein concentrations of cyclooxygenases, lipoxygenase-12, cytokines (IL-1ß), nuclear factor (NF) κB subunit, chemokines, and receptors (CCL20, CXCR1, and CXCLI2) and increased (P < 0.1) TLR4/ERK /P38/JNK in the heart of Se-insufficient chicks. CONCLUSIONS: Dietary Se insufficiency induces infiltration of mononuclear inflammatory cells in the heart of egg-type chicks. This cardiac injury was mediated by decreased functional expressions of selenoproteins, which resulted in apparent elevated oxidative stress and subsequent activations of the TLR4 pathway and NF κB.

Association between autonomic dysfunction with motor and non-motor symptoms in patients with Parkinson's disease.

To investigate the association between autonomic dysfunction (AutD) and motor as well as non-motor symptoms (NMS) in patients with Parkinson's disease (PD). Fifty-three PD patients were divided into two groups based on the number of domains affected by AutD: a multi-domain AutD group (AutD-M) and a single-domain AutD group (AutD-S), as evaluated using the Scale for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT), which assesses autonomic symptoms, one of the NMS. A comprehensive comparison was conducted between the two groups, including clinical measures such as clinical scales, quantitative evaluations of motor function and exercise capacity. Spearman correlation analysis was employed to investigate the relationship between AutD severity and PD symptoms. Additionally, we performed multiple linear regression model analysis to determine whether associations between SCOPA-AUT scores and clinical assessments remained significant after adjusting for Hoehn and Yahr stage, sex, and age. PD patients in the AutD-M group exhibited significantly more severe NMS and motor symptoms compared to those in the AutD-S group. In correlation analysis, SCOPA-AUT scores showed significant correlations with multiple clinical symptoms, such as most of the NMS, 10-MWT and CPET parameters. Furthermore, regression analysis also revealed that more pronounced fatigue, anxiety, depressive symptoms, worse walking speed and impaired exercise capacity were associated with higher SCOPA-AUT scores. The presence of AutD is correlated with emotional disturbances, decreased exercise endurance, and impaired gait function in patients with PD. Early management of AutD may prove beneficial in alleviating some NMS and motor symptoms in PD.

The Efficacy of Wearable Cueing Devices on Gait and Motor Function in Parkinson Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To summarize the efficacy of wearable cueing devices for improving gait and motor function of patients with Parkinson disease (PWP). DATA SOURCES: PubMed, Embase, and Cochrane CENTRAL databases were searched for papers published in English, from inception to October 23, 2022. STUDY SELECTION: Randomized controlled trials focusing on the effects of wearable cueing devices on gait and motor function in PWP were included. DATA EXTRACTION: Two reviewers independently selected articles and extracted the data. The Cochrane Bias Risk Assessment Tool was used to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation was used to evaluate the quality of evidence. DATA SYNTHESIS: Seven randomized controlled trials with 167 PWP were included in the meta-analysis. Significant effect of wearable cueing devices on walking speed (mean difference [MD]=0.07 m/s, 95% confidence interval [CI]: [0.05, 0.09], P<.00001) was detected; however, after sensitivity analysis, no significant overall effect on walking speed was noted (MD=0.04 m/s, 95% CI: [-0.03, 0.12], P=.25). No significant improvements were found in stride length (MD=0.06 m, 95% CI: [0.00, 0.13], P=.05), the Unified Parkinson's Disease Rating Scale-III score (MD=-0.61, 95% CI: [-4.10, 2.88], P=.73), Freezing of Gait Questionnaire score (MD=-0.83, 95% CI: [-2.98, 1.33], P=.45), or double support time (MD=-0.91, 95% CI: [-3.09, 1.26], P=.41). Evidence was evaluated as low quality. CONCLUSIONS: Wearable cueing devices may result in an immediate improvement on walking speed; however, there is no evidence that their use results in a significant improvement in other gait or motor functions.

Ancient DNA and multimethod dating confirm the late arrival of anatomically modern humans in southern China.

The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U-Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS 14C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS 14C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.

Effects of home-based telemedicine and mHealth interventions on blood pressure in stroke patients: a systematic evaluation and meta-analysis of randomized controlled trials.

BACKGROUND: Stroke is a common cerebrovascular disease. Elevated blood pressure is the most significant manageable factor for both initial and recurrent strokes. Despite the potential benefits of telemedicine and mobile health technology (mHealth) in managing blood pressure among stroke patients, there remains skepticism. OBJECTIVES: This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to assess the effectiveness of telemedicine and mHealth interventions in managing blood pressure in stroke patients. METHODS: We identified randomized controlled trials (RCTs) evaluating telemedicine and mHealth technology interventions for blood pressure in patients with stroke or transient ischemic attack (TIA) from the inception date of each database up to January 2, 2024 by systematic searches of the PubMed, EMBASE, Web of Science, and Cochrane Library databases. The Cochrane Risk of Bias tool (ROB 2.0) was used to evaluate study quality. Sources of heterogeneity were explored through Meta-regression, subgroup analyses, sensitivity analyses and publication bias assessment. Meta-analysis was performed using R 4.2.2 statistical software. RESULTS: A total of 13 randomized controlled trials with 3803 participants were included. The meta-analysis found that telemedicine and mHealth improved control of both systolic [MD = -4.37, 95 % CI (-5.50, -3.24), I2 = 43 %, P<0.00001] and diastolic blood pressures [MD = -1.72, 95 % CI (-2.45, -0.98), I2 = 0 %, P<0.00001] in stroke patients compared to the conventional care group. Stroke patients who received telemedicine and mHealth interventions showed improved medication adherence than usual care [SMD=0.52, 95 % CI (0.03, 1.00), I2 = 90 %, P<0.00001]. Meta-regression and subgroup analyses identified several key factors influencing systolic and diastolic blood pressure control in stroke patients, including whether stroke patients have hypertension, the specific forms of telemedicine and mHealth interventions employed, the duration of these interventions, and the frequency of intervention intervals. CONCLUSIONS: Overall, telemedicine and mHealth reduced stroke patients' systolic blood pressure by an average of 4.37 mm Hg and diastolic blood pressure by an average of 1.72 mm Hg and improved medication adherence compared with usual care. As an emerging medical model, telemedicine and mHealth intervention create a good prospect for the management of blood pressure in stroke patients in the future.

The effect of extracellular polymeric substances on MICP solidifying rare earth slags and stabilizing Th and U.

Microbially induced carbonate precipitation (MICP) has been used to cure rare earth slags (RES) containing radionuclides (e.g. Th and U) and heavy metals with favorable results. However, the role of microbial extracellular polymeric substances (EPS) in MICP curing RES remains unclear. In this study, the EPS of Lysinibacillus sphaericus K-1 was extracted for the experiments of adsorption, inducing calcium carbonate (CaCO3) precipitation and curing of RES. The role of EPS in in MICP curing RES and stabilizing radionuclides and heavy metals was analyzed by evaluating the concentration and morphological distribution of radionuclides and heavy metals, and the compressive strength of the cured body. The results indicate that the adsorption efficiencies of EPS for Th (IV), U (VI), Cu2+, Pb2+, Zn2+, and Cd2+ were 44.83%, 45.83%, 53.7%, 61.3%, 42.1%, and 77.85%, respectively. The addition of EPS solution resulted in the formation of nanoscale spherical particles on the microorganism surface, which could act as an accumulating skeleton to facilitate the formation of CaCO3. After adding 20 mL of EPS solution during the curing process (Treat group), the maximum unconfined compressive strength (UCS) of the cured body reached 1.922 MPa, which was 12.13% higher than the CK group. The contents of exchangeable Th (IV) and U (VI) in the cured bodies of the Treat group decreased by 3.35% and 4.93%, respectively, compared with the CK group. Therefore, EPS enhances the effect of MICP curing RES and reduces the potential environmental problems that may be caused by radionuclides and heavy metals during the long-term sequestration of RES.

The fate and prospects of stem cell therapy in the treatment of hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of long-term neurological disability in neonates and adults. Despite emerging advances in supportive care, like the most effective approach, hypothermia, poor prognosis has still been present in current clinical treatment for HIE. Stem cell therapy has been adopted for treating cerebral ischemia in preclinical and clinical trials, displaying its promising therapeutic value. At present, reported treatments for stroke employed stem cells to replace the lost neurons and integrate them into the existing host circuitry, promoting the release of growth factors to support and stimulate endogenous repair processes and so on. In this review, a meaningful overview to numerous studies published up to now was presented by introducing the preclinical and clinical research status of stem cell therapy for cerebral ischemia and hypoxia, discussing potential therapeutic mechanisms of stem cell transplantation for curing HI-induced brain injury, summarizing a series of approaches for marking transplanted cells and existing imaging systems for stem cell labelling and in vivo tracking and expounding the endogenous regeneration capability of stem cells in the newborn brain when subjected to an HI insult. Additionally, it is promising to combine stem therapy with neuromodulation through specific regulation of neural circuits. The crucial neural circuits across different brain areas related to functional recovery are of great significance for the application of neuromodulation strategies after the occurrence of neonatal hypoxic-ischemic encephalopathy (NHIE).

Evaluation of NG-Test CARBA 5 version 2, Cepheid Xpert Carba-R, and carbapenem inactivation methods in comparison to whole-genome sequencing for the identification of carbapenemases in non-fermenting Gram-negative bacilli.

NG-Test CARBA 5 (NG-Biotech) is a rapid in vitro multiplex immunoassay for the phenotypic detection and differentiation of the "big five" carbapenemase families (KPC, OXA-48-like, VIM, IMP, and NDM). Version 2 of this assay was evaluated alongside the Xpert Carba-R assay (Cepheid, Inc.), the modified carbapenem inactivation method (mCIM), and the CIMTris assay, with a collection of carbapenem-resistant non-fermenting Gram-negative bacilli comprising 138 Pseudomonas aeruginosa and 97 Acinetobacter baumannii isolates. Whole-genome sequencing (WGS) was used as the reference standard. For P. aeruginosa, NG-Test CARBA 5 produced an overall percentage agreement (OPA) with WGS of 97.1%, compared with 92.8% forXpert Carba-R and 90.6% for mCIM. For A. baumannii, as OXA-type carbapenemases (non-OXA-48) are not included, both the NG-Test CARBA 5 and Xpert Carba-R only had an OPA of 6.2%, while the CIMTris performed well with an OPA of 99.0%. The majority of A. baumannii isolates (95.9%) tested falsely positive for IMP on NG-Test CARBA 5; no IMP genes were found on WGS. No clear cause was found for this phenomenon; a cross-reacting protein antigen unique to A. baumannii is a possible culprit. NG-Test CARBA 5 performed well for carbapenemase detection in P. aeruginosa. However, results from A. baumannii isolates should be interpreted with caution.

Quantitative Cytochrome P450 3A4 Induction Risk Assessment Using Human Hepatocytes Complemented with Pregnane X Receptor-Activating Profiles.

Reliable in vitro to in vivo translation of cytochrome P450 (CYP) 3A4 induction potential is essential to support risk mitigation for compounds during pharmaceutical discovery and development. In this study, a linear correlation of CYP3A4 mRNA induction potential in human hepatocytes with the respective pregnane-X receptor (PXR) activation in a reporter gene assay using DPX2 cells was successfully demonstrated for 13 clinically used drugs. Based on this correlation, using rifampicin as a positive control, the magnitude of CYP3A4 mRNA induction for 71 internal compounds at several concentrations up to 10 µM (n = 90) was predicted within 2-fold error for 64% of cases with only a few false positives (19%). Furthermore, the in vivo area under the curve reduction of probe CYP substrates was reasonably predicted for eight marketed drugs (carbamazepine, dexamethasone, enzalutamide, nevirapine, phenobarbital, phenytoin, rifampicin, and rufinamide) using the static net effect model using both the PXR activation and CYP3A4 mRNA induction data. The liver exit concentrations were used for the model in place of the inlet concentrations to avoid false positive predictions and the concentration achieving twofold induction (F2) was used to compensate for the lack of full induction kinetics due to cytotoxicity and solubility limitations in vitro. These findings can complement the currently available induction risk mitigation strategy and potentially influence the drug interaction modeling work conducted at clinical stages. SIGNIFICANCE STATEMENT: The established correlation of CYP3A4 mRNA in human hepatocytes to PXR activation provides a clear cut-off to identify a compound showing an in vitro induction risk, complementing current regulatory guidance. Also, the demonstrated in vitro-in vivo translation of induction data strongly supports a clinical development program although limitations remain for drug candidates showing complex disposition pathways, such as involvement of auto-inhibition/induction, active transport and high protein binding.

Effects of provisioning on the activity budget and foraging strategies of black-and-white snub-nosed monkeys (Rhinopithecus bieti) in the Baima Snow Mountain Nature Reserve, Yunnan, China.

Provisioning can significantly affect the ranging patterns, foraging strategies, and time budget of wild primates. In this study, we document for the first time, the effects of provisioning on the activity budget and foraging effort in an Asian colobine. Over 3-years, we used an instantaneous scanning method at 10-min intervals to collect data on the activity budget of a semiprovisioned breeding band (SPB) of black-and-white snub-nosed monkeys (Rhinopithecus bieti) (42-70 individuals) at Xiangguqing (Tacheng), Yunnan, China. We then compared the effects of provisioning in our study band with published data on a sympatric wild nonprovisioned breeding band (NPB) of R. bieti (ca. 360 monkeys) at the same field site. The SPB spent 25.6% of their daytime feeding, 17.1% traveling, 46.9% resting, and 10.3% socializing. In comparison, the NPB devoted more time to feeding (34.9%) and socializing (14.1%), less time to resting (31.3%), and was characterized by a greater foraging effort (1.74 versus 0.96, foraging effort = (feeding + traveling)/resting; see Methods). There was no difference between bands in the proportion of their activity budget devoted to traveling (15.7% vs. 17.1%). In addition, the SPB exhibited a more consistent activity budget and foraging effort across all seasons of the year compared to the NPB. These findings suggest that the distribution, availability, and productivity of naturally occurring feeding sites is a major determinant of the behavioral strategies and activity budget of R. bieti. Finally, a comparison of our results with data on six nonprovisioned R. bieti bands indicates that caution must be raised in meta-analyses or intraspecific comparisons of primate behavioral ecology that contain data generated from both provisioned and nonprovisioned groups.

Deceleration of China's human water use and its key drivers.

Increased human water use combined with climate change have aggravated water scarcity from the regional to global scales. However, the lack of spatially detailed datasets limits our understanding of the historical water use trend and its key drivers. Here, we present a survey-based reconstruction of China's sectoral water use in 341 prefectures during 1965 to 2013. The data indicate that water use has doubled during the entire study period, yet with a widespread slowdown of the growth rates from 10.66 km3⋅y-2 before 1975 to 6.23 km3⋅y-2 in 1975 to 1992, and further down to 3.59 km3⋅y-2 afterward. These decelerations were attributed to reduced water use intensities of irrigation and industry, which partly offset the increase driven by pronounced socioeconomic development (i.e., economic growth, population growth, and structural transitions) by 55% in 1975 to 1992 and 83% after 1992. Adoptions for highly efficient irrigation and industrial water recycling technologies explained most of the observed reduction of water use intensities across China. These findings challenge conventional views about an acceleration in water use in China and highlight the opposing roles of different drivers for water use projections.

The Effects of Adopting Mobile Health and Fitness Apps on Hospital Visits: Quasi-Experimental Study.

BACKGROUND: Overcrowding in public hospitals, a common issue in many countries, leads to a range of negative outcomes, such as insufficient access to medical services and patient dissatisfaction. Prior literature regarding solutions to reducing hospital overcrowding primarily focuses on organizational-level operational efficiency. However, few studies have investigated the strategies from the individual patient perspective. Specifically, we considered using mobile health and fitness apps to promote users' health behaviors and produce health benefits, thereby reducing hospital visits. OBJECTIVE: This study estimated the causal effect of health and fitness app adoption on hospital visits by exploiting the staggered timing of adoption. We also investigated how the effect varied with users' socioeconomic status and digital literacy. This study provides causal evidence for the effects of health apps, extends the digital health literature, and sheds light on mobile health policies. METHODS: This study used a data set containing health and fitness app use and hospital-related geolocation data of 267,651 Chinese mobile phone users from January to December 2019. We used the difference-in-differences and difference-in-difference-in-differences designs to estimate the causal effect. We performed a sensitivity analysis to establish the robustness of the findings. We also conducted heterogeneity analyses based on the interactions of postadoption indicators with users' consumption levels, city tiers, and digital literacy. RESULTS: The preferred model (difference-in-difference-in-differences) showed a significant decrease in hospital visits after the adoption of health and fitness apps. App adoption led to a 5.8% (P<.001), 13.1% (P<.001), and 18.4% reduction (P<.001) in hospital visits 1, 2, and 3 months after adoption, respectively. In addition, the moderation analysis shows that the effect is greater for users with high consumption levels, in high-tier cities, or with high digital literacy. CONCLUSIONS: This study estimated the causal effect of health and fitness app adoption on hospital visits. The results and sensitivity analysis showed that app adoption can reduce users' hospital visits. The effect varies with users' consumption levels, city tiers, and digital literacy. These findings provide useful insights for multiple stakeholders in the Chinese health care context.

The analysis of risk factors for accidental parathyroid resection during thyroid surgery: a retrospective analysis of 1775 patients.

PURPOSE: The present study discussed the effects of accidental parathyroid resection on hypoparathyroidism and investigated the risk factors associated with accidental parathyroid resection. METHODS: Clinical data from patients who have undergone thyroidectomy at a university hospital in the period from November 2018 and October 2020 were entered into the database and analyzed. Risk factors for accidental parathyroid resection were recorded. RESULTS: A total of 1775 cases were included in this study. The analysis showed that lymph-node dissection (p < 0.001), T staging (p = 0.037), and treatment group (p < 0.001) were independent risk factors for accidental parathyroid resection. Different treatment groups were important risk factors for accidental parathyroid resection. There were significant differences between the professional and non-professional groups in the following aspects: accidental parathyroid resection (p < 0.001), Scope (p < 0.001), T stage (p = 0.009), N stage (p < 0.001), range of lymph-node dissection (p < 0.001), number of lymph nodes dissected in central area (p < 0.001), and number of lymph-node metastases in the central region (p < 0.001). CONCLUSIONS: The causes of accidental parathyroid resection are multifactorial. The predictors for accidental parathyroid resection include lymph-node dissection in the central region, T staging, as well as the operating surgeons' experience.

[Effects of Qilan Prescription on the proliferation and apoptosis of human prostate cancer DU145 cells and its action mechanism].

OBJECTIVE: To investigate the effects of different concentrations of Qilan Prescription (QLP) on the proliferation and apoptosis of human PCa DU145 cells and its underlying mechanism. METHODS: We treated human PCa DU145 cells with QLP at 400, 200, 100, 50, 25, 12.5, 6.25, 3.125 or 1.56 µg/ml for 24, 48 and 72 hours respectively. Then we observed the morphological changes of the cells, examined their viability by CCK-8 assay, detected their cell cycle and apoptosis by flow cytometry, and determined the protein expressions of cyclin D1, Bax, Bcl-2 and cleaved-caspase 3 in the DU145 cells by Western blot, followed by comparison of the parameters with those obtained from the blank control group. RESULTS: QLP significantly inhibited the growth, reduced the contour clarity and adhesion ability of the DU145 cells at the concentrations of 100, 200 and 400 µg/ml, and markedly decreased the activity of the cells at 200 and 400 µg/ml, most significantly at 400 µg/ml. The number of the G2-phase DU145 cells was dramatically increased in all the concentration groups (P < 0.01), so was the total number of apoptotic DU145 cells (P < 0.01), while that of the S-phase cells remarkably decreased in the 400 µg/ml QLP (P < 0.01) and 200 µg/ml QLP (P < 0.05) groups. The expression of the cyclin D1 protein was significantly down-regulated in the 400 µg/ml QLP group (P < 0.01). That of Bcl-2 was also down-regulated (P < 0.01) while those of Bax and cleaved-caspase 3 up-regulated in the 400 and 200 µg/ml QLP groups (P < 0.01). CONCLUSION: QLP can inhibit the proliferation and promote the apoptosis of human PCa DU145 cells, which may be associated with its effects of down-regulating the expression of the cell cycle-related protein cyclin D1, disrupting the Bax-Bcl-2 balance, and up-regulating the expression of cleaved-caspase 3.

[Oral Microbiome and Systemic Diseases].

As one of the most diverse microbial communities within the human body, the oral microbiome is an important component that contributes to the maintenance of human health. The microbial composition of different sites in the oral cavity varies significantly and a dynamic equilibrium is maintained through communications with the environment and oral and distal organs of the host. It has been reported that there is significant correlation between dysbiotic oral microbiome and the occurrence or progression of a variety of systemic diseases. In this review, we summarized recent advances in research on the relationship between oral microbiome and systemic health, focusing on the interaction and pathological mechanisms between oral microbiome and systemic health and hoping to provide new avenues for the early prevention and clinical diagnosis and treatment of systemic diseases.

Osteoblast MR deficiency protects against adverse ventricular remodeling after myocardial infarction.

RATIONALE: Mineralocorticoid receptor (MR) antagonists have been clinically used to treat heart failure. However, the underlying cellular and molecular mechanisms remain incompletely understood. METHODS AND RESULTS: Using osteoblast MR knockout (MRobko) mouse in combination with myocardial infarction (MI) model, we demonstrated that MR deficiency in osteoblasts significantly improved cardiac function, promoted myocardial healing, as well as attenuated cardiac hypertrophy, fibrosis and inflammatory response after MI. Gene expression profiling using RNA sequencing revealed suppressed expression of osteocalcin (OCN) in calvaria from MRobko mice compared to littermate control (MRfl/fl) mice with or without MI. Plasma levels of undercarboxylated OCN (ucOCN) were also markedly decreased in MRobko mice compared to MRfl/fl mice. Administration of ucOCN abolished the protective effects of osteoblast MR deficiency on infarcted hearts. Mechanistically, ucOCN treatment promoted proliferation and inflammatory cytokine secretion in macrophages. Spironolactone, an MR antagonist, significantly inhibited the expression and secretion of OCN in post-MI mice. More importantly, spironolactone decreased plasma levels of ucOCN and inflammatory cytokines in heart failure patients. CONCLUSIONS: MR deficiency in osteoblasts alleviates pathological ventricular remodeling after MI, likely through its regulation on OCN. Spironolactone may work through osteoblast MR/OCN axis to exert its therapeutic effects on pathological ventricular remodeling and heart failure in mice and human patients.

Validation of ISARIC 4C Mortality and Deterioration Scores in a Mixed Vaccination Status Cohort of Hospitalized Coronavirus Disease 2019 (COVID-19) Patients in Singapore.

In this cross-sectional study, we studied performance of the International Severe Acute Respiratory and Emerging Infections Consortium mortality and deterioration scores in a cohort of 410 hospitalized patients (51.2% fully vaccinated). area under the receiver operating characteristic curves were 0.778 and 0.764, respectively, comparable to originally published validation cohorts. Subgroup analysis showed equally good performance in vaccinated and partially or unvaccinated patients.

Mineralocorticoid receptor deficiency in Treg cells ameliorates DSS-induced colitis in a gut microbiota-dependent manner.

Mineralocorticoid receptor (MR) is a classic nuclear receptor and an effective drug target in the cardiovascular system. The function of MR in immune cells such as macrophages and T cells has been increasingly appreciated. The aim of this study was to investigate the function of Treg MR in the process of inflammatory bowel disease (IBD). We treated Treg MR-deficient (MRflox/flox Foxp3YFP-Cre , KO) mice and control (Foxp3YFP-Cre , WT) mice with dextran sodium sulphate (DSS) to induce colitis and found that the severity of DSS-induced colitis was markedly alleviated in Treg MR-deficient mice, accompanied by reduced production of inflammatory cytokines, and relieved infiltration of monocytes, neutrophils and interferon γ+ T cells in colon lamina propria. Faecal microbiota of mice with colitis was analysed by 16S rRNA gene sequencing and the composition of gut microbiota was vastly changed in Treg MR-deficient mice. Furthermore, depletion of gut microbiota by antibiotics abolished the protective effects of Treg MR deficiency and resulted in similar severity of DSS-induced colitis in WT and KO mice. Faecal microbiota transplantation from KO mice attenuated DSS-induced colitis characterized by alleviated inflammatory infiltration compared to that from WT mice. Hence, our study demonstrates that Treg MR deficiency protects against DSS-induced colitis by attenuation of colonic inflammatory infiltration. Gut microbiota is both sufficient and necessary for Treg MR deficiency to exert the beneficial effects.

Global benefits of non-continuous flooding to reduce greenhouse gases and irrigation water use without rice yield penalty.

Non-continuous flooding is an effective practice for reducing greenhouse gas (GHG) emissions and irrigation water use (IRR) in rice fields. However, advancing global implementation is hampered by the lack of comprehensive understanding of GHGs and IRR reduction benefits without compromising rice yield. Here, we present the largest observational data set for such effects as of yet. By using Random Forest regression models based on 636 field trials at 105 globally georeferenced sites, we identified the key drivers of effects of non-continuous flooding practices and mapped maximum GHGs or IRR reduction benefits under optimal non-continuous flooding strategies. The results show that variation in effects of non-continuous flooding practices are primarily explained by the UnFlooded days Ratio (UFR, that is the ratio of the number of days without standing water in the field to total days of the growing period). Non-continuous flooding practices could be feasible to be adopted in 76% of global rice harvested areas. This would reduce the global warming potential (GWP) of CH4 and N2 O combined from rice production by 47% or the total GWP by 7% and alleviate IRR by 25%, while maintaining yield levels. The identified UFR targets far exceed currently observed levels particularly in South and Southeast Asia, suggesting large opportunities for climate mitigation and water use conservation, associated with the rigorous implementation of non-continuous flooding practices in global rice cultivation.

Local and non-local drivers of consumption-based water use in China during 2007-2015: Perspective of metacoupling.

Increasingly growing consumption-based water use (WU) combined with climate change have exacerbated water stress globally and regionally, yet little is known about how the WU change is affected by metacoupled processes which involve human-nature interactions across space; within and across adjacent and distant places. This study aims to unveil the spatio-temporal pattern of China's WUs during 2007-2015 and its underlying local and non-local drivers. Results show that China's total WU exhibited an upward trend from 386.7 billion m³; in 2007 to 431.2 billion m³ in 2012 but dropped to 412.6 billion m³ by 2015. Widespread and continuous water use efficiency improvement contributed most to offsetting the increase in WU driven by the rising affluence and growing population in the context of rapid urbanization and industrialization. Economic structure drove a relatively large WU reduction (responsible for -23.7% of the WU change during 2007-2015), in line with China's ongoing transform from a capital investment-driven economy to a consumption-driven one and decoupling economic growth from environmental pressure. The population share representing the non-local factor of migration effect was large enough to be seen clearly in the changing WUs across China: the WUs of coastal areas ascended while inland areas descended, which was in accordance with migration patterns. Our findings could make a valuable contribution to decision-making in identifying hotspot areas, charting systematic courses for sustainable water use, and combining demand-oriented and supply-oriented measures.