An alleviative effect of Lonicerae japonicae flos water extract against liver fibrogenesis in vitro and in vivo.

Lonicerae japonicae (L. japonicae) flos is a medical and food homology herb. This study investigated the phenolic acid and flavonoid contents in L. japonicae flos water extract solution (LJWES) and the preventive effects of LJWES against liver fibrogenesis via FL83B cells and rats. LJWES contains many polyphenols, such as chlorogenic acid, morin, and epicatechin. LJWES increased cell viability and decreased cytotoxicity in thioacetamide (TAA)-treated FL83B cells (75 mM) (p < .05). LJWES decreased (p < .05) gene expressions of Tnf-α, Tnfr1, Bax, and cytochrome c but upregulated Bcl-2 and Bcl-xl in TAA-treated cells; meanwhile, increased protein levels of P53, cleaved caspase 3, and cleaved caspase 9 in TAA treated cells were downregulated (p < .05) by LJWES supplementation. In vivo, results indicated that TAA treatment increased serum liver damage indices (alanine aminotransferase [ALT] and alkaline phosphatase [ALP]) and cytokines (interleukin-6 and transforming growth factor-ß1) levels and impaired liver antioxidant capacities (increased thiobarbituric acid reactive substance value but decreased catalase/glutathione peroxidase activities) in rats (p < .05) while LJWES supplementation amended (p < .05) them. Liver fibrosis scores, collagen deposition, and alpha-smooth muscle actin deposition in TAA-treated rats were also decreased by LJWES supplementation (p < .05). To sum up, LJWES could be a potential hepatoprotective agent against liver fibrogenesis by enhancing antioxidant ability, downregulating inflammation in livers, and reducing apoptosis in hepatocytes.

Sex identification of birds in Taipei Zoo.

As a conservation and breeding institution for birds, Taipei Zoo plays an important role in restoring endangered species. As approximately half of all bird species are monomorphic, precisely confirming the sex of individuals is critical for the management of ex-situ conservation breeding populations, as well as for understanding the sex ratio of those in the wild. Generally, PCR is used more reliably for sex determination versus traditional methods such as plumage, behavior or hormone levels. Nevertheless, the various primer sets and annealing temperatures vary between species, and so inaccurate sexing can occasionally happen due to inadequate PCR conditions. To reduce the probability of misidentification, and to establish a PCR condition database for sex determination across the diverse range of avian taxa, we tested multiple primer sets and annealing temperatures for amplification of the bird sex-specific gene fragments (CHD1) for each captive or rescued avian species held at Taipei Zoo since 2014. A total of 162 species across 22 orders were tested using one or two primer sets. One hundred and fifty-five species were successfully sexed by the primer set 2550F/2718R and the success rate of sex typing reached over 90% of species tested in each order. Most species have suitable PCR annealing temperatures between 45°C and 55°C, and the species in the same avian taxa showed similar results in temperature. This indicates that it is possible to select the annealing temperature of other species in the same family when the species had not been tested before. We expect this study will improve the success rate of identifying sex by using applicable PCR conditions and reduce the time for searching references every time before attempts to PCR sex birds.

Heart rate variability in patients with anxiety disorders: A systematic review and meta-analysis.

AIMS: Patients with anxiety disorders (AD) have been found to have lower heart rate variability (HRV) than healthy individuals in some studies, but this was inconsistent. Furthermore, the influence of distinct diagnoses, study design, and demographic factors on the results was not comprehensively examined. METHODS: We gathered studies comparing HRV in patients with AD and in healthy controls. The parasympathetic activity in the hierarchical order principle was adopted in the main analysis. We adopted the random effects model to calculate the standardized mean difference. RESULTS: Of the 7805 screened studies, 99 were included in the quantitative analysis, with a total of 4897 AD patients and 5559 controls finally entered the meta-analysis. AD patients had a significantly lower resting-state HRV for parasympathetic activity compared to control (Hedges' g = -0.3897). For the diagnostic subgroup analysis relative to the controls, resting-state HRV was significantly lower in post-traumatic stress disorder, panic disorder, generalized anxiety disorder, and social anxiety disorder patients. HRV reactivity (all reactivity data, data on physiological challenge, and psychological challenge) did not show significant inter-group differences between AD patients and healthy subjects. CONCLUSIONS: The results supported that patients with AD had significantly lower resting-state HRV than the healthy population, but no alterations were found for HRV reactivity.

Serum uric acid is associated with incident metabolic syndrome independent of body shape index and body roundness index in healthy individuals.

BACKGROUND AND AIMS: Elevated serum uric acid (SUA) levels, body shape index (BSI) and body roundness index (BRI) were associated with incident metabolic syndrome (MetS). We aimed to investigate the relationship among the SUA level, BSI, and BRI on the incidence of MetS. METHODS AND RESULTS: We retrospectively included 6221 healthy individuals from annual health exams at our hospital between 2016/1/1 and 2016/12/31. We defined hyperuricemia as SUA levels greater than 7 mg/dl in men and 6 mg/dl in women and MetS according to the contemporary definition. The study cohort included 6221 healthy individuals with an overall incidence rate of MetS of 9.8%. Compared with the normouricemic group, the hyperuricemic group had a greater incidence of MetS (17.2% vs. 9.6%, P < 0.001). After full adjustment for confounders, the SUA level was significantly associated with incident MetS in addition to body mass index (BMI) (adjusted OR [aOR]: 1.161, 95% CI: 1.071-1.259, P < 0.001), BRI (aOR: 1.196, 95% CI: 1.104-1.296, P < 0.001), and BSI (aOR: 1.297, 95% CI: 1.200-1.403, P < 0.001). Regarding the anthropometric indices, BMI and BRI were independent predictors of incident MetS, but the BSI lost its significant association in multivariate logistic regression analyses. In sensitivity analyses, various thresholds of elevated SUA levels remained associated with incident MetS. CONCLUSION: We showed a dose-response effect of SUA on incident MetS independent of BMI, BRI and BSI in healthy individuals. Future studies can use SUA levels to stratify cardiometabolic risk in healthy individuals. CLINICAL TRIALS: ClinicalTrials.gov with the identification number NCT03473951.

Elevated serum uric acid is associated with incident hypertension in the health according to various contemporary blood pressure guidelines.

BACKGROUND AND AIMS: Elevated serum uric acid (SUA) is associated with hypertension according to its traditional definition. We investigated the association between SUA and incident hypertension according to the European Society of Cardiology (ESC) and American Society of Cardiology (ACC) guidelines. METHODS AND RESULTS: In this retrospective cohort study, we enrolled 10,537 healthy individuals ≥30 years old who underwent a routine annual health examination with office blood pressure recorded at our hospital in 2016; of the participants, 7349 repeated the exam in 2017. According to the ESC and ACC guidelines, hypertension was defined as office BP ≥ 140/90 mmHg or ≥130/80 mmHg. Hyperuricemia (HUA) was defined as SUA ≥7 mg/dL in men and ≥6 mg/dL in women. The hypertension incidence was 5.8% among 6378 individuals in the ESC cohort and 19% among 4330 individuals in the ACC cohort. Incident hypertension was significantly more common in the hyperuricemic group than in the normouricemic group (ESC: 8.6% vs. 4.7%, P < 0.001; ACC: 25.5% vs. 16.9%, P < 0.001). In the fully adjusted multivariate logistic regression analyses, each increase in SUA was associated with an increase in incident hypertension risk (ESC: adjusted OR: 1.167, 95% CI: 1.061-1.284, P = 0.001; ACC: adjusted OR: 1.125, 95% CI: 1.044-1.213, P = 0.002). The association can be explained by a significant correlation of baseline SUA with the BP in the following year (r = 0.24, P < 0.001 for baseline SUA and SBP in the following year; r = 0.239, P < 0.001 for baseline SUA and DBP in the following year). CONCLUSION: Elevated SUA was associated with incident hypertension in healthy individuals according to various contemporary BP guidelines (ClinicalTrials.gov: NCT03473951). CLINICAL TRIALS: ClinicalTrials.gov with the identification number of NCT03473951.

Anti-inflammatory effects of Flos Lonicerae Japonicae Water Extract are regulated by the STAT/NF-κB pathway and HO-1 expression in Virus-infected RAW264.7 cells.

This study examined the effect of the Flos Lonicerae Japonicae water extract (FLJWE), chlorogenic acid, and luteolin on pseudorabies virus (PRV)-induced inflammation in RAW264.7 cells and elucidated related molecular mechanisms. The results revealed that FLJWE and luteolin, but not chlorogenic acid, inhibited the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines in PRV-infected RAW 264.7 cells. We found that the FLJWE and luteolin suppressed nuclear factor (NF)-κB activation by inhibiting the phosphorylation of signal transducer and activator of transcription 1 and 3 (STAT1 and STAT3, respectively). Moreover, the FLJWE significantly upregulated the expression of pNrf2 and its downstream target gene heme oxygenase-1 (HO-1). Our data indicated that FLJWE and luteolin reduced the expression of proinflammatory mediators and inflammatory cytokines, such as COX-2 and iNOS, through the suppression of the JAK/STAT1/3-dependent NF-κB pathway and the induction of HO-1 expression in PRV-infected RAW264.7 cells. The findings indicate that the FLJWE can be used as a potential antiviral agent.

Association between Low-Grade Inflammation and Left Ventricular Diastolic Dysfunction in Patients with Metabolic Syndrome and Hyperuricemia.

BACKGROUND: Hyperuricemia (HUA) induces inflammation and insulin resistance and is reportedly associated with left ventricular hypertrophy (LVH) and possibly with left ventricular diastolic dysfunction (LVDD). OBJECTIVES: To investigate associations among HUA, inflammation, and insulin resistance with LVDD. METHODS: We enrolled patients with metabolic syndrome (MetS) between August 1, 2017, and December 31, 2017. All participants underwent fasting blood tests and transthoracic echocardiography. HUA was defined as an serum uric acid level ≥ 7 mg/dl in men or ≥ 6 mg/dl in women. MetS was defined as at least three of the following Taiwanese criteria: central obesity, prehypertension, fasting glucose impairment, hypertriglyceridemia, and lower values of high-density lipoprotein cholesterol. LVDD was defined according to contemporary guidelines. RESULTS: The study included 63 patients (60% male) with a mean age of 53 ± 14 years and body mass index (BMI) of 29.4 ± 4.0 kg/m2. Prevalence rates of HUA, LVH, LVDD were 40%, 18%, and 10%, respectively. Baseline characteristics were similar between the HUA and normouricemia groups, except that the HUA group had significantly higher serum high-sensitivity interleukin 6 and tumor necrosis factor-alpha (TNF-α) levels. LVDD occurred more frequently in the HUA group (20.0% vs. 2.6%, p = 0.032). HUA was associated with LVDD [crude odds ratio (OR): 9.25, 95% confidence interval (CI): 1.01-84.7, p = 0.049]. In multivariate analysis, the most relevant factor associated with LVDD was TNF-α after adjustments for age, male sex, and body mass index (adjusted OR for TNF-α: 4.1, 95% CI: 1.02-16.5, p = 0.047). CONCLUSIONS: The association between HUA and LVDD partially reflected a low-grade inflammation due to elevated TNF-α rather than increased insulin resistance in MetS patients.

The net clinical benefits of febuxostat versus allopurinol in patients with gout or asymptomatic hyperuricemia - A systematic review and meta-analysis.

BACKGROUND AND AIMS: Systemic reviews and meta-analyses suggest hyperuricemia is a cardiovascular risk factor. The effects of xanthine oxidase inhibitors on cardiac outcomes remain unclear. We assessed the effects of febuxostat and allopurinol on mortality and adverse reactions in adult patients with hyperuricemia. METHODS AND RESULTS: PubMed and EMBASE were searched to retrieve randomized controlled trials of febuxostat and allopurinol from January 2005 to July 2018. The meta-analysis consisted of 13 randomized controlled trials with a combined sample size of 13,539 patients. Febuxostat vs. allopurinol was not associated with an increased risk of cardiac-related mortality in the overall population (OR: 0.72, 95% CI: 0.24-2.13, P = 0.55). Regarding adverse skin reactions, the patients receiving febuxostat had significantly fewer adverse skin reactions than those receiving allopurinol treatment (OR: 0.50, 95% CI: 0.30-085, P = 0.01). Compared with allopurinol, febuxostat was associated with an improved safety outcome of cardiac-related mortality and adverse skin reactions (OR: 0.72, 95% CI: 0.55-0.96, P = 0.02). The net clinical outcome, composite of incident gout and the safety outcome, was not different significantly in the patients receiving febuxostat or allopurinol (OR: 1.04, 95% CI: 0.76-0.1.42, P = 0.79). In sensitivity analyses, a borderline significance was found in the patients randomized to febuxostat vs. allopurinol regarding cardiac-related mortality (OR: 1.29, 95% CI: 1.00-1.67, P = 0.05) after the CARES study was included. CONCLUSION: Febuxostat vs. allopurinol was associated with the improved safety outcome and have comparable mortality and net clinical outcome in patients with hyperuricemia. REGISTRATION NUMBER: PROSPERO(CRD42018091657).

Systemic lupus erythematosus is associated with poor outcome after acute myocardial infarction.

BACKGROUND: Systemic lupus erythematosus (SLE) is associated with a higher risk of cardiovascular disease. However, it is not clear whether or not SLE is associated with poor outcomes after acute myocardial infarction (AMI). METHODS AND RESULTS: Using the Taiwan National Health Insurance Database, we identified the SLE group as patients with AMI who have a concurrent discharge diagnosis of SLE. We also selected an age-, sex-, hospital level-, and admission calendar year-matched non-SLE group at a ratio of 1:3 from the total non-SLE group. One hundred fifty-one patients with SLE, 113,791 patients without SLE, and 453 matched patients without SLE were admitted with a diagnosis of AMI. Patients with SLE were significantly younger, predominantly female, and more likely to have chronic kidney disease than those without SLE. The in-hospital mortality rates were 12.6%, 9.0%, and 4.2% in the SLE, total non-SLE, and matched non-SLE groups, respectively. The in-hospital mortality was significantly higher in the SLE group than in the total non-SLE group (OR = 1.98; 95% CI = 1.2-3.26) and the matched non-SLE group (mortality OR = 2.20; 95% CI = 1.06-4.58). In addition, the SLE group was associated with a borderline significant risk of prolonged hospitalization when compared with the non-SLE group. CONCLUSION: SLE is associated with a higher risk of in-hospital mortality and a borderline significantly higher risk of prolonged hospitalization after AMI.

Carbon Nanodots with Sub-Nanosecond Spontaneous Emission Lifetime.

Compared with most mature cadmium-containing quantum dots (QDs), carbon nanodots (CNDs) are a new class of colloidal nanomaterials that exhibit unique photoluminescence (PL) properties while being nontoxic and easily manufactured using low-cost precursor materials. However, solid-state CNDs exhibit poor PL quantum yields (PL-QYs) and inefficient radiative transition, which significantly hinders their practical use in optoelectronic devices. To address this issue, plasmonic nanoantennas consisting of Au nanorods (Au-NRs) deposited on a flat Au film with inserted dielectric layers were used to enhance the spontaneous emission of solid-state CNDs with broad spectral linewidth. Using steady-state, time-resolved, and spatial-resolved PL measurements, we found that after coupling to plasmonic nanogaps (PNGs), the PL emission was significantly enhanced, accompanied by a PL lifetime shortening to the sub-nanosecond range (≈140 ps). According to the experimental data, the radiative transition is strongly accelerated and can thus overcome the metal loss, leading to a large PL enhancement. Our demonstration can pave the way to the design of eco-friendly nanoemitters with sub-nanosecond PL lifetime for promising applications in light-emitting devices.

SYNTAX Score of Infarct-Related Artery Other Than the Number of Coronary Balloon Inflations and Deflations as an Independent Predictor of Contrast-Induced Acute Kidney Injury in Patients with ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Although remote ischemic post-conditioning (RIPC) has been shown to prevent contrast-induced acute kidney injury (CIAKI) in patients with acute coronary syndrome, its efficacy in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear. We examined the relationship among balloon inflations and deflations (BID) times, SYNTAX score of infarction-related artery (SI), periprocedural complications, and CIAKI in STEMI patients undergoing primary percutaneous coronary intervention (pPCI). METHODS: Patients with STEMI undergoing pPCI with Mehran risk score (MRS) ≥ 5 were enrolled between February 2007 and September 2012. The study end point was the development of CIAKI. RESULTS: Of 206 patients, the median age was 65 years [interquartile range (IQR): 55-77] with 72.8% male and Mehran risk score (MRS) 8 (IQR: 6-12). Receiver operating characteristic curve showed that BID times > 9 times or SI > 10 was the best cut-off associated with CIAKI. In univariate analysis, significant association with CIAKI existed in BID > 9 times [odds ratio (OR): 3.106, 95% confidence interval (CI): 1.284-7.513, p = 0.012] and SI > 10 (OR: 3.909, 95% CI: 1.570-9.735, p = 0.003). Other variables associated with CIAKI included creatinine, hemoglobin, angiotensin converting enzyme inhibitor or angiotensin receptor blocker use at discharge. In multivariate analysis, SI > 10 remained an independent predictor of CIAKI in different adjustment model, even on top of MRS (adjusted OR: 3.498, 95% CI: 1.086-11.268, p = 0.036). CONCLUSIONS: Vascular complexity of infarct-related artery rather than higher BID times (> 9) was the major determinant of the development of CIAKI after pPCI in STEMI patients.

Use of intra-aortic balloon pump support for oozing-type cardiac rupture after acute myocardial infarction.

Left ventricular free wall rupture usually leads to acute hemopericardium and sudden cardiac death resulting in cardiac tamponade. Rarely, only a few patients with subacute free wall rupture such as oozing-type ventricular rupture or left ventricular false aneurysm may permit time for pericardiocentesis and surgery. We report a 63-year-old man with ST-elevation myocardial infarction who underwent primary percutaneous coronary intervention about 12 hours from the onset, and cardiac tamponade occurred on the second day. An intra-aortic balloon pump (IABP) was immediately inserted for hemodynamic support. After 100 mL of pericardial fresh blood was drained from the percardial cavity, his hemodynamic collapse was promptly improved with IABP support. In the following 24 hours, about 600 mL of hemorrhagic pericardial fluid was drained. The most likely diagnosis was concerning for oozing-type ventricular rupture, and a conservative approach was decided. The patient survived to the acute phase under IABP support and was discharged with complete recovery.

Baseline Hemoglobin Levels Associated with One-Year Mortality in ST-Segment Elevation Myocardial Infarction Patients.

BACKGROUND: The association between hemoglobin (Hb) levels and mortality in patients with ST-segment elevation myocardial infarction (STEMI) remains controversial. The purpose of this study was to examine the mortality among STEMI patients with anemia or erythrocytosis, and further establish the relationship between mortality and the increment of Hb level. METHODS: Between 2006 and 2012, 951 consecutive patients with STEMI undergoing primary percutaneous coronary intervention in a medical center in Northern Taiwan were enrolled in our study, including 535 patients with normal Hb level, 148 with anemia (male Hb ≤ 13 g/dl, female ≤ 12) and 268 with erythrocytosis (male Hb ≥ 16, female ≥ 15). RESULTS: Patients in the anemia group were the oldest, and had higher morbidity than the normal Hb group, followed by the erythrocytosis group. In regression analyses, neither anemia nor erythrocytosis was associated with 30-day and 1-year mortality. Each 1-g/dl increment of Hb level was not associated with 30-day mortality both in patients with anemia or erythrocytosis. However, it was associated with a decreased risk of 1-year mortality in anemic patients [hazard ratio (HR): 0.756, 95% confidence interval (CI): 0.608-0.938, p = 0.011] and an increased risk of 1-year mortality in those with erythrocytosis (HR: 2.086, 95%CI: 1.106-3.937, p = 0.023). In multivariate analysis, each 1-g/dl increment of Hb level was associated with 1-year mortality both in anemic patients and those with erythrocytosis (HR: 0.788, 95%CI: 0.621-0.999, p = 0.049; HR: 2.302, 95%CI: 1.051-5.04, p = 0.037). CONCLUSIONS: Higher hemoglobin levels in STEMI patients with anemia were associated with decreased risks of 1-year mortality, whereas higher hemoglobin levels in those with erythrocytosis were associated with increased risks of one-year mortality.

Quantum versus classical annealing: insights from scaling theory and results for spin glasses on 3-regular graphs.

We discuss an Ising spin glass where each S=1/2 spin is coupled antiferromagnetically to three other spins (3-regular graphs). Inducing quantum fluctuations by a time-dependent transverse field, we use out-of-equilibrium quantum Monte Carlo simulations to study dynamic scaling at the quantum glass transition. Comparing the dynamic exponent and other critical exponents with those of the classical (temperature-driven) transition, we conclude that quantum annealing is less efficient than classical simulated annealing in bringing the system into the glass phase. Quantum computing based on the quantum annealing paradigm is therefore inferior to classical simulated annealing for this class of problems. We also comment on previous simulations where a parameter is changed with the simulation time, which is very different from the true Hamiltonian dynamics simulated here.

Kidney disease in trials of perioperative tranexamic acid.

STUDY OBJECTIVE: To assess how kidney disease is handled in randomized trials evaluating the safety and efficacy of perioperative tranexamic acid, and to evaluate its effects across levels of kidney function. DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING: We screened studies from a previous comprehensive systematic review, and updated its search of PubMed, Embase, and Cochrane CENTRAL to July 31, 2023. PATIENTS: Patients undergoing non-obstetric surgery. INTERVENTIONS: Intravenous tranexamic acid compared to placebo or usual care without tranexamic acid. MEASUREMENT: We summarized the handling of kidney disease in eligibility criteria, dose adjustments for kidney function, and effects of tranexamic acid on thrombotic events, seizures, and bleeding by subgroups of kidney function. MAIN RESULTS: We evaluated 300 trials with 53,085 participants; 45,958 participants (86.6%) were enrolled in 228 trials (76.0%) that explicitly excluded patients with kidney disease. Definitions of kidney diseased used for exclusion varied widely. Most were non-specific and some corresponded to mild disease. Only 5 trials adjusted dosing for kidney function. Meta-analysis of two large trials found tranexamic acid unlikely to substantially increase or decrease the occurrence of thrombotic events in patients with eGFR <60 mL/min/1.73m2 (RR, 0.95; 95% CI: 0.83 to 1.07) or ≥ 60 mL/min/1.73m2 (RR, 1.00; 95% CI, 0.91 to 1.11; P for subgroup difference = 0.47), but both trials excluded patients with severe kidney disease. No analysis could be performed regarding seizure risk. One large trial in noncardiac surgery reported similar reduction in bleeding across subgroups of kidney function but excluded patients with creatinine clearance <30 mL/min. CONCLUSIONS: The large evidence base supporting perioperative tranexamic acid suffers from broad and unjustified exclusion of patients with kidney disease. Typical perioperative dosing of tranexamic acid is likely safe and effective in patients with creatinine clearance >30 mL/min, but effects in more severe kidney disease are unknown.

COVID-19 vaccine uptake among Ontario physicians: a descriptive population-based retrospective cohort study.

OBJECTIVES: To determine COVID-19 vaccine uptake among physicians in Ontario, Canada from 14 December 2020 to 13 February 2022. DESIGN: Population-based retrospective cohort study. SETTING: All registered physicians in Ontario, Canada using data from linked provincial administrative healthcare databases. PARTICIPANTS: 41 267 physicians (including postgraduate trainees) who were Ontario residents and registered with the College of Physicians and Surgeons of Ontario were included. Physicians who were out of province, had not accessed Ontario Health Insurance Plan-insured services for their own care for ≥5 years and those with missing identifiers were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were the proportions of physicians who were recorded to have received at least one, at least two and three doses of a Health Canada-approved COVID-19 vaccine by study end date. Secondary outcomes were how uptake varied by physician characteristics (including age, sex, specialty and residential location) and time elapsed between doses. RESULTS: Of 41 267 physicians, (56% male, mean age 47 years), 39 359 (95.4%) received at least one dose, 39 148 (94.9%) received at least two doses and 35 834 (86.8%) received three doses of a COVID-19 vaccine. Of those who received three doses, the proportions were 90.4% among those aged ≥60 years and 81.2-89.5% among other age groups; 88.7% among family physicians and 89% among specialists. 1908 physicians (4.6%) had no record of vaccination, and this included 3.4% of family physicians and 4.1% of specialists; however, 28% of this group had missing specialty information. CONCLUSIONS: In Ontario, within 14 months of COVID-19 vaccine availability, 86.8% of physicians had three doses of a COVID-19 vaccine, compared with 45.6% of the general population. Findings may signify physicians' confidence in the safety and effectiveness of COVID-19 vaccines.

MCT1-mediated transport of valeric acid promotes porcine preimplantation embryo development by improving mitochondrial function and inhibiting the autophagic AMPK-ULK1 pathway.

Oocytes and embryos are highly sensitive to environmental stress in vivo and in vitro. During in vitro culture, many stressful conditions can affect embryo quality and viability, leading to adverse clinical outcomes such as abortion and congenital abnormalities. In this study, we found that valeric acid (VA) increased the mitochondrial membrane potential and ATP content, decreased the level of reactive oxygen species that the mitochondria generate, and thus improved mitochondrial function during early embryonic development in pigs. VA decreased expression of the autophagy-related factors LC3B and BECLIN1. Interestingly, VA inhibited expression of autophagy-associated phosphorylation-adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylation-UNC-51-like autophagy-activated kinase 1 (p-ULK1, Ser555), and ATG13, which reduced apoptosis. Short-chain fatty acids (SCFAs) can signal through G-protein-coupled receptors on the cell membrane or enter the cell directly through transporters. We further show that the monocarboxylate transporter 1 (MCT1) was necessary for the effects of VA on embryo quality, which provides a new molecular perspective of the pathway by which SCFAs affect embryos. Importantly, VA significantly inhibited the AMPK-ULK1 autophagic signaling pathway through MCT1, decreased apoptosis, increased expression of embryonic pluripotency genes, and improved embryo quality.

Reduced-Dose Rivaroxaban Is Associated with Lower All-Cause Mortality in Older Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: Reduced-dose rivaroxaban (10 mg) was used in the J-ROCKET AF trial, demonstrating safety in the Asian population. It remains unclear whether treatment with reduced-dose versus full-dose rivaroxaban (20 mg/15 mg) is associated with all-cause mortality in older patients with nonvalvular atrial fibrillation. Proposed: To evaluate the effects of reduced-dose rivaroxaban on all-cause mortality in patients over 85. METHODS: We retrospectively enrolled medical records representing the period from October 2012 to November 2016. The 2 × 2 factorial design incorporated age (≥85 vs. <85) and rivaroxaban use (reduced vs. full dose). The primary study outcomes were all-cause and cardiac-related mortality. RESULTS: The study enrolled 2386 patients with a mean age of 76.6 ± 10.4 years; 51.8% were male. In the ≥85 group (n = 593), the reduced-dose subgroup had lower all-cause (5.3% vs. 10.6%, p = 0.02) and cardiac-related mortality (1.9% vs. 5.1%, p = 0.04), whereas the younger patients receiving reduced-dose rivaroxaban had higher all-cause mortality (3.7% vs. 1.8%, p = 0.01) but no difference in cardiac-related mortality (1.2% vs. 0.7%, p = 0.33). The rate of hospitalization for heart failure was significantly lower in the elderly group with reduced-dose rivaroxaban (7.2% vs. 15.7%, p < 0.01) but not in the younger group. After adjusting for confounders in the older group, treatment with reduced-dose rivaroxaban was associated with lower risk of all-cause mortality (adjusted HR (aHR): 0.40, 95% CI: 0.21-0.74, p < 0.01) and hospitalization for heart failure (aHR: 0.54, 95% CI: 0.29-0.99, p = 0.05). No associations were found between rivaroxaban dose and cardiac-related mortality in either group, nor between younger age and any outcome. CONCLUSIONS: Reduced-dose rivaroxaban was associated with lower risks of all-cause mortality and hospitalization for heart failure in older patients with nonvalvular atrial fibrillation. Future studies can investigate the effect of reduced-dose rivaroxaban on prognoses in elderly individuals ≥85 years in the west.