Fabrication of large-area photonic crystal-modified X-ray scintillator imager for optical coding imaging.

The limited pattern area of periodic nanostructures limits the development of practical devices. This study introduces an X-ray interference lithography (XIL) stitching technique to fabricate a large-area (1.5 cm × 1.5 cm) two-dimensional photonic crystal (PhC) on the YAG: Ce scintillator, which functions as an encoder in a high numerical aperture optical encoding imaging system to effectively capture high-frequency information. An X-ray imaging experiment revealed a substantial 7.64 dB improvement in the signal-to-noise ratio (SNR) across a large field of view (2.6 mm × 2.6 mm) and achieved comparable or superior image quality with half the exposure dose. These findings have significant implications for advancing practical applications of X-ray imaging.

Association between systemic immune-inflammation index and serum uric acid in U.S. adolescents: A population-based study.

BACKGROUND AND AIMS: Serum uric acid (SUA) has been reported to be associated with inflammation, and elevated SUA is increasingly prevalent in adolescents. The systemic immune-inflammation index (SII) is an innovative and integrated inflammatory indicator that has not yet been studied with SUA in adolescents. We therefore aimed to investigate the potential relationship between SII and SUA in U.S. adolescents. METHODS AND RESULTS: A total of 5,568 adolescents aged 12-19 years from NHANES 2009-2018 were analyzed. SII was calculated as platelet count × neutrophil count/lymphocyte count. Elevated SUA was defined as ≥ 5.5 mg/dL. SII was Ln-transformed for analysis for the skewed distribution. Multivariate linear and multiple logistic regression analyses were conducted to explore the association of SII with SUA and elevated SUA. A generalized additive model and a fitted smoothing curve were also performed. The prevalence of elevated SUA was 35.4 %. Multivariate linear regression analyses indicated that LnSII was positively associated with SUA level (ß = 0.15, 95 % CI: 0.09-0.20). Multiple logistic analyses indicated that LnSII was associated with a 38 % increased risk of elevated SUA (OR = 1.38, 95 % CI: 1.11-1.70). The smooth curve fitting showed that the associations of LnSII with SUA and elevated SUA were linear. Besides, subgroup analyses showed a stronger association between LnSII and SUA in adolescents aged ≥17 years (P for interaction <0.05). CONCLUSIONS: SII was positively associated with SUA level and elevated SUA in U.S. adolescents, particularly in populations aged ≥17 years.

Efficacy and safety of ongericimab given by prefilled syringe or autoinjector in primary hypercholesterolemia and mixed hyperlipidemia.

BACKGROUND AND AIMS: Limited evidence exist regarding the association between ongericimab, a novel recombinant humanized anti-PCSK9 monoclonal antibody, and primary hypercholesterolemia and mixed dyslipidemia. This study aimed to evaluate the efficacy and safety of ongericimab administered by prefilled syringe (PFS) or autoinjector (AI) in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia on stable optimized lipid-lowering therapy. METHODS AND RESULTS: A total of 255 patients on stable optimized lipid-lowering therapy were randomized in a 2:1:2:1 ratio to receive PFS for the subcutaneous injection of ongericimab 150 mg every 2 weeks (Q2W) or a matching placebo, or AI for the subcutaneous injection of ongericimab 150 mg Q2W or a matching placebo. The primary efficacy endpoint was the percent change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Safety was also evaluated. At week 12, the least squares mean percent changes were -72.7% (3.9%) for PFS and -71.1% (3.8%) for AI (all P < 0.001) compared to respective matching placebo groups. Beneficial effects were also seen for all secondary lipid parameters, notably with robust reduction in Lp (a). Treatment-emergent adverse events (TEAEs) and serious AEs with ongericimab were reported in 46.2% and 2.4% of patients, compared to 44.2% and 3.5% with placebo. CONCLUSION: In Chinese patients with primary hypercholesterolemia and mixed dyslipidemia, a 12-week treatment regimen with ongericimab administered by PFS or AI significantly reduced LDL-C and other lipid parameters, proving to be safe and well tolerated. Patients experienced consistent effects from PFS or AI devices. CLINICAL TRIAL REGISTRATION: CTR20220027; January 11, 2022; http://www.chinadrugtrials.org.cn/index.html.

Molecular characterization and ontogenetic expression profiles of LPXRFa and its receptor in Japanese flounder (Paralichthys olivaceus).

Investigations concerning the LPXRFa system are rarely conducted in flatfish species. Here, we first identified and characterized lpxrfa and its cognate receptor lpxrfa-r genes in the Japanese flounder (Paralichthys olivaceus). The coding DNA sequence of lpxrfa was 579 bp in length, wich encoded a 192-aa preprohormone that can produce three mature LPXRFa peptides. The open reading frame (ORF) of lpxrfa-r was 1446 bp in size, and encoded a 481-aa LPXRFa-R protein that encompassed seven hydrophobic transmembrane domains. Subsequently, tissue distribution expression profiles of lpxrfa and lpxrfa-r transcripts were assayed by quantitative real-time PCR. The results indicated that expressions of lpxrfa transcripts were detected at the highest levels in the brain of both females and males, however, lpxrfa-r transcripts were remarkablely expressed in the brain tissue of female fish and in the testis tissue of male fish. Furthermore, transcript levels of lpxrfa and lpxrfa-r genes were investigated during early ontogenetic development, with the maximum expression levels at 30 days post-hatching. Overall, these data contribute to providing preliminary proof for the existence and structure of the LPXRFa system in Japanese flounder, and the study is just the foundation for researching physiological function of LPXRFa system in this species.

The heart rate response to the 6-min walk test in atrial fibrillation patients with or without beta-blockers: Referring to patients with sinus rhythm.

BACKGROUND: The aim was to evaluate the effect of beta-blockers (BB) on the response of heart rate (HR) to 6-min walk test (6MWT) in atrial fibrillation (AF) and whether the AF patients treated with BB have a similar HR response to 6MWT as the AF and sinus rhythm (SR) patients without BB treatment at the same resting HR level. METHODS: The before-after study involving 74 AF patients was to evaluate the effect of BB treatment (pre-BB and with BB). The comparison study included 74 BB-treated AF patients (with BB), 74 matched AF patients without BB (no BB), and 74 SR patients. The percentage increase amplitude of HR (HR-PIA) in 6MWT was calculated: [(the exercise HR - the resting HR)/(the resting HR)] × 100%. RESULTS: The before-after study showed that BB treatment decreased the resting and mean exercise HR (98.6 ± 15.2 vs. 85.5 ± 11.2 bpm and 121.3 ± 17.3 vs. 109.0 ± 16.7 bpm) during 6MWT. The comparison study demonstrated that against the SR, the AF with BB and no BB groups have higher mean exercise HR-PIA (28.2 ± 17.1% and 22.0 ± 9.6%, vs. 6.9 ± 3.7%) when their resting HR is similar. Moreover, the mean exercise HR-PIA was also significantly higher in the with BB group than in the no BB group. CONCLUSION: In AF patients with relatively higher resting HR, BB treatment could decrease the resting and exercise HR during 6MWT. However, BB treatment could not effectively attenuate the exercise HR rise as compared with AF without BB treatment, even with similar resting HR levels.

Association between Reactive Oxygen Species, Transcription Factors, and Candidate Genes in Drought-Resistant Sorghum.

Drought stress is one of the most severe natural disasters in terms of its frequency, length, impact intensity, and associated losses, making it a significant threat to agricultural productivity. Sorghum (Sorghum bicolor), a C4 plant, shows a wide range of morphological, physiological, and biochemical adaptations in response to drought stress, paving the way for it to endure harsh environments. In arid environments, sorghum exhibits enhanced water uptake and reduced dissipation through its morphological activity, allowing it to withstand drought stress. Sorghum exhibits physiological and biochemical resistance to drought, primarily by adjusting its osmotic potential, scavenging reactive oxygen species, and changing the activities of its antioxidant enzymes. In addition, certain sorghum genes exhibit downregulation capabilities in response to drought stress. Therefore, in the current review, we explore drought tolerance in sorghum, encompassing its morphological characteristics and physiological mechanisms and the identification and selection of its functional genes. The use of modern biotechnological and molecular biological approaches to improving sorghum resistance is critical for selecting and breeding drought-tolerant sorghum varieties.

Bivalirudin plus a high-dose infusion versus heparin monotherapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomised trial.

BACKGROUND: Previous randomised trials of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) have reported conflicting results, in part because of treatment with different pharmacological regimens. We designed a large-scale trial examining bivalirudin with a post-PCI high-dose infusion compared with heparin alone, the regimens that previous studies have shown to have the best balance of safety and efficacy. METHODS: BRIGHT-4 was an investigator-initiated, open-label, randomised controlled trial conducted at 87 clinical centres in 63 cities in China. Patients with STEMI undergoing primary PCI with radial artery access within 48 h of symptom onset who had not received previous fibrinolytic therapy, anticoagulants, or glycoprotein IIb/IIIa inhibitors were randomly assigned (1:1) to receive bivalirudin with a post-PCI high-dose infusion for 2-4 h or unfractionated heparin monotherapy. There was no masking. Glycoprotein IIb/IIIa inhibitor use was reserved for procedural thrombotic complications in both groups. The primary endpoint was a composite of all-cause mortality or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding at 30 days. This trial is registered with ClinicalTrials.gov (NCT03822975), and is ongoing. FINDINGS: Between Feb 14, 2019, and April 7, 2022, a total of 6016 patients with STEMI undergoing primary PCI were randomly assigned to receive either bivalirudin plus a high-dose infusion after PCI (n=3009) or unfractionated heparin monotherapy (n=3007). Radial artery access was used in 5593 (93·1%) of 6008 patients. Compared with heparin monotherapy, bivalirudin reduced the 30-day rate of the primary endpoint (132 events [4·39%] in the heparin group vs 92 events [3·06%] in the bivalirudin group; difference, 1·33%, 95% CI 0·38-2·29%; hazard ratio [HR] 0·69, 95% CI 0·53-0·91; p=0·0070). All-cause mortality within 30 days occurred in 118 (3·92%) heparin-assigned patients and in 89 (2·96%) bivalirudin-assigned patients (HR 0·75; 95% CI 0·57-0·99; p=0·0420), and BARC types 3-5 bleeding occurred in 24 (0·80%) heparin-assigned patients and five (0·17%) bivalirudin-assigned patients (HR 0·21; 95% CI 0·08-0·54; p=0·0014). There were no significant differences in the 30-day rates of reinfarction, stroke, or ischaemia-driven target vessel revascularisation between the groups. Within 30 days, stent thrombosis occurred in 11 (0·37%) of bivalirudin-assigned patients and 33 (1·10%) of heparin-assigned patients (p=0·0015). INTERPRETATION: In patients with STEMI undergoing primary PCI predominantly with radial artery access, anticoagulation with bivalirudin plus a post-PCI high-dose infusion for 2-4 h significantly reduced the 30-day composite rate of all-cause mortality or BARC types 3-5 major bleeding compared with heparin monotherapy. FUNDING: Chinese Society of Cardiology Foundation (CSCF2019A01), and a research grant from Jiangsu Hengrui Pharmaceuticals.

SIRT3 ameliorates diabetes-associated cognitive dysfunction via regulating mitochondria-associated ER membranes.

BACKGROUND: Diabetes is associated with an increased risk of cognitive decline and dementia. These diseases are linked with mitochondrial dysfunction, most likely as a consequence of excessive formation of mitochondria-associated membranes (MAMs). Sirtuin3 (SIRT3), a key mitochondrial NAD+-dependent deacetylase, is critical responsible for mitochondrial functional homeostasis and is highly associated with neuropathology. However, the role of SIRT3 in regulating MAM coupling remains unknown. METHODS: Streptozotocin-injected diabetic mice and high glucose-treated SH-SY5Y cells were established as the animal and cellular models, respectively. SIRT3 expression was up-regulated in vivo using an adeno-associated virus in mouse hippocampus and in vitro using a recombinant lentivirus vector. Cognitive function was evaluated using behavioural tests. Hippocampus injury was assessed using Golgi and Nissl staining. Apoptosis was analysed using western blotting and TUNEL assay. Mitochondrial function was detected using flow cytometry and confocal fluorescence microscopy. The mechanisms were investigated using co-immunoprecipitation of VDAC1-GRP75-IP3R complex, fluorescence imaging of ER and mitochondrial co-localisation and transmission electron microscopy of structural analysis of MAMs. RESULTS: Our results demonstrated that SIRT3 expression was significantly reduced in high glucose-treated SH-SY5Y cells and hippocampal tissues from diabetic mice. Further, up-regulating SIRT3 alleviated hippocampus injuries and cognitive impairment in diabetic mice and mitigated mitochondrial Ca2+ overload-induced mitochondrial dysfunction and apoptosis. Mechanistically, MAM formation was enhanced under high glucose conditions, which was reversed by genetic up-regulation of SIRT3 via reduced interaction of the VDAC1-GRP75-IP3R complex in vitro and in vivo. Furthermore, we investigated the therapeutic effects of pharmacological activation of SIRT3 in diabetic mice via honokiol treatment, which exhibited similar effects to our genetic interventions. CONCLUSIONS: In summary, our findings suggest that SIRT3 ameliorates cognitive impairment in diabetic mice by limiting aberrant MAM formation. Furthermore, targeting the activation of SIRT3 by honokiol provides a promising therapeutic candidate for diabetes-associated cognitive dysfunction. Overall, our study suggests a novel role of SIRT3 in regulating MAM coupling and indicates that SIRT3-targeted therapies are promising for diabetic dementia patients.

Association study of urinary iodine concentrations and coronary artery disease among adults in the USA: National Health and Nutrition Examination Survey 2003-2018.

Iodine is a vital trace element in the human body and is associated with several important coronary artery disease (CAD) risk factors. We aimed to explore the correlation between urinary iodine concentration (UIC) and CAD. Data from 15 793 US adults in the National Health and Nutrition Examination Survey (2003-2018) were analysed. We conducted multivariable logistic regression models and fitted smoothing curves to study the correlation between UIC and CAD. Furthermore, we performed subgroup analysis to investigate possible effect modifiers between them. We found a J-shaped association between UIC and CAD, with an inflection point at Lg UIC = 2·65 µg/l. This result indicated a neutral association (OR 0·89; 95 % CI 0·68, 1·16) between UIC and CAD as Lg UIC < 2·65 µg/l, but the per natural Lg [UIC] increment was OR 2·29; 95 % CI 1·53, 3·43 as Lg UIC ≥ 2·65 µg/l. An interaction between diabetes and UIC might exist. The increase in UIC results in an increase in CAD prevalence (OR 1·84, 95 % CI 1·32, 2·58) in diabetes but results in little to no difference in non-diabetes (OR 0·98, 95 % CI 0·77, 1·25). The J-shaped correlation between UIC and CAD and the interaction between diabetes and UIC should be confirmed in a prospective study with a series of UIC measurements. If excessive iodine precedes CAD, then this new finding could guide clinical practice and prevent iodine deficiency from being overcorrected.

Association between weight-adjusted-waist index and risk of cardiovascular diseases in United States adults: a cross-sectional study.

BACKGROUND: As a new obesity-related index, the weight-adjusted-waist index (WWI) appears to be a good predictor of cardiovascular disease (CVD) in East Asian populations. This study aimed to validate the association between WWI and CVD in United States (US) adults and also evaluate its relationships with the prevalence of specific CVDs. METHODS: The data were obtained from the 2009-2016 National Health and Nutrition Examination Survey. WWI was calculated as waist circumference divided by the square root of weight, and CVD was ascertained based on self-reported physician diagnoses. Multivariable logistic regression models and subgroup analyses were performed to evaluate the association between WWI and CVD. RESULTS: A total of 21,040 participants were included. There was a positive linear relationship between WWI and the odds of CVD (P = 0.310). After adjusting for all covariates, each unit of increased WWI was associated with 48% increased risk of CVD (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.25-1.74). Moreover, compared with the lowest quintile (< 10.3 cm/√kg), the multivariable-adjusted OR was 3.18 (95% CI: 1.80-5.59) in the highest quintile (≥ 11.8 cm/√kg). Besides, positive associations were also found between WWI and increased prevalence of congestive heart failure (OR: 1.47, 95% CI: 1.11-1.96), coronary heart disease (OR: 1.27, 95% CI: 1.01-1.60), angina (OR: 1.44, 95% CI: 1.06-1.96), heart attack (OR: 1.66, 95% CI: 1.29-2.12), and stroke (OR: 1.32, 95% CI: 1.02-1.70). Subgroup analyses showed that stronger associations between WWI and CVD were detected in participants younger than 50 years of age (P < 0.001). CONCLUSIONS: High levels of WWI were significantly associated with an increased risk of CVD in US adults, particularly in people under 50 years of age. These findings indicate that WWI may be an intervention indicator to reduce the risk of CVD in the general adult population.

Effect of continuous positive pressure ventilation on left ventricular diastolic function E/A ratio in patients with obstructive sleep apnea: a meta-analysis.

PURPOSE: Many studies have shown that obstructive sleep apnea (OSA) is related to reduced left ventricular diastolic function. Continuous positive airway pressure (CPAP) is generally recognized as the preferred therapy for OSA. Yet, the effect of CPAP on left ventricular diastolic function in patients with OSA is inconclusive. In order to assess the influence of CPAP on left ventricular diastolic function in patients with OSA, we performed this meta-analysis of clinical experiments. METHODS: PubMed, Web of Science, OVID, Embase, and Cochrane Library from the establishment of the database to July 6, 2022, were searched for clinical trial data. Inclusion criteria for this meta-analysis were: (1) Patients in the experimental group were diagnosed with OSA by polysomnography; (2) CPAP treatment course ≥ 4 weeks; (3) baseline and follow-up data of the diastolic function parameter E/A ratio were reported in the literature. Exclusion criteria were: (1) Central sleep apnea (CSA); (2) comorbid organic heart diseases such as coronary heart disease; (3) age < 18 years old; (4) conference abstracts or duplicate publications. RESULTS: After exclusions, 7 studies (2 RCTs and 5 prospective studies) with 473 subjects (225 in the treatment group and 248 in the matched control group) were included in the meta-analysis. Subgroup analysis indicated that after CPAP therapy, the left ventricular (LV) E/A ratio was significantly increased in patients with OSA (weighted mean difference (WMD) = 0.22, 95% CI = - 0.06-0.38; P = 0.007). Sensitivity analyses showed that the combined results were not influenced by single studies. Publication bias was not significant (Egger's test, P = 0.813). CONCLUSIONS: The results of this meta-analysis suggest that CPAP may improve the E/A ratio in patients with OSA patients. However, the small number of studies (n = 7) decreases confidence in the findings. Thus, carefully designed randomized controlled trials are needed to confirm the findings.

Improved Self-Heating in Short-Channel Monolayer WS2 Transistors with High-Thermal Conductivity BeO Dielectrics.

Two-dimensional semiconducting transition metal dichalcogenides (TMDs) enable ultimate channel length scaling of transistor technology due to their atomic-thin body nature, which also brings the challenge of a pronounced self-heating effect inside the ultrathin channel. In particular, high current density under high electric field could lead to negative differential resistance behavior due to self-heating, not only limiting the current carrying capability of the TMDs transistors but also leading to severe reliability issues. Here, we report high-performance monolayer WS2 transistors on a high-thermal-conductivity BeO dielectric with effective suppression of the self-heating effects, eliminating the negative differential resistance behavior at high field, as observed in the case of the HfO2 dielectric. The monolayer CVD WS2 device on BeO with a 50 nm channel length exhibits a record-high on-state current of 325 µA/µm, transconductance (gm) of 150 µS/µm, and a on/off ratio of 1.8 × 108 at Vds = 1 V, far exceeding previous results.

Progress of Research on the Physiology and Molecular Regulation of Sorghum Growth under Salt Stress by Gibberellin.

Plant growth often encounters diverse abiotic stresses. As a global resource-based ecological problem, salinity is widely distributed and one of the major abiotic stresses affecting crop yields worldwide. Sorghum, a cereal crop with medium salt tolerance and great value for the development and utilization of salted soils, is an important source of food, brewing, energy, and forage production. However, in soils with high salt concentrations, sorghum experiences low emergence and suppressed metabolism. It has been demonstrated that the effects of salt stress on germination and seedling growth can be effectively mitigated to a certain extent by the exogenous amendment of hormonal gibberellin (GA). At present, most of the studies on sorghum salt tolerance at home and abroad focus on morphological and physiological levels, including the transcriptome analysis of the exogenous hormone on sorghum salt stress tolerance, the salt tolerance metabolism pathway, and the mining of key salt tolerance regulation genes. The high-throughput sequencing technology is increasingly widely used in the study of crop resistance, which is of great significance to the study of plant resistance gene excavation and mechanism. In this study, we aimed to review the effects of the exogenous hormone GA on leaf morphological traits of sorghum seedlings and further analyze the physiological response of sorghum seedling leaves and the regulation of sorghum growth and development. This review not only focuses on the role of GA but also explores the signal transduction pathways of GA and the performance of their responsive genes under salt stress, thus helping to further clarify the mechanism of regulating growth and production under salt stress. This will serve as a reference for the molecular discovery of key genes related to salt stress and the development of new sorghum varieties.

The Roles of Mepiquate Chloride and Melatonin in the Morpho-Physiological Activity of Cotton under Abiotic Stress.

Cotton growth and yield are severely affected by abiotic stress worldwide. Mepiquate chloride (MC) and melatonin (MT) enhance crop growth and yield by reducing the negative effects of abiotic stress on various crops. Numerous studies have shown the pivotal role of MC and MT in regulating agricultural growth and yield. Nevertheless, an in-depth review of the prominent performance of these two hormones in controlling plant morpho-physiological activity and yield in cotton under abiotic stress still needs to be documented. This review highlights the effects of MC and MT on cotton morpho-physiological and biochemical activities; their biosynthetic, signaling, and transduction pathways; and yield under abiotic stress. Furthermore, we also describe some genes whose expressions are affected by these hormones when cotton plants are exposed to abiotic stress. The present review demonstrates that MC and MT alleviate the negative effects of abiotic stress in cotton and increase yield by improving its morpho-physiological and biochemical activities, such as cell enlargement; net photosynthesis activity; cytokinin contents; and the expression of antioxidant enzymes such as catalase, peroxidase, and superoxide dismutase. MT delays the expression of NCED1 and NCED2 genes involved in leaf senescence by decreasing the expression of ABA-biosynthesis genes and increasing the expression of the GhYUC5, GhGA3ox2, and GhIPT2 genes involved in indole-3-acetic acid, gibberellin, and cytokinin biosynthesis. Likewise, MC promotes lateral root formation by activating GA20x genes involved in gibberellin catabolism. Overall, MC and MT improve cotton's physiological activity and antioxidant capacity and, as a result, improve the ability of the plant to resist abiotic stress. The main purpose of this review is to present an in-depth analysis of the performance of MC and MT under abiotic stress, which might help to better understand how these two hormones regulate cotton growth and productivity.

Clinical Characteristics and Outcomes of Chinese Patients with Premature Acute Coronary Syndrome.

This study aimed to investigate the clinical characteristics and major adverse cardiovascular events (MACEs) of Chinese patients with premature acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This study was a secondary retrospective analysis involving 2114 ACS patients undergoing PCI at a single center in China. The patients were divided into two groups according to age (premature ACS group: ≤ 55 years in men, ≤ 65 years in women; nonpremature ACS group: > 55 years in men, > 65 years in women). The primary endpoint was all-cause death, and the secondary endpoint was a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, target vessel revascularization, and recurrent angina at follow-up, defined as MACEs. The incidence of all-cause death and MACEs was significantly lower in the premature than in the nonpremature ACS group (P < 0.001). Female sex, higher triglyceride levels, and higher low-density lipoprotein cholesterol levels were identified as independent risk factors that accelerated the development of ACS, whereas higher high-density lipoprotein cholesterol levels were identified as protective factors. Furthermore, in patients with premature ACS, non-ST-elevation ACS, cardiac insufficiency, multivessel disease, and left main lesion were risk factors for MACEs. Younger individuals, especially females, are advised to undergo early screening for the risk factors of premature ACS. Primary prevention of dyslipidemia should be more aggressively promoted at a young age. For premature ACS patients undergoing PCI, strengthened management and regular re-examinations are necessary to avoid adverse cardiovascular events as much as possible.

Bioglass promotes wound healing by inhibiting endothelial cell pyroptosis through regulation of the connexin 43/reactive oxygen species (ROS) signaling pathway.

Bioactive glass (BG) has recently shown great promise in soft tissue repair, especially in wound healing; however, the underlying mechanism remains unclear. Pyroptosis is a novel type of programmed cell death that is involved in various traumatic injury diseases. Here, we hypothesized that BG may promote wound healing through suppression of pyroptosis. To test this scenario, we investigated the possible effect of BG on pyroptosis in wound healing both in vivo and in vitro. This study showed that BG can accelerate wound closure, granulation formation, collagen deposition, and angiogenesis. Moreover, western blot analysis and immunofluorescence staining revealed that BG inhibited the expression of pyroptosis-related proteins in vivo and in vitro. In addition, while BG regulated the expression of connexin43 (Cx43), it inhibited reactive oxygen species (ROS) production. Cx43 activation and inhibition experiments further indicate that BG inhibited pyroptosis in endothelial cells by decreasing Cx43 expression and ROS levels. Taken together, these studies suggest that BG promotes wound healing by inhibiting pyroptosis via Cx43/ROS signaling pathway.

Pyroptosis in acute pancreatitis and its therapeutic regulation.

Pyroptosis defines a new type of GSDMs-mediated programmed cell death, distinguishes from the classical concepts of apoptosis and necrosis-mediated cell death and is prescribed by cell swelling and membrane denaturation, leading to the extensive secretion of cellular components and low-grade inflammatory response. However, NLRP3 inflammasome activation can trigger its downstream inflammatory cytokines, leading to the activation of pyroptosis-regulated cell death. Current studies reveal that activation of caspase-4/5/11-driven non-canonical inflammasome signaling pathways facilitates the pathogenesis and progression of acute pancreatitis (AP). In addition, a large number of studies have reported that NLRP3 inflammasome-dependent pyroptosis is a crucial player in driving the course of the pathogenesis of AP. Excessive uncontrolled GSDMD-mediated pyroptosis has been implicated in AP. Therefore, the pyroptosis-related molecule GSDMD may be an independent prognostic biomarker for AP. The present review paper summarizes the molecular mechanisms of pyroptotic signaling pathways and their pathophysiological impacts on the progress of AP. Moreover, we briefly present some experimental compounds targeting pyroptosis-regulated cell death for exploring novel therapeutic directions for the treatment and management of AP. Our review investigations strongly suggest that targeting pyroptosis could be an ideal therapeutic approach in AP.

WDFY1, a WD40 repeat protein, is not essential for spermatogenesis and male fertility in mice.

The mouse WD repeat and FYVE domain containing 1 (Wdfy1) gene is located in chromosome 1qC4 and spans over 73.7 kilobases. It encodes a protein of 410-amino acid protein that shares 97.8% amino acid sequence identity with the human WDFY1 protein. However, the expression pattern of WDFY1 in reproductive organs and its function in male fertility remain unknown. In this study, we generated transgenic mice expressing FLAG-Wdfy1-mCherry cDNA driven by the Wdfy1 promoter to clarify the expression of WDFY1. The results showed that WDFY1 is highly expressed in mouse testes and located in the cytoplasm of late pachytene spermatocytes to elongated spermatids. Interestingly, the global Wdfy1 knockout (KO) male mice displayed normal growth, development, and fertility. Further histological analysis of Wdfy1 knockout mouse testes revealed that all spermatogenic cells are present in Wdfy1 KO seminiferous tubules. Together, our data demonstrate that WDFY1 is dispensable for mouse spermatogenesis and male fertility.

UHRF1 is indispensable for meiotic sex chromosome inactivation and interacts with the DNA damage response pathway in mice†.

During male meiosis, the constitutively unsynapsed XY chromosomes undergo meiotic sex chromosome inactivation (MSCI), and the DNA damage response (DDR) pathway is critical for MSCI establishment. Our previous study showed that UHRF1 (ubiquitin-like, with PHD and ring finger domains 1) deletion led to meiotic arrest and male infertility; however, the underlying mechanisms of UHRF1 in the regulation of meiosis remain unclear. Here, we report that UHRF1 is required for MSCI and cooperates with the DDR pathway in male meiosis. UHRF1-deficient spermatocytes display aberrant pairing and synapsis of homologous chromosomes during the pachytene stage. In addition, UHRF1 deficiency leads to aberrant recruitment of ATR and FANCD2 on the sex chromosomes and disrupts the diffusion of ATR to the XY chromatin. Furthermore, we show that UHRF1 acts as a cofactor of BRCA1 to facilitate the recruitment of DDR factors onto sex chromosomes for MSCI establishment. Accordingly, deletion of UHRF1 leads to the failure of meiotic silencing on sex chromosomes, resulting in meiotic arrest. In addition to our previous findings, the present study reveals that UHRF1 participates in MSCI, ensuring the progression of male meiosis. This suggests a multifunctional role of UHRF1 in the male germline.

Valve implantation for successful sealing of a balloon predilatation-induced annular rupture during transcatheter aortic valve replacement.

Annular rupture is a rare and dreaded complication of transcatheter aortic valve replacement (TAVR) and even rarer when caused by predilatation balloon aortic valvuloplasty. This complication often presents as sudden cardiac tamponade with hypotension and requires urgent intervention. The traditional rescue strategy for patients with annular rupture is emergency surgical repair. However, the mortality rate is still high, considering that most patients who undergo TAVR are not candidates for conventional cardiac surgery. Therefore, there is a need for additional emergency treatment strategies to decrease mortality. This report describes a case of predilatation-induced annular rupture during TAVR that was successfully sealed at the rupture site by valve implantation. This case suggests that continuing with valve deployment may be a successful treatment for predilatation-induced annular rupture during TAVR.