Achieving climate sustainability in the Republic of Congo: The role of economic growth, biomass energy consumption, rule of law and government effectiveness- a NARDL Approach.

This study explores the relationship between economic growth (GDP), biomass energy consumption (BEC), Rule of Law, and Government Effectiveness on climate change (CO2 emissions) in the Republic of Congo from 1990 to 2020. We employed a nonlinear autoregressive distributed Lag (NARDL) model to analyse data from World Bank databases. Higher GDP leads to lower CO2 emissions in the long run. Increased BEC also reduces emissions, but a decrease can have a small negative impact. Interestingly, a stronger Rule of Law and Government Effectiveness is associated with higher CO2 emissions in the short run, potentially due to relaxed environmental regulations. However, a stronger Rule of Law and Government Effectiveness leads to lower emissions in the long run, suggesting a potential shift towards sustainable practices. These findings provide valuable insights for policymakers aiming to achieve economic growth and climate stability in the Republic of Congo.

Safety and efficacy of bilateral superselective adrenal arterial embolization for treatment of idiopathic hyperaldosteronism: a prospective single-center study.

OBJECTIVE: This study aimed to assess the efficacy and safety of bilateral superselective adrenal arterial embolization (SAAE) in patients with bilateral idiopathic hyperaldosteronism (IHA), a subtype of PA. METHODS: Ninety-eight patients with bilateral IHA underwent bilateral SAAE between August 2022 and August 2023. Sixty-eight patients were followed up for up to 12 months. The study outcomes were evaluated using the criteria provided by the Primary Aldosteronism Surgical Outcome (PASO) guidelines. RESULTS: The mean reductions in systolic and diastolic blood pressure were 27.4 ± 21.3 mmHg and 23.1 ± 17.4 mmHg, respectively (p < 0.001). The rates of clinical success and biochemical success after adrenal artery ablation were 63.2% (43/68) and 39.7% (27/68), respectively. Overall, there were significant reductions in daily defined doses (DDD), aldosterone/renin ratio (ARR), and plasma aldosterone levels (p < 0.001). Plasma renin levels increased by a mean value of 10.4 ± 39.0 pg/mL (p = 0.049), and potassium levels increased by 0.40 ± 0.63 mmol/L (p < 0.001). No significant adverse events were reported during SAAE or the follow-up period of up to one year. Additionally, no abnormalities were detected by adrenal 68Ga-Pentixafor PET/CT scans before or after SAAE. CONCLUSION: Bilateral SAAE appears to lead to sustained improvements in blood pressure and biochemical parameters in patients with bilateral PA, with minimal adverse effects. This suggests that bilateral SAAE could serve as an effective alternative approach for treating bilateral IHA, potentially curing this condition.

Local Excitation of Kagome Spin Ice Magnetism Seen by Scanning Tunneling Microscopy.

The kagome spin ice can host frustrated magnetic excitations by flipping its local spin. Under an inelastic tunneling condition, the tip in a scanning tunneling microscope can flip the local spin, and we apply this technique to kagome metal HoAgGe with a long-range ordered spin ice ground state. Away from defects, we discover a pair of pronounced dips in the local tunneling spectrum at symmetrical bias voltages with negative intensity values, serving as a striking inelastic tunneling signal. This signal disappears above the spin ice formation temperature and has a dependence on the magnetic fields, demonstrating its intimate relation with the spin ice magnetism. We provide a two-level spin-flip model to explain the tunneling dips considering the spin ice magnetism under spin-orbit coupling. Our results uncover a local emergent excitation of spin ice magnetism in a kagome metal, suggesting that local electrical field induced spin flip climbs over a barrier caused by spin-orbital locking.

Ribosomal modification protein rimK-like family member A activates betaine-homocysteine S-methyltransferase 1 to ameliorate hepatic steatosis.

Nonalcoholic fatty liver disease (NAFLD) is a serious threat to public health, but its underlying mechanism remains poorly understood. In screening important genes using Gene Importance Calculator (GIC) we developed previously, ribosomal modification protein rimK-like family member A (RIMKLA) was predicted as one essential gene but its functions remained largely unknown. The current study determined the roles of RIMKLA in regulating glucose and lipid metabolism. RIMKLA expression was reduced in livers of human and mouse with NAFLD. Hepatic RIMKLA overexpression ameliorated steatosis and hyperglycemia in obese mice. Hepatocyte-specific RIMKLA knockout aggravated high-fat diet (HFD)-induced dysregulated glucose/lipid metabolism in mice. Mechanistically, RIMKLA is a new protein kinase that phosphorylates betaine-homocysteine S-methyltransferase 1 (BHMT1) at threonine 45 (Thr45) site. Upon phosphorylation at Thr45 and activation, BHMT1 eliminated homocysteine (Hcy) to inhibit the activity of transcription factor activator protein 1 (AP1) and its induction on fatty acid synthase (FASn) and cluster of differentiation 36 (CD36) gene transcriptions, concurrently repressing lipid synthesis and uptake in hepatocytes. Thr45 to alanine (T45A) mutation inactivated BHMT1 to abolish RIMKLA's repression on Hcy level, AP1 activity, FASn/CD36 expressions, and lipid deposition. BHMT1 overexpression rescued the dysregulated lipid metabolism in RIMKLA-deficient hepatocytes. In summary, RIMKLA is a novel protein kinase that phosphorylates BHMT1 at Thr45 to repress lipid synthesis and uptake. Under obese condition, inhibition of RIMKLA impairs BHMT1 activity to promote hepatic lipid deposition.

Exploring the impact of women-specific reproductive factors on phenotypic aging and the role of life's essential 8.

BACKGROUND: Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear. METHODS: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015-2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life's Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values. RESULTS: In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause. CONCLUSION: Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.

How the root bacterial community of Ficus tikoua responds to nematode infection: enrichments of nitrogen-fixing and nematode-antagonistic bacteria in the parasitized organs.

Plant-parasitic nematodes (PPNs) are among the most damaging pathogens to host plants. Plants can modulate their associated bacteria to cope with nematode infections. The tritrophic plant-nematode-microbe interactions are highly taxa-dependent, resulting in the effectiveness of nematode agents being variable among different host plants. Ficus tikoua is a versatile plant with high application potential for fruits or medicines. In recent years, a few farmers have attempted to cultivate this species in Sichuan, China, where parasitic nematodes are present. We used 16S rRNA genes to explore the effects of nematode parasitism on root-associated bacteria in this species. Our results revealed that nematode infection had effects on both endophytic bacterial communities and rhizosphere communities in F. tikoua roots, but on different levels. The species richness increased in the rhizosphere bacterial communities of infected individuals, but the community composition remained similar as compared with that of healthy individuals. Nematode infection induces a deterministic assembly process in the endophytic bacterial communities of parasitized organs. Significant taxonomic and functional changes were observed in the endophytic communities of root knots. These changes were characterized by the enrichment of nitrogen-fixing bacteria, including Bradyrhizobium, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, and nematode-antagonistic bacteria, such as Pseudonocardia, Pseudomonas, Steroidobacter, Rhizobacter, and Ferrovibrio. Our results would help the understanding of the tritrophic plant-nematode-bacterium interactions in host plants other than dominant crops and vegetables and would provide essential information for successful nematode management when F. tikoua were cultivated on large scales.

Release dynamics, risk evolution and driving mechanisms of heavy metals in superalkaline fly ash co-disposed by MSW landfill.

Fly ash from waste incineration is growing rapidly and has become a global problem. Landfill is the main treatment method, but the release behavior of ultra-alkaline fly ash needs further study. In this study, the release pattern of heavy metals from fly ash, the long-term risk after seepage, and the main control mechanisms were explored by indoor simulation experiments and process simulation modeling. The results show that carbonation is the main control mechanism for the release rate of heavy metals from super-alkaline fly ash, and the release rate is slow at the initial stage, but the release concentration of Zn and Pb may increase tens of times with the continuous reaction between the acidic substances in the leachate and the alkaline substances in the fly ash. The heavy metals released into the leachate can cause the concentration of Zn, Cd and Pb in the groundwater to exceed the standard by 39.50, 6.70 and 5.99 times due to seepage. Furnace type is the key controlling factor for background concentrations of heavy metals in ultra-alkaline fly ash, and the exposure concentrations of Cu, Cd, Zn, and Pb in ultra-alkaline fly ash from grate furnaces as well as the GT1 facility are 4.19, 4.19, 4.14, and 37.5 times greater than those of fluidized beds, respectively, with a higher risk of long-term landfill. Regionally, the regional occupancy rate of heavy metal concentrations indicated that the risk of adequate rainfall was high in the southeastern coastal region, which was five times higher than that in the inland northwest. Therefore, the long-term dynamics and risk evolution of Zn, Cd, and Pb in the groundwater around MSWLs in the coastal area should be paid attention to after the landfilling of ultra-alkaline fly ash in order to ensure the safety of the shallow groundwater environment after landfilling.

PANX1-mediated ATP release confers FAM3A's suppression effects on hepatic gluconeogenesis and lipogenesis.

BACKGROUND: Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with sequence similarity 3 member A (FAM3A) in controlling hepatic glucolipid metabolism, islet ß cell function, adipocyte differentiation, blood pressure, and other biological and pathophysiological processes. Although mitochondrial protein FAM3A plays crucial roles in the regulation of glucolipid metabolism via stimulating ATP release to activate P2 receptor pathways, its mechanism in promoting ATP release in hepatocytes remains unrevealed. METHODS: db/db, high-fat diet (HFD)-fed, and global pannexin 1 (PANX1) knockout mice, as well as liver sections of individuals, were used in this study. Adenoviruses and adeno-associated viruses were utilized for in vivo gene overexpression or inhibition. To evaluate the metabolic status in mice, oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT), insulin tolerance test (ITT), and magnetic resonance imaging (MRI) were conducted. Protein-protein interactions were determined by coimmunoprecipitation with mass spectrometry (MS) assays. RESULTS: In livers of individuals and mice with steatosis, the expression of ATP-permeable channel PANX1 was increased (P < 0.01). Hepatic PANX1 overexpression ameliorated the dysregulated glucolipid metabolism in obese mice. Mice with hepatic PANX1 knockdown or global PANX1 knockout exhibited disturbed glucolipid metabolism. Restoration of hepatic PANX1 rescued the metabolic disorders of PANX1-deficient mice (P < 0.05). Mechanistically, ATP release is mediated by the PANX1-activated protein kinase B-forkhead box protein O1 (Akt-FOXO1) pathway to inhibit gluconeogenesis via P2Y receptors in hepatocytes. PANX1-mediated ATP release also activated calmodulin (CaM) (P < 0.01), which interacted with c-Jun N-terminal kinase (JNK) to inhibit its activity, thereby deactivating the transcription factor activator protein-1 (AP1) and repressing fatty acid synthase (FAS) expression and lipid synthesis (P < 0.05). FAM3A stimulated the expression of PANX1 via heat shock factor 1 (HSF1) in hepatocytes (P < 0.05). Notably, FAM3A overexpression failed to promote ATP release, inhibit the expression of gluconeogenic and lipogenic genes, and suppress gluconeogenesis and lipid deposition in PANX1-deficient hepatocytes and livers. CONCLUSIONS: PANX1-mediated release of ATP plays a crucial role in maintaining hepatic glucolipid homeostasis, and it confers FAM3A's suppressive effects on hepatic gluconeogenesis and lipogenesis.

[Mechanism of Kuntai Capsules in treatment of polycystic ovary syndrome rat models based on AGE-RAGE signal pathway].

This study aims to investigate the impact of Kuntai Capsules(KTC) on polycystic ovarian syndrome(PCOS) rat models and explore the underlying mechanism. Fifty female SD rats were randomly divided into five groups(10 rats in each group), including control group, model group, low-, medium-, and high-dose KTC group. Except for the control group, the other groups were injected with dehydroepiandrosterone(DHEA) combined with a high-fat diet(HFD) to induce the PCOS rat model for 28 days. 0.315, 0.63, and 1.26 g·kg~(-1)·d~(-1) KTC was dissolved in the same amount of normal saline and given to low-, medium-, and high-dose KTC groups by gavage. Both control group and model group were given the same amount of normal saline for 15 days. After administration, fasting blood glucose(FBG) was measured by a glucose meter. Fasting insulin(FINS), luteinizing hormone(LH), testosterone(T), and follicle-stimulating hormone(FSH) were detected by enzyme-linked immunosorbent assay(ELISA), and LH/FSH ratio and insulin resistance index(HOMA-IR) were calculated. The pathological morphology of ovarian tissue was observed by hematoxylin-eosin(HE) staining. The expression levels of collagen α type Ⅲ 1 chain(COL3A1), apoptotic factors Bax, and Bcl-2 were detected using Western blot and immunofluorescence. The mRNA expressions of COL3A1, Bax, and Bcl-2 in ovarian tissue were performed by real-time PCR(RT-PCR). The results show that compared with the control group, the body weight, serum levels of FBG, FINS, LH, T, LH/FSH, and HOMA-IR are higher in model group(P<0.05 or P<0.01), and the level of FSH is lower(P<0.05). In model group, a large number of white blood cells are found in the vaginal exfoliated cells, mainly in the interictal phase. There are more cystic prominences on the surface of the ovary. The thickness of the granular cell layer is reduced, and oocytes are absent. COL3A1 and Bax protein expression levels are increased(P<0.01), while Bcl-2 protein expression levels are decreased(P<0.05) in the ovarian tissue COL3A1 and Bax mRNA expression levels are increased in ovarian tissue(P<0.05). Compared with the model group, the body weight, FBG, FINS, LH, T, LH/FSH, and HOMA-IR in low-, medium-, and high-dose KTC groups are decreased(P<0.05 or P<0.01), while the levels of FSH in medium-, and high-dose KTC groups are increased(P<0.05 or P<0.01). Low-, medium-, and high-dose KTC groups gradually show a stable interictal phase. The surface of the ovary is smooth. Oocytes and mature follicles can be seen in ovarian tissue, and the thickness of the granular cell layer is increased. The expression level of COL3A1 protein decreases in low-and medium-dose KTC groups(P<0.05 or P<0.01), and that of Bax protein decreases in low-dose KTC group(P<0.05 or P<0.01), and the expression level of Bcl-2 protein increases in low-dose KTC group(P<0.01). The expression levels of COL3A1 and Bax mRNA decreased in the low-dose KTC group(P<0.05), while the expression levels of Bcl-2 mRNA increased(P<0.05). In summary, KTC can inhibit ovarian granulosa cell apoptosis and reduce follicular atresia by regulating the AGE-RAGE signaling pathway. It can promote insulin secretion, reduce blood sugar and body weight, restore serum hormone levels, improve symptoms of PCOS, alleviate morphological damage of the ovary, and restore ovarian function, which is of great value in the treatment of PCOS.

Release potential, neglected leakage and reduction countermeasures of COD and Ammonia in MSWLs.

In order to eliminate the impact of the industrial revolution on the environment and improve the water ecological environment, pollutant discharge reduction is imperative. With the acceleration of global discharge reduction process, the huge pollutant release potential and potential environmental effects of municipal solid waste landfills gradually appear, but its release amount and intensity have not been quantitatively revealed. We propose a coupling method of parameter stochastic simulation and physical process model simulation to estimate the hidden leakage of large-scale regional municipal solid waste landfills, and provide a methodology for estimating the hidden leakage of landfills in other countries and even in the whole world by taking China, which has the largest amount of waste generation among developing countries, as an example. Prior to the implementation of stringent construction quality control and assurance management requirements, the average annual leachate generation potential over the entire life cycle of 2600 landfills in China was estimated to be 4.66 × 108 m3, in which the concentrations of COD and NH3-N are 5.38 × 102-6.48 × 104 mg/L and 6.10-3.50 × 103 mg/L, respectively, and the total amounts are 5.21 × 103-7.81 × 108 t and 8.09 × 102-6.65 × 107 t, respectively. About 14 % of these pollutants may leak into the environmental media through the landfill liner with the average number of holes of 21.5/ha. For different regions, the overall release, discharge and leakage of COD and NH3-N in East China account for 35.70 %, 36.68 % and 29.60 % respectively, making it the region with the highest potential for discharge and risk of leakage. Meanwhile, the implementation of mandatory regulations related to leachate generation and control has led to a significant reduction in the leakage of pollutants. For instance, comprehensively detecting and repair of holes in the impermeable liner has reduced the number of holes to 2/ha, resulting in a reduction of >90 % in the leakage of pollutants.

Multistimuli-Responsive Shape-Memory Composites with a Water-Assisted Self-Healing Function Based on Sodium Carboxymethyl Cellulose/Poly(vinyl alcohol)/MXene.

Recent advancements in artificial intelligence have propelled the development of shape-memory polymers (SMPs) with sophisticated, environment-sensitive capabilities. Despite the progress, most of the existing SMPs are limited to responding to a single stimulus and show poor functionality, which has severely hindered their future applications. Herein, we report a high-performance multistimuli-responsive shape-memory and self-healing composite film fabricated by embedding MXene nanosheets into a conventional shape-memory sodium carboxymethyl cellulose (CMC) and poly(vinyl alcohol) (PVA) matrix. The incorporation of photothermal MXene nanosheets not only enhances the composite films' mechanical strength but also provides efficient solar-thermal conversion and robust light-actuated shape-memory properties. The resultant composite films exhibit an exceptional shape-memory response to various stimuli including heat, light, and water. Meanwhile, the interfacial interactions can be modulated by adjusting the MXene content, thereby enabling precise manipulation of the shape-memory performance. Moreover, thanks to the intrinsic hydrophilicity of the components and the unique physically cross-linked network, the composite films also demonstrate an effective water-assisted self-healing capability with an impressive healing efficiency of 85.7%. This work offers insights into the development of multifunctional, multistimuli-responsive shape-memory composites, opening up new possibilities for future applications in smart technologies.

A Novel Multi-compartment Rotating Bioreactor for Improving ADSC--Spheroid Formation and its Application in Neurogenic Erectile Dysfunction.

OBJECTIVE: The aim of this study was to construct a multicompartment synchronous rotating bioreactor (MCSRB) for batch-production of homogenized adipose-derived stem cell (ADSC) microspheres and treat neurogenic erectile dysfunction (ED). METHODS: Firstly, an MCSRB was constructed using a centrifugal device and hinged trays. Secondly, influence factors (density, rotational speed) on the formation of ADSC-spheroids were explored. Finally, a neurogenic ED model was established to verify the effectiveness and safety of ADSC-spheroids for ED treatment. RESULTS: An MCSRB promoted ADSCs to gather microspheres, most of which were 90-130 µm in diameter. Supernatant from three-dimensional culture led to a significant increase in cytokine expression in ADSCs and migration rate in human umbilical vein endothelial cells (HUVECs) compared to control groups. The erectile function and pathological changes of the penis were improved in the ADSC-spheroids treatment group compared to the traditional ADSCs treatment group (p < 0.01). CONCLUSION: Efficient, batch, controlled and homogenized production of ADSC stem cell microspheres, and effective improvement of erectile dysfunction in neurogenic rats can be achieved using the MCSRB device.

Observation of plaid-like spin splitting in a noncoplanar antiferromagnet.

Spatial, momentum and energy separation of electronic spins in condensed-matter systems guides the development of new devices in which spin-polarized current is generated and manipulated1-3. Recent attention on a set of previously overlooked symmetry operations in magnetic materials4 leads to the emergence of a new type of spin splitting, enabling giant and momentum-dependent spin polarization of energy bands on selected antiferromagnets5-10. Despite the ever-growing theoretical predictions, the direct spectroscopic proof of such spin splitting is still lacking. Here we provide solid spectroscopic and computational evidence for the existence of such materials. In the noncoplanar antiferromagnet manganese ditelluride (MnTe2), the in-plane components of spin are found to be antisymmetric about the high-symmetry planes of the Brillouin zone, comprising a plaid-like spin texture in the antiferromagnetic (AFM) ground state. Such an unconventional spin pattern, further found to diminish at the high-temperature paramagnetic state, originates from the intrinsic AFM order instead of spin-orbit coupling (SOC). Our finding demonstrates a new type of quadratic spin texture induced by time-reversal breaking, placing AFM spintronics on a firm basis and paving the way for studying exotic quantum phenomena in related materials.

Thiyl Radical Trapped by Cobalt Catalysis: An Approach to Markovnikov Thiol-Ene Reaction.

In the presence of a thiyl radical species, the catalytic Markovnikov thiol-ene reaction is challenging because it prefers to proceed via a radical pathway, thereby leading to anti-Markovnikov selectivity. In this work, a rare example of thiyl radical engaged in Markovnikov thiol-ene reaction enabled by cobalt catalysis is reported. This protocol features the avoidance of unique oxidants, exclusive regioselectivity, and broad substrate scope. Scalable synthesis and late-stage modification of complex molecules demonstrate the practicability of the protocol.

FAM3A Deficiency - Induced Mitochondrial Dysfunction Underlies Post-Infarct Mortality and Heart Failure.

Mitochondrial protein sequence similarity 3 gene family member A (FAM3A) plays important roles in the electron transfer chain, while its functions in the heart are still unknown. This study aims to explore the roles and mechanisms of FAM3A after myocardial infarction (MI). FAM3A-deficient (Fam3a-/-) mice were implemented with MI injury and showed lower survival rates at 4 weeks as well as decreased cardiac systolic function. Isolated cardiomyocytes of Fam3a-/- mice showed reduced basal, ATP-linked respiration and respiratory reserve compared to that of wild-type mice. Transmission electron microscopy studies showed Fam3a-/- mice had a larger size and elevated density of mitochondria. FAM3A deficiency also induced elevated mitochondrial Ca2+, higher opening level of mPTP, lower mitochondrial membrane potential and elevated apoptotic rates. Further analyses demonstrated that mitochondrial dynamics protein Opa1 contributed to the effects of FAM3A in cardiomyocytes. Our study discloses the important roles of mitochondrial protein FAM3A in the heart.

Metabolic improvements of novel microbial fermentation on black tea by Eurotium cristatum.

Due to its traditional fermentation, there are obvious limits on the quality improvements in black tea. However, microbial fermentation can provide an abundance of metabolites and improve the flavor of tea. The "golden flower" fungi are widely used in the microbial fermentation of tea and has unique uses in healthcare. To further explore the improvements in black tea quality achieved via microbial fermentation, we used widely targeted metabolomics and metagenomics analyses to investigate the changes in and effects of metabolites and other microorganisms during the interaction between the "golden flower" fungi and black tea. Five key flavor metabolites were detected, the levels of catechin, epigallocatechin gallate, (-)-epicatechin gallate were decreased by different degrees after the inoculation of the "golden flower" fungus, whereas the levels of caffeine and (+)-gallocatechin increased. Botryosphaeriaceae, Botryosphaeriales, Dothideomycetes, Aspergillaceae, Trichocomaceae, and Lecanoromycetes play a positive role in the black tea fermentation process after inoculation with the "golden flower" fungi. D-Ribose can prevent hypoxia-induced apoptosis in cardiac cells, and it shows a strong correlation with Botryosphaeriaceae and Botryosphaeriales. The interaction between microorganisms and metabolites is manifested in tryptophan metabolism, starch and sucrose metabolism, and amino sugar and nucleotide sugar metabolism. In conclusion, the changes in metabolites observed during the fermentation of black tea by "golden flower" fungi are beneficial to human health. This conclusion extends the knowledge of the interaction between the "golden flower" fungi and black tea, and it provides important information for improving the quality of black tea.

BTSC-TNAS: A neural architecture search-based transformer for brain tumor segmentation and classification.

Glioblastoma (GBM), isolated brain metastasis (SBM), and primary central nervous system lymphoma (PCNSL) possess a high level of similarity in histomorphology and clinical manifestations on multimodal MRI. Such similarities have led to challenges in the clinical diagnosis of these three malignant tumors. However, many existing models solely focus on either the task of segmentation or classification, which limits the application of computer-aided diagnosis in clinical diagnosis and treatment. To solve this problem, we propose a multi-task learning transformer with neural architecture search (NAS) for brain tumor segmentation and classification (BTSC-TNAS). In the segmentation stage, we use a nested transformer U-shape network (NTU-NAS) with NAS to directly predict brain tumor masks from multi-modal MRI images. In the tumor classification stage, we use the multiscale features obtained from the encoder of NTU-NAS as the input features of the classification network (MSC-NET), which are integrated and corrected by the classification feature correction enhancement (CFCE) block to improve the accuracy of classification. The proposed BTSC-TNAS achieves an average Dice coefficient of 80.86% and 87.12% for the segmentation of tumor region and the maximum abnormal region in clinical data respectively. The model achieves a classification accuracy of 0.941. The experiments performed on the BraTS 2019 dataset show that the proposed BTSC-TNAS has excellent generalizability and can provide support for some challenging tasks in the diagnosis and treatment of brain tumors.

Uric acid and evaluate the coronary vascular stenosis gensini score correlation research and in gender differences.

BACKGROUND AND AIMS: Recent studies have shown that the negative effect of uric acid (UA) on coronary arteries determines the severity of atherosclerotic disease. This study aims to explore the relationship between serum UA level and Gensini score, which reflects the severity of coronary artery disease. METHODS: A total of 860 patients with suspected coronary heart disease who were admitted to hospital due to angina pectoris or myocardial ischemia related symptoms and received coronary angiography were selected. Based on the findings of the angiography, they were categorized into two groups: the coronary heart disease (CHD) group (n = 625) and the control group (n = 235). The uric acid levels and other clinical data were compared between these groups. Additionally, the prevalence of coronary heart disease and Gensini score were compared between the groups, considering gender-specific quartiles of uric acid levels. The clinical baseline data were analyzed using appropriate statistical methods, and multivariate logistic regression analysis was conducted to identify independent risk factors for coronary heart disease. RESULTS: Of 860 patients (mean age, 63.97 ± 11.87 years), 528 were men (mean age, 62.06 ± 11.5 years) and 332 were women (mean age, 66.99 ± 10.11 years). The proportion of smoking, diabetes, hypertension, and hyperlipidemia in the coronary heart disease group was higher than that in the control group (P < 0.05). HbA1C, Gensini score, BMI, TG and hsCRP in the coronary heart disease group were higher than those in the control group (P < 0.05), and HDL-C was lower than that in the control group (P < 0.05). There were no significant differences in age, heart rate, Cr, TC and LDL-C between the two groups (P > 0.05).Multivariate logistic regression analysis showed that age, hypertension, hsCRP and SUA levels increased the risk of coronary heart disease, and the difference was statistically significant(OR = 1.034,95%CI 1.016-1.052, P = 0.001; OR = 1.469,95%CI 1.007-2.142, P = 0.046;OR = 1.064,95%CI 1.026-1.105, P = 0.001; OR = 1.011,95%CI 1.008-1.014, P < 0.001). CONCLUSION: Serum uric acid is positively correlated with Gensini score in patients with coronary heart disease, which is an independent factor for evaluating the degree of coronary artery stenosis and has a predictive effect.

Mendelian randomization studies of depression: evidence, opportunities, and challenges.

BACKGROUND: Major depressive disorder (MDD) poses a significant social and economic burden worldwide. Identifying exposures, risk factors, and biological mechanisms that are causally connected to MDD can help build a scientific basis for disease prevention and development of novel therapeutic approaches. METHODS: In this systematic review, we assessed the evidence for causal relationships between putative causal risk factors and MDD from Mendelian randomization (MR) studies, following PRISMA. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions. RESULTS: We included methodological details and results from 52 articles. A causal link between lifestyle, metabolic, inflammatory biomarkers, particular pathological states and MDD is supported by MR investigations, although results for each category varied substantially. CONCLUSIONS: While this review shows how MR can offer useful information for examining prospective treatment targets and better understanding the pathophysiology of MDD, some methodological flaws in the existing literature limit reliability of results and probably underlie their heterogeneity. We highlight perspectives and recommendations for future works on MR in psychiatry.

A first-in-human phase 1 study of simnotrelvir, a 3CL-like protease inhibitor for treatment of COVID-19, in healthy adult subjects.

Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence of adverse events (AEs) was 22.2% (17/72) and 6.3% (1/16) in intervention and placebo groups, respectively. The simnotrelvir apparent clearance was 135-369 L/h with simnotrelvir alone, and decreased significantly to 19.5-29.8 L/h with simnotrelvir/ritonavir. The simnotrelvir exposure increased in an approximately dose-proportional manner between 250 and 750 mg when co-administered with ritonavir. After consecutive twice daily dosing of simnotrelvir/ritonavir, simnotrelvir had a low accumulation index ranging from 1.39 to 1.51. The area under the curve of simnotrelvir increased 44.0 % and 47.3 % respectively, after high fat and normal diet compared with fasted status. In conclusion, simnotrelvir has adequate safety and tolerability. Its pharmacokinetics indicated a trough concentration above the level required for 90 % inhibition of SARS-CoV-2 in vitro at 750 mg/100 mg simnotrelvir/ritonavir twice daily under fasted condition, supporting further development using this dosage as the clinically recommended dose regimen.