Fe-single-atom catalysts boosting electrochemiluminescence via bipolar electrode integrated with its peroxidase-like activity for bioanalysis.

Multifunctional single-atom catalysts (SACs) have been extensively investigated as outstanding signal amplifiers in bioanalysis field. Herein, a type of Fe single-atom catalysts with Fe-nitrogen coordination sites in nitrogen-doped carbon (Fe-N/C SACs) was synthesized and demonstrated to possess both catalase and peroxidase-like activity. Utilizing Fe-N/C SACs as dual signal amplifier, an efficient bipolar electrode (BPE)-based electrochemiluminescence (ECL) immunoassay was presented for determination of prostate-specific antigen (PSA). The cathode pole of the BPE-ECL platform modified with Fe-N/C SACs is served as the sensing side and luminol at the anode as signal output side. Fe-N/C SACs could catalyze decomposition of H2O2 via their high catalase-like activity and then increase the Faraday current, which can boost the ECL of luminol due to the electroneutrality in a closed BPE system. Meanwhile, in the presence of the target, glucose oxidase (GOx)-Au NPs-Ab2 was introduced through specific immunoreaction, which catalyzes the formation of H2O2. Subsequently, Fe-N/C SACs with peroxidase-like activity catalyze the reaction of H2O2 and 4-chloro-1-naphthol (4-CN) to generate insoluble precipitates, which hinders electron transfer and then inhibits the ECL at the anode. Thus, dual signal amplification of Fe-N/C SACs was achieved by increasing the initial ECL and inhibiting the ECL in the presence of target. The assay exhibits sensitive detection of PSA linearly from 1.0 pg/mL to 100 ng/mL with a detection limit of 0.62 pg/mL. The work demonstrated a new ECL enhancement strategy of SACs via BPE system and expands the application of SACs in bioanalysis field.

Progress of the acyl-Coenzyme A thioester hydrolase family in cancer.

In recent years, the acyl-Coenzyme A thioester hydrolase family (ACOTs) has received wide attention as a key link in lipid metabolism. This family is a class of enzymes that catalyze the hydrolysis of fatty acyl-Coenzyme A, disrupting the thioester bond present within acyl-CoA ester molecules to produce free fatty acids (FFA) and the corresponding coenzyme A (CoA). Such enzymes play a very important role in lipid metabolism through maintaining appropriate levels of intracellular FFA and fatty acyl-CoA as well as CoA. It is broadly divided into two distinct subgroups, the type-I α/ß-hydrolase fold enzyme superfamily and the type-II 'hot dog' fold superfamily. There are currently four human type-I genes and eight human type-II genes. Although the two subgroups catalyze the same reaction, they are not structurally similar, do not share the same sequence homology, and differ greatly in protein executive functions. This review summarizes the classification of the acyl-CoA thioester hydrolase family, an overview of the structural sequences, and advances in digestive, respiratory, and urinary systemic tumors. In order to explore potential specific drug targets and effective interventions, to provide new strategies for tumor prevention and treatment.

Discovery of an Ortho-Substituted N-Cyclopropylmethyl-7α-phenyl-6,14-endoethano-tetrahydronorthebaine Derivative as a Selective and Potent Kappa Opioid Receptor Agonist with Subsided Sedative Effect.

Research into kappa opioid receptor (KOR) agonists with attenuated central-nervous-system side effects is a critical focus for developing productive and safe analgesics. Herein, a series of ortho-substituted N-cyclopropylmethyl-7α-phenyl-6,14-endoethano-tetrahydronorthebaines were designed, synthesized, and subjected to bioassays. Compound 7a exhibited high subtype selectivity and potent agonistic activity toward KOR (KOR, Ki = 3.9 nM, MOR/KOR = 270, DOR/KOR = 1075; [35S]GTPγS binding, EC50 = 3.4 nM). Additionally, this compound exhibited robust and persistent antinociceptive effects in rodent models with different animal strains (hot plate test, ED50 = 0.20-0.30 mg/kg, i.p.; abdominal constriction test, ED50 = 0.20-0.60 mg/kg, i.p.), with its KOR-mediated mechanism for antinociception firmly established. Notably, compound 7a, unlike conventional KOR agonists, displayed minimal sedation and aversion at the antinociceptive ED50 dose. This feature addresses a crucial limitation in existing KOR agonists, positioning compound 7a as a promising novel therapeutic agent.

Light-harvesting iridium (III) complex-sensitized NiO photocathode for photoelectrochemical bioanalysis.

A novel iridium (III) complex bearing boron dipyrromethene (Bodipy) as the light-harvesting antenna has been synthesized and is firstly employed as photosensitizer to assemble a dye-sensitized NiO photocathode. The assembled photocathode exhibits significantly improved photoelectrochemical (PEC) performance. Integrating the prepared photocathode with hybridization chain reaction (HCR)--based signal amplification strategy, a cathodic PEC biosensor is proposed for the detection of microRNA-133a (miRNA-133a). In the presence of the target, HCR is triggered to form long duplex concatamers on the photocathode, which allows numerous manganese porphyrins (MnPP) to bind in the dsDNA groove. With the help of H2O2, MnPP with peroxidase-like activity catalyzes 4--chloro-1-naphthol (4-CN) to produce benzo--4--chlorohexadienone (4-CD) precipitate on the electrode, leading to a significant decrease of photocurrent signal. The decreased photocurrent correlates linearly with the target concentration from 0.1 fM to 1 nM with a detection limit of 66.2 aM (S/N = 3). The proposed PEC strategy exhibits delightful selectivity, reproducibility and stability.

Constructing WS2/WO3-x heterostructured electrocatalyst enriched with oxygen vacancies for accelerated hydrogen evolution reaction.

H2 produced through hydrogen evolution reaction (HER) is a shining star in the field of clean energy. Significant efforts have been dedicated to develop efficient and stable electrocatalysts to reduce the energy barrier and accelerate the kinetics of Hydrogen evolution reaction (HER) under various environments. Herein, we propose a strategy to accelerate the kinetics of HER under acid and alkaline environments by combining heterostructure engineering with defect engineering. We have successfully synthesized a series of WS2/WO3-x heterostructured catalysts, accompanied with substantial oxygen vacancies using a two-step synthesis method. With the partially sulfurization of WO3-x, the heterojunction interface of WS2 and WO3-x was formed along with the appearance of oxygen vacancies, which can facilitate the migration of electrons. The heterostructured catalyst enriched with oxygen vacancies (defined as WS2/WO3-x-2) demonstrates superior HER performance in acidic and alkaline electrolytes. At a current density of 10 mA cm-2, the WS2/WO3-x-2 heterostructured catalyst manifests an overpotential of 120 mV in the acidic electrolytes and a slightly higher overpotential of 150 mV in an alkaline environment. The overpotentials offer an improvement compared to reported W-based catalysts in terms of HER performance. This work provides guiding significance on the design of heterostructured catalysts with promising performance for HER in acidic and alkaline environments.

Metabolic perturbation of Streptomyces albulus by introducing NADP-dependent glyceraldehyde 3-phosphate dehydrogenase.

The available resources of Streptomyces represent a valuable repository of bioactive natural products that warrant exploration. Streptomyces albulus is primarily utilized in the industrial synthesis of ε-poly-L-lysine (ε-PL). In this study, the NADP-dependent glyceraldehyde 3-phosphate dehydrogenase (GapN) from Streptococcus mutans was heterologously expressed in S. albulus CICC11022, leading to elevated intracellular NADPH levels and reduced NADH and ATP concentrations. The resulting perturbation of S. albulus metabolism was comprehensively analyzed using transcriptomic and metabolomic methodologies. A decrease in production of ε-PL was observed. The expression of gapN significantly impacted on 23 gene clusters responsible for the biosynthesis of secondary metabolites. A comprehensive analysis revealed a total of 21 metabolites exhibiting elevated levels both intracellularly and extracellularly in the gapN expressing strain compared to those in the control strain. These findings underscore the potential of S. albulus to generate diverse bioactive natural products, thus offering valuable insights for the utilization of known Streptomyces resources through genetic manipulation.

Study of ischemic progression in different intestinal tissue layers during acute intestinal ischemia using swept-source optical coherence tomography angiography.

In acute intestinal ischemia, the progression of ischemia varies across different layers of intestinal tissue. We established a mouse model and used swept-source optical coherence tomography (OCT) to observe the intestinal ischemic process longitudinally in different tissue layers. Employing a method that combines asymmetric gradient filtering with adaptive weighting, we eliminated the vessel trailing phenomenon in OCT angiograms, reducing the confounding effects of superficial vessels on the imaging of deeper vasculature. We quantitatively assessed changes in vascular perfusion density (VPD), vessel length, and vessel average diameter across various intestinal layers. Our results showed a significant reduction in VPD in all layers during ischemia. The mucosa layer experienced the most significant impact, primarily due to disrupted capillary blood flow, followed by the submucosa layer, where vascular constriction or decreased velocity was the primary factor.

Effect of composite organic amendment on Cd(II) ions stabilization and microbial activity under various ammonium sulfate levels.

To attenuate the risk of Cadmium(Cd) contamination and the deterioration of soil quality caused by excessive nitrogen fertilizer application in greenhouse, a composite organic amendment (spend mushroom substrate and its biochar) was prepared to remedy Cd(II) ions contaminated soil (0.6 mg/kg) under different N fertilizer levels. The results showed that in the absence of a composite organic amendment, the soil pH decreased by 0.15 when the N level increased from 0.1 to 0.8 g N⋅kg-1. However, the pH increased by 0.86-0.91, the exchangeable Cd(II) ions content decreased by 26.0%-26.7%, the microbial biomass increased by 34.34%-164.46%, and the number of copies of the AOB gene increased by 13-20 times with the application of composite organic amendment and the increase of N level. Both Pearson correlation analysis and Mantel test demonstrated the reduction in Cd(II) ions availability, the restoration of soil properties and the increase in microbial biomass all contributed to the composite organic amendment, which is of importance for soil remediation under excessive N fertilizer.

Psychometric evaluation of the Chinese version of the breast cancer perception scale for community women: a translation and validation study.

BACKGROUND: Breast cancer perception is closely associated with the incidence of breast cancer among community-dwelling women. Consequently, it is crucial to enhance their breast cancer survival rate by assessing their cognitive status and implementing targeted interventions. This study aimed to translate the breast cancer perception scale into Chinese and validate its psychometric properties among community women. DESIGN: A cross-sectional study method was introduced in this study. METHODS: After obtaining the original author's authorization, the breast cancer perception scale was translated into Chinese using the Brislin back-translation method. Item analysis was employed to examine the discriminative power of the items, and the Delphi method was utilized to assess content validity. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to evaluate the scale's construct validity. Internal consistency and test-retest reliability were calculated to analyze reliability. RESULTS: A total of 24 items were retained in the item analysis, and the content validity index of the translated scale was 0.964. In the EFA, six common factors were extracted, namely perceived knowledge, perceived treatment belief, perceived need for health checks, perceived stigma, perceived fear, and perceived risk, accounting for 74.911% of the cumulative variance. The CFA results were as follows: χ2/df = 1.301, GFI = 0.903, NFI = 0.913, TLI = 0.975, CFI = 0.978, IFI = 0.979, RMSEA = 0.037. The Cronbach's α coefficients, split-half reliability, and test-retest reliability of the translated scale were 0.895, 0.661, and 0.865, respectively. CONCLUSIONS: The Chinese version of the breast cancer perception scale demonstrated suitable psychometric properties among community women. By evaluating results according to the scale, medical staff can enhance breast cancer prevention awareness and care for community-dwelling women and subsequently implement corresponding modifications.

Mechanical and Biological Properties of Titanium and Its Alloys for Oral Implant with Preparation Techniques: A Review.

Dental implants have revolutionised restorative dentistry, offering patients a natural-looking and durable solution to replace missing or severely damaged teeth. Titanium and its alloys have emerged as the gold standard among the various materials available due to their exceptional properties. One of the critical advantages of titanium and its alloys is their remarkable biocompatibility which ensures minimal adverse reactions within the human body. Furthermore, they exhibit outstanding corrosion resistance ensuring the longevity of the implant. Their mechanical properties, including hardness, tensile strength, yield strength, and fatigue strength, align perfectly with the demanding requirements of dental implants, guaranteeing the restoration's functionality and durability. This narrative review aims to provide a comprehensive understanding of the manufacturing techniques employed for titanium and its alloy dental implants while shedding light on their intrinsic properties. It also presents crucial proof-of-concept examples, offering tangible evidence of these materials' effectiveness in clinical applications. However, despite their numerous advantages, certain limitations still exist necessitating ongoing research and development efforts. This review will briefly touch upon these restrictions and explore the evolving trends likely to shape the future of titanium and its alloy dental implants.

A novel sacrificial solvent method to synthesize self-supporting Co9S8/Ni3S2 heterostructure catalyst for efficient oxygen evolution reaction.

Synthesizing catalysts for efficient oxygen evolution reaction (OER) with lower cost and simpler design is of significant importance to achieve sustainable hydrogen production. In this work, we propose a novel "sacrificial solvent method" for the first time. Dicobalt octacarbonyl (Co2(CO)8), dimethyl sulfoxide (DMSO), and Ni foam (NF) were used as the raw materials in the solvothermal process. DMSO played the role of both the sacrificial solvent and the sulfur source. Through the self-consumption of DMSO, we finally obtained the Co9S8/Ni3S2 heterostructure supported on the NF (Co9S8/Ni3S2@NF) in one step. The Co9S8/Ni3S2@NF catalyst exhibited excellent OER activity in alkaline environment, with an overpotential of only 264 mV at a current density of 20 mA cm-2, a low Tafel slope of 68.28 mV dec-1 and maintained its current density after 20 h of constant potential testing. This work introduces a new method for synthesizing metal sulfide catalysts using DMSO as a sacrificial solvent. It provides broader opportunities for the development of more efficient and sustainable catalysts for energy conversion and storage.

Study of Foveal Avascular Zone Growth in Individuals With Mild Diabetic Retinopathy by Optical Coherence Tomography.

Purpose: The purpose of this study was to investigate the association between foveal vessels and retinal thickness in individuals with diabetic retinopathy (DR) and control subjects, and to reveal foveal avascular zone (FAZ) growth in early individuals with DR. Methods: The regions with a thickness less than 60 µm were marked from the intima thickness maps and named FAZThic. The avascular zones extracted from the deep vascular plexus were designated as FAZAngi. The boundary of the two FAZ forms a ring region, which we called FAZRing. The FAZ growth rate was defined as the ratio of the FAZRing area to the FAZThic area. Thirty healthy controls and 30 individuals with mild nonproliferative DR were recruited for this study. Results: The FAZThic area in individuals with mild DR and control subjects showed similar distribution. The FAZAngi area in individuals with mild DR are higher than that in control subjects on the whole, but there was no significant difference (P > 0.05). The FAZRing area in individuals with mild DR was significantly higher than that in control subjects (P < 0.001). However, there is still a small amount of overlap data between the two groups. For the FAZ growth rate, the individuals with mild DR were also significantly larger than the control subjects (P < 0.001). But there were no overlapping data between the two groups. Conclusions: The growth of FAZ in individuals with mild DR can be inferred by comparing FAZAngi with FAZThic. This method minimizes the impact of individual variations and helps researchers to understand the progression mechanism of DR more deeply.

An intracellular transporter OsNRAMP7 is required for distribution and accumulation of iron into rice grains.

Iron (Fe) is an essential micronutrient for plant growth and human health. Plants have evolved an efficient transport system for absorbing and redistributing Fe from the soil to other organs; however, the molecular mechanisms underlying Fe loading into grains are poorly understood. Our study shows that OsNRAMP7, a member of the natural resistance-associated macrophage protein (NRAMP) family, is a rice Fe transporter that localizes to the Golgi and trans-Golgi network (TGN). OsNRAMP7 was highly expressed in leaf blade, node I, pollen, and vascular tissues of almost tissues at the rice flowering stage. OsNRAMP7 knockdown by RNA interference (RNAi) increased Fe accumulation in the flag leaf blade, but decreased the Fe concentration in node I and rice grains. In addition, the knockdown of OsNRAMP7 also reduced grain fertility, pollen viability, and grain Fe concentration in the paddy fields; OsNRAMP7 overexpression significantly promoted Fe accumulation in the grains. Thus, our results suggest that OsNRAMP7 is required for the distribution and accumulation of Fe in rice grains and its overexpression could be a novel strategy for Fe biofortification in staple food crops.

Effects of Stigmasterol on 3-Chloropropane-1,2-diol Fatty Acid Esters and Aldehydes Formation in Heated Soybean Oil.

In this study, we investigated the inhibitory effects of three soybean isoflavones and two soybean phytosterols on the formation of 3-chloropropane-1,2-diol fatty acid esters (3-MCPDE) and aldehydes in heated soybean oil model. 0.4 mM of genistin, genistein, daidzein, stigmasterol, and ß-sitosterol significantly reduced 3-MCPDE formation by 25.7, 51.4, 21.4, 61.6, and 55.7%, and total aldehydes formation by 42.03, 43.94, 28.36, 54.74, and 39.23%, respectively. Further study showed that stigmasterol reduced the content of glycidyl esters (GEs) and glycidol, two key intermediates of 3-MCPDE, and prevented fatty acids degradation in the oils. Moreover, the effects of continuous frying time on the content of stigmasterol and the migration of stigmasterol were evaluated in the fried dough sticks model system. The content of stigmasterol in soybean oil was found to be significantly decreased with prolonged heating time. The concentrations of stigmasterol in fried dough sticks and the migration rates of stigmasterol from soybean oil to fried dough sticks decreased with repeated frying sessions. In addition, stigmasterol undergoes oxidative changes during heat treatment, and the oxidation products including 5,6α-epoxystigmasterol, 5,6ß-epoxystigmasterol, 7α-hydroxystigmasterol, 7ß-hydroxystigmasterol, stigmasterlol-3ß,5α,6ß-triol, and 7-ketostigmasterol were identified in the frying oils but not in the fried dough sticks. Overall, stigmasterol could be added to soybean oil to reduce 3-MCPDE and aldehydes formation, and reacting with GEs/glycidol and protection of lipid acids from oxidation may be the mechanism of action of stigmasterol.

SIRT3 Regulates Clearance of Apoptotic Cardiomyocytes by Deacetylating Frataxin.

BACKGROUND: Efferocytosis is an activity of macrophages that is pivotal for the resolution of inflammation in hypertension. The precise mechanism by which macrophages coordinate efferocytosis and internalize apoptotic cardiomyocytes remains unknown. The aim of this study was to determine whether SIRT3 (sirtuin-3) is required for both apoptotic cardiomyocyte engulfment and anti-inflammatory responses during efferocytosis. METHODS: We generated myeloid SIRT3 knockout mice and FXN (frataxin) knock-in mice carrying an acetylation-defective lysine to arginine K189R mutation (FXNK189R). The mice were given Ang II (angiotensin II) infusion for 7 days. We analyzed cardiac macrophages' mitochondrial iron levels, efferocytosis activity, and phenotype both in vivo and in vitro. RESULTS: We showed that SIRT3 deficiency exacerbated Ang II-induced downregulation of the efferocytosis receptor MerTK (c-Mer tyrosine kinase) and proinflammatory cytokine production, accompanied by disrupted mitochondrial iron homeostasis in cardiac macrophages. Quantitative acetylome analysis revealed that SIRT3 deacetylated FXN at lysine 189. Ang II attenuated SIRT3 activity and enhanced the acetylation level of FXNK189. Acetylated FXN further reduced the synthesis of ISCs (iron-sulfur clusters), resulting in mitochondrial iron accumulation. Phagocytic internalization of apoptotic cardiomyocytes increased myoglobin content, and derived iron ions promoted mitochondrial iron overload and lipid peroxidation. An iron chelator deferoxamine improved the levels of MerTK and efferocytosis, thereby attenuating proinflammatory macrophage activation. FXNK189R mice showed improved macrophage efferocytosis, reduced cardiac inflammation, and suppressed cardiac fibrosis. CONCLUSIONS: The SIRT3-FXN axis has the potential to resolve cardiac inflammation by increasing macrophage efferocytosis and anti-inflammatory activities.

Identification of plant cadmium resistance gene family in Brassica napus and functional analysis of BnPCR10.1 involved in cadmium and copper tolerance.

The plant cadmium resistance (PCR) family proteins play important roles in maintaining metal homeostasis and detoxification. However, few functional PCR genes have been well-characterized in plants. In this study, we identified and cloned 26 BnPCR genes from the rapeseed (Brassica napus) genome. They were divided into four groups (I-IV) based on their phylogenetic relationship. Yeast functional complementation experiments showed that BnPCRs can transport copper (Cu) and cadmium (Cd) in yeast. The expression levels of the BnPCRs were variable among different organs. Moreover, most of the genes were induced by Cu2+ and Cd2+ stress. Among these genes, BnPCR10.1 was highly expressed in various organs and induced by Cu2+ and Cd2+. Therefore, we studied the function of BnPCR10.1 in more detail. BnPCR10.1 was localized to the plasma membrane (PM), and expression in yeast enhanced yeast cells to export Cu and Cd. Furthermore, overexpression of BnPCR10.1 transgenic lines pro35S::BnPCR10.1;athma5 had lower concentration of Cu in roots than athma5 mutants. In addition, transgenic plants pro35S::BnPCR10.1;atpdr8 had lower concentration of Cd in shoots and roots than atpdr8 mutants. Net Cu2+ and Cd2+ efflux assay showed that there was decreased absorption of Cu2+ and Cd2+ in the transgenic Arabidopsis elongation zone of roots than in athma5 and atpdr8 mutants, respectively. These results provide new information on BnPCRs and their roles in response to heavy metals and reveal the mechanism used by BnPCR10.1 to detoxify Cu and Cd. Our findings facilitate a theoretical basis for the genetic improvement of Cu-Cd tolerance in rapeseed.

Psychometric evaluation of the Chinese version of the Positive Health Behaviours Scale for clinical nurses: a cross-sectional translation.

BACKGROUND: Occupational health is essential for nurses in clinical nursing practice. However, there is no specific tool for measuring the health behaviour of clinical nurses in China. This study aimed to translate the Positive Health Behaviours Scale into Chinese and validate its psychometric properties among clinical nurses. DESIGN: A cross-sectional design with repeated measures. METHODS: A total of 633 clinical nurses were recruited by convenience sampling from hospitals in Liaoning Province, China. After obtaining the authorization of the original author, the PHBS was translated into Chinese by the Brislin back-translation method. Item analysis was completed to evaluate item discrimination, and the Delphi method was adopted to analyse content validity. Exploratory factor analysis and confirmatory factor analysis were conducted to explore and validate the underlying factor structure. Internal consistency and test-retest reliability were calculated to evaluate reliability. RESULTS: A total of 29 items were retained in the item analysis, and the content validity index of the translated scale was 0.956. In the EFA, four common factors were extracted (nutrition, physical activity, relaxation and behaviours related to mental health and preventive behaviours), explaining 60.81% of the total variance. The results of the CFA were as follows: χ2/df = 1.363, GFI = 0.902, NFI = 0.909, IFI = 0.974, TLI = 0.971, CFI = 0.974, RMSEA = 0.034, and RMR = 0.023. The results of the EFA and CFA showed that the translated scale had good structural validity. Cronbach's α coefficient, the split-half reliability and the test-retest reliability of the Chinese version of the PHBS were 0.928, 0.953 and 0.891, respectively. At the same time, the translated scale had good reliability. CONCLUSIONS: The Chinese version of the PHBS for clinical nurses had good psychometric properties. The results of the questionnaire survey effectively and comprehensively reflect the level of health behaviours in clinical nurses, which provides a scientific reference for determining the intervention target.

Latent profile analysis of depression in non-hospitalized elderly patients with hypertension and its influencing factors.

BACKGROUND: Hypertension is a common chronic disease in the elderly, which seriously affects people's physical and mental health, leading to anxiety, depression and other symptoms. To analyze the types of depression that may occur in elderly patients with non-hospitalized hypertension and explore its influencing factors can reduce the level of depression and improve the quality of life. METHODS: Based on the data of the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS), latent profile analysis (LPA) was used to establish the potential profile model of elderly hypertensive patients with depression, and multiple logistic regression analysis was employed to explore the influencing factors of patients with depression. RESULTS: 3514 elderly patients with hypertension could be divided into three potential characteristics of depression: low-level (13.9 %), medium-level (51.9 %) and high-level (34.2 %). Multiple logistic regression showed that anxiety, IADL, age, exercise, economic level, hearing difficulty, self-reported health and visual function predicted the depression of the medium-level in the comparison between the low-level and the medium-level; taking low levels as a reference, anxiety, IADL, co-residence of interviewee, age, exercise, self-reported health marital status and visual function can predict the depression of high-level; anxiety, exercise, self-reported health and marital status predicted the depression of the high-level in the comparison between the medium-level and the high-level. LIMITATIONS: (1) This study is a cross-sectional study; (2) due to data limitations, other influencing factors may be ignored. CONCLUSION: Depression in elderly patients with hypertension was divided into three potential profiles, which had obvious classification characteristics.

Reversal of subtype-selectivity and function by the introduction of a para-benzamidyl substituent to N-cyclopropylmethyl nornepenthone.

The discovery and development of novel µ-opioid receptor (MOR) antagonists is a significant area to combat Opioid Use Disorder (OUD). In this work, a series of para-substituted N-cyclopropylmethyl-nornepenthone derivatives were designed and synthesized and pharmacologically assayed. Compound 6a was identified as a selective MOR antagonist both in vitro and in vivo. Its molecular basis was elucidated using molecular docking and MD simulations. A subpocket on the extracellular side of the TM2 domain of MOR, in particular the residue Y2.64, was proposed to be responsible for the reversal of subtype selectivity and functional reversal of this compound.

A metabolomics-based analysis of the metabolic pathways associated with the regulation of branched-chain amino acids in rats fed a high-fructose diet.

Previous studies have shown that the elevated levels of circulating branched-chain amino acids (BCAAs) are associated with the development of insulin resistance and its complications, including obesity, type 2 diabetes, cardiovascular disease and some cancers. However, animal models that can mimic the metabolic state of chronically elevated BCAAs in humans are rare. Therefore, the aim of this study was to establish the above animal model and analyse the metabolic changes associated with high BCAA levels. Sixteen 8-week-old Sprague-Dawley (SD) rats were randomly divided into two groups and given either a high fructose diet or a normal diet. BCAA levels as well as blood glucose and lipid levels were measured at different time points of feeding. The mRNA expression levels of two key enzymes of BCAA catabolism, ACAD (acyl-CoA dehydrogenase) and BCKDH (branched-chain α-keto acid dehydrogenase), were measured by qPCR, and the protein expression levels of these two enzymes were analysed by immunohistochemistry. Finally, the metabolite expression differences between the two groups were analysed by Q300 metabolomics technology. Our study confirms that defects in the catabolic pathways of BCAAs lead to increased levels of circulating BCAAs, resulting in disorders of glucose and lipid metabolism characterized by insulin resistance by affecting metabolic pathways associated with amino acids and bile acids.