Application of metal-organic frameworks and their derivates for thermal-catalytic C1 molecules conversion.

One-carbon (C1) catalysis refers to the conversion of compounds with a single carbon atom, especially carbon monoxide (CO), carbon dioxide (CO2), and methane (CH4), into clean fuels and valuable chemicals via catalytic strategy is crucial for sustainable and green development. Among various catalytic strategies, thermal-driven process seems to be one of the most promising pathways for C1 catalysis due to the high efficiency and practical application prospect. Notably, the rational design of thermal-driven C1 catalysts plays a vital role in boosting the targeted products synthesis of C1 catalysis, which relies heavily on the choice of ideal active site support, catalyst fabrication precursor, and catalytic reaction field. As a novel crystalline porous material, metal-organic frameworks (MOFs) has made significant progress in the design and synthesis of various functional nanomaterials. However, the application of MOFs in C1 catalysis faces numerous challenges, such as thermal stability, mechanical strength, yield of MOFs, and so on. To overcome these limitations and harness the advantages of MOFs in thermal-driven C1 catalysis, researchers have developed various catalyst/carrier preparation strategies. In this review, we provide a concise overview of the recent advancements in the conversion of CO, CO2, and CH4 into clean fuels and valuable chemicals via thermal-catalytic strategy using MOFs-based catalysts. Furthermore, we discuss the main challenges and opportunities associated with MOFs-based catalysts for thermal-driven C1 catalysis in the future.

Protocol for evaluating the effects of the Reducing Cardiometabolic Diseases Risk dietary pattern in the Chinese population with dyslipidaemia: a single-centre, open-label, dietary intervention study.

INTRODUCTION: Cardiometabolic disease (CMD) is the leading cause of mortality in China. A healthy diet plays an essential role in the occurrence and development of CMD. Although the Chinese heart-healthy diet is the first diet with cardiovascular benefits, a healthy dietary pattern that fits Chinese food culture that can effectively reduce the risk of CMD has not been found. METHODS/DESIGN: The study is a single-centre, open-label, randomised controlled trial aimed at evaluating the effect of the Reducing Cardiometabolic Diseases Risk (RCMDR) dietary pattern in reducing the risk of CMDs in people with dyslipidaemia and providing a reference basis for constructing a dietary pattern suitable for the prevention of CMDs in the Chinese population. Participants are men and women aged 35-45 years with dyslipidaemia in Tianjin. The target sample size is 100. After the run-in period, the participants will be randomised to the RCMDR dietary pattern intervention group or the general health education control group with a 1:1 ratio. The intervention phases will last 12 weeks, with a dietary intervention of 5 working days per week for participants in the intervention group. The primary outcome variable is the cardiometabolic risk score. The secondary outcome variables are blood lipid, blood pressure, blood glucose, body composition indices, insulin resistance and 10-year risk of cardiovascular diseases. ETHICS AND DISSEMINATION: The study complies with the Measures for Ethical Review of Life Sciences and Medical Research Involving Human Beings and the Declaration of Helsinki. Signed informed consent will be obtained from all participants. The study has been approved by the Medical Ethics Committee of the Second Hospital of Tianjin Medical University (approval number: KY2023020). The results from the study will be disseminated through publications in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2300072472).

Superoxide Dismutase Modified the Association of Serum Malondialdehyde Levels with Cognitive Decline Among Older Adults: Findings from the Chinese Longitudinal Healthy Longevity Survey.

Background: Numerous studies have investigated the correlation between malondialdehyde (MDA) and cognitive decline. However, limited research has explored the interplay between superoxide dismutase (SOD), C-reactive protein (CRP), and MDA. Objective: This study aims to scrutinize the association between MDA and cognitive function in older adults, while also elucidating the roles of SOD and CRP within this relationship. Methods: Utilizing data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) spanning 2008-2009, 2011-2012, and 2014, this study included 2,696 eligible subjects. Cognitive function was evaluated using the Chinese version of the Mini-Mental State Examination (MMSE). Linear mixed-effects models were employed to examine the links between MDA, SOD, CRP, and their interactions with cognitive function. Results: Elevated serum levels of MDA and CRP, as well as decreased serum SOD levels, were related to decreased cognitive function (ß= -0.220 and -0.346, 95% CI: -0.399, -0.041 and -0.526, -0.167 for MDA and CRP; ß= 0.384, 95% CI: 0.204, 0.564 for SOD). Notably, a significant interaction between MDA and SOD was detected (p = 0.001). An increase per standard deviation in serum MDA levels was significantly associated with a 0.347-point lower MMSE score only in participants with normal cognitive function and high SOD levels (ß= -0.347, 95% CI: -0.497, -0.197; p <  0.001). Conclusions: Elevated serum MDA levels in the normal population with high SOD levels suggested diminished cognitive performance. Combining MDA with SOD could be pivotal in identifying older adults at risk of cognitive decline in clinical settings.

Photoactivated full-API nanodrug (FAND): harnessing transition metal complexes and MTH1 inhibitor for enhanced DNA damage in cancer cells.

The effectiveness of photodynamic therapy (PDT) has been greatly restricted by the hypoxic tumor microenvironment and the susceptible resistance of monotherapy. Although nanodrugs based on transition metal complexes capable of integrating PDT with photoactivated chemotherapy (PACT) have garnered tremendous attention as promising candidates for overcoming the above limitations, the therapeutic efficacy of these nanodrugs is still hampered by inadequate loading of active pharmaceutical ingredients (APIs) and the inherent ability of cancer cells to repair damaged DNA. Herein, we developed a photoactivated full-API nanodrug, Ru-T FAND, by one-step self-assembly of RuDPB and TH287. By virtue of its 100 wt% API content and favorable stability in water, the Ru-T FAND exhibited improved cellular uptake behavior and intracellular 1O2 generation. Attractively, the Ru-T FAND with triple anti-cancer modalities can photogenerate 1O2, photo-release DPB ligand and inhibit the repair of DNA damage, ultimately enhancing its phototherapeutic effect on cancer cells. Importantly, the uncaged DPB ligand from RuDPB emits red fluorescence, enabling real-time monitoring of the drug's absorption, distribution and efficacy. Collectively, the presented photoactivated Ru-T FANDs with multiple anti-cancer mechanisms will expand new horizons for the development of safe, efficient and synergistic tumor phototherapy strategies.

Associations of Dynapenic Abdominal Obesity and Frailty Progression: Evidence from Two Nationwide Cohorts.

The associations of dynapenic abdominal obesity and transitions with frailty progression remain unclear among middle-aged and older adults. We included 6937 participants from the China Health and Retirement Longitudinal Study (CHARLS) and 3735 from the English Longitudinal Study of Aging (ELSA). Participants were divided into non-dynapenia and non-abdominal obesity (ND/NAO), abdominal obesity alone (AO), dynapenia alone (D), and dynapenic abdominal obesity (D/AO). Frailty status was assessed by the frailty index (FI), and a linear mixed-effect model was employed to analyze the associations of D, AO, D/AO, and transitions with frailty progression. Participants with AO, D, and D/AO had increased FI progression compared with ND/NAO in both cohorts. D/AO possessed the greatest additional annual FI increase of 0.383 (95% CI: 0.152 to 0.614), followed by D and AO in the CHARLS. Participants with D in the ELSA had the greatest magnitude of accelerated FI progression. Participants who transitioned from ND/NAO to D and from AO to D/AO presented accelerated FI progression in the CHARLS and ELSA. In conclusion, dynapenic abdominal obesity, especially for D/AO and D, presented accelerated frailty progression. Our findings highlighted the essential intervention targets of dynapenia and abdominal obesity for the prevention of frailty progression.

Protein Kinase A Is a Master Regulator of Physiological and Pathological Cardiac Hypertrophy.

BACKGROUND: The sympathoadrenergic system and its major effector PKA (protein kinase A) are activated to maintain cardiac output coping with physiological or pathological stressors. If and how PKA plays a role in physiological cardiac hypertrophy (PhCH) and pathological CH (PaCH) are not clear. METHODS: Transgenic mouse models expressing the PKA inhibition domain (PKAi) of PKA inhibition peptide alpha (PKIalpha)-green fluorescence protein (GFP) fusion protein (PKAi-GFP) in a cardiac-specific and inducible manner (cPKAi) were used to determine the roles of PKA in physiological CH during postnatal growth or induced by swimming, and in PaCH induced by transaortic constriction (TAC) or augmented Ca2+ influx. Kinase profiling was used to determine cPKAi specificity. Echocardiography was used to determine cardiac morphology and function. Western blotting and immunostaining were used to measure protein abundance and phosphorylation. Protein synthesis was assessed by puromycin incorporation and protein degradation by measuring protein ubiquitination and proteasome activity. Neonatal rat cardiomyocytes (NRCMs) infected with AdGFP (GFP adenovirus) or AdPKAi-GFP (PKAi-GFP adenovirus) were used to determine the effects and mechanisms of cPKAi on myocyte hypertrophy. rAAV9.PKAi-GFP was used to treat TAC mice. RESULTS: (1) cPKAi delayed postnatal cardiac growth and blunted exercise-induced PhCH; (2) PKA was activated in hearts after TAC due to activated sympathoadrenergic system, the loss of endogenous PKIα (PKA inhibition peptide α), and the stimulation by noncanonical PKA activators; (3) cPKAi ameliorated PaCH induced by TAC and increased Ca2+ influxes and blunted neonatal rat cardiomyocyte hypertrophy by isoproterenol and phenylephrine; (4) cPKAi prevented TAC-induced protein synthesis by inhibiting mTOR (mammalian target of rapamycin) signaling through reducing Akt (protein kinase B) activity, but enhancing inhibitory GSK-3α (glycogen synthase kinase-3α) and GSK-3ß signals; (5) cPKAi reduced protein degradation by the ubiquitin-proteasome system via decreasing RPN6 phosphorylation; (6) cPKAi increased the expression of antihypertrophic atrial natriuretic peptide (ANP); (7) cPKAi ameliorated established PaCH and improved animal survival. CONCLUSIONS: Cardiomyocyte PKA is a master regulator of PhCH and PaCH through regulating protein synthesis and degradation. cPKAi can be a novel approach to treat PaCH.

Synthesis of Mono- and Dinuclear Aluminum Complexes Bearing Aromatic Amino-Phenolato Ligands: A Comparative Study in the Ring-Opening Polymerization of Cyclohexene Oxide.

Dinuclear aluminum methyl complexes bearing aromatic diamine-bridged tetra(phenolato) ligands and the mononuclear aluminum methyl complex with the phenylamine-bridged bis(phenolato) ligand have been synthesized and characterized. Structure determination revealed that the Al-Al distances in these dinuclear aluminum complexes are tunable by the choice of the suitable aromatic backbone of the diamine-bridged tetra(phenolato) ligands. The catalytic behaviors of these mono- and dinuclear aluminum complexes for cyclohexene oxide (CHO) polymerization were investigated. The activities of these dinuclear Al complexes were observed to increase with the decrease of Al-Al distances, and the dinuclear Al complexes appeared to have better catalytic activity than the mononuclear Al complex, even if the Al-Al distance is as long as 9.401 Å. Dinuclear aluminum complex 2, with the shortest Al-Al distance (7.236 Å), showed the highest activity toward CHO polymerization with TOFs up to 6460 h-1 in neat CHO at 30 °C. Furthermore, comparative kinetic studies revealed that the polymerization is first-order for CHO concentration, and the reaction orders for initiator concentration are different for the mono- and dinuclear Al complexes. The polymerization mechanism study revealed that both the methyl and phenolate groups were involved in the initiation process.

Sarcopenia Transitions and Influencing Factors Among Chinese Older Adults With Multistate Markov Model.

Background and Objectives: Little is known about the sarcopenia transition process across different stages among Chinese community-dwelling older adults. We aimed to explore dynamic transitions of sarcopenia and its influencing factors in Chinese older adults. Research Design and Methods: Data were derived from the China Health and Retirement Longitudinal Study. A total of 2856 older adults with complete data in the 2011, 2013, and 2015 waves were included in our study. Participants were categorized into 3 states: no sarcopenia, possible sarcopenia, and sarcopenia according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019) criteria. Continuous-time multistate Markov model was performed to estimate the 1-year transition probabilities and the associated factors of sarcopenia transitions. The association strength was expressed as hazard ratio and 95% confidence interval. Results: The progression and reversion rates between no sarcopenia and sarcopenia state were 6.01 and 9.20 per 100 person-years, respectively. The 1-year progression probability to possible sarcopenia was higher compared with the likelihood of moving to the sarcopenia state (0.127 vs 0.034). The reversion probability to no sarcopenia was also higher among those with possible sarcopenia (0.281 vs 0.157). Older age, rural living, worse cognition status, higher chronic disease numbers, and lower nutrition status measured by body mass index accelerated the sarcopenia progression. Cognition status and body mass index level were related to higher chances of reverting. Discussion and Implications: Possible sarcopenia might be a critical time window to promote sarcopenia reversion. Timely interventions aimed at delaying the progression and facilitating sarcopenia recovery should focus on improving cognitive function and nutrition levels.

Application and Comparison of Different Regression Models in Iodine Balance Experiment on Women of Childbearing Age and Pregnant Women.

The iodine balance experiment is a traditional approach to evaluate the physiological requirement for iodine, while the simple linear regression model (SLM) and the mixed effects model (MEM) are two primary methods used to analyze iodine balance experiments. In the present study, we aimed to compare the effects of these two regression models on the evaluation of iodine balance experiments to investigate appropriate valuation methods. By constructing SLM and MEM, zero iodine balance values (IBV) were determined, and the evaluation effects were compared. No changes were made to the experimental data for women of childbearing age, and cutoff values of 600 µg/day and 1000 µg/day, respectively, were chosen for further processing of the experimental data for pregnant women. Equation combinations 1-3 (EC1-3) were obtained by fitting SLM, and zero IBV were calculated as 110.26 µg/day, 333.06 µg/day, and 434.84 µg/day, respectively. EC4-6 were obtained by fitting MEM, and zero IBV were calculated as 110.44 µg/day, 335.79 µg/day, and 418.06 µg/day, respectively. The inclusion of inter-measurement variation as a random factor in the MEM yielded EC7-8, which reduced the test power of the iodine balance experiment on women of childbearing age. Our study suggested that when experimental conditions were tightly controlled, with fewer uncertainties or significant influences, computationally straightforward and well-understood SLM was preferred. If some uncertain factors might cause large changes in the experimental results, it was advised to use a more "conservative" MEM to calculate the zero IBV. ClinicalTrials.gov Identifier: Registered at Clinicaltrials.gov, NCT03279315 (17th September 2017, retrospectively registered), NCT03710148 (18th October 2018, retrospectively registered).

New Monoterpene Glycoside Paeoniflorin Derivatives as NO and IL-1ß Inhibitors: Synthesis and Biological Evaluation.

Several monoterpene glycoside compounds were extracted from Paeonia lactiflora Pall. Among them, paeoniflorin, a water-soluble monoterpene glycoside found in the root of Paeonia lactiflora Pall, exhibits excellent antioxidant pharmacological functions. Initially, Sc(CF3SO3)3 was employed as the catalyst for paeoniflorin's dehydration and rearrangement reactions with alcohols. Subsequently, structural modifications were performed on paeoniflorin through a series of responses, including acetylation, deacetylation, and debenzoylation, ultimately yielding 46 monoterpene glycoside derivatives. The potential inhibitory effects on the pro-inflammatory mediators interleukin-1 beta (IL-1ß) and nitric oxide (NO) were assessed in vitro. The results revealed that compounds 29 and 31 demonstrated notable inhibition of NO production, while eight derivatives (3, 8, 18, 20, 21, 29, 34, and 40) displayed substantial inhibitory effects on the secretion of IL-1ß. Computational research was also undertaken to investigate the binding affinity of the ligands with the target proteins. Interactions between the proteins and substrates were elucidated, and corresponding binding energies were calculated accordingly. The findings of this study could provide valuable insights into the design and development of novel anti-inflammatory agents with enhanced pharmacological properties.

Bone-targeting exosome nanoparticles activate Keap1 / Nrf2 / GPX4 signaling pathway to induce ferroptosis in osteosarcoma cells.

BACKGROUND: In recent years, the development of BMSCs-derived exosomes (EXO) for the treatment of osteosarcoma (OS) is a safe and promising modality for OS treatment, which can effectively deliver drugs to tumor cells in vivo. However, the differences in the drugs carried, and the binding of EXOs to other organs limit their therapeutic efficacy. Therefore, improving the OS-targeting ability of BMSCs EXOs and developing new drugs is crucial for the clinical application of targeted therapy for OS. RESULTS: In this study, we constructed a potential therapeutic nano platform by modifying BMSCs EXOs using the bone-targeting peptide SDSSD and encapsulated capreomycin (CAP) within a shell. These constructed nanoparticles (NPs) showed the ability of homologous targeting and bone-targeting exosomes (BT-EXO) significantly promotes cellular endocytosis in vitro and tumor accumulation in vivo. Furthermore, our results revealed that the constructed NPs induced ferroptosis in OS cells by prompting excessive accumulation of reactive oxygen species (ROS), Fe2+ aggregation, and lipid peroxidation and further identified the potential anticancer molecular mechanism of ferroptosis as transduced by the Keap1/Nrf2/GPX4 signaling pathway. Also, these constructed NP-directed ferroptosis showed significant inhibition of tumor growth in vivo with no significant side effects. CONCLUSION: These results suggest that these constructed NPs have superior anticancer activity in mouse models of OS in vitro and in vivo, providing a new and promising strategy for combining ferroptosis-based chemotherapy with targeted therapy for OS.

Deficiency in AK9 causes asthenozoospermia and male infertility by destabilising sperm nucleotide homeostasis.

BACKGROUND: Asthenozoospermia is the primary cause of male infertility; however, its genetic aetiology remains poorly understood. Adenylate kinase 9 (AK9) is highly expressed in the testes of humans and mice and encodes a type of adenosine kinase that is functionally involved in cellular nucleotide homeostasis and energy metabolism. We aimed to assess whether AK9 is involved in asthenozoospermia. METHODS: One-hundred-and-sixty-five Chinese men with idiopathic asthenozoospermia were recruited. Whole-exome sequencing (WES) and Sanger sequencing were performed for genetic analyses. Papanicolaou staining, Haematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy were used to observe the sperm morphology and structure. Ak9-knockout mice were generated using CRISPR-Cas9. Sperm adenosine was detected by liquid chromatography-mass spectrometry. Targeted sperm metabolomics was performed. Intracytoplasmic sperm injection (ICSI) was used to treat patients. FINDINGS: We identified five patients harbouring bi-allelic AK9 mutations. Spermatozoa from men harbouring bi-allelic AK9 mutations have a decreased ability to sustain nucleotide homeostasis. Moreover, bi-allelic AK9 mutations inhibit glycolysis in sperm. Ak9-knockout male mice also presented similar phenotypes of asthenozoospermia. Interestingly, ICSI was effective in bi-allelic AK9 mutant patients in achieving good pregnancy outcomes. INTERPRETATION: Defects in AK9 induce asthenozoospermia with defects in nucleotide homeostasis and energy metabolism. This sterile phenotype could be rescued by ICSI. FUNDING: The National Natural Science Foundation of China (82071697), Medical Innovation Project of Fujian Province (2020-CXB-051), open project of the NHC Key Laboratory of Male Reproduction and Genetics in Guangzhou (KF202004), Medical Research Foundation of Guangdong Province (A2021269), Guangdong Provincial Reproductive Science Institute Innovation Team grants (C-03), and Outstanding Young Talents Program of Capital Medical University (B2205).

Overage labor, intergenerational financial support, and depression among older rural residents: evidence from China.

Background: Depression is a major factor affecting the happiness of older rural residents. With the increasing aging of the Chinese population, overage labor is becoming more prevalent in rural areas of China. This study aimed to assess whether, and if so, how, overage labor affects depression status in older rural residents. Methods: Using data from the China Health and Retirement Longitudinal Study, this study explored the association between overage labor and depression among older rural residents by using ordinary least squares and moderated mediation models. Results: The results show that overage labor significantly reduced levels of depression in older rural residents. This result remained robust after using propensity score matching and double machine learning. Furthermore, the improvement of older rural residents' depression via overage labor is mainly achieved through work income, but this mediating effect is negatively moderated by intergenerational financial support. This implies that in traditional Chinese rural society, intergenerational financial support from children plays an important role in reducing depression among older rural residents. Conclusion: Our findings have potential policy implications for China and other developing countries in terms of addressing issues related to aging and depression in older adults.

Scutellarin Inhibits Glioblastoma Growth in a Dose-dependent Manner by Suppressing the p63 Signaling Pathway.

Although scutellarin has been extensively investigated, its effects on glioma are unclear. This study intended to reveal this regulation and the underlying mechanisms. The U251, M059K, and SF-295 cell lines were treated with gradient concentrations of scutellarin and then IC50 was calculated. SF-295 cells selected for subsequent procedures were treated with four concentrations of scutellarin. Then, proliferation, apoptosis, and cell cycle, as well as the protein and mRNA expression of significantly differentially expressed genes identified by next-generation sequencing (NGS), were examined. The curative effect of scutellarin was validated by 5-FU as the positive control. Scutellarin inhibited proliferation and induced apoptosis and G2/M cell cycle arrest in the SF-295 cell line in a dose-dependent manner. The effect of scutellarin was similar to but significantly weaker than the effect of 5-FU. The NGS results showed that genes associated with anti-apoptosis signaling pathways were significantly reduced after treatment. The Western blotting results indicated that the expressions of TP63/BIRC3/TRAF1/Bcl-2 were reduced in a dose-dependent manner, as well as the mRNA levels determined by qRT‒PCR. Our original conclusion revealed that scutellarin may inhibit glioma growth in a dose-dependent manner via the p63 signaling pathway which may provide a potential medicine for glioma chemotherapy.

Comparative Genomic Analysis Identifies Great-Ape-Specific Structural Variants and Their Evolutionary Relevance.

During the origin of great apes about 14 million years ago, a series of phenotypic innovations emerged, such as the increased body size, the enlarged brain volume, the improved cognitive skill, and the diversified diet. Yet, the genomic basis of these evolutionary changes remains unclear. Utilizing the high-quality genome assemblies of great apes (including human), gibbon, and macaque, we conducted comparative genome analyses and identified 15,885 great ape-specific structural variants (GSSVs), including eight coding GSSVs resulting in the creation of novel proteins (e.g., ACAN and CMYA5). Functional annotations of the GSSV-related genes revealed the enrichment of genes involved in development and morphogenesis, especially neurogenesis and neural network formation, suggesting the potential role of GSSVs in shaping the great ape-shared traits. Further dissection of the brain-related GSSVs shows great ape-specific changes of enhancer activities and gene expression in the brain, involving a group of GSSV-regulated genes (such as NOL3) that potentially contribute to the altered brain development and function in great apes. The presented data highlight the evolutionary role of structural variants in the phenotypic innovations during the origin of the great ape lineage.

Role of ceRNA network in inflammatory cells of rheumatoid arthritis. / CeRNAç½‘ç»œåœ¨ç±»é£Žæ¹¿å ³èŠ‚ç‚Žçš„ç‚Žç—‡ç»†èƒžä¸­çš„ä½œç”¨.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease caused by inflammatory cells. Various inflammatory cells involved in RA include fibroblast-like synoviocytes, macrophages, CD4+T-lymphocytes, B lymphocytes, osteoclasts and chondrocytes. The close interaction between various inflammatory cells leads to imbalance of immune response and disorder of the expression of mRNA in inflammatory cells. It helps to drive production of pro-inflammatory cytokines and stimulate specific antigen-specific T- and B-lymphocytes to produce autoantibodies which is an important pathogenic factor for RA. Competing endogenous RNA (ceRNA) can regulate the expression of mRNA by competitively binding to miRNA. The related ceRNA network is a new regulatory mechanism for RNA interaction. It has been found to be involved in the regulation of abnormal biological processes such as proliferation, apoptosis, invasion and release of inflammatory factors of RA inflammatory cells. Understanding the ceRNA network in 6 kinds of RA common inflammatory cells provides a new idea for further elucidating the pathogenesis of RA, and provides a theoretical basis for the discovery of new biomarkers and effective therapeutic targets.

The expression and distribution of TACAN in human and rat bladders.

OBJECTIVES: A lot of ion channels participate in the regulation of bladder function. TACAN, a new mechanosensitive ion channel, was first discovered in 2020. TACAN has been found to be expressed in many tissues, such as the dorsal root ganglia (DRG) and adipose tissue. However, it is unclear whether or not TACAN is expressed in the bladder. In this work, we decided to study the expression and distribution of TACAN in human and rat bladders. Meanwhile, the expression of TACAN in the rat model of interstitial cystitis/bladder pain syndrome (IC/BPS) was studied. METHODS: Human bladder tissues were obtained from female patients. Cyclophosphamide (CYP) was used to build the rat model of IC/BPS. Real-time polymerase chain reaction, agarose gel electrophoresis, and western blotting were used to assess the expression of TACAN in human and rat bladders. Immunohistochemistry and immunofluorescence were used to observe the distribution of TACAN in human and rat bladders. Hematoxylin-eosin stain, withdrawal threshold, and micturition interval were used to evaluate animal models. RESULTS: The results of agarose gel electrophoresis and western blotting suggested that TACAN was expressed in human and rat bladders. Immunohistochemical results suggested that TACAN showed positive immunoreaction in the urothelial and detrusor layers. The immunofluorescence results indicated that TACAN was co-stained with UPKIII, α-SMA, and PGP9.5. The IC/BPS model was successfully established with CYP. The mRNA and protein expression of TACAN was upregulated in the CYP-induced rat model of IC/BPS. CONCLUSIONS: TACAN was found in human and rat bladders. TACAN was mainly distributed in the urothelial and detrusor layers and bladder nerves. The expression of TACAN was upregulated in the CYP-induced rat model of IC/BPS. This new discovery will provide a theoretical basis for future research on the function of TACAN in the bladder and a potential therapeutic target for IC/BPS.

Study on antitumor activity of three ruthenium arene complexes in vitro.

Three ruthenium arene complexes, namely {[(η6-p-cymene)Ru(Cl)]2(dpb)}(PF6)2 (1), [(η6-p-cymene)Ru(dpb)Cl](PF6) (2) and [(η6-p-cymene) Ru(dpb)py](PF6) (3) (dpb = 2,3-bis(2-pyridyl)benzo-quinoxaline, py = pyridine), were synthesized and their antitumor properties were introduced. Complexes 1-3 were characterized by 1H NMR, MS, and elemental analysis. As a binuclear ruthenium structure, the absorption of metal ligand electron transfer (MLCT) of 1 extended to 700 nm. Complex 1 was significantly hydrolyzed under dark conditions. The cytotoxicity in vitro study showed that complexes 1 and 2 are more toxic to human lung cancer cells (A549) and human cervial cancer cells (Hela) than cisplatin. Moreover, there was almost no cross-resistance between complex 1-2 and cisplatin. Under the irradiation at 478 nm, complexes 1-3 all produced singlet oxygen (1O2), and the 1O2 quantum yield of complex 1 in PBS is the highest among complexes 1-3. Complex 1 also produced 1O2 under 600 nm light irradiation. DNA gel electrophoresis showed that 1 caused the photocleavage of plasmid DNA. The hydrolysis rate of complex 1 was accelerated under light (λ > 600 nm). And the phototoxicity of complex 1 to Hela cells under light (λ > 600 nm) was much greater than its dark toxicity, which may be due to its generation of 1O2 and the promotion of its hydrolysis under long-wave light irradiation.

Association of Unhealthy Lifestyle and Genetic Risk Factors With Mild Cognitive Impairment in Chinese Older Adults.

Importance: Apolipoprotein E polymorphism ε4 (APOE ε4) and methylenetetrahydrofolate reductase (MTHFR) TT genotype are genetic risk factors of mild cognitive impairment (MCI), but whether this risk can be changed by modifiable lifestyle factors is unknown. Objective: To explore whether unhealthy lifestyle (unhealthy dietary intake, current smoking, nonlimited alcohol consumption, and irregular physical activities) is associated with a higher risk of age-related MCI considering genetic risk. Design, Setting, and Participants: This population-based cohort study used data from Tianjin Elderly Nutrition and Cognition (TENC) study participants, recruited from March 1, 2018, through June 30, 2021, and followed up until November 30, 2022. Participants were Chinese adults aged 60 years or older who completed the neuropsychological assessments, general physical examinations, and a personal interview. Exposures: Healthy lifestyle was defined according to the Chinese Dietary Guidelines 2022, including healthy diet, regular physical activity, limited alcohol consumption, and no current smoking, categorized into healthy and unhealthy lifestyles according to weighted standardized lifestyle score. Genetic risk was defined by MTHFR TT genotype and APOE ε4, categorized into low and high genetic risk according to weighted standardized genetic risk score. Main Outcomes and Measures: The main outcome was newly diagnosed MCI as identified using a modified version of Petersen criteria. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazard regression models. Results: A total of 4665 participants were included (mean [SD] age, 67.9 [4.9] years; 2546 female [54.6%] and 2119 male [45.4%]); 653 participants with new-onset MCI (mean [SD] age, 68.4 [5.4] years; 267 female [40.9%] and 386 male [59.1%]) were identified after a median follow-up of 3.11 years (range, 0.82-4.61 years). Individuals with a low genetic risk and an unhealthy lifestyle (HR, 3.01; 95% CI, 2.38-3.79), a high genetic risk and a healthy lifestyle (HR, 2.65; 95% CI, 2.03-3.44), and a high genetic risk and an unhealthy lifestyle (HR, 3.58; 95% CI, 2.73-4.69) had a higher risk of MCI compared with participants with a low genetic risk and a healthy lifestyle. There was a synergistic interaction between lifestyle categories and genetic risk (ß = 3.58; 95% CI, 2.73-4.69). Conclusions and Relevance: In this cohort study of TENC participants, the findings show that unhealthy lifestyle and high genetic risk were significantly associated with a higher risk of MCI among Chinese older adults. Unhealthy lifestyle factors were associated with a higher risk of MCI regardless of genetic risk, and lifestyle and genetic risk had synergistic interactions. These findings could contribute to the development of dietary guidelines and the prevention of early-stage dementia.