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Objective: Cardiomyocyte senescence is an important contributor to cardiovascular diseases and can be induced by stressors including DNA damage, oxidative stress, mitochondrial dysfunction, epigenetic regulation, etc. However, the underlying mechanisms for the development of cardiomyocyte senescence remain largely unknown. Sulfur dioxide (SO2) is produced endogenously by aspartate aminotransferase 2 (AAT2) catalysis and plays an important regulatory role in the development of cardiovascular diseases. The present study aimed to explore the effect of endogenous SO2 on cardiomyocyte senescence and the underlying molecular mechanisms. Approach and results: We interestingly found a substantial reduction in the expression of AAT2 in the heart of aged mice in comparison to young mice. AAT2-knockdowned cardiomyocytes exhibited reduced SO2 content, elevated expression levels of Tp53, p21Cip/Waf, and p16INk4a, enhanced SA-β-Gal activity, and elevated level of γ-H2AX foci. Notably, supplementation with a SO2 donor ameliorated the spontaneous senescence phenotype and DNA damage caused by AAT2 deficiency in cardiomyocytes. Mechanistically, AAT2 deficiency suppressed the sulphenylation of signal transducer and activator of transcription 3 (STAT3) facilitated its nuclear translocation and DNA-binding capacity. Conversely, a mutation in the cysteine (Cys) 259 residue of STAT3 blocked SO2-induced STAT3 sulphenylation and subsequently prevented the inhibitory effect of SO2 on STAT3-DNA-binding capacity, DNA damage, and cardiomyocyte senescence. Additionally, cardiomyocyte (cm)-specific AAT2 knockout (AAT2cmKO) mice exhibited a deterioration in cardiac function, cardiomegaly, and cardiac aging, whereas supplementation with SO2 donors mitigated the cardiac aging and remodeling phenotypes in AAT2cmKO mice. Conclusion: Downregulation of the endogenous SO2/AAT2 pathway is a crucial pathogenic mechanism underlying cardiomyocyte senescence. Endogenous SO2 modifies STAT3 by sulphenylating Cys259, leading to the inhibition of DNA damage and the protection against cardiomyocyte senescence.

Placenta accreta spectrum disorder (PAS) is a kind of disease of placentation defined as abnormal trophoblast invasion of part or all of the placenta into the myometrium, even penetrating the uterus. Decidual deficiency, abnormal vascular remodeling in the maternal–fetal interface, and excessive invasion by extravillous trophoblast (EVT) cells contribute to its onset. However, the mechanisms and signaling pathways underlying such phenotypes are not fully understood, partly due to the lack of suitable experimental animal models. Appropriate animal models will facilitate the comprehensive and systematic elucidation of the pathogenesis of PAS. Due to the remarkably similar functional placental villous units and hemochorial placentation to humans, the current animal models of PAS are based on mice. There are various mouse models induced by uterine surgery to simulate different phenotypes of PAS, such as excessive invasion of EVT or immune disturbance at the maternal–fetal interface, which could define the pathological mechanism of PAS from the perspective of the “soil.” Additionally, genetically modified mouse models could be used to study PAS, which is helpful to exploring the pathogenesis of PAS from the perspectives of both “soil” and “seed,” respectively. This review details early placental development in mice, with a focus on the approaches of PAS modeling. Additionally, the strengths, limitations and the applicability of each strategy and further perspectives are summarized to provide the theoretical foundation for researchers to select appropriate animal models for various research purposes. This will help better determine the pathogenesis of PAS and even promote possible therapy.

Pool boiling is the heat-transfer mechanism of many heat exchangers inside ocean nuclear power plants working under the complex marine circumstances. Also, ocean conditions will create a new acceleration field other than gravity for the fluid, which induces some unique thermal–hydraulic characteristics. In this study, pool boiling under heaving conditions is numerically simulated using multiple relaxation time phase change lattice Boltzmann method. Firstly, the simulated results under static condition have been validated with recognized empirical equations, such as Rohsenow’s correlation at nucleate boiling, Zuber’s model, and Kandlikar’s model about critical heat flux (CHF). Then, pool boiling patterns, the boiling curve of time-averaged heat flux, transient heat flux, and heaving effects on different pool boiling regions are investigated. The results show that pool boiling curves of time-averaged heat flux between heaving conditions and static conditions with middle superheat degrees are similar. Heat transfer under heaving conditions at low superheat is somewhat enhanced, and it is weakened at high superheat, which leads to a slightly smaller critical heat flux with larger superheat compared with that under static conditions. Moreover, distinct fluctuation of the transient heat flux of pool boiling under heaving conditions is found for all boiling regimes. Furthermore, the heaving condition shows both positive and negative effects on pool boiling heat transfer at high-gravity and low-gravity regions, respectively. Besides, both the larger heaving height and shorter period time bring out more violent heaving motion and make a greater impact on pool boiling heat transfer.

Rolling motion caused by ocean condition will induce more complicated inertial forces with their force directions changing all the time, which results more complex bubble behaviors and unique heat transfer characteristics. In this work, pool boiling under rolling condition is numerically simulated using multiple relaxation time phase change lattice Boltzmann method (LBM). Pool boiling patterns, boiling curve of time-averaged heat flux, transient heat flux and rolling effects on different pool boiling regions are investigated. The results show that pool boiling curve of time-averaged heat flux between rolling condition and static condition are not obvious until close to critical heat flux, and 9.3% higher CHF is achieved under rolling condition while worse heat transfer is discovered at film boiling. Moreover, distinct fluctuation of transient heat flux of pool boiling under rolling condition is found for all boiling regimes, and its variation pattern along with the rolling motion and bubble behavior is investigated. Furthermore, tangential inertial force caused by rolling motion has positive influence on heat transfer of pool boiling, while the centrifugal force has negative influence on heat transfer, since it is opposite to the gravity and hence decreases the buoyancy force. Besides, larger rolling amplitude and smaller rolling period will induce larger additional inertial forces, and thus make greater influences on the bubbles’ behavior and pool boiling heat transfer.

Dilated cardiomyopathy (DCM) is a severe disorder caused by medications or genetic mutations. D5 dopamine receptor (D5R) gene knockout (D5-/-) mice have cardiac hypertrophy and high blood pressure. To investigate the role and mechanism by which the D5R regulates cardiac function, we generated cardiac-specific human D5R F173L(hD5F173L-TG) and cardiac-specific human D5R wild-type (hD5WT-TG) transgenic mice, and H9c2 cells stably expressing hD5F173L and hD5WT. We found that cardiac-specific hD5F173L-TG mice, relative to hD5WT-TG mice, presented with DCM and increased cardiac expression of cardiac injury markers, NADPH oxidase activity, Nrf2 degradation, and activated ERK1/2/JNK pathway. H9c2-hD5F173L cells also had an increase in NADPH oxidase activity, Nrf2 degradation, and phospho-JNK (p-JNK) expression. A Nrf2 inhibitor also increased p-JNK expression in H9c2-hD5F173L cells but not in H9c2-hD5WT cells. We suggest that the D5R may play an important role in the preservation of normal heart function by inhibiting the production of reactive oxygen species, via inhibition of NADPH oxidase, Nrf2 degradation, and ERK1/2/JNK pathways. Keywords: Dilated cardiomyopathy (DCM), Dopamine D5 receptor (D5R), Reactive oxygen species (ROS), Nrf2

Background. To determine the exact role of estrogen in vaginal tissue morphology and estrogen receptor-alpha (ERα) distribution in the vagina, which remains controversial. Methods. Sixty rats were randomly categorized: sham-operated (sham), ovariectomy (OVX), and four estradiol treatments (estradiol valerate at 0.4, 0.8, 1.6, and 3.2 mg/kg/day) for 2 weeks. Thereafter, vaginal samples were biopsied from the distal- and proximal-half portions. The percentage of ERα-immunoreactive cells and the ERα score were quantified using immunohistochemistry to assess changes in ERα expression and distribution. Results. OVX induced significant vaginal atrophy and organic index. Estrogen-replacement therapy (ERT) reversed vaginal atrophy. The vaginal distal-half areas showed lower ERα% than the proximal-half areas. The ERα% increased sharply 4 weeks after OVX, especially in the epithelial layer (P=0.023). ERT elicited different degrees of reductions in tissues after the 2-week treatment, but the ERα% in only the epithelium recovered in parallel with that in the sham group (P=0.001). The OVX group showed higher ERα histological scores than the sham group, and the distal-half area changed more evidently than the proximal-half area. ERα expression was nearly unchanged after ERT (P>0.05). Conclusions. ERT is effective for treating obesity and vulvovaginal atrophy caused by hypoestrogenism and advancing age in menopausal women but cannot recover the distribution and expression of ERα.

Maternal high-fat diet intake has profound effects on the long-term health of offspring, predisposing them to a higher susceptibility to obesity and metabolic dysfunction-associated steatotic liver disease. However, the detailed mechanisms underlying the role of a maternal high-fat diet in hepatic lipid accumulation in offspring, especially at the weaning age, remain largely unclear. In this study, female C57BL/6J mice were randomly assigned to either a high-fat diet or a control diet, and lipid metabolism parameters were assessed in male offspring at weaning. Gut microbiota analysis and targeted metabolomics of short-chain fatty acids (SCFAs) in these offspring were further performed. Both in vivo and in vitro studies were conducted to explore the role of butyrate in hepatic cholesterol excretion in the liver and HepG2 cells. Our results showed that maternal high-fat feeding led to obesity and dyslipidemia, and exacerbated hepatic lipid accumulation in the livers of offspring at weaning. We observed significant decreases in the abundance of the Firmicutes phylum and the Allobaculum genus, known as producers of SCFAs, particularly butyrate, in the offspring of dams fed a high-fat diet. Additionally, maternal high-fat diet feeding markedly decreased serum butyrate levels and down-regulated ATP-binding cassette transporters G5 (ABCG5) in the liver, accompanied by decreased phosphorylated AMP-activated protein kinase (AMPK) and histone deacetylase 5 (HADC5) expressions. Subsequent in vitro studies revealed that butyrate could induce ABCG5 activation and alleviate lipid accumulation via the AMPK-pHDAC5 pathway in HepG2 cells. Moreover, knockdown of HDAC5 up-regulated ABCG5 expression and promoted cholesterol excretion in HepG2 cells. In conclusion, our study provides novel insights into how maternal high-fat diet feeding inhibits hepatic cholesterol excretion and down-regulates ABCG5 through the butyrate-AMPK-pHDAC5 pathway in offspring at weaning. [ABSTRACT FROM AUTHOR]

Maternal overnutrition can dramatically increase the susceptibility of offspring to metabolic diseases, whereas maternal exercise may improve glucose metabolism in offspring. However, the underlying mechanism programming the intergenerational effects of maternal exercise on the benefits of glucose metabolism has not been fully elaborated. C57BL/6 female mice were randomly assigned to four subgroups according to a diet and exercise paradigm before and during pregnancy as follows: NC (fed with normal chow diet and sedentary), NCEx (fed with normal chow diet and running), HF (fed with high-fat diet and sedentary), and HFEx (fed with high-fat diet and running). Integrative 16S rDNA sequencing and mass spectrometry-based metabolite profiling were synchronously performed to characterize the effects of maternal exercise on the gut microbiota composition and metabolite alterations in offspring. Maternal exercise, acting as a natural pharmaceutical intervention, prevented deleterious effects on glucose metabolism in offspring. 16S rDNA sequencing revealed remarkable changes in the gut microbiota composition in offspring. Metabolic profiling indicated multiple altered metabolites, which were enriched in butanoate metabolism signaling in offspring. We further found that maternal exercise could mediate gene expression related to intestinal gluconeogenesis in offspring. In conclusion, our study indicated that maternal running significantly improved glucose metabolism in offspring and counteracted the detrimental effects of maternal high-fat feeding before and during pregnancy. We further demonstrated that maternal voluntary wheel running could integratively program the gut microbiota composition and fecal metabolite changes and then regulate butanoate metabolism and mediate intestinal gluconeogenesis in offspring. [ABSTRACT FROM AUTHOR]

The browning on the cut surface is a big problem reducing the quality of fresh-cut taro (FCT), which causes severe postharvest losses and may raise environmental impacts. Citronellal (CA) is a natural compound in several aromatic plants. This study investigated the effects of CA treatments in different concentrations (0.2, 0.5, and 1 mL/L) on the browning of FCT under cold storage at 5°C. The results indicated that low-dose (0.2 mL/L) CA treatment showed best anti-browning effects, reflecting at the maintained L* values but the reduced a*, b* and browning index values by CA treatment during cold storage. A repeated experiment using 0.2 mL/L CA confirmed fine anti-browning effects again. Furthermore, CA (0.2 mL/L) treatment markedly reduced the contents of total phenolic compounds and soluble quinones, restrained the activities of phenylalanine ammonia lyase, peroxidase and polyphenol oxidase, down-regulated the gene expression of 18 browning-related enzymes in FCT. These results together strongly demonstrate the validity of CA on FCT browning prevention. Given that CA is a natural compound existing in plants, low concentration of CA possesses strong anti-browning effects on FCT and also inhibitory effects on pathogens, implying that its application has potentiality to preserve high quality of fresh-cut produce for processing and storage. Moreover, CA treatment significantly decreased malondialdehyde contents and lipoxygenase activity. Correlation analysis indicated that the lipid peroxidation of cell membrane was mostly correlated with FCT browning. The results suggest that membrane lipid peroxidation was a possible reason for FCT browning and CA treatment reduced browning, in part, through alleviating the lipid peroxidation of cell membrane. Overall, our results demonstrate that CA is a novel browning mitigator for FCT under cold storage condition.

Taro (Colocasia esculenta) is a major root crop or vegetable in the world, and the corm is a good source of many nutrients including starch, vitamins, and minerals. Taro corms are processed into various forms before consumption, which makes them perishable, reduces the shelf life, and increases postharvest losses. The surface browning of fresh-cut taros is one of the major factors that limits storage life and affects consumer acceptance. In this study, the effects of ferulic acid (FA) as an effective agent in the prevention of quality deterioration were investigated. Fresh-cut taros were immersed in distilled water and different concentrations of FA (1, 2, 5, 10, and 20 mM) solutions for 30 min, air-dried at 25°C for 30 min, and then stored at 5°C for 12 days to investigate the effects of FA on browning. Among the FA concentrations tested, 10 mM resulted in significantly higher L* values, lower a* and b*, and browning index values. FA treatment (10 mM) also induced de novo biosynthesis of two volatile compounds, including non-anal and octanoic acid ethyl ester in fresh-cut taros following extended cold storage. The results suggest that FA treatment maintains the quality of fresh-cut taros under cold conditions. FA treatment enhanced PAL activity and gene expression but reduced total phenolic content and the expression of six C4H, 4CL, and CHS genes, suggesting that FA treatment reduced phenolic biosynthesis. FA treatment reduced PPO activity and gene expression and decreased soluble quinone content, suggesting that FA treatment suppressed the phenolic oxidation. FA treatment enhanced the activity and gene expression of CAT and POD, reduced those of LOX, and decreased MDA and H2O2 levels, suggesting that FA treatment activated the antioxidant defense system and thereby reduced oxidative damage. These findings demonstrated that FA treatment could serve as an effective approach to retard the browning of fresh-cut taros and provided a basis for the feasible application of FA in the preservation of fresh-cut foods.

In order to deeply study the characteristics of Kirchhoff equation, the existence result of the least energy sign-changing solutions to Kirchhoff equation with Hartree term and critical growth nonlinear term was discussed. The technical result of the space E compact embedding L6([WTHZ]R3)[WTBZ] was obtained by using the infimum of the energy functional on the sign-changing Nehari manifold convergences to zero. The results shows that the minimum point corresponding to the minimizing sequence obtained by the restricted variational method and quantitative deformation lemma is the nontrivial solutions for the problem. The research method in theoretical proof gets effective results and has a certain guiding significance for studying the existence of solutions of other Kirchhoff equations.

In order to expound the influence of sign-changing potential on logarithmic nonlinearity and Hatree nonlinearity. By the variational method, a weak solution to the problem is a critical point of the energy functional. Then, by the logarithmic inequality, the energy functional of Schrdinger problem satisfies the mountain geometry and (PS) condition. The existence of nontrivial solutions is obtained by mountain pass theorem. The research method has good expected results in theoretical proof and laid a good foundation for the study of Schrdinger problem with logarithmic nonlinearity with double sign-changing potential.

In this paper we consider nonlinear Choquard equation \begin{equation*} -\Delta u+V(x)u=(I_\alpha*F(u))f(u)\quad {\rm in}\ \mathbb{R}^{N}, \end{equation*} where $V\in C(\mathbb{R}^N)$, $I_\alpha$ denotes the Riesz potential, $f(t)=|t|^{p-2}t+|t|^{q-2}t$ for all $t\in\mathbb{R}$, $N\geqslant5$ and $\alpha\in(0,N-4)$. Under suitable conditions on $V$, we obtain that the Choquard equation with doubly critical growth nonlinearity, i.e., $p=(N+\alpha)/N,q=(N+\alpha)/(N-2)$, has a nonnegative ground state solution by variational methods.

Objective: Primary care in China is facing mounting challenges with multimorbidity as the aging population grows. Knowing how patients experience primary care may highlight the deficiencies of the care system and guide health system reform. The purpose of this study was to compare the quality of primary care experienced by patients with and without multimorbidity at community health centers (CHCs) in Shanghai, China and to examine the factors influencing these experiences.Methods: A cross-sectional survey was conducted from August to December 2019 using the validated Chinese Primary Care Assessment Tool-Adult Edition (PCAT-AE). ANOVA was performed to compare the overall and domain-specific quality of primary care for patients with and without multimorbidity. Multivariate linear regressions were used to assess the factors associated with primary care quality while controlling for patients' sociodemographic and healthcare characteristics.Results: From 2,404 completed questionnaires, patients with multimorbidity reported higher PCAT scores in the domains of first contact-utilization (3.54 ± 0.55 vs. 3.48 ± 0.56, P < 0.01), accessibility (2.93 ± 0.49 vs. 2.86 ± 0.47, P < 0.001), and ongoing care (3.20 ± 0.39 vs. 3.14 ± 0.43, P < 0.001), while reporting lower scores in coordination (information system) (2.72 ± 0.41 vs. 2.79 ± 0.35, P < 0.001) and family-centeredness (3.23 ± 0.63 vs. 3.30 ± 0.64, P < 0.01). Multimorbidity (ß = 0.355, P < 0.01), education level (ß = 0.826, P < 0.01), district (suburb: ß = 1.475, P < 0.001), and self-perceived good health status (ß = 0.337, P < 0.05) were associated with better patient experiences in primary care. Patients between the age 61 and 70 (ß = −0.623, P < 0.001; >70 years: ß = −0.573, P < 0.01), with a monthly household income ≥6,000 RMB (ß = −1.385, P < 0.001) and with more than 20 outpatient visits the previous year (ß = −1.883, P < 0.001) reported lower total PCAT scores.Conclusion: The findings of our study suggest that CHCs in China have contributed to better primary care experiences for patients with multimorbidity in certain quality domains, including first contact-utilization, accessibility, and ongoing care. However, there is still room for improvement in care coordination and family-centeredness.