A GABAergic system in atrioventricular node pacemaker cells controls electrical conduction between the atria and ventricles.

Physiologically, the atria contract first, followed by the ventricles, which is the prerequisite for normal blood circulation. The above phenomenon of atrioventricular sequential contraction results from the characteristically slow conduction of electrical excitation of the atrioventricular node (AVN) between the atria and the ventricles. However, it is not clear what controls the conduction of electrical excitation within AVNs. Here, we find that AVN pacemaker cells (AVNPCs) possess an intact intrinsic GABAergic system, which plays a key role in electrical conduction from the atria to the ventricles. First, along with the discovery of abundant GABA-containing vesicles under the surface membranes of AVNPCs, key elements of the GABAergic system, including GABA metabolic enzymes, GABA receptors, and GABA transporters, were identified in AVNPCs. Second, GABA synchronously elicited GABA-gated currents in AVNPCs, which significantly weakened the excitability of AVNPCs. Third, the key molecular elements of the GABAergic system markedly modulated the conductivity of electrical excitation in the AVN. Fourth, GABAA receptor deficiency in AVNPCs accelerated atrioventricular conduction, which impaired the AVN's protective potential against rapid ventricular frequency responses, increased susceptibility to lethal ventricular arrhythmias, and decreased the cardiac contractile function. Finally, interventions targeting the GABAergic system effectively prevented the occurrence and development of atrioventricular block. In summary, the endogenous GABAergic system in AVNPCs determines the slow conduction of electrical excitation within AVNs, thereby ensuring sequential atrioventricular contraction. The endogenous GABAergic system shows promise as a novel intervention target for cardiac arrhythmias.

The Relationship between Addictive Use of Short-Video Platforms and Marital Satisfaction in Older Chinese Couples: An Asymmetrical Dyadic Process.

Increasing evidence indicates that the addictive use of social media can have a detrimental effect on marital satisfaction, due mainly to the decrease in time and focus given to one's spouse. However, the impact of social media use among older couples remains under-investigated, and the research that does exist relies on individual-level data that do not allow the exploration of the dynamics between the dyadic partners. Therefore, the present study focused on older adults' use of short-video platforms, as these have been shown to be particularly addictive for older adults. A sample of 264 older couples was gathered (meanage = 68.02, SD = 8.68), and both spouses completed surveys reporting addictive use of short-video platforms, negative emotions, and marital satisfaction. Using an actor-partner interdependence model, we found an asymmetrical dyadic process in that the addictive use of short-video platforms by the wives was not only related to their own negative emotions, but also those of their spouse, as well as to decreased marital satisfaction. Meanwhile, addictive use by the husbands seemed to relate only to their own increased negative emotions, as well as to decreased marital satisfaction. Together, the findings from this study reveal dyadic dynamics with delineated pathways through which the addictive use of short-video platforms can damage older couples' interactive processes and marital satisfaction.

Developing Polymeric Carbon Nitrides for Photocatalytic H2O2 Production.

Hydrogen peroxide (H2O2) plays a crucial role in various applications, such as green oxidation processes and the production of high-quality fuels. Currently, H2O2 is primarily manufactured using the indirect anthraquinone method, known for its significant energy consumption and the generation of intensive by-products. Extensive research has been conducted on the photocatalytic production of H2O2 via oxygen reduction reaction (ORR), with polymeric carbon nitride (PCN) emerging as a promising catalyst for this conversion. This review article is organized around two approaches. The first part main consists of the chemical optimization of the PCN structure, while the second focuses on the physical integration of PCN with other functional materials. The objective is to clarify the correlation between the physicochemical properties of PCN photocatalysts and their effectiveness in H2O2 production. Through a thorough review and analysis of the findings, this article seeks to stimulate new insights and achievements, not only in the domain of H2O2 production via ORR but also in other redox reactions.

Deficiency of Transcription Factor Sp1 Contributes to Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disorder. However, the pathogenesis of HCM, especially its nongenetic mechanisms, remains largely unclear. Transcription factors are known to be involved in various biological processes including cell growth. We hypothesized that SP1 (specificity protein 1), the first purified TF in mammals, plays a role in the cardiomyocyte growth and cardiac hypertrophy of HCM. METHODS: Cardiac-specific conditional knockout of Sp1 mice were constructed to investigate the role of SP1 in the heart. The echocardiography, histochemical experiment, and transmission electron microscope were performed to analyze the cardiac phenotypes of cardiac-specific conditional knockout of Sp1 mice. RNA sequencing, chromatin immunoprecipitation sequencing, and adeno-associated virus experiments in vivo were performed to explore the downstream molecules of SP1. To examine the therapeutic effect of SP1 on HCM, an SP1 overexpression vector was constructed and injected into the mutant allele of Myh6 R404Q/+ (Myh6 c. 1211C>T) HCM mice. The human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with HCM were used to detect the potential therapeutic effects of SP1 in human HCM. RESULTS: The cardiac-specific conditional knockout of Sp1 mice developed a typical HCM phenotype, displaying overt myocardial hypertrophy, interstitial fibrosis, and disordered myofilament. In addition, Sp1 knockdown dramatically increased the cell area of hiPSC-CMs and caused intracellular myofibrillar disorganization, which was similar to the hypertrophic cardiomyocytes of HCM. Mechanistically, Tuft1 was identified as the key target gene of SP1. The hypertrophic phenotypes induced by Sp1 knockdown in both hiPSC-CMs and mice could be rescued by TUFT1 (tuftelin 1) overexpression. Furthermore, SP1 overexpression suppressed the development of HCM in the mutant allele of Myh6 R404Q/+ mice and also reversed the hypertrophic phenotype of HCM hiPSC-CMs. CONCLUSIONS: Our study demonstrates that SP1 deficiency leads to HCM. SP1 overexpression exhibits significant therapeutic effects on both HCM mice and HCM hiPSC-CMs, suggesting that SP1 could be a potential intervention target for HCM.

Mining host candidate regulators of schistosomiasis-induced liver fibrosis in response to artesunate therapy through transcriptomics approach.

BACKGROUND: Artesunate (ART) has been reported to have an antifibrotic effect in various organs. The underlying mechanism has not been systematically elucidated. We aimed to clarify the effect of ART on liver fibrosis induced by Schistosoma japonicum (S. japonicum) in an experimentally infected rodent model and the potential underlying mechanisms. METHODS: The effect of ART on hepatic stellate cells (HSCs) was assessed using CCK-8 and Annexin V-FITC/PI staining assays. The experimental model of liver fibrosis was established in the Mongolian gerbil model infected with S. japonicum cercariae and then treated with 20 mg/kg or 40 mg/kg ART. The hydroxyproline (Hyp) content, malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities in liver tissue were measured and histopathological changes of liver tissues were observed. Whole-transcriptome RNA sequencing (RNA-seq) of the liver tissues was performed. Differentially expressed genes (DEGs) were identified using bioinformatic analysis and verified by quantitative PCR (qPCR) and western blot assay. RESULTS: ART significantly inhibited the proliferation and induce the apoptosis of HSCs in a dose-dependent manner. In vivo, Hyp content decreased significantly in the ART-H group compared to the model (MOD) group and GPX activity was significantly higher in the ART-H group than in the MOD group. Besides, ART treatment significantly reduced collagen production (p <0.05). A total of 158 DEGs and 44 differentially expressed miRNAs related to ART-induced anti-schistosomiasis liver fibrosis were identified. The qPCR and western blot results of selected DEGs were consistent with the sequencing results. These DEGs were implicated in key pathways such as immune and inflammatory response, integrin-mediated signaling and toll-like receptor signaling pathways. CONCLUSION: ART is effective against liver fibrosis using Mongolian gerbil model induced by S. japonicum infection. We identified host candidate regulators of schistosomiasis-induced liver fibrosis in response to ART through transcriptomics approach.

Biocatalytic asymmetric reduction of fluoroalkyl ketones to access enantiopure fluoroalkyl secondary alcohols.

An efficient biocatalytic reduction of difluoroalkyl ketones for accessing chiral fluoroalkyl secondary alcohols is reported using commercial NADPH-dependent ketoreductase K234 with 2-propanol as a co-substrate for NADPH regeneration. This bioreduction reaction could be applied to a broad range of prochiral fluoroketones including aryl difluoroketones, aliphatic difluoroketones, and trifluoroacetophenones with excellent conversion and favorable enantioselectivity at high substrate concentrations (100 g L-1). These results indicate the potential of K234 for the industrial production of valuable chiral fluorohydrins. Moreover, this biocatalytic protocol could also be effective without the addition of an external nicotinamide cofactor, which provides useful guidance for further application of ketoreductase K234 in the asymmetric synthesis of chiral secondary alcohols.

Transcriptomes reveal microRNAs and mRNAs in different photoperiods influencing cashmere growth in goat.

Cashmere goat has a typical characteristic in seasonal growth of cashmere. Studies have shown that one of the main factors affecting the cyclical growth of the cashmere is the photoperiod, however, its molecular mechanism remains unclear. Inner Mongolia Arbas cashmere goat was used to reveal the mRNA-microRNA regulatory mechanisms of cashmere growth in different photoperiod. Skin samples from cashmere goats under light control (short photoperiod) and normal conditions (long photoperiod) were collected. Sequencing was performed after RNA extraction. The differentially expressed miRNA and mRNA expression profiles were successfully constructed. We found 56 significantly differentially expressed known mRNAs (P<0.01) and 14 microRNAs (P<0.05). The association analysis of the microRNAs and mRNAs showed that two differentially expressed miRNAs might be targeted by six differentially expressed genes. Targeting relationships of these genes and miRNAs are revealed and verified. In all, the light control technology provides a new way to promote cashmere growth. Our results provide some references in the cashmere growth and development.

Endothelial deletion of PTBP1 disrupts ventricular chamber development.

The growth and maturation of the ventricular chamber require spatiotemporally precise synergy between diverse cell types. Alternative splicing deeply affects the processes. However, the functional properties of alternative splicing in cardiac development are largely unknown. Our study reveals that an alternative splicing factor polypyrimidine tract-binding protein 1 (PTBP1) plays a key role in ventricular chamber morphogenesis. During heart development, PTBP1 colocalizes with endothelial cells but is almost undetectable in cardiomyocytes. The endothelial-specific knockout of Ptbp1, in either endocardial cells or pan-endothelial cells, leads to a typical phenotype of left ventricular noncompaction (LVNC). Mechanistically, the deletion of Ptbp1 reduces the migration of endothelial cells, disrupting cardiomyocyte proliferation and ultimately leading to the LVNC. Further study shows that Ptbp1 deficiency changes the alternative splicing of ß-arrestin-1 (Arrb1), which affects endothelial cell migration. In conclusion, as an alternative splicing factor, PTBP1 is essential during ventricular chamber development, and its deficiency can lead to congenital heart disease.

Antibody Response to SARS-CoV-2 in the First Batch of COVID-19 Patients in China by a Self-Developed Rapid IgM-IgG Test.

It has been over two years since the COVID-19 pandemic began and it is still an unprecedented global challenge. Here, we aim to characterize the antibody profile from a large batch of early COVID-19 cases in China, from January - March 2020. More than 1,000 serum samples from participants in Hubei and Zhejiang province were collected. A series of serum samples were also collected along the disease course from 70 patients in Shanghai and Chongqing for longitudinal analysis. The serologic assay (ALLtest) we developed was confirmed to have high sensitivity (92.58% - 97.55%) and high specificity (92.14% - 96.28%) for the detection of SARS-CoV-2 nucleocapsid-specific antibodies. Confirmed cases found in the Hubei Provincial Center for Disease Control and Prevention (HBCDC), showed a significantly (p = 0.0018) higher positive rate from the ALLtest than RNA test. Then, we further identified the disease course, age, sex, and symptoms that were correlating factors with our ALLtest results. In summary, we confirmed the high reliability of our ALLtest and its important role in COVID-19 diagnosis. The correlating factors we identified will require special attention during future clinical application.

LRP5 regulates cardiomyocyte proliferation and neonatal heart regeneration by the AKT/P21 pathway.

The neonatal heart can efficiently regenerate within a short period after birth, whereas the adult mammalian heart has extremely limited capacity to regenerate. The molecular mechanisms underlying neonatal heart regeneration remain elusive. Here, we revealed that as a coreceptor of Wnt signalling, low-density lipoprotein receptor-related protein 5 (LRP5) is required for neonatal heart regeneration by regulating cardiomyocyte proliferation. The expression of LRP5 in the mouse heart gradually decreased after birth, consistent with the time window during which cardiomyocytes withdrew from the cell cycle. LRP5 downregulation reduced the proliferation of neonatal cardiomyocytes, while LRP5 overexpression promoted cardiomyocyte proliferation. The cardiac-specific deletion of Lrp5 disrupted myocardial regeneration after injury, exhibiting extensive fibrotic scars and cardiac dysfunction. Mechanistically, the decreased heart regeneration ability induced by LRP5 deficiency was mainly due to reduced cardiomyocyte proliferation. Further study identified AKT/P21 signalling as the key pathway accounting for the regulation of cardiomyocyte proliferation mediated by LRP5. LRP5 downregulation accelerated the degradation of AKT, leading to increased expression of the cyclin-dependent kinase inhibitor P21. Our study revealed that LRP5 is necessary for cardiomyocyte proliferation and neonatal heart regeneration, providing a potential strategy to repair myocardial injury.

Multilayer Structure Ammoniated Collagen Fibers for Fast Adsorption of Anionic Dyes.

Dye wastewater has become one of the difficult industrial wastewaters due to its significant characteristics such as high chroma and poor biodegradability. Here, we use collagen fibers (CFs) as the matrix, glutaraldehyde as the cross-linking agent, and polyethyleneimine (PEI) as the ammoniating modifier to prepare cationic-modified collagen fibers (CF-PEI). The CF-PEI still maintained the original fibrous structure with a larger adsorption area. The content of primary amino groups on CF-PEI was significantly increased, which not only improved the hydrophilic swelling performance of CFs but also improved the adsorption capacity. The adsorption capacity of CF-PEI for soap yellow and acid red could reach 538.2 and 369.7 mg g-1, respectively. The adsorption rate was fast, and the adsorption equilibrium could be reached in about 60 min. Desorption regeneration studies have shown that 0.1 mol L-1 HCl could achieve a better desorption effect, and the CF-PEI had a good recycling performance. The ammoniated modified CF-PEI was an excellent adsorption treatment material for anionic dye wastewater. It is expected to become an effective way for high-value resource utilization of waste dander in the leather industry.

LRP6 downregulation promotes cardiomyocyte proliferation and heart regeneration.

The adult mammalian heart is thought to be a terminally differentiated organ given the postmitotic nature of cardiomyocytes. Consequently, the potential for cardiac repair through cardiomyocyte proliferation is extremely limited. Low-density lipoprotein receptor-related protein 6 (LRP6) is a Wnt co-receptor that is required for embryonic heart development. In this study we investigated the role of LRP6 in heart repair through regulation of cardiomyocyte proliferation. Lrp6 deficiency increased cardiomyocyte cell cycle activity in neonatal, juvenile and adult mice. Cardiomyocyte-specific deletion of Lrp6 in the mouse heart induced a robust regenerative response after myocardial infarction (MI), led to reduced MI area and improvement in left ventricular systolic function. In vivo genetic lineage tracing revealed that the newly formed cardiomyocytes in Lrp6-deficient mouse hearts after MI were mainly derived from resident cardiomyocytes. Furthermore, we found that the pro-proliferative effect of Lrp6 deficiency was mediated by the ING5/P21 signaling pathway. Gene therapy using the adeno-associated virus (AAV)9 miRNAi-Lrp6 construct promoted the repair of heart injury in mice. Lrp6 deficiency also induced the proliferation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Our study identifies LRP6 as a critical regulator of cardiomyocyte proliferation, which may lead to the development of a novel molecular strategy to promote myocardial regeneration and repair.

Enhancing the Phase Stability of Inorganic α-CsPbI3 by the Bication-Conjugated Organic Molecule for Efficient Perovskite Solar Cells.

Inorganic CsPbI3 perovskite has demonstrated promising potentials for photovoltaic applications, whereas the black perovskite polymorph (α phase) of CsPbI3 was easily prone to converting into yellow phase (δ phase) under ambient moist environment, which restrained its practical application and further studies severely. In this study, p-phenylenediammonium iodide (PPDI) was employed to posttreat CsPbI3 films for controlling the phase conversion, strengthening moisture resistance, and improving device performance. The multiple roles of PPDI were as follows: (1) avoiding spontaneous octahedral tilting by ionic bonds between NH3+ of PPD2+ and I- of [PbI6]4-; (2) enhancing the hydrophobicity induced by exactly exposed oil-wet (hydrophobic) benzene rings; and (3) passivating surface defects and filling I vacancies. As a result, after the treatment, mutable a-CsPbI3 could maintain its α phase for at least 30 d in dry air (<20% RH). The perovskite solar cells with PPDI treatment exhibited reproductive photovoltaic performance with a champion power conversion efficiency (PCE) of 10.4, and 91% of the initial PCE was retained after storage for 504 h in a dark dry box without any encapsulation.

Enhanced Capture Ability of Sludge-Derived Mesoporous Biochar with a Template-like Method.

Sewage sludge-derived mesoporous biochars (SS-MBCs) were prepared by using cationic polyacrylamide (PAM+) as a template agent through a template-like method under high temperature and employed for getting rid of methylene blue (MB) from water. Textural evolution, mesostructured morphology, thermodynamic properties, and surface chemical groups of SS-MBCs were analyzed. It showed that PAM+ not only played an important role in good nucleation that brought well-developed texture and novel pore size distribution to SS-MBCs but also improved the MB adsorption capacities of SS-MBCs by increasing the specific surface area and the content of oxygen functional groups, especially the lactone. Preparation factor analysis indicated that PAM+ concentration, dosage of additive sludge, and carbonization temperature had distinct effects on material structure and adsorption performance especially above the pyrolytic temperature of 800 °C. The adsorption kinetics and isotherms were analyzed in detail, and it revealed that the kinetics and equilibrium adsorptions of SS-MBCs could be well-described by the Langmuir isotherm model and pseudo-second-order kinetics, respectively. Remarkably, the SS-MBCs showed higher removal efficiency and adsorption capacity than commercial activated carbon and most reported sludge-based adsorbents.

[Ecological environmental effects of land consolidation:Mechanism of action and application path]. / 土地整治的生态环境效应:作用机制及应用路径.

With the continuous implementation of ecological civilization and the transformation of multi-functional land management, the ecologicalization of land consolidation has entered a critical period of theoretic innovation and practical application. Systematically combing the development of theoretical research and practical exploration of ecological environment effect of land consolidation, and clarifying the service direction and implementation path of the land science discipline research under the "New Era" are urgent for the implementation of the "ecological" land consolidation stra-tegy. We reviewed the literatures on the ecological environment effects of land consolidation in the past 18 years. Using Citespace 1.0 software as analysis tool, we identified the research hotspots of ecological environmental effects of land consolidation, and discussed the mechanism of ecological environmental effects of land consolidation based on the analysis of relationship among ecological environment elements, ecological landscape and ecosystem services. Further, we proposed a new application path of "ecological" land consolidation from the measurement of regional ecosystem service level and the diagnosis of obstacle factors, the impact of land consolidation on regional ecosystem services and its mechanism, and the construction of ecological land consolidation model based on the promotion of ecosystem services, which aimed to provide a scientific basis for the restoration and construction of the life community of "mountains, rivers, forests, fields, lakes and grasses" in China.

LRP5 controls cardiac QT interval by modulating the metabolic homeostasis of L-type calcium channel.

BACKGROUND: Low-density lipoprotein receptor-related protein 5 (LRP5) has been intensively studied as a co-receptor for ß-catenin-dependent Wnt signaling. Emerging evidences have demonstrated ß-catenin-independent functions of LRP5. However, the biological role of LRP5 in the mammalian heart is largely unknown. METHODS AND RESULTS: Conditional cardiac-specific Lrp5 knockout (Lrp5-CKO) mice were generated by crossing Lrp5flox/flox mice with αMHC/MerCreMer mice. Lrp5-CKO mice consistently displayed normal cardiac structure and function. Telemetric electrocardiogram recordings revealed a short QT interval in Lrp5-CKO mice, which was tightly linked to the striking abbreviation of action potential duration (APD) in ventricular myocytes. The analysis of whole-cell currents indicated that a reduction in activity and protein expression of L-type calcium channel (LTCC), rather than other ion channels, contributed to the abnormality in APD. Furthermore, we showed that Lrp5 ablation induced a significant convergence of CaV1.2α1c proteins to the endoplasmic reticulum. Consequently, increased proteasomal degradation of these proteins was observed, which was independent of the Wnt/ß-catenin signaling pathway. CONCLUSIONS: LRP5 directly modulates the degradation of LTCC to control cardiac QT interval. These findings provide compelling evidence for the potential role of LRPs in cardiac electrophysiology.

Incorporating 4-tert-Butylpyridine in an Antisolvent: A Facile Approach to Obtain Highly Efficient and Stable Perovskite Solar Cells.

The synthesis and growth of CH3NH3PbI3 films with controlled nucleation is a key issue for the high efficiency and stability of solar cells. Here, 4-tert-butylpyridine (tBP) was introduced into a CH3NH3PbI3 antisolvent to obtain high quality perovskite layers. In situ optical microscopy and X-ray diffraction patterns were used to prove that tBP significantly suppressed perovskite nucleation by forming an intermediate phase. In addition, a gradient perovskite structure was obtained by this method, which greatly improved the efficiency and stability of perovskites. An effective power conversion efficiency (PCE) of 17.41% was achieved via the tBP treatment, and the high-efficiency device could maintain over 89% of the initial PCE after 30 days at room temperature.

LRP6 acts as a scaffold protein in cardiac gap junction assembly.

Low-density lipoprotein receptor-related protein 6 (LRP6) is a Wnt co-receptor in the canonical Wnt/ß-catenin signalling. Here, we report the scaffold function of LRP6 in gap junction formation of cardiomyocytes. Cardiac LRP6 is spatially restricted to intercalated discs and binds to gap junction protein connexin 43 (Cx43). A deficiency in LRP6 disrupts Cx43 gap junction formation and thereby impairs the cell-to-cell coupling, which is independent of Wnt/ß-catenin signalling. The defect in Cx43 gap junction resulting from LRP6 reduction is attributable to the defective traffic of de novo Cx43 proteins from the endoplasmic reticulum to the Golgi apparatus, leading to the lysosomal degradation of Cx43 proteins. Accordingly, the hearts of conditional cardiac-specific Lrp6-knockout mice consistently exhibit overt reduction of Cx43 gap junction plaques without any abnormality in Wnt signalling and are predisposed to lethal arrhythmias. These findings uncover a distinct role of LRP6 as a platform for intracellular protein trafficking.

miR-134 Modulates the Proliferation of Human Cardiomyocyte Progenitor Cells by Targeting Meis2.

Cardiomyocyte progenitor cells play essential roles in early heart development, which requires highly controlled cellular organization. microRNAs (miRs) are involved in various cell behaviors by post-transcriptional regulation of target genes. However, the roles of miRNAs in human cardiomyocyte progenitor cells (hCMPCs) remain to be elucidated. Our previous study showed that miR-134 was significantly downregulated in heart tissue suffering from congenital heart disease, underlying the potential role of miR-134 in cardiogenesis. In the present work, we showed that the upregulation of miR-134 reduced the proliferation of hCMPCs, as determined by EdU assay and Ki-67 immunostaining, while the inhibition of miR-134 exhibited an opposite effect. Both up- and downregulation of miR-134 expression altered the transcriptional level of cell-cycle genes. We identified Meis2 as the target of miR-134 in the regulation of hCMPC proliferation through bioinformatic prediction, luciferase reporter assay and western blot. The over-expression of Meis2 mitigated the effect of miR-134 on hCMPC proliferation. Moreover, miR-134 did not change the degree of hCMPC differentiation into cardiomyocytes in our model, suggesting that miR-134 is not required in this process. These findings reveal an essential role for miR-134 in cardiomyocyte progenitor cell biology and provide new insights into the physiology and pathology of cardiogenesis.