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Eleutheroside B (EB) is the main active constituent derived from the Chinese herb Acanthopanax senticosus (AS) that has been reported to possess cardioprotective effects. In this study we investigated the effects of EB on cardiac electrophysiology and its suppression on atrial fibrillation (AF). Whole-cell recording was conducted in isolated rabbit atrial myocytes. The intracellular calcium ([Ca 2+ ] i ) concentration was measured using calcium indicator Fura-2/AM fluorescence. Monophasic action potential (MAP) and electrocardiogram (ECG) synchronous recordings were conducted in Langendorff-perfused rabbit hearts using ECG signal sampling and analysis system. We showed that EB dose-dependently inhibited late sodium current ( I NaL ), transient sodium current ( I NaT ), and sea anemone toxin II (ATX II)-increased I NaL with IC 50 values of 167, 1582, and 181 μM, respectively. On the other hand, EB (800 μM) did not affect L-type calcium current ( I CaL ), inward rectifier potassium channel current ( I K ), and action potential duration (APD). Furthermore, EB (300 μM) markedly decreased ATX II-prolonged the APD at 90% repolarization (APD 90 ) and eliminated ATX II-induced early afterdepolarizations (EADs), delayed afterdepolarizations (DADs), and triggered activities (TAs). Moreover, EB (200 μM) significantly suppressed ATX II-induced Na + -dependent [Ca 2+ ] i overload in atrial myocytes. In the Langendorff-perfused rabbit hearts, application of EB (200 μM) or TTX (2 μM) substantially decreased ATX II-induced incidences of atrial fibrillation (AF), ventricular fibrillation (VF), and heart death. These results suggest that augmented I NaL alone is sufficient to induce AF, and EB exerts anti-AF actions mainly via blocking I NaL , which put forward the basis of pharmacology for new clinical application of EB.

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood–air barrier, blood–testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.

Fecal microbiota transplantation (FMT) has become an effective strategy to treat metabolic diseases, including type 2 diabetes mellitus (T2DM). We previously reported that the intestinal microbiome had significant difference between individuals with normal glucose tolerance and T2DM in Chinese Kazak ethnic group. In this study, we investigated the effects of transplanted fecal bacteria from Kazaks with normal glucose tolerance (KNGT) in db/db mice. The mice were treated with 0.2 mL of fecal bacteria solution from KNGT daily for 10 weeks. We showed that the fecal bacteria from KNGT successfully colonized in the intestinal tract of db/db mice detected on day 14. In the FMT-treated db/db mice, the levels of fasting blood glucose, postprandial glucose, total cholesterol, triglyceride, and low-density lipoprotein–cholesterol were significantly downregulated, whereas high-density lipoprotein–cholesterol levels were upregulated. In the FMT-treated db/db mice, Desulfovibrio and Clostridium coccoides levels in gut were significantly decreased, but the fecal levels of Akkermansia muciniphila and colon histone deacetylase-3 (HDAC3) protein expression were increased. At 8 weeks, both intestinal target bacteria and HDAC3 were correlated with glycolipid levels; Akkermansia muciniphila level was positively correlated with HDAC3 protein expression ( r  = +0.620, P  = 0.037). Our results suggest that fecal bacteria from KNGT could potentially be used to treat diabetic patients.

Background Urethral hemangioma is an exceptionally rare benign vascular tumor, with scarce data available on its natural history and therapeutic strategies. The coexistence of carcinoma in situ within urethral hemangioma has not been previously documented in medical literature. Case presentation A 62-year-old woman presented with a protruding mass at the external urethral orifice. The lesion was completely excised by surgical resection. Histopathological analysis revealed squamous cell carcinoma in situ (SC-CIS) within the urethral hemangioma. The patient refused to undergo repeat surgical treatment again for SC-CIS due to surgical complications. The patient received adjuvant radiotherapy (total dose 50 Gy/25 fractions) following pathological confirmation of involved surgical margins. Long-term follow-up, including annual CT scans and cystoscopies, showed no evidence of disease recurrence at 7 years post-treatment. Conclusion Few cases of urethral hemangioma have been documented in the literature, and no previous reports have descried urethral hemangiomas coexisting with SC-CIS. Surgical treatment emphasizes the complete resection of the lesions. When margin involvement by malignant cells was identified, adjuvant radiotherapy is an essential component of the combined-modality approach. The 7-year recurrence-free survival in this case suggests that this combined-modality approach provides durable local control.

The formation of the anther wall and the development of pollen processes, central to rice fertility and yield, are highly dependent on the synthesis and accumulation of lipid polymers. Although several regulatory factors related to lipid biosynthesis during pollen wall development have been identified, the molecular mechanisms controlling these processes remain poorly understood. In this study, a male-sterile rice mutant, lap3 , was identified, characterized by normal vegetative growth but complete male sterility due to delayed programmed cell death (PCD) in tapetal cells and defects in anther cuticle and pollen exine formation. Map-based cloning revealed that OsLAP3 is a new allele of the strictosidine synthase-like gene, OsSTRL2 . Functional analysis, including complementation and CRISPR/Cas9-based gene editing, confirmed that the 2-nucleotide deletion in the OsLAP3 is responsible for the male sterility phenotype. OsLAP3 is homologous to the maize ZmMS45 , the core recessive nuclear sterile gene of maize Seed Production Technology (SPT), and localizes to the endoplasmic reticulum and plays a conserved role in anther development and pollenformation. Gene expression analysis revealed a significant downregulation of key genes involved in anther development and sporopollenin biosynthesis in lap3 anthers. Furthermore, lipid profiling demonstrated a marked reduction in both wax and cutin content. These findings establish OsLAP3 as a critical regulator of fatty acid synthesis and highlight its role in anther cuticle formation and pollen exine development. The findings of this study provide valuable insights into the molecular regulation of lipid biosynthesis during rice male reproductive development and offer potential applications for hybrid rice breeding.

According to the geological conditions of the study area, the measured data of in situ stress was analyzed and the influence degree of buried depth was obtained. A numerical simulation research model with full consideration of fault structure and surface characteristics is established, and boundary condition functions with variables are used. The neural network optimized by genetic algorithm is used to establish the nonlinear relationship between the measured value and the simulated value of the variable boundary condition, and the optimal boundary condition function is obtained. Finally, the in situ stress in the study area was predicted. Through the analysis of the in situ stress field in the research target area, the stress boundary conditions are provided for the follow-up study, and the practical basis for the division of the dangerous area of the surrounding rock of the deep and long tunnel is provided.

Protein homeostasis (proteostasis) deficiency is an important contributing factor to neurological and metabolic diseases. However, how the proteostasis network orchestrates the folding and assembly of multi-subunit membrane proteins is poorly understood. Previous proteomics studies identified Hsp47 (Gene: SERPINH1 ), a heat shock protein in the endoplasmic reticulum lumen, as the most enriched interacting chaperone for gamma-aminobutyric acid type A (GABA A ) receptors. Here, we show that Hsp47 enhances the functional surface expression of GABA A receptors in rat neurons and human HEK293T cells. Furthermore, molecular mechanism study demonstrates that Hsp47 acts after BiP (Gene: HSPA5 ) and preferentially binds the folded conformation of GABA A receptors without inducing the unfolded protein response in HEK293T cells. Therefore, Hsp47 promotes the subunit-subunit interaction, the receptor assembly process, and the anterograde trafficking of GABA A receptors. Overexpressing Hsp47 is sufficient to correct the surface expression and function of epilepsy-associated GABA A receptor variants in HEK293T cells. Hsp47 also promotes the surface trafficking of other Cys-loop receptors, including nicotinic acetylcholine receptors and serotonin type 3 receptors in HEK293T cells. Therefore, in addition to its known function as a collagen chaperone, this work establishes that Hsp47 plays a critical and general role in the maturation of multi-subunit Cys-loop neuroreceptors.

Key messageRice male fertility gene Baymax1, isolated through map-based cloning, encodes a MYB transcription factor and is essential for rice tapetum and microspore development.Abstract The mining and characterization of male fertility gene will provide theoretical and material basis for future rice production. In Arabidopsis, the development of male organ (namely anther), usually involves the coordination between MYB (v-myb avian myeloblastosis viral oncogene homolog) and bHLH (basic helix-loop-helix) members. However, the role of MYB proteins in rice anther development remains poorly understood. In this study, we isolated and characterized a male sterile mutant (with normal vegetative growth) of Baymax1 (BM1), which encodes a MYB protein. The bm1 mutant exhibited slightly lagging meiosis, aborted transition of the tapetum to a secretory type, premature tapetal degeneration, and abnormal pollen exine formation, leading to ultimately lacks of visible pollens in the mature white anthers. Map-based cloning, complementation and targeted mutagenesis using CRISPR/Cas9 technology demonstrated that the mutated LOC_Os04g39470 is the causal gene in bm1. BM1 is preferentially expressed in rice anthers from stage 5 to stage 10. Phylogenetic analysis indicated that rice BM1 and its homologs in millet, maize, rape, cabbage, and pigeonpea are evolutionarily conserved. BM1 can physically interacts with bHLH protein TIP2, EAT1, and PHD (plant homeodomain)-finger member TIP3, respectively. Moreover, BM1 affects the expression of several known genes related to tapetum and microspore development. Collectively, our results suggest that BM1 is one of key regulators for rice male fertility and may serve as a potential target for rice male-sterile line breeding and hybrid seed production.

The simultaneous construction of two different chiralities via a simple operation poses considerable challenge. Herein a cationic gold-catalyzed asymmetric hydroarylation of ortho-alkynylaryl ferrocenes derivatives is developed, which enable the simultaneous construction of axial and planar chirality. The here identified TY-Phos derived gold complex is responsible for the high yield, good diastereoselectivity (>20:1 dr), high enantioselectivities (up to 99% ee) and mild conditions. The catalyst system also shows potential application in the synthesis of chiral biaryl compounds. The cause of high enantioselectivity of this hydroarylation is investigated with density functional theory caculation. The simultaneous construction of two different types of chiralities is challenging. Here, the authors report a cationic gold-catalyzed asymmetric hydroarylation of ortho-alkynylaryl ferrocene derivatives, which enabled the simultaneous construction of axial and planar chirality.

Flexible and stretchable light emitting devices are driving innovation in myriad applications, such as wearable and functional electronics, displays and soft robotics. However, the development of flexible electroluminescent devices via conventional techniques remains laborious and cost-prohibitive. Here, we report a facile and easily-accessible route for fabricating a class of flexible electroluminescent devices and soft robotics via direct ink writing-based 3D printing. 3D printable ion conducting, electroluminescent and insulating dielectric inks were developed, enabling facile and on-demand creation of flexible and stretchable electroluminescent devices with good fidelity. Robust interfacial adhesion with the multilayer electroluminescent devices endowed the 3D printed devices with attractive electroluminescent performance. Integrated our 3D printed electroluminescent devices with a soft quadrupedal robot and sensing units, an artificial camouflage that can instantly self-adapt to the environment by displaying matching color was fabricated, laying an efficient framework for the next generation soft camouflages. Flexible electroluminescent devices are usually arduous to create. Liu et al report a 3D printing strategy to produce flexible and robust electroluminescent devices that can be integrated with soft robots for camouflage applications.