AAV9-mediated MYBPC3 gene therapy with optimized expression cassette enhances cardiac function and survival in MYBPC3 cardiomyopathy models.

Hypertrophic cardiomyopathy (HCM) affects approximately 600,000 people in the United States. Loss-of-function mutations in Myosin Binding Protein C3, MYBPC3, are the most common genetic cause of HCM, with the majority of mutations resulting in haploinsufficiency. To restore cardiac MYBPC3, we use an adeno-associated virus (AAV9) vector and engineer an optimized expression cassette with a minimal promoter and cis-regulatory elements (TN-201) to enhance packaging efficiency and cardiomyocyte expression.

Trps1 regulates mouse zygotic genome activation and preimplantation embryo development via the PDE4D/AKT/CREB signaling pathway.

Despite zygotic genome activation (ZGA) is crucial for early embryonic development, its regulatory mechanism is still unclear in mammals. In the present study, we demonstrate that TRPS1, a maternal factor, plays an essential role in mouse early embryogenesis by regulating the transition from 2-cell to 4-cell embryos during preimplantation development. The absence of Trps1 could leads to impaired ZGA through AKT/CREB signaling pathway.

Measurement of ocean currents by seafloor distributed optical-fiber acoustic sensing.

Ocean current measurements play a crucial role in aiding our understanding of ocean dynamics and circulation systems. Traditional methods, such as drifters and ocean buoys, are sparsely distributed and of limited effectiveness due to the nature of the marine environment and high operating expenses. Distributed acoustic sensing (DAS) is an emerging technology using submarine optical-fiber (OF) cables as dense seismo-acoustic arrays, offering a new perspective for ocean observations.

Monitoring ocean currents during the passage of Typhoon Muifa using optical-fiber distributed acoustic sensing.

In situ observations under typhoon conditions are sparse and limited. Distributed acoustic sensing (DAS) is an emerging technology that uses submarine optical-fiber (OF) cables to monitor the sea state. Here, we present DAS-based ocean current observations when a super typhoon passed overhead.

Improved Cardiac Function in Postischemic Rats Using an Optimized Cardiac Reprogramming Cocktail Delivered in a Single Novel Adeno-Associated Virus.

Background: Cardiac reprogramming is a technique to directly convert nonmyocytes into myocardial cells using genes or small molecules. This intervention provides functional benefit to the rodent heart when delivered at the time of myocardial infarction or activated transgenically up to 4 weeks after myocardial infarction. Yet, several hurdles have prevented the advancement of cardiac reprogramming for clinical use.

Prevalence and risk factors of diabetic retinopathy among Chinese adults with type 2 diabetes in a suburb of Shanghai, China.

Background: To investigate the prevalence and risk factors of diabetic retinopathy (DR) in a Chinese population with type 2 diabetes mellitus (T2DM) in a suburb (Qingpu) of Shanghai, China.

Methods: A population-based cross-sectional study. A total of 7462 residents with T2DM in Qingpu were enrolled according to the resident health archives from January 2020 to December 2020.

Icariin promotes mouse Leydig cell testosterone synthesis via the Esr1/Src/Akt/Creb/Sf-1 pathway.

Icariin (ICA), extracted from Epimedium, is a flavonoid used in traditional Chinese medicine. Di(2-ethylhexyl) phthalate (DEHP) is a phthalate used in commercial products as a plasticizer that can influence the human endocrine and reproduction system. We previously found that ICA reversed DEHP-induced damage through the prevention of reactive oxygen species accumulation and promotion of testosterone secretion.

Nuclear-localized eukaryotic translation initiation factor 1A is involved in mouse preimplantation embryo development.

Preimplantation embryo development is characterized by drastic nuclear reprogramming and dynamic stage-specific gene expression. Key regulators of this earliest developmental stage have not been revealed. In the present study, a "non-classical" nuclear-localization pattern of eIF1A was observed during early developmental stages of mouse preimplantation embryo before late-morula.

Trps1 targets Ccnd1 to regulate mouse Leydig cell proliferation.

Background: The tricho-rhino-phalangeal syndrome-1 gene (Trps1) is an atypical GATA family member. Although current studies of Trps1 mainly focus on tumors, whether Trps1 plays a role in the male reproductive system remains unknown.

Objectives: The purpose of this study was to elucidate the function of Trps1 in Leydig cells, indicating its regulatory mechanism on the cell cycle.

Upregulation of microRNA-181a-5p increases the sensitivity of HS578T breast cancer cells to cisplatin by inducing vitamin D receptor-mediated cell autophagy.

Breast cancer (BC) is the leading cause of death in females worldwide. Although cisplatin is a strong-effect and broad-spectrum chemotherapy drug, resistance to cisplatin remains a significant factor effecting clinical efficacy. The underlying mechanism of cancer cell resistance to cisplatin is not fully understood.

Chloroplast genome of silverleaf nightshade ( Cav.), a Weed of National Significance in Australia.

Cav. is a widely distributed weed and recognized as a Weed of National Significance in Australia. This study sequenced the chloroplast () genome of which is 155,049 bp in length, including a large single-copy region at 85, 426 bp, a small single-copy region at 18,419 bp and two inverted repeats at 25,602 bp.

Improving seismic remote sensing of typhoon with a three-dimensional Earth model.

Typhoon-induced P-wave microseisms can be observed using seismological arrays and analyzed for the seismic monitoring of ocean storms. This paper presents a frequency-domain beamforming (FB) method that integrates a three-dimensional (3-D) Earth model to better capture the heterogeneities in the subsurface structure, and therefore yield more accurate ray-tracing and travel-time predictions. This method is applied to the Super Typhoon Lupit (2009) using seismological array observations from the Northeast China Extended Seismic Array (NECESSArray) and high-sensitivity seismograph network in Japan (Hi-net).

Akt plays indispensable roles during the first cell lineage differentiation of mouse.

The first cell lineage differentiation occurs during the development of mouse 8-cell embryo to blastocyst. Akt is a potent kinase whose role during blastocyst formation has not been elucidated. In the present study, immunofluorescence results showed that the Akt protein was specifically localized to the outer cells of the morula.

Icariin protects mouse Leydig cell testosterone synthesis from the adverse effects of di(2-ethylhexyl) phthalate.

Infertility caused by environmental pollution is becoming a global problem, but an effective prevention or treatment is lacking. Icariin (ICA) is a flavonoid used in traditional Chinese medicine. The present study investigated the possible roles of ICA in preventing testicular dysfunction caused by di(2-ethylhexyl) phthalate (DEHP), one of the most studied environmental endocrine disruptors.

Species Identification of Assisted by Chloroplast Genome Sequencing.

Flaxleaf fleabane ( [L.] Cronquist) is one of the most difficult weeds to control worldwide. There are more than 150 species in the world and eight species in Australia.

Targeting endosialin/CD248 through antibody-mediated internalization results in impaired pericyte maturation and dysfunctional tumor microvasculature.

Over-expression of endosialin/CD248 (herein referred to as CD248) has been associated with increased tumor microvasculature in various tissue origins which makes it an attractive anti-angiogenic target. In an effort to target CD248, we have generated a human CD248 knock-in mouse line and MORAb-004, the humanized version of the mouse anti-human CD248 antibody Fb5. Here, we report that MORAb-004 treatment significantly impacted syngeneic tumor growth and tumor metastasis in the human CD248 knock-in mice.

The antitumor activity of the human FOLR1-specific monoclonal antibody, farletuzumab, in an ovarian cancer mouse model is mediated by antibody-dependent cellular cytotoxicity.

Because of its high mortality rate, ovarian cancer is a leading cause of death among women and a highly unmet medical need. New therapeutic agents that are effective and well tolerated are needed and cancer antigen-specific monoclonal antibodies that have direct pharmacologic effects or can stimulate immunological responses represent a promising class of agents for the treatment of this disease. The human folate receptor α (FOLR1), which is overexpressed in ovarian cancer but largely absent in normal tissues, appears to play a role in the transformed phenotype in ovarian cancer, cisplatin sensitivity, and growth in depleted folate conditions and therefore has potential as a target for passive immunotherapy.

A novel mutation in the myeloperoxidase gene in a Chinese female with complete myeloperoxidase deficiency: the role of nonsense-mediated mRNA decay.

Myeloperoxidase (MPO) is an important enzyme in innate immunity. Here, we describe the first identified Chinese individual with complete MPO deficiency. The proband was ascertained through routine automated complete blood analysis.

Fabrication and photocatalytic property of Pt-intercalated layered perovskite niobates H(1-x)LaNb(2-x)Mo(x)O(7) (x=0-0.15).

H(1-x)LaNb(2-x)Mo(x)O(7) was prepared by solid-state reaction followed by an ion-exchange reaction. Pt was incorporated in the interlayer of H(1-x)LaNb(2-x)Mo(x)O(7) by the stepwise intercalation reaction. The H(1-x)LaNb(2-x)Mo(x)O(7) showed hydrogen production activity and the activities were greatly enhanced by Pt co-incorporating.

Established B16 tumors are rejected following treatment with GM-CSF-secreting tumor cell immunotherapy in combination with anti-4-1BB mAb.

Immunization with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific and long lasting anti-tumor immunity in clinical and preclinical settings. Efforts to further increase immunotherapy efficacy with immune-modulatory agents are under evaluation. Based on the immune-modulatory properties of 4-1BB (CD137), it has been postulated that agonistic 4-1BB antibodies may add additional anti-tumor efficacy to GM-CSF-secreting tumor cell immunotherapy.

Inhibition of lymphogenous metastasis using adeno-associated virus-mediated gene transfer of a soluble VEGFR-3 decoy receptor.

The presence of metastases in regional lymph nodes is a strong indicator of poor patient survival in many types of cancer. It has recently been shown that the lymphangiogenic growth factor, vascular endothelial growth factor-C (VEGF-C), and its receptor, VEGF receptor-3 (VEGFR3), may play a pivotal role in the promotion of metastasis to regional lymph nodes. In this study, human prostate and melanoma tumor models that preferentially metastasize to the lymph nodes following s.

Anti-tumor efficacy of human angiostatin using liver-mediated adeno-associated virus gene therapy.

Angiostatin is a potent endogenous inhibitor of angiogenesis and tumor growth in vivo. The therapeutic potential of adeno-associated viral (AAV) gene delivery of angiostatin in modulating tumor growth in vivo was evaluated. Sustained levels of angiostatin were detected in the sera of mice for up to 6 months after they received a single injection of AAV-angiostatin.

[Study on a test of screening to predict stroke-using cerebral vascular hemodynamic indexes].

Objective: To evaluate efficacy and optimal cut-off-point through cerebral vascular hemodynamic indexes (CVHI) examination to predict stroke.

Methods: A number of 20,333 people at 35 years old and over were checked by CVHI and accumulative score was calculated according to the value of detected indexes. Risk factors of stroke were investigated simultaneously.