Warnerkhan0117

We further investigated the effects of a significantly upregulated circRNA, circHGF, on the proliferation and osteogenic differentiation of BMSCs in vitro. Results showed that circHGF suppressed the proliferation and osteogenic differentiation of BMSCs in ONFH by targeting miR-25-3p/SMAD7 axis. Our findings provided a potential diagnostic and therapeutic strategy for ONFH.Strategies to modulate cellular DNA repair pathways hold immense potential to enhance the efficiency of CRISPR-Cas9 genome editing platform. In the absence of a repair template, CRISPR-Cas9-induced DNA double-strand breaks are repaired by the endogenous cellular DNA repair pathways to generate loss-of-function edits. Here, we describe a reporter-based assay for expeditious measurement of loss-of-function editing by CRISPR-Cas9. An unbiased chemical screen performed using this assay enabled the identification of small molecules that promote loss-of-function editing. Iterative rounds of screens reveal Repsox, a TGF-β signaling inhibitor, as a CRISPR-Cas9 editing efficiency enhancer. Repsox invariably increased CRISPR-Cas9 editing in a panel of commonly used cell lines in biomedical research and primary cells. Furthermore, Repsox-mediated editing enhancement in primary human CD4+ T cells enabled the generation of HIV-1-resistant cells with high efficiency. This study demonstrates the potential of transiently targeting cellular pathways by small molecules to improve genome editing for research applications and is expected to benefit gene therapy efforts.Androgen receptor splice variant 7 (AR-v7), a constitutively active transcription factor, plays a crucial role in the progression of castration-resistant prostate cancer (CRPC). Here, we found that the cleavage and polyadenylation specificity factor 1 (CPSF1) (the largest subunit of the multi-protein cleavage and polyadenylation specificity complex), regulated by the E3 ubiquitin ligases SIAH1, promoted AR-v7 expression. The data from microarray-based analysis and clinical specimen-based analysis showed that SIAH1 expression was decreased in PCa and was negatively correlated with aggressive phenotypes of PCa. SIAH1 repressed PCa cell growth and invasion under castrate conditions. SIAH1 directly interacted with CPSF1 and promoted ubiquitination and degradation of CPSF1. CPSF1 expression was negatively correlated with SIAH1 expression, but positively with PCa progression. CPSF1 overexpression switched the AR splicing pattern and facilitated the generation of the oncogenic isoform (AR-v7) by binding to the AAUAAA polyadenylation signal contained in AR-cryptic exon CE3. Functionally, SIAH1 acted as a tumor suppressor in PCa pathogenesis by repressing CPSF1-mediated AR-v7 generation. Finally, we demonstrated that m6A methylation was concerned with the repression of SIAH1 in PCa. Our results define SIAH1/CPSF1/AR-v7 axis as a regulatory factor of PCa progression, providing a promising target for treating PCa.Loss of cerebral cholinergic neurons and decreased levels of acetylcholine (ACh) are considered to be major factors causing cognitive dysfunction in Alzheimer's disease (AD). Abnormally elevated levels of acetylcholinesterase (AChE) resulting in decreased levels of ACh are common in AD patients; thus, AChE inhibitors (AChEIs) are widely used for the treatment of AD. In our previous work, we acquired DNA aptamers Ob1, Ob2, and Ob3 against human brain AChE from systematic evolution of ligands by exponential enrichment (SELEX). In this study, we investigated the effect of these aptamers on learning and memory abilities, as well as the underlying mechanism in a 5×FAD transgenic AD mouse model. Here, we showed that only aptamer Ob2 exhibits a good inhibitory effect on both mouse and human AChE activity. In addition, chronic treatment with aptamer Ob2 significantly improved cognitive ability of 5×FAD mice in the Morris water maze. Moreover, the mechanism of aptamer Ob2 in 5×FAD mice may be associated with its inhibition of AChE activity, alleviation of the levels of Aβ by lowering the expression of β-secretase (BACE1), and activation of astrocytes in the brains of 5×FAD mice. These results indicate that aptamer Ob2 exhibits potential as an effective AChEI for the treatment of AD.Duchenne muscular dystrophy (DMD) is a lethal muscle disease caused by mutations in the dystrophin gene. CRISPR/Cas9 genome editing has been used to correct DMD mutations in animal models at young ages. However, the longevity and durability of CRISPR/Cas9 editing remained to be determined. To address these issues, we subjected ΔEx44 DMD mice to systemic delivery of AAV9-expressing CRISPR/Cas9 gene editing components to reframe exon 45 of the dystrophin gene, allowing robust dystrophin expression and maintenance of muscle structure and function. We found that genome correction by CRISPR/Cas9 confers lifelong expression of dystrophin in mice and that corrected skeletal muscle is highly durable and resistant to myofiber necrosis and fibrosis, even in response to chronic injury. In contrast, when muscle fibers were ablated by barium chloride injection, we observed a loss of gene edited dystrophin expression. Analysis of on- and off-target editing in aged mice confirmed the stability of gene correction and the lack of significant off-target editing at 18 months of age. These findings demonstrate the long-term durability of CRISPR/Cas9 genome editing as a therapy for maintaining the integrity and function of DMD muscle, even under conditions of stress.Doxorubicin is a chemotherapeutic medication commonly used to treat many types of cancers, but it has side effects including vomiting, rash, hair loss, and bone marrow suppression. The most dangerous side effects are cardiomyopathy, cardiofibrosis, and heart failure, as doxorubicin generates cytotoxicity and stops DNA replication. There is no treatment to block these side effects. We have developed a transgenic mouse line overexpressing the circular RNA circNlgn and shown that circNlgn is a mediator of doxorubicin-induced cardiofibrosis. Increased expression of circNlgn decreased cardiac function and induced cardiofibrosis by upregulating Gadd45b, Sema4C, and RAD50 and activating p38 and pJNK in circNlgn transgenic heart. Silencing circNlgn decreased the effects of doxorubicin on cardiac cell activities and prevented doxorubicin-induced expression of fibrosis-associated molecules. The protein (Nlgn173) translated by circNlgn could bind and activate H2AX, producing γH2AX, resulting in upregulation of IL-1b, IL-2Rb, IL-6, EGR1, and EGR3. We showed that silencing these molecules in the signaling pathway prevented doxorubicin-induced cardiomyocyte apoptosis, increased cardiomyocyte viability, decreased cardiac fibroblast proliferation, and inhibited collagen production. This mechanism may hold therapeutic implications for mitigating the side effects of doxorubicin therapy in cancer patients.Social media use has previously been shown to have negative implications for cognition. Scarce research has examined underlying pathways through which social media use may influence cognition. One potential pathway involves the consequences of social comparison, such that those who use social media more frequently may feel worse about themselves and more envious toward others. In turn, these negative socioemotional states could compromise memory. Further, whether an individual uses social media actively or passively may moderate these associations. Using an online adult lifespan sample (n=592), the current cross-sectional study examined whether socioemotional consequences of social comparison (self-esteem and envy) mediated relationships between social media use and memory (everyday memory failures and episodic memory) and whether active/passive use moderated these associations. Mediation models revealed that higher envy, but not lower self-esteem, partially explained the relationship between higher social media use and more self-reported everyday memory failures. Neither envy nor self-esteem mediated the relationship between higher social media use and lower objective episodic memory performance. Additionally, higher social media use was associated with higher envy to a greater extent for active users compared to passive users. These findings may suggest that high social media use has negative ramifications for both subjective and objective memory and that increased feelings of envy may partially explain these effects for subjective, but not objective, memory.

On 6 October 2019, Petaling District Health Office received notification of a possible foodborne outbreak involving a mass gathering event. This report presents the processes of diagnosis verification, case identification, determination of associated risk factors and commencement of control measures in managing the outbreak.

Cases were defined as those who attended the mass gathering event on 6 October 2019, consumed the pre-packaged food and subsequently developed vomiting, abdominal pain, diarrhoea or other symptoms (e.g. fever, nausea and dizziness). Epidemiological, environmental and laboratory investigations were performed. Data were analysed using SPSS software (version 24.0).

A total of 169 cases were identified. The attack rate was 7.2%, and cases ranged in age from 7 to 50 years, with a median of 20 years. A total of 156 (92.3%) cases had vomiting, 137 (81.1%) had abdominal pain and 83 (49.1%) had diarrhoea. Consuming nasi lemak at the mass gathering was found to be significantly associated with developing illness (odds ratio 9.90, 95% confidence interval 6.46-15.16). The samples from suspected food, food handlers and the environment were positive for

,

or coliforms.

The outbreak at this mass gathering was probably caused by food contaminated with

and

. To prevent future outbreaks, we recommend mass gathering events use certified catering services that have adequate food safety training.

The outbreak at this mass gathering was probably caused by food contaminated with B. cereus and S. aureus. To prevent future outbreaks, we recommend mass gathering events use certified catering services that have adequate food safety training.

Coronavirus disease 2019 (COVID-19) was declared a pandemic on 11 March 2020. Severe illness requires intensive care facilities, which are limited in smaller, resource-constrained settings.

Maldives and Trinidad and Tobago are small island developing states with comparable climates. Similar to island nations in the Western Pacific Region, they are prone to natural disasters and so engage in planning and preparedness activities on an ongoing basis. This paper describes the initial measures taken by both countries during the first wave of COVID-19, from March to May 2020.

In both countries, multisectoral high-level leadership allowed for timely and decisive actions. Early school closures, early border closures and early lockdowns were enforced. ZEN-3694 Mandatory mask wearing and physical distancing were instituted. Cases and contacts were isolated in facilities away from public sector hospitals, and isolation was implemented at the government's expense. Volunteers were trained to manage dedicated hotlines. Additi from the experience of Maldives and Trinidad and Tobago could serve as a model for other small island developing states, including those in the Western Pacific Region.