Pathogenesis of Central Serous Chorioretinopathy and the Link Between Choroidal Hyperpermeability and Retinal Pigment Epithelium Pump Reversal.

Purpose: To describe 6 cases of acute central serous chorioretinopathy (CSCR) and the response to laser treatment, focusing on the underlying pathogenic mechanism.

Methods: Multimodal imaging from 6 eyes of 6 patients with acute and recurrent CSCR were reviewed, including fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT) at baseline and after laser therapy.

Results: In 3 of the 6 cases with acute CSCR, the hyporeflective lucency sign was identified with cross-sectional and en face OCT and co-localized with an intense active inkblot retinal pigment epithelium (RPE) leak on FA.

Asparagine Synthetase Marks a Distinct Dependency Threshold for Cardiomyocyte Dedifferentiation.

Background: Adult mammalian cardiomyocytes have limited proliferative capacity, but in specifically induced contexts they traverse through cell-cycle reentry, offering the potential for heart regeneration. Endogenous cardiomyocyte proliferation is preceded by cardiomyocyte dedifferentiation (CMDD), wherein adult cardiomyocytes revert to a less matured state that is distinct from the classical myocardial fetal stress gene response associated with heart failure. However, very little is known about CMDD as a defined cardiomyocyte cell state in transition.

Risk of Incident Thyroid Dysfunction in the Post-Acute Phase of COVID-19: A Population-Based Cohort Study in Hong Kong.

Objective: The evidence of thyroid dysfunction in the post-acute phase of SARS-CoV-2 infection is limited. This study aimed to evaluate the risk of incident thyroid dysfunction in the post-acute phase of COVID-19.

Methods: This retrospective, propensity-score matched, population-based study included COVID-19 patients and non-COVID-19 individuals between January 2020 and March 2022, identified from the electronic medical records of the Hong Kong Hospital Authority.

Risks of incident major osteoporotic fractures following SARS-CoV-2 infection among older individuals: a population-based cohort study in Hong Kong.

Population-based epidemiological studies on post-acute phase coronavirus 2019 (COVID-19)-related fractures in older adults are lacking. This study aims to examine the risk of incident major osteoporotic fractures following SARS-CoV-2 infection among individuals aged ≥50, compared to individuals without COVID-19. It was a retrospective, propensity-score matched, population-based cohort study of COVID-19 patients and non-COVID individuals identified from the electronic database of the Hong Kong Hospital Authority from January 2020 to March 2022.

Genome-Wide Identification and Characterization of Effector Candidates with Conserved Motif in .

Microbes employ effectors to disrupt immune responses and promote host colonization. Conserved motifs including RXLR, LFLAK-HVLVxxP (CRN), Y/F/WxC, CFEM, LysM, Chitin-bind, DPBB_1 (PNPi), and Cutinase have been discovered to play crucial roles in the functioning of effectors in filamentous fungi. Nevertheless, little is known about effectors with conserved motifs in endophytes.

Single-Cell Transcriptomics Reveals Cellular Heterogeneity and Complex Cell-Cell Communication Networks in the Mouse Cornea.

Purpose: To generate a single-cell RNA-sequencing (scRNA-seq) map and construct cell-cell communication networks of mouse corneas.

Methods: C57BL/6 mouse corneas were dissociated to single cells and subjected to scRNA-seq. Cell populations were clustered and annotated for bioinformatic analysis using the R package "Seurat.

Efficacy and Safety of Ocedurenone: Subgroup Analysis of the BLOCK-CKD Study.

Background: Ocedurenone (KBP-5074), a nonsteroidal mineralocorticoid receptor antagonist, is documented to lower blood pressure in patients with stage 3b/4 chronic kidney disease (CKD) with uncontrolled or resistant hypertension (BLOCK-CKD study). However, the efficacy and safety of Ocedurenone in subgroups such as Hispanic patients or those with stage 4 CKD, diabetes, or very high albuminuria have not been reported.

Methods: A total of 162 patients were enrolled in the BLOCK-CKD study.

Compounds activating VCP D1 ATPase enhance both autophagic and proteasomal neurotoxic protein clearance.

Enhancing the removal of aggregate-prone toxic proteins is a rational therapeutic strategy for a number of neurodegenerative diseases, especially Huntington's disease and various spinocerebellar ataxias. Ideally, such approaches should preferentially clear the mutant/misfolded species, while having minimal impact on the stability of wild-type/normally-folded proteins. Furthermore, activation of both ubiquitin-proteasome and autophagy-lysosome routes may be advantageous, as this would allow effective clearance of both monomeric and oligomeric species, the latter which are inaccessible to the proteasome.

Rewiring of 3D Chromatin Topology Orchestrates Transcriptional Reprogramming and the Development of Human Dilated Cardiomyopathy.

Background: Transcriptional reconfiguration is central to heart failure, the most common cause of which is dilated cardiomyopathy (DCM). The effect of 3-dimensional chromatin topology on transcriptional dysregulation and pathogenesis in human DCM remains elusive.

Methods: We generated a compendium of 3-dimensional epigenome and transcriptome maps from 101 biobanked human DCM and nonfailing heart tissues through highly integrative chromatin immunoprecipitation (H3K27ac [acetylation of lysine 27 on histone H3]), in situ high-throughput chromosome conformation capture, chromatin immunoprecipitation sequencing, assay for transposase-accessible chromatin using sequencing, and RNA sequencing.

Ablation of Plasma Prekallikrein Decreases Low-Density Lipoprotein Cholesterol by Stabilizing Low-Density Lipoprotein Receptor and Protects Against Atherosclerosis.

Background: High blood cholesterol accelerates the progression of atherosclerosis, which is an asymptomatic process lasting for decades. Rupture of atherosclerotic plaques induces thrombosis, which results in myocardial infarction or stroke. Lowering cholesterol levels is beneficial for preventing atherosclerotic cardiovascular disease.

COMP (Cartilage Oligomeric Matrix Protein), a Novel PIEZO1 Regulator That Controls Blood Pressure.

Background: Vascular endothelial cells are critical for maintaining blood pressure (BP) by releasing biologically active molecules, such as nitric oxide. A non-endothelial cell resident matricellular protein, COMP (cartilage oligomeric matrix protein), plays a pivotal role in maintaining cardiovascular homeostasis, but little is known about its regulatory effect on BP.

Methods: Mice were infused with AngII (angiotensin II; 450 ng/kg per minute) for 3 days via an osmotic minipump, and BP was monitored by a tail-cuff system.

Molecular surveillance of anti-malarial resistance pfcrt, pfmdr1, and pfk13 polymorphisms in African Plasmodium falciparum imported parasites to Wuhan, China.

Background: Imported malaria parasites with anti-malarial drug resistance (ADR) from Africa is a serious public health challenge in non-malarial regions, including Wuhan, China. It is crucial to assess the ADR status in African Plasmodium falciparum isolates from imported malaria cases, as this will provide valuable information for rational medication and malaria control.

Methods: During 2017-2019, a cross-sectional study was carried out in Wuhan, China.

LncRNA PROX1-AS1 promotes proliferation, invasion, and migration in prostate cancer via targeting miR-647.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA PROX1-AS1 promotes proliferation, invasion, and migration in prostate cancer via targeting miR-647, by C. Qian, C.-H.

Prioritizing Candidates of Post-Myocardial Infarction Heart Failure Using Plasma Proteomics and Single-Cell Transcriptomics.

Background: Heart failure (HF) is the most common long-term complication of acute myocardial infarction (MI). Understanding plasma proteins associated with post-MI HF and their gene expression may identify new candidates for biomarker and drug target discovery.

Methods: We used aptamer-based affinity-capture plasma proteomics to measure 1305 plasma proteins at 1 month post-MI in a New Zealand cohort (CDCS [Coronary Disease Cohort Study]) including 181 patients post-MI who were subsequently hospitalized for HF in comparison with 250 patients post-MI who remained event free over a median follow-up of 4.

An Important Role for DNMT3A-Mediated DNA Methylation in Cardiomyocyte Metabolism and Contractility.

Background: DNA methylation acts as a mechanism of gene transcription regulation. It has recently gained attention as a possible therapeutic target in cardiac hypertrophy and heart failure. However, its exact role in cardiomyocytes remains controversial.

Phase 1 Trial of a Therapeutic Anti-Yellow Fever Virus Human Antibody.

Background: Insufficient vaccine doses and the lack of therapeutic agents for yellow fever put global health at risk, should this virus emerge from sub-Saharan Africa and South America.

Methods: In phase 1a of this clinical trial, we assessed the safety, side-effect profile, and pharmacokinetics of TY014, a fully human IgG1 anti-yellow fever virus monoclonal antibody. In a double-blind, phase 1b clinical trial, we assessed the efficacy of TY014, as compared with placebo, in abrogating viremia related to the administration of live yellow fever vaccine (YF17D-204; Stamaril).

Epigenomes of Human Hearts Reveal New Genetic Variants Relevant for Cardiac Disease and Phenotype.

Rationale: Identifying genetic markers for heterogeneous complex diseases such as heart failure is challenging and requires prohibitively large cohort sizes in genome-wide association studies to meet the stringent threshold of genome-wide statistical significance. On the other hand, chromatin quantitative trait loci, elucidated by direct epigenetic profiling of specific human tissues, may contribute toward prioritizing subthreshold variants for disease association.

Objective: Here, we captured noncoding genetic variants by performing epigenetic profiling for enhancer H3K27ac chromatin immunoprecipitation followed by sequencing in 70 human control and end-stage failing hearts.

Sickle Cell Anemia Mediates Carotid Artery Expansive Remodeling That Can Be Prevented by Inhibition of JNK (c-Jun N-Terminal Kinase).

Objective: Sickle cell anemia (SCA) causes chronic inflammation and multiorgan damage. Less understood are the arterial complications, most evident by increased strokes among children. Proteolytic mechanisms, biomechanical consequences, and pharmaceutical inhibitory strategies were studied in a mouse model to provide a platform for mechanistic and intervention studies of large artery damage due to sickle cell disease.

Robust CTCF-Based Chromatin Architecture Underpins Epigenetic Changes in the Heart Failure Stress-Gene Response.

Background: The human genome folds in 3 dimensions to form thousands of chromatin loops inside the nucleus, encasing genes and cis-regulatory elements for accurate gene expression control. Physical tethers of loops are anchored by the DNA-binding protein CTCF and the cohesin ring complex. Because heart failure is characterized by hallmark gene expression changes, it was recently reported that substantial CTCF-related chromatin reorganization underpins the myocardial stress-gene response, paralleled by chromatin domain boundary changes observed in CTCF knockout.

Infant dietary patterns and early childhood caries in a multi-ethnic Asian cohort.

Dental caries, although preventable, remains one of the most prevalent chronic disease worldwide. Most studies focused on the relationship between sugar intake and caries. However, examining multidimensional dietary patterns is becoming increasingly important.

A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery.

Cell penetrating peptides (CPPs) offer great potential to deliver therapeutic molecules to previously inaccessible intracellular targets. However, many CPPs are inefficient and often leave their attached cargo stranded in the cell's endosome. We report a versatile platform for the isolation of peptides delivering a wide range of cargos into the cytoplasm of cells.

Data on the construction of a recombinant HEK293 cell line overexpressing hERG potassium channel and examining the presence of hERG mRNA and protein expression.

The data presented in this article are related to the research article entitled "The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (I) and human ether-a-go-go-related gene (hERG) expression" (Y.F. Teah, M.

On developing a pragmatic strategy for clinical trials: A case study of hepatocellular carcinoma.

Randomised controlled trials (RCTs) with sufficiently high statistical power are not always feasible for patients when the administration of the treatment is burdensome. Nevertheless, useful information concerning the relative effectiveness of the Test and Standard therapies, may be gleaned from under powered trials, non-randomised comparative studies and/or clinician's beliefs: the latter possibly additionally providing some suggestion of the strength of evidence required in order to adopt the Test therapy into clinical practice. In such circumstances, a Bayesian synthesis may be useful in quantifying the evidence of treatment effectiveness.