Cardiac bridging integrator 1 gene therapy rescues chronic non-ischemic heart failure in minipigs.

Heart failure (HF) is a major cause of mortality and morbidity worldwide, yet with limited therapeutic options. Cardiac bridging integrator 1 (cBIN1), a cardiomyocyte transverse-tubule (t-tubule) scaffolding protein which organizes the calcium handling machinery, is transcriptionally reduced in HF and can be recovered for functional rescue in mice. Here we report that in human patients with HF with reduced ejection fraction (HFrEF), left ventricular cBIN1 levels linearly correlate with organ-level ventricular remodeling such as diastolic diameter.

Effect of surfactin on microbial content, appearance quality, and starch properties of fresh noodles during storage.

Fresh noodles (FNs) are prone to quality deterioration during storage, negatively affecting their edibility. This study investigated the impacts of different surfactin concentrations on microbial content, appearance quality, and starch properties in FNs to enhance storage stability and shelf life. The addition of surfactin effectively controlled the microbial growth in FNs during storage, FNs containing 0.

Perturbing TET2 condensation promotes aberrant genome-wide DNA methylation and curtails leukaemia cell growth.

The ten-eleven translocation (TET) family of dioxygenases maintain stable local DNA demethylation during cell division and lineage specification. As the major catalytic product of TET enzymes, 5-hydroxymethylcytosine is selectively enriched at specific genomic regions, such as enhancers, in a tissue-dependent manner. However, the mechanisms underlying this selectivity remain unresolved.

Selenium Treatment Ameliorates the Adverse Effects Caused by Dynamin Gene Knockdown in Bombyx mori.

Our previous research reported the influence of 50 μM selenium (Se) on the cytosolization (endocytosis) pathway, which in turn stimulates the growth and development of Bombyx mori. Lately, dynamin is recognized as one of the key proteins in endocytosis. To explore the underlying mechanisms of Se impact, the dynamin gene was knocked down by injecting siRNAs (Dynamin-1, Dynamin-2, and Dynamin-3).

Preparation of DNA nanoflower-modified capillary silica monoliths for chiral separation.

Innovative chiral capillary silica monoliths (CSMs) were developed based on DNA nanoflowers (DNFs). Baseline separation of enantiomers such as atenolol, tyrosine, histidine, and nefopam was achieved by using DNF-modified CSMs, and the obtained resolution value was higher than 1.78.

Single-nucleus multiomics unravels the genetic mechanisms underlying musk secretion in Chinese forest musk deer (Moschus berezovskii).

Musk secreted by the musk glands in male forest musk deer (FMD; Moschus berezovskii) is highly valued for its pharmaceutical and perfumery applications. However, the regulatory mechanisms underlying musk secretion are not well understood. This study aimed to investigate the genes and transcription factors involved in musk secretion across different periods and ages.

Adapting cytoskeleton-mitochondria patterning with myocyte differentiation by promyogenic PRR33.

Coordinated cytoskeleton-mitochondria organization during myogenesis is crucial for muscle development and function. Our understanding of the underlying regulatory mechanisms remains inadequate. Here, we identified a novel muscle-enriched protein, PRR33, which is upregulated during myogenesis and acts as a promyogenic factor.

From individuals to families: design and application of self-similar chiral nanomaterials.

Establishing an intimate relationship between similar individuals is the beginning of self-extension. Various self-similar chiral nanomaterials can be designed using an individual-to-family approach, accomplishing self-extension. This self-similarity facilitates chiral communication, transmission, and amplification of synthons.

Selenium Treatment Alleviates the Inhibition Caused by Nep-L Gene Knockdown in Silkworm (Bombyx mori).

Recent studies have emphasized the beneficial effects of 50 μM selenium (Se) on the growth and development of the silkworm, Bombyx mori; however, less is known about its underlying mechanism. To unravel the effect of 50 μM Se on the silkworms with neutral endopeptidase 24.11-like gene (NEP-L) knockdown, we injected small interfering RNA (siRNA) into the body cavity of silkworms.

Single-nucleus transcriptomics and chromatin accessibility analysis of musk gland development in Chinese forest musk deer (Moschus berezovskii).

Musk secreted by male forest musk deer (Moschus berezovskii) musk glands is an invaluable component of medicine and perfume. Musk secretion depends on musk gland maturation; however, the mechanism of its development remains elusive. Herein, using single cell multiome ATAC + gene expression coupled with several bioinformatic analyses, a dynamic transcriptional cell atlas of musk gland development was revealed, and key genes and transcription factors affecting its development were determined.

Association between serum PCSK9 and coronary heart disease in patients with type 2 diabetes mellitus.

Background And Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered a new biomarker for atherosclerosis, but its ability to predict cardiovascular outcomes has been controversial. This study aimed to address the lack of data on PCSK9, coronary heart disease (CHD) severity, and major cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM).

Methods: A total of 2984 T2DM patients underwent selective coronary angiography, and their serum PCSK9 levels were measured using enzyme-linked immunosorbent assay.

The obesogenic side of Genistein.

Genistein (GN) has been highly recommended for its medicinal properties like anticancer, antidiabetic, antihyperlipidemic, antiviral, and antioxidant activities among others. Recently, scientists realized that Genistein is an endocrine disruptor. It is an obesogen that interferes with the endocrine system causing obesity through many mechanisms like inducing adipocyte differentiation, lipid accumulation, and transformation of some stem cells into adipocytes (bone marrow mesenchymal stem cells for example) .

Reduced Mitochondrial Protein Translation Promotes Cardiomyocyte Proliferation and Heart Regeneration.

Background: The importance of mitochondria in normal heart function are well recognized and recent studies have implicated changes in mitochondrial metabolism with some forms of heart disease. Previous studies demonstrated that knockdown of the mitochondrial ribosomal protein S5 (MRPS5) by small interfering RNA (siRNA) inhibits mitochondrial translation and thereby causes a mitonuclear protein imbalance. Therefore, we decided to examine the effects of MRPS5 loss and the role of these processes on cardiomyocyte proliferation.

TET2 modulates spatial relocalization of heterochromatin in aged hematopoietic stem and progenitor cells.

DNA methylation deregulation at partially methylated domains (PMDs) represents an epigenetic signature of aging and cancer, yet the underlying molecular basis and resulting biological consequences remain unresolved. We report herein a mechanistic link between disrupted DNA methylation at PMDs and the spatial relocalization of H3K9me3-marked heterochromatin in aged hematopoietic stem and progenitor cells (HSPCs) or those with impaired DNA methylation. We uncover that TET2 modulates the spatial redistribution of H3K9me3-marked heterochromatin to mediate the upregulation of endogenous retroviruses (ERVs) and interferon-stimulated genes (ISGs), hence contributing to functional decline of aged HSPCs.

Effect of sourdough on the quality of whole wheat fresh noodles fermented with exopolysaccharide lactic acid bacteria.

In this study, the impact of exopolysaccharides (EPS)-positive strain Weissella cibaria (W. cibaria) fermented sourdough on the quality of whole wheat fresh noodles (WWNs) and its improvement mechanisms were studied. The optimal fermentation conditions were found to be 30% sucrose content, fermented at 25 °C for 12 h, which yielded the highest EPS, 28.

Inhibitory effect of cyclodextrin on Maillard reaction and its mechanism.

Maillard reaction in pharmaceutical preparations refers to a complex chemical reaction existing between reducing excipients and amino-containing drugs in preparations, which can cause a series of quality problems in preparations. Maillard reaction belongs to chemical incompatibility in preparations, and measures should be taken to reduce or avoid it. In this study, the effect of cyclodextrins (commonly used pharmaceutical excipients) on the Maillard reaction and its mechanism in the lysine hydrochloride-lactose solid preparation model were explored for the first time.

A cooperation tale of biomolecules and nanomaterials in nanoscale chiral sensing and separation.

The cooperative relationship between biomolecules and nanomaterials makes up a beautiful tale about nanoscale chiral sensing and separation. Biomolecules are considered a fabulous chirality 'donor' to develop chiral sensors and separation systems. Nature has endowed biomolecules with mysterious chirality.

Cardiac gene therapy treats diabetic cardiomyopathy and lowers blood glucose.

Diabetic cardiomyopathy, an increasingly global epidemic and a major cause of heart failure with preserved ejection fraction (HFpEF), is associated with hyperglycemia, insulin resistance, and intracardiomyocyte calcium mishandling. Here we identify that, in db/db mice with type 2 diabetes-induced HFpEF, abnormal remodeling of cardiomyocyte transverse-tubule microdomains occurs with downregulation of the membrane scaffolding protein cardiac bridging integrator 1 (cBIN1). Transduction of cBIN1 by AAV9 gene therapy can restore transverse-tubule microdomains to normalize intracellular distribution of calcium-handling proteins and, surprisingly, glucose transporter 4 (GLUT4).

Construction of chiral capillary electrochromatography microsystems based on Aspergillus sp. CM96.

Novel chiral capillary electrochromatography (CEC) microsystems were constructed based on Aspergillus sp. CM96. As a newly discovered intrinsic characteristic of the cell, cell chirality occupies an essential position in life evolution.

Echocardiography Recording in Awake Miniature Pigs.

Echocardiography uses ultrasonic waves to non-invasively assess cardiac structure and function and is the standard of care for cardiac assessment and monitoring. The miniature pig, or minipig, is increasingly being used as a model of cardiac disease in medical research. Pigs are notoriously difficult to restrain and handle safely, and, therefore, research echocardiography in this species is almost always performed under anesthesia or heavy sedation.

Enhancing Enzyme Activity and Thermostability of Bacillus amyloliquefaciens Chitosanase BaCsn46A Through Saturation Mutagenesis at Ser196.

Chitosanase plays an important role in chitooligosaccharides (COS) production. We found that the chitosanase (BaCsn46A) of Bacillus amyloliquefacien was a good candidate for chitosan hydrolysis of COS. In order to further improve the enzyme properties of BaCsn46A, the S196 located near the active center was found to be a critical site impacts on enzyme properties by sequence alignment analysis.

A canine model of chronic ischemic heart failure.

Preclinical large animal models of chronic heart failure (HF) are crucial to both understanding pathological remodeling and translating fundamental discoveries into novel therapeutics for HF. Canine models of ischemic cardiomyopathy are historically limited by either high early mortality or failure to develop chronic heart failure. Twenty-nine healthy adult dogs (30 ± 4 kg, 15/29 male) underwent thoracotomy followed by one of three types of left anterior descending (LAD) coronary artery ligation procedures: ( = 4) (simple LAD: proximal and distal LAD ligation); ( = 14) (simple LAD plus lateral wall including ligation of the distal first diagonal and proximal first obtuse marginal); and ( = 11) (total LAD devascularization or TLD: simple LAD plus ligation of proximal LAD branches to both the right and left ventricles).

A defect in mitochondrial protein translation influences mitonuclear communication in the heart.

The regulation of the informational flow from the mitochondria to the nucleus (mitonuclear communication) is not fully characterized in the heart. We have determined that mitochondrial ribosomal protein S5 (MRPS5/uS5m) can regulate cardiac function and key pathways to coordinate this process during cardiac stress. We demonstrate that loss of Mrps5 in the developing heart leads to cardiac defects and embryonic lethality while postnatal loss induces cardiac hypertrophy and heart failure.

Regulated Intramuscular Fat by Targeting Gene via an mA-YTHDF2-dependent Manner in Rex Rabbits.

N6-methyladenosine (mA) regulates fat development in many ways. Low intramuscular fat (IMF) in rabbit meat seriously affects consumption. In order to improve meat quality, we explored the law of IMF deposition.