Biallelic loss-of-function variants in lead to retinal degeneration.

Background: Inherited retinal diseases (IRDs) are a group of disorders often resulting in progressive vision loss, ultimately leading to blindness. A significant portion of their genetic causes remain unresolved, partly due to undiscovered disease-associated genes or variants. This study aimed to identify novel genetic links to IRDs.

Generation of four human pluripotent stem cell lines harboring OPA1-related optic atrophy variant.

We have generated four human iPSC lines from skin biopsy-derived fibroblast cells with pathogenic variants in OPA1. Donors have a clinical diagnosis of optic atrophy. Three harbor heterozygous presumed loss-of-function (pLOF) variants, c.

SLC4A11 is a targetable marker correlated with therapeutic responses in ovarian cancer.

Background: Solute carrier family 4 member 11 (SLC4A11) is involved in borate homeostasis, metabolism reprogramming, cell growth, and cell adhesion. However, the biological function of SLC4A11 in ovarian cancer (OC) is still unclear. This study explores the anti-tumor and biological activities of SLC4A11 in OC.

Germin-like protein 1 interacts with proteasome regulator 1 to regulate auxin signaling by controlling Aux/IAA homeostasis.

Auxin regulates various aspects of plant growth and development by modulating the transcription of target genes through the degradation of auxin/indole-3-acetic acid (Aux/IAA) repressors via the 26S proteasome. Proteasome regulator 1 (PTRE1), a positive regulator of proteasome activity, has been implicated in auxin-mediated proteasome suppression; however, the mechanism by which auxin modulates PTRE1 function remains unclear. Here, we demonstrate that auxin promotes the interaction between germin-like protein 1 (GLP1) and PTRE1, facilitating PTRE1 retention at the plasma membrane.

Arabidopsis phospholipase Dζ2 facilitates vacuolar acidification and autophagy under phosphorus starvation by interacting with VATD.

Vacuolar acidification is crucial for the homeostasis of intracellular pH and the recycling of proteins and nutrients in cells, thereby playing important roles in various physiological processes related to vacuolar function. The key factors regulating vacuolar acidification and underlying mechanisms remain unclear. Here, we report that Arabidopsis phospholipase Dζ2 (PLDζ2) promotes the acidification of the vacuolar lumen to stimulate autophagic degradation under phosphorus deficiency.

FOXP4 Variants Are Associated With Plateau Iris and Angle Closure Glaucoma.

Purpose: Angle closure glaucoma (ACG) is a common cause of adult-onset vision loss that often presents with iris abnormalities and short axial lengths. Although it is heritable, little is known about the genetic risk factors underlying this condition. We thus conducted a disease gene discovery study in a family exhibiting an autosomal dominant triad of ACG, plateau iris, and short axial lengths.

Variants in NR6A1 cause a novel oculo vertebral renal syndrome.

Colobomatous microphthalmia is a potentially blinding congenital ocular malformation that can present either in isolation or together with other syndromic features. Despite a strong genetic component to disease, many cases lack a molecular diagnosis. We describe an autosomal dominant oculo-vertebral-renal (OVR) syndrome in six independent families characterized by colobomatous microphthalmia, missing vertebrae and congenital kidney abnormalities.

Development of CSOARG: a single-cell and multi-omics-based machine learning model for ovarian cancer prognosis and drug response prediction.

Objective: Ovarian cancer is the most deadly gynaecological malignancy. This study aims to generate a predictive model for prognosis and therapeutic responses in ovarian cancer using defined specific genes.

Methods: The cellular senescence-associated gene sets and the ovarian aging-associated gene sets from the TCGA and GEO databases were analyzed using Cox regression with LASSO approach and employed to construct a prognostic model of Cellular Senescence and Ovarian Aging-Related Genes (CSOARG).

Integration of 3D-Printed Micro/Nanostructures with Interdigitated Electrodes for Low-Matrix-Effect Sensing.

Electrochemical sensors offer the advantages of low cost, high sensitivity, and miniaturization for a wide range of biological applications, including in situ detection of cell metabolites and monitoring cell behavior in real time. However, the complex matrix in biosystems often leads to electrode fouling and inferior sensing performance. In addition to chemical barriers featuring assorted antifouling molecules or coatings, creating micro/nano hierarchical structures on top of electrodes can provide physical barriers to mitigate matrix interference without affecting electron transfer.

Case Report: Association of Ocular Colobomas With a Novel Missense Variant in CDC42, a Member of the Rho Family of Small GTPases.

We present a 2-year-old male with bilateral iris and chorioretinal colobomas, speech delays, and facial and digital anomalies. Trio exome sequencing demonstrated a de novo, novel heterozygous variant, c.379G>A p.

The effective molecular characteristics of PD-1 inhibitor combination regimen as the first-line treatment for Chinese patients with HER2-positive gastric cancer: a real-world retrospective analysis study.

Background: The prognosis of gastric cancer (GC) patients with human epidermal growth factor receptor 2 (HER2) positive was poor. To illustrate the underlying effective and distinctive molecular characteristics of programmed cell death protein 1 (PD-1) blockade in the treatment of GC with HER2 positive, we analyzed the survival outcome of PD-1 inhibitors combination regimen as the first-line treatment for GC patients with HER2-positive in China.

Methods: This retrospective real-world study compared the prognoses of first-line systemic treatment of PD-1 inhibitors combined with trastuzumab and chemotherapy (PTC group) and trastuzumab and chemotherapy (TC group) in Chinese patients with HER2-positive GC, and then further to identify the specific and molecular characteristics of PD-1 inhibitors treatment by hierarchical analysis.

Splicing variants in MYRF cause partial loss of function in the retinal pigment epithelium.

Myelin Regulatory Factor (MYRF) regulates retinal pigment epithelial (RPE) development and variants in the C-terminus are linked to isolated nanophthalmos, while loss-of-function variants cause syndromic disease. To define the molecular mechanism of this discrepancy, and animal studies were performed on a pathogenic C-terminal variant (p.Gly1126fs30* or dG-MYRF).

Role of evolving sea surface temperature modes of variability in improving seasonal precipitation forecasts.

The value of improving longer-lead precipitation forecasting in the water-stressed, semi-arid western United States cannot be overstated, especially considering the severity and frequency of droughts that have plagued the region for much of the 21 century. Seasonal prediction skill of current operational forecast systems, however, remain insufficient for decision-making purposes across a variety of applications. To address this capability gap, we develop a seasonal forecasting system that leverages the long-term memory of leading global and basin-scale modes of sea surface temperature variability.

A zebrafish model of loss of function has small and misshapen lenses with dysregulated and expression.

Introduction: Heterozygous deletions predicting haploinsufficiency for the Cysteine Rich Motor Neuron 1 () gene have been identified in two families with macrophthalmia, colobomatous, with microcornea (MACOM), an autosomal dominant trait. encodes a type I transmembrane protein that is expressed at the cell membrane of lens epithelial and fiber cells at the stage of lens pit formation. Decreased Crim1 expression in the mouse reduced the number of lens epithelial cells and caused defective adhesion between lens epithelial cells and between the epithelial and fiber cells.

FLOT1 Is a Novel Serum Biomarker of Ovarian Cancer Targeted by N6-methyladenosine Modification Inhibition.

Ovarian cancer (OC) is a deadly disease and lacks a precise marker for diagnosis worldwide. Our previous work has shown the overexpression of flotillin-1 (FLOT1) in OC tissue. To improve diagnostic sensitivity and accuracy, we evaluated the serum level of FLOT1 in OC patients and found that the serum concentration of FLOT1 as well as CA125 was significantly increased in patients with OC compared with healthy control (p < 0.

Photo-induced dehalogenative deuteration and elimination of alkyl halides enabled by phosphine-mediated halogen-atom transfer.

Dehalogenative deuteration of organic halides is an efficient and straightforward method for incorporating deuterium atoms at specific locations within target molecules. However, utilizing organic halides in photoredox chemistry, particularly unactivated alkyl halides, presents challenges due to their low reduction potentials. In this work, we present a general and effective photoinduced dehalogenative deuteration method for a diverse array of alkyl halides, employing DO as an economical source of deuterium.

Genotype-Phenotype Spectrum of eyeGENE Patients With Familial Exudative Vitreoretinopathy: Novel Variants in Norrin/β-Catenin Signaling Pathway Genes.

Purpose: To report the variants and genotype-phenotype correlations in patients with familial exudative vitreoretinopathy (FEVR) included in the eyeGENE database.

Methods: A retrospective study was conducted in a cohort of 122 eyeGENE patients from 114 families with FEVR. Clinical details and genetic test results were provided by referring clinicians and clinical laboratories in the eyeGENE network, respectively.

A novel frameshift variant in the gene is associated with recessive oculodentodigital dysplasia.

Background: Oculodentodigital dysplasia (ODDD) is a rare syndrome that causes a constellation of facial, ophthalmic, dental, and limb abnormalities. Variants in the gap junction alpha-1 () gene have been described in patients with ODDD. Hereby we present the ocular manifestations in a patient with recessive ODDD due to a novel homozygous frameshift variant in .

Analysis of the Distribution Pattern and Prophage Types in Asiaticus 'Cuimi' Kumquat.

The 'Cuimi' kumquat is a unique citrus cultivar known for its thin, crisp pulp and sweet, aromatic flavor. In addition to its use in fresh consumption and processing, this variety exhibits certain medicinal properties. This study aims to investigate the genetic diversity of the Huanglongbing (HLB) bacterium across different tissues of the 'Cuimi' kumquat, offering a theoretical basis for understanding the HLB epidemic in Dechang County, Sichuan.

Variants in cause a novel oculo-vertebral-renal (OVR) syndrome.

Colobomatous microphthalmia is a potentially blinding congenital ocular malformation that can present either in isolation or together with other syndromic features. Despite a strong genetic component to disease, many cases lack a molecular diagnosis. We describe a novel autosomal dominant oculo-vertebral-renal (OVR) syndrome in six independent families characterized by colobomatous microphthalmia, missing vertebrae and congenital kidney abnormalities.

Seasonality and climate modes influence the temporal clustering of unique atmospheric rivers in the Western U.S.

Atmospheric rivers (ARs) are narrow corridors of intense water vapor transport, shaping precipitation, floods, and economies. Temporal clustering of ARs tripled losses compared to isolated events, yet the reasons behind this clustering remain unclear. AR orientation further modulates hydrological impacts through terrain interaction.

In silicon desinging of RANKL-targeting vaccine for protection of osteoporosis based on the epitope of Denosumab.

Background: Life quality of osteoporosis patients is affected significantly due to the severely complications of fracture and pain. RANKL, indicated as the key mediator of osteoporosis, plays a pathogenic role of osteoclasts induction. To target this program, two medications, bisphosphonate and Denosumab, were developed and achieved remarkable advantages in clinics.

SLC16A8 is a causal contributor to age-related macular degeneration risk.

Age-related macular degeneration (AMD), a complex neurodegenerative disease, is a leading cause of visual impairment worldwide with a strong genetic component. Genetic studies have identified several loci, but few causal genes with functional characterization. Here we highlight multiple lines of evidence which show a causal role in AMD for SLC16A8, which encodes MCT3, a retinal pigment epithelium (RPE) specific lactate transporter.