Longitudinal In Vivo Imaging of Retinal Cells with Tailored Adeno-Associated Virus Serotypes via Confocal Scanning Laser Ophthalmoscopy.

The dynamic nature of retinal cellular processes necessitates advancements in gene delivery and live monitoring techniques to enhance the understanding and treatment of ocular diseases. This study introduces an optimized adeno-associated virus (AAV) approach, utilizing specific serotypes and promoters to achieve optimal transfection efficiency in targeted retinal cells, including retinal ganglion cells (RGCs) and Müller glia. Leveraging the precision of confocal scanning laser ophthalmoscopy (CSLO), this work presents a non-invasive method for in vivo imaging that captures the longitudinal expression of AAV-mediated green fluorescent protein (GFP).

ESC-sEVs alleviate non-early-stage osteoarthritis progression by rejuvenating senescent chondrocytes via FOXO1A-autophagy axis but not inducing apoptosis.

Osteoarthritis (OA) is a common joint degenerative disease which currently lacks satisfactory disease-modifying treatments. Oxidative stress-mediated senescent chondrocytes accumulation is closely associated with OA progression, which abrogates cartilage metabolism homeostasis by secreting senescence-associated secretory phenotype (SASP) factors. Numerous studies suggested mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) have been regarded as promising candidates for OA therapy.

Cartilage progenitor cells derived extracellular vesicles-based cell-free strategy for osteoarthritis treatment by efficient inflammation inhibition and extracellular matrix homeostasis restoration.

Osteoarthritis (OA) is a common degenerative joint disease which currently lacks of effective agents. It is therefore urgent and necessary to seek an effective approach that can inhibit inflammation and promote cartilage matrix homeostasis. Cartilage progenitor cells (CPCs) are identified as a cell population of superficial zone in articular cartilage which possess strong migration ability, proliferative capacity, and chondrogenic potential.

Hesperidin ameliorates HO-induced bovine mammary epithelial cell oxidative stress via the Nrf2 signaling pathway.

Background: Hesperidin is a citrus flavonoid with anti-inflammatory and antioxidant potential. However, its protective effects on bovine mammary epithelial cells (bMECs) exposed to oxidative stress have not been elucidated.

Results: In this study, we investigated the effects of hesperidin on HO-induced oxidative stress in bMECs and the underlying molecular mechanism.

A segmentation model to detect cevical lesions based on machine learning of colposcopic images.

Background: Semantic segmentation is crucial in medical image diagnosis. Traditional deep convolutional neural networks excel in image classification and object detection but fall short in segmentation tasks. Enhancing the accuracy and efficiency of detecting high-level cervical lesions and invasive cancer poses a primary challenge in segmentation model development.

Purification and functional validation of LtCas12a protein.

Here, we present a protocol for generating LtCas12a protein recognizing distinct TTNA (N represented A, T, C, G) protospacer adjacent motif sequence. We describe steps for transforming and harvesting bacterial cells and protein purification including nickel affinity chromatography and dialysis. We then detail procedures for verification of LtCas12a with cis- and trans-cleavage activities.

Massively parallel CRISPR off-target detection enables rapid off-target prediction model building.

Background: CRISPR (clustered regularly interspaced short palindromic repeats) genome editing holds tremendous potential in clinical translation. However, the off-target effect has always been a major concern.

Methods: Here, we have developed a novel sensitive and specific off-target detection method, AID-seq (adaptor-mediated off-target identification by sequencing), that can comprehensively and faithfully detect the low-frequency off targets generated by different CRISPR nucleases (including Cas9 and Cas12a).

A Cas12a ortholog with distinct TTNA PAM enables sensitive detection of HPV16/18.

CRISPR-associated (Cas) nucleases are multifunctional tools for gene editing. Cas12a possesses several advantages, including the requirement of a single guide RNA and high fidelity of gene editing. Here, we tested three Cas12a orthologs from human gut samples and identified a LtCas12a that utilizes a TTNA protospacer adjacent motif (PAM) distinct from the canonical TTTV PAM but with equivalent cleavage ability and specificity.

Changes in Bacterial Communities and Their Effects on Soil Carbon Storage in Invasion Areas, Coastal Wetland Bare Flats, and Areas.

is considered an invasive species that has affected the biogeochemical circle of carbon in coastal wetlands around the world. Nevertheless, it is still unclear how invasion affects the carbon storage capacity of coastal wetlands as carbon pools through bacterial changes. Herein, bacterial communities and soil carbon content in coastal wetland native areas and invasion areas were detected.

HPV integration generates a cellular super-enhancer which functions as ecDNA to regulate genome-wide transcription.

Human papillomavirus (HPV) integration is a critical step in cervical cancer development; however, the oncogenic mechanism at the genome-wide transcriptional level is still poorly understood. In this study, we employed integrative analysis on multi-omics data of six HPV-positive and three HPV-negative cell lines. Through HPV integration detection, super-enhancer (SE) identification, SE-associated gene expression and extrachromosomal DNA (ecDNA) investigation, we aimed to explore the genome-wide transcriptional influence of HPV integration.

VIS Atlas: A Database of Virus Integration Sites in Human Genome from NGS Data to Explore Integration Patterns.

Integration of oncogenic DNA viruses into the human genome is a key step in most virus-induced carcinogenesis. Here, we constructed a virus integration site (VIS) Atlas database, an extensive collection of integration breakpoints for three most prevalent oncoviruses, human papillomavirus, hepatitis B virus, and Epstein-Barr virus based on the next-generation sequencing (NGS) data, literature, and experimental data. There are 63,179 breakpoints and 47,411 junctional sequences with full annotations deposited in the VIS Atlas database, comprising 47 virus genotypes and 17 disease types.

FrCas9 is a CRISPR/Cas9 system with high editing efficiency and fidelity.

Genome editing technologies hold tremendous potential in biomedical research and drug development. Therefore, it is imperative to discover gene editing tools with superior cutting efficiency, good fidelity, and fewer genomic restrictions. Here, we report a CRISPR/Cas9 from Faecalibaculum rodentium, which is characterized by a simple PAM (5'-NNTA-3') and a guide RNA length of 21-22 bp.

Gene knock-out chain reaction enables high disruption efficiency of HPV18 / genes in cervical cancer cells.

A genome editing tool targeting the high-risk human papillomavirus (HPV) oncogene is a promising therapeutic strategy to treat HPV-related cervical cancer. To improve gene knockout efficiency, we developed a gene knockout chain reaction (GKCR) method for continually generating mutagenic disruptions and used this method to disrupt the HPV18 and genes. We verified that the GKCR Cas9/guide RNA (gRNA) cassettes could integrated into the targeted loci via homology-independent targeted insertion (HITI).

Triple Generative Adversarial Networks.

We propose a unified game-theoretical framework to perform classification and conditional image generation given limited supervision. It is formulated as a three-player minimax game consisting of a generator, a classifier and a discriminator, and therefore is referred to as Triple Generative Adversarial Network (Triple-GAN). The generator and the classifier characterize the conditional distributions between images and labels to perform conditional generation and classification, respectively.

Prevalence and relevant factors of positive RF in brucellosis patients with arthralgia.

Background: Brucellosis is a critical zoonotic disease in the world, it is the non-specific arthralgia that make brucellosis patients easily misdiagnosed as rheumatoid arthritis (RA) in endemic regions. Elevated rheumatoid factor (RF) is an essential indicator of RA, and the RF in brucellosis patients is significantly higher than healthy people. Therefore, this study further explored the distribution of RF and the relevant factors of the RF positivity in brucellosis patients with arthralgia, in order to strengthen the recognition of physicians for brucellosis patients with RF positivity, especially in brucellosis-endemic areas, so as to avoid misdiagnosis and untimely treatment that may lead to malignant outcomes.

Advances in Ultrasound-Guided Vacuum-Assisted Biopsy of Breast Microcalcifications.

Microcalcification is one of the significant indications for or can even be the sole mammographic feature of breast cancer, especially occult breast cancer. Biopsy and pathologic examination are the most important methods used to identify the nature of suspicious microcalcifications. Stereotactic vacuum-assisted breast biopsy (S-VAB) is the most commonly used biopsy method for microcalcifications currently because of the high detection rate of mammography for microcalcifications.

Clinical study on the status of transient thyrotoxicosis after surgery for secondary hyperparathyroidism patients with end-stage renal disease and normal thyroid function.

Objective: Secondary hyperparathyroidism (SHPT) is a common complication of end-stage renal disease (ESRD), and part of SHPT patients need receive parathyroidectomy (PTX). However, as an important postoperative complication of SHPT, thyrotoxicosis has received little attention. Therefore, in this article, we aimed to study the status of transient thyrotoxicosis after PTX for SHPT patients with ESRD and normal thyroid function.

Association Between Breast and Thyroid Lesions: A Cross-Sectional Study Based on Ultrasonography Screening in China.

Prior research has shown an association between breast and thyroid cancers, although their relationship is unclear. In China, asymptomatic women undergoing regular health checkups usually undergo breast and thyroid ultrasonography screening. The present cross-sectional ultrasound-based study estimated the prevalence of breast masses (BM) and thyroid nodules (TN) and their relationship among a population-based cohort of Chinese women.

Cognitive impairments in breast cancer survivors treated with chemotherapy: a study based on event-related potentials.

Purpose: Chemotherapy-related cognitive impairments in breast cancer patients were usually reported through cognitive questionnaires or scales which may be subjective and insensitive. This study is to assess the effect of chemotherapy on cognitive function in breast cancer patients stratified by age using objective electrophysiological measure, the P300 component of event-related potentials (ERPs) with a large sample size.

Methods: Totally, 529 primary breast cancer patients, including 178 cases at initial diagnosis stage and before chemotherapy (Group1), 167 cases during chemotherapy (Group2), and 184 cases post chemotherapy and during follow-up period (Group3), were examined with ERPs (P300 component) to assess the effect of chemotherapy on their cognitive function.

Distribution, transformation and toxicity evaluation of 2,6-Di-tert-butyl-hydroxytotulene in aquatic environment.

2,6-Di-tert-butyl-hydroxytotulene (BHT), as a significant synthetic phenolic antioxidant (SPA), has received increasing attention in the environmental field. In the present study, the BHT is confirmed to be mainly distributed in the liquid phase in the environment base on the Aspen PLUS simulation results. The mechanism and kinetics of BHT transformation initiated by OH radicals were conducted in aquatic environment using density functional theory (DFT) method.

Aminotriazole alleviates acetaminophen poisoning via downregulating P450 2E1 and suppressing inflammation.

Aminotriazole (ATZ) is commonly used as a catalase (CAT) inhibitor. We previously found ATZ attenuated oxidative liver injury, but the underlying mechanisms remain unknown. Acetaminophen (APAP) overdose frequently induces life-threatening oxidative hepatitis.