Global, regional, and national burden of syphilis, 1990-2021 and predictions by Bayesian age-period-cohort analysis: a systematic analysis for the global burden of disease study 2021.

Objective: To comprehensively assess the global burden of syphilis and related risk factors over 1990-2021, forecast future disease trends, and understand the impact of syphilis on global health.

Methods: Global Burden of Disease Study 2021 (GBD 2021) data were used for age-, sex-, and region-stratified analysis of the numbers and age-standardized rates (per 100,000 population) of syphilis incidence, prevalence, deaths, and disability-adjusted life years (DALYs). Next, a differential analysis of syphilis risk factors was performed.

[Role of podocyte injury signaling pathway in steroid-resistant nephrotic syndrome and research progress in traditional Chinese medicine intervention].

As one of the main diseases leading to end-stage renal disease, steroid-resistant nephrotic syndrome(SRNS) can cause serious complications such as infection. Without effective control, this disease can further lead to the malignant development of the renal function, bringing serious social and economic burdens. As previously reported, the formation of SRNS is mostly related to the podocyte injury in the body, i.

A DddA ortholog-based and transactivator-assisted nuclear and mitochondrial cytosine base editors with expanded target compatibility.

Bacterial double-stranded DNA (dsDNA) cytosine deaminase DddA-derived cytosine base editor (DdCBE) and its evolved variant, DddA11, guided by transcription-activator-like effector (TALE) proteins, enable mitochondrial DNA (mtDNA) editing at TC or HC (H = A, C, or T) sequence contexts, while it remains relatively unattainable for GC targets. Here, we identified a dsDNA deaminase originated from a Roseburia intestinalis interbacterial toxin (riDddA) and generated CRISPR-mediated nuclear DdCBEs (crDdCBEs) and mitochondrial CBEs (mitoCBEs) using split riDddA, which catalyzed C-to-T editing at both HC and GC targets in nuclear and mitochondrial genes. Moreover, transactivator (VP64, P65, or Rta) fusion to the tail of DddA- or riDddA-mediated crDdCBEs and mitoCBEs substantially improved nuclear and mtDNA editing efficiencies by up to 3.

Phase evolution for oxidizing bismuth selenide.

The novel BiOSe, produced by the oxidation of the layered BiSe, has been considered as one of the most promising candidates for the next-generation electronics owing to its high carrier mobility and air-stability. In this work, by using crystal structure prediction and first-principles calculations, we report the phase transformations from the hexagonal BiSeto the monoclinic BiOSe, and then to the tetragonal BiOSe with the gradual oxidization. Owing to the difference in electronegativity between selenium (Se) and oxygen (O), the oxidation process is accompanied by an increase in bond ionicity.

Functional Phosphoproteomics in Cancer Chemoresistance Using CRISPR-Mediated Base Editors.

Selective inhibition of targeted protein kinases is an effective therapeutic approach for treatment of human malignancies, which interferes phosphorylation of cellular substrates. However, a drug-imposed selection creates pressures for tumor cells to acquire chemoresistance-conferring mutations or activating alternative pathways, which can bypass the inhibitory effects of kinase inhibitors. Thus, identifying downstream phospho-substrates conferring drug resistance is of great importance for developing poly-pharmacological and targeted therapies.

Helper-Polymer Based Five-Element Nanoparticles (FNPs) for Lung-Specific mRNA Delivery with Long-Term Stability after Lyophilization.

Lipid nanoparticles (LNPs) carrying therapeutic mRNAs hold great promise in treating lung-associated diseases like viral infections, tumors, and genetic disorders. However, because of their thermodynamically unstable nature, traditional LNPs carrying mRNAs need to be stored at low temperatures, which hinders their prevalence. Herein, an efficient lung-specific mRNA delivery platform named five-element nanoparticles (FNPs) is developed in which helper-polymer poly(β-amino esters) (PBAEs) and DOTAP are used in combination.

Engineering of near-PAMless adenine base editor with enhanced editing activity and reduced off-target.

About 47% of pathogenic point mutations could be corrected by ABE-induced A·T-to-G·C conversions. However, the applications of ABEs are still hindered by undesired editing efficiency, limited editing scopes, and off-targeting effects. Here, we develop a new adenine base editor, by embedding TadA-8e monomer into SpRY-nCas9, named as CE-8e-SpRY, which exhibits higher activity at NRN than NYN PAMs favored by SpRY nuclease.

PPARγ phase separates with RXRα at PPREs to regulate target gene expression.

Peroxisome proliferator-activated receptor (PPAR)-γ is a key transcription activator controlling adipogenesis and lipid metabolism. PPARγ binds PPAR response elements (PPREs) as the obligate heterodimer with retinoid X receptor (RXR) α, but exactly how PPARγ orchestrates the transcriptional response is unknown. This study demonstrates that PPARγ forms phase-separated droplets in vitro and solid-like nuclear condensates in cell, which is intriguingly mediated by its DNA binding domain characterized by the zinc finger motif.

San-Huang-Yi-Shen Capsule Ameliorates Diabetic Nephropathy in Rats Through Modulating the Gut Microbiota and Overall Metabolism.

San-Huang-Yi-Shen capsule (SHYS) has been used in the treatment of diabetic nephropathy (DN) in clinic. However, the mechanisms of SHYS on DN remain unknown. In this study, we used a high-fat diet (HFD) combined with streptozotocin (STZ) injection to establish a DN rat model.

Correction of the pathogenic mutation in TGM1 gene by adenine base editing in mutant embryos.

A couple diagnosed as carriers for lamellar ichthyosis, an autosomal recessive rare disease, encountered two pregnancy losses. Their blood samples showed the same heterozygous c.607C>T mutation in the TGM1 gene.

Structure-guided engineering of adenine base editor with minimized RNA off-targeting activity.

Both adenine base editors (ABEs) and cytosine base editors (CBEs) have been recently revealed to induce transcriptome-wide RNA off-target editing in a guide RNA-independent manner. Here we construct a reporter system containing E.coli Hokb gene with a tRNA-like motif for robust detection of RNA editing activities as the optimized ABE, ABEmax, induces highly efficient A-to-I (inosine) editing within an E.

Harnessing A3G for efficient and selective C-to-T conversion at C-rich sequences.

Background: Site-specific C>T DNA base editing has been achieved by recruiting cytidine deaminases to the target C using catalytically impaired Cas proteins; the target C is typically located within 5-nt editing window specified by the guide RNAs. The prototypical cytidine base editor BE3, comprising rat APOBEC1 (rA1) fused to nCas9, can indiscriminately deaminate multiple C's within the editing window and also create substantial off-target edits on the transcriptome. A powerful countermeasure for the DNA off-target editing is to replace rA1 with APOBEC proteins which selectively edit C's in the context of specific motifs, as illustrated in eA3A-BE3 which targets TC.

A natural DNMT1 mutation elevates the fetal hemoglobin level via epigenetic derepression of the γ-globin gene in β-thalassemia.

DNA methyltransferase 1 (DNMT1) is a major epigenetic regulator of the formation of large macromolecular complexes that repress human γ-globin expression by maintaining DNA methylation. However, very little is known about the association of DNMT1 variants with β-thalassemia phenotypes. We systematically investigated associations between variants in DNMT1 and phenotypes in 1142 β-thalassemia subjects and identified a novel missense mutation (c.

Cas12a Base Editors Induce Efficient and Specific Editing with Low DNA Damage Response.

The advent of base editors (BEs) holds great potential for correcting pathogenic-related point mutations to treat relevant diseases. However, Cas9 nickase (nCas9)-derived BEs lead to DNA double-strand breaks, which can trigger unwanted DNA damage response (DDR). Here, we show that the original version of catalytically dead Cas12a (dCas12a)-conjugated BEs induce a basal level of DNA breaks and minimally activate DDR proteins, including H2AX, ATM, ATR, and p53.

Network Analysis of Transcriptome and LC-MS Reveals a Possible Biosynthesis Pathway of Anthocyanins in .

Anthocyanins, a group of flavonoids, are widely present in plants and determine the colors of the peels of stems, fruits, and flowers. In this study, we used UHPLC-ESI-MS to identify anthocyanins in the herbal plant , which has been used for centuries in China. The results indicated that the total anthocyanin content in samples from Guangxi was the highest.

CRISPR/Cas12a technology combined with immunochromatographic strips for portable detection of African swine fever virus.

African swine fever virus (ASFV), the aetiological agent of African swine fever (ASF), causes lethal haemorrhagic fever in domestic pigs with high mortality and morbidity and has devastating consequences on the global swine industry. On-site rapid and sensitive detection of ASFV is key to the timely implementation of control. In this study, we developed a rapid, sensitive and instrument-free ASFV detection method based on CRISPR/Cas12a technology and lateral flow detection (named CRISPR/Cas12a-LFD).

Increasing the targeting scope and efficiency of base editing with Proxy-BE strategy.

Base editors (BEs) are widely used in precise gene editing due to their simplicity and versatility. However, their efficiencies are hindered by various obstacles. Considering the chromatin microenvironment as a possible obstacle, here, we demonstrate a further development of the proxy-clustered regularly interspaced short palindromic repeats strategy, termed Proxy-BE, to increase gene editing efficiency.

[Cluster analysis of Dendrobium officinale from different populations through agronomy characterization].

Through resources investigation and sample collection,a total number of 392 Dendrobium officinale from 38 different populations,9 provinces were processed for measuring and observing.Fourteen agronomy characterizations like stem height,stem diameter,number of node in stem were selected for further classification.The cluster analysis was performed using Ward and Euclidean method.

Structural Characterization of Polysaccharides from and Their Effects on Apoptosis of HeLa Cell Line.

is a widely used medicinal plant in China with numerous bio-activities. However, the main structure and anti-tumor activity of the polysaccharides from this plant have not been investigated. In this study, we elucidated the main structure of polysaccharides purified with DEAE and Sephadex G-25 from grown under different planting conditions.

Correction of the Marfan Syndrome Pathogenic FBN1 Mutation by Base Editing in Human Cells and Heterozygous Embryos.

There are urgent demands for efficient treatment of heritable genetic diseases. The base editing technology has displayed its efficiency and precision in base substitution in human embryos, providing a potential early-stage treatment for genetic diseases. Taking advantage of this technology, we corrected a Marfan syndrome pathogenic mutation, FBN1.

Association of systolic blood pressure with cardiovascular outcomes in elderly patients with hypertension in Northern China.

Objective: The aim of this study was to investigate the association of systolic blood pressure (SBP) with cardiovascular disease and all-cause mortality among elderly hypertensive patients in northern China.

Participants And Methods: In this prospective cohort study, 9655 elderly hypertensive patients from Kailuan study were followed up with the incidence of primary outcomes (composite outcomes including myocardial infarction, stroke, and all-cause death) and the incidence of secondary outcomes (stroke, myocardial infarction, and all-cause death). Patients were categorized into five groups on the basis of SBP levels: Q1 (SBP<130 mmHg), Q2 (130≤SBP<140 mmHg), Q3 (140≤SBP<150 mmHg), Q4 (150≤SBP<160 mmHg), and Q5 (SBP≥160 mmHg).

Efficient generation of mouse models of human diseases via ABE- and BE-mediated base editing.

A recently developed adenine base editor (ABE) efficiently converts A to G and is potentially useful for clinical applications. However, its precision and efficiency in vivo remains to be addressed. Here we achieve A-to-G conversion in vivo at frequencies up to 100% by microinjection of ABE mRNA together with sgRNAs.