Characterizing mutation-treatment effects using clinico-genomics data of 78,287 patients with 20 types of cancers.

Evaluating the effectiveness of cancer treatments in relation to specific tumor mutations is essential for improving patient outcomes and advancing the field of precision medicine. Here we represent a comprehensive analysis of 78,287 U.S.

Employing splice-switching oligonucleotides and AAVrh74.U7 snRNA to target insulin receptor splicing and cancer hallmarks in osteosarcoma.

Patients with osteosarcoma (OS), a debilitating pediatric bone malignancy, have limited treatment options to combat aggressive disease. OS thrives on insulin growth factor (IGF)-mediated signaling that can facilitate cell proliferation. Previous efforts to target IGF-1R signaling were mostly unsuccessful, likely due to compensatory signaling through alternative splicing of the insulin receptor () to the proliferative isoform.

Proposal of one new family, seven new genera and seventy new basidiomycetous yeast species mostly isolated from Tibet and Yunnan provinces, China.

More than 2 000 yeast strains isolated from 1 200 samples mostly collected from Tibet and Yunnan provinces in China were identified as 462 species according to the internal transcribed spacer including the 5.8S rDNA (ITS) and the D1/D2 domains of the large subunit rDNA (LSU) sequence analyses. Among them, 70 new basidiomycetous yeast species were proposed based on the multi-locus phylogenetic analyses including the D1/D2 domains, the ITS, the small subunit rDNA (SSU), the largest subunit of RNA polymerase II (), the second largest subunit of RNA polymerase II () and translation elongation factor 1-α (), as well as the phenotypic comparisons.

Acute systemic macrophage depletion in osteoarthritic mice alleviates pain-related behaviors and does not affect joint damage.

Background: Osteoarthritis (OA) is a painful degenerative joint disease and a leading source of years lived with disability globally due to inadequate treatment options. Neuroimmune interactions reportedly contribute to OA pain pathogenesis. Notably, in rodents, macrophages in the DRG are associated with onset of persistent OA pain.

Middle Meningeal Artery Embolization for Nonacute Subdural Hematoma.

Background: The effect of embolization of the middle meningeal artery in patients with subacute or chronic subdural hematoma is uncertain.

Methods: We performed a multicenter, open-label, randomized trial in China, involving patients with symptomatic nonacute subdural hematoma with mass effect. Patients were assigned to undergo burr-hole drainage or receive nonsurgical treatment at the surgeon's discretion, and patients in each group were then randomly assigned, in a 1:1 ratio, to undergo middle meningeal artery embolization with liquid embolic material or to receive usual care.

Impact of S-PRG/Giomer and Bulk-fill technologies on the hygroscopic profile of resin composites under erosive condition.

Objective: The emergence of new resin composites (RCs) incorporating bioactive ingredients and/or used as bulk-fill materials aims to enhance restorative potential beyond just the mechanical properties. However, this innovation may affect their performance under clinically simulated conditions, such as erosive challenges (EC). This study evaluated the impact of different technologies on the hygroscopic properties of RCs.

Impact of functional monomers, bioactive particles, and HEMA, on the adhesive performance of self-etch adhesive systems applied to simulated altered dentin.

Objectives: This study aimed to evaluate how self-etching/universal dental adhesive systems (DASs) with differing compositions interact with sound (S), post-radiotherapy (irradiated; I), and artificially eroded (E) dentin in terms of bonding properties.

Methods: The DASs tested were Adper Scotchbond Multipurpose (MP; control), Clearfil SE Bond (SE), FL Bond II (FL), Adper Single Bond Universal (SU) and BeautiBond Xtreme (BX). They were analyzed for initial and 6-month microtensile bond strength (µTBS, n = 12), mode of failure (40 x), scanning electron microscopy (SEM), surface wettability (W, n = 10), and degree of conversion (DC, n = 3) via Fourier-transform infrared spectroscopy (FTIR).

A PD-1-targeted, receptor-masked IL-2 immunocytokine that engages IL-2Rα strengthens T cell-mediated anti-tumor therapies.

The clinical use of interleukin-2 (IL-2) for cancer immunotherapy is limited by severe toxicity. Emerging IL-2 therapies with reduced IL-2 receptor alpha (IL-2Rα) binding aim to mitigate toxicity and regulatory T cell (Treg) expansion but have had limited clinical success. Here, we show that IL-2Rα engagement is critical for the anti-tumor activity of systemic IL-2 therapy.

Evolved cytidine and adenine base editors with high precision and minimized off-target activity by a continuous directed evolution system in mammalian cells.

Continuous directed evolution of base editors (BEs) has been successful in bacteria cells, but not yet in mammalian cells. Here, we report the development of a Continuous Directed Evolution system in Mammalian cells (CDEM). CDEM enables the BE evolution in a full-length manner with Cas9 nickase.

Effective knockdown-replace gene therapy in a novel mouse model of DNM1 developmental and epileptic encephalopathy.

Effective gene therapy for gain-of-function or dominant-negative disease mutations may require eliminating expression of the mutant copy together with wild-type replacement. We evaluated such a knockdown-replace strategy in a mouse model of DNM1 disease, a debilitating and intractable neurodevelopmental epilepsy. To challenge the approach robustly, we expressed a patient-based variant in GABAergic neurons-which resulted in growth delay and lethal seizures evident by postnatal week three-and delivered to newborn pups an AAV9-based vector encoding a ubiquitously expressed, Dnm1-specific interfering RNA (RNAi) bivalently in tail-to-tail configuration with a neuron-specific, RNAi-resistant, codon-optimized Dnm1 cDNA.

Genotype Associated With Visual Prognosis in Patients With Congenital Ectopia Lentis Following Lens Surgery: A Prospective Cohort Study.

Purpose: To investigate the relationship between visual prognosis and genotype in patients undergoing lens surgery for congenital ectopia lentis (EL).

Design: Prospective clinical cohort study.

Methods: Patients with congenital EL who underwent lens removal and intraocular lens implantation received panel-based next-generation sequencing.

Metagenomic analysis reveals a dynamic rumen microbiome with diversified adaptive functions in response to dietary protein restriction and re-alimentation.

Understanding the dynamics of the rumen microbiome is crucial for optimizing ruminal fermentation to improve feed efficiency and addressing concerns regarding antibiotic resistance in the livestock production industry. This study aimed to investigate the adaptive effects of microbiome and the properties of carbohydrate-active enzymes (CAZy) and antibiotic resistance genes (ARGs) in response to dietary protein shifts. Twelve Charolais bulls were randomly divided into two groups based on initial body weight: 1) Treatment (REC), where the animals received a 7 % CP diet in a 4-week restriction period, followed by a 13 % CP diet in a 2-week re-alimentation period; 2) Control (CON), where the animals were fed the 13 % CP diet both in the restriction period and the re-alimentation period.

Efficacy and safety of sintilimab in combination with chemotherapy for recurrent extensive-stage small cell lung cancer: a real-world retrospective study.

Background: Immune checkpoint inhibitors (ICIs) no longer are approved for second-line or later treatment of extensive-stage small cell lung cancer (ES-SCLC), and have not been studied in combination with chemotherapy. Exploring the efficacy and safety of second-line or later immunotherapy for ES-SCLC is an urgent clinical question that needs to be addressed, and combination therapies are an important research direction. This study intended to investigate the efficacy and safety of the sintilimab in combination with chemotherapy as a second-line and beyond treatment option for ES-SCLC.

Development of deaminase-free T-to-S base editor and C-to-G base editor by engineered human uracil DNA glycosylase.

DNA base editors enable direct editing of adenine (A), cytosine (C), or guanine (G), but there is no base editor for direct thymine (T) editing currently. Here we develop two deaminase-free glycosylase-based base editors for direct T editing (gTBE) and C editing (gCBE) by fusing Cas9 nickase (nCas9) with engineered human uracil DNA glycosylase (UNG) variants. By several rounds of structure-informed rational mutagenesis on UNG in cultured human cells, we obtain gTBE and gCBE with high activity of T-to-S (i.

A culture method with berbamine, a plant alkaloid, enhances CAR-T cell efficacy through modulating cellular metabolism.

Memory T cells demonstrate superior in vivo persistence and antitumor efficacy. However, methods for manufacturing less differentiated T cells are not yet well-established. Here, we show that producing chimeric antigen receptor (CAR)-T cells using berbamine (BBM), a natural compound found in the Chinese herbal medicine Berberis amurensis, enhances the antitumor efficacy of CAR-T cells.

Water, nitrogen, and phosphorus coupling improves gray jujube fruit quality and yield.

Irrigation and fertilization are indispensable links in the jujube planting industry in southern Xinjiang, China. Regulating the relationship between fertilization and irrigation can effectively reduce costs and improve economic efficiency. A 2-year water and fertilizer optimization coupling test was conducted to determine the optimal water and nutrient supply scheme.

First Principles Study of the Structure-Performance Relation of Pristine WC and Oxygen-Functionalized WCO MXenes as Cathode Catalysts for Li-O Batteries.

Li-O batteries are considered a highly promising energy storage solution. However, their practical implementation is hindered by the sluggish kinetics of the oxygen reduction (ORR) and oxygen evolution (OER) reactions at cathodes during discharging and charging, respectively. In this work, we investigated the catalytic performance of WC and WCO MXenes (n = 1, 2, and 3) as cathodes for Li-O batteries using first principles calculations.

Improved Adenoma Detection Rate Using a Novel Colonoscopic Distal Attachment: A Multicenter Randomized Controlled Trial.

Introduction: To evaluate the effect of Embrella, a novel-designed colonoscopic distal attachment, on adenoma detection rate (ADR) and adenoma per colonoscopy (APC), compared with standard colonoscopy in routine practice.

Methods: All consecutive participants who underwent routine colonoscopic examinations at 3 endoscopy centers in China were enrolled. Participants were randomly assigned in a 1:1 ratio to the Embrella-assisted colonoscopy (EAC) or standard colonoscopy (SC) groups.

Reciprocal antagonism of PIN1-APC/C governs mitotic protein stability and cell cycle entry.

Induced oncoproteins degradation provides an attractive anti-cancer modality. Activation of anaphase-promoting complex (APC/C) prevents cell-cycle entry by targeting crucial mitotic proteins for degradation. Phosphorylation of its co-activator CDH1 modulates the E3 ligase activity, but little is known about its regulation after phosphorylation and how to effectively harness APC/C activity to treat cancer.

Effects of occupational exposure to dust, gas, vapor and fumes on chronic bronchitis and lung function.

Background: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality worldwide, and therefore the identification of the modifiable risk factors [such as exposure to vapors, gases, dust and fumes (VGDF)] for accelerate disease progression has important significance.

Methods: We conducted COPD surveillance in six cities of southern China between 2014 and 2019. We recorded the diagnosis of chronic bronchitis, respiratory symptoms, occupational exposure to VGDF and other covariates by using a structured questionnaire.