Heterozygous de novo dominant negative mutation of REXO2 results in interferonopathy.

Mitochondrial RNA (mtRNA) in the cytosol can trigger the innate immune sensor MDA5, and autoinflammatory disease due to type I IFN. Here, we show that a dominant negative mutation in the gene encoding the mitochondrial exonuclease REXO2 may cause interferonopathy by triggering the MDA5 pathway. A patient characterized by this heterozygous de novo mutation (p.

A Light-Driven In Vitro Enzymatic Biosystem for the Synthesis of α-Farnesene from Methanol.

Terpenoids of substantial industrial interest are mainly obtained through direct extraction from plant sources. Recently, microbial cell factories or in vitro enzymatic biosystems have emerged as promising alternatives for terpenoid production. Here, we report a route for the synthesis of α-farnesene based on an in vitro enzyme cascade reaction using methanol as an inexpensive and renewable C1 substrate.

Bio-Inspired Underwater Superoleophobic Aramid Nanofiber-Based Aerogel Membranes for Highly Efficient Removal of Emulsified Oils and Organic Dyes.

Effective elimination of insoluble emulsified oils and soluble organic dyes has received extensively attention in wastewater treatment. In this work, a chitosan and polydopamine @ aramid nanofibers (CS&PDA@ANFs) aerogel membrane was fabricated through an integration methodology consisting of phase inversion and successive deposition of PDA and CS. The as-prepared aerogel membrane possessed a satisfactory three-dimensional interpenetrating network architecture with high porosity and desirable mechanical property.

Atherosclerosis Is a Smooth Muscle Cell-Driven Tumor-Like Disease.

Background: Atherosclerosis, a leading cause of cardiovascular disease, involves the pathological activation of various cell types, including immunocytes (eg, macrophages and T cells), smooth muscle cells (SMCs), and endothelial cells. Accumulating evidence suggests that transition of SMCs to other cell types, known as phenotypic switching, plays a central role in atherosclerosis development and complications. However, the characteristics of SMC-derived cells and the underlying mechanisms of SMC transition in disease pathogenesis remain poorly understood.

Rare-Earth Metalloligands for LowValent Cobalt Complexes: Fine Electronic Tuning Co→RE Dative Interactions.

Rare-earth metalloligand supported low-valent cobalt complexes were synthesized by utilizing a small-sized heptadentate phosphinomethylamine H and a large-sized arene-anchored hexadentate phosphinomethylamine H ligand precursors. The RE(III)-Co(-I)-N (RE = Sc, Lu, Y, Gd, La) complexes containing rare-earth metals including the smallest Sc and largest La were characterized by multinuclear NMR spectroscopy, X-ray diffraction analysis, electrochemistry, and computational studies. The Co(-I)→RE(III) dative interactions were all polarized with major contributions from the 3d orbital of the cobalt center, which was slightly affected by the identity of rare-earth metalloligands.

Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial.

The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months' median follow-up).

Conductive nanofiltration membranes via in situ PEDOT-polymerization for electro-assisted membrane fouling mitigation.

Nanofiltration (NF) membranes play a pivotal role in water treatment; however, the persistent challenge of membrane fouling hampers their stable application. This study introduces a novel approach to address this issue through the creation of a poly(3,4-ethylenedioxythiophene) (PEDOT)-based conductive membrane, achieved by synergistically coupling interfacial polymerization (IP) with in situ self-polymerization of EDOT. During the IP reaction, the concurrent generation of HCl triggers the protonation of EDOT, activating its self-polymerization into PEDOT.

Electrically Redox-Active Membrane with Switchable Selectivity to Contaminants for Water Purification.

Membrane technology provides an attractive approach for water purification but faces significant challenges in separating small molecules due to its lack of satisfactory permselectivity. In this study, a polypyrrole-based active membrane with a switchable multi-affinity that simultaneously separates small ionic and organic contaminants from water was created. Unlike conventional passive membranes, the designed membrane exhibits a good single-pass filtration efficiency (>99%, taking 1-naphthylamine and Pb as examples) and high permeability (227 L/m/h).

Anomalous water molecular gating from atomic-scale graphene capillaries for precise and ultrafast molecular sieving.

The pressing crisis of clean water shortage requires membranes to possess effective ion sieving as well as fast water flux. However, effective ion sieving demands reduction of pore size, which inevitably hinders water flux in hydrophilic membranes, posing a major challenge for efficient water/ion separation. Herein, we introduce anomalous water molecular gating based on nanofiltration membranes full of graphene capillaries at 6 Å, which were fabricated from spontaneous π-π restacking of island-on-nanosheet graphitic microstructures.

Marein Alleviates High Glucose-Induced Human Retinal Microvascular Endothelial Cell Injury by Up-Regulating Expression.

Background: Marein has been shown to possess therapeutic effects against diabetic retinopathy, but whether it can protect against high glucose (HG)-induced human retinal microvascular endothelial cell (HRMEC) injury remains unclear. Our study aimed to explore the effect of marein on HG-induced HRMEC injury and the mechanism underlying this purported therapeutic effect.

Methods: HRMEC was divided into normal glucose group, high glucose (HG) group, HG+marein low, medium and high (L, M, H) concentrations group, HG+pcDNA group, HG+pcDNA-small nucleolar RNA host gene 7 () group, HG+marein+si-negative control (NC) group, and HG+marein+si- group.

Engineering P-FeO-CoP nanosheets for overall freshwater and seawater splitting.

Tailoring surface composition and coordinative environment of catalysts in a nano-meter region often influence their chemical performance. It is reported that CoP exhibits a low dissociation ability of H-OH, originating from the poor desorption of intermediate species. Herein, we provide a feasible method to construct P-FeO-CoP nanosheets through a gas-phase phosphorization process.

Electrically Controlled Adsorptive Membranes with Tunable Affinity for Selective Chromium (VI) Separation from Water.

Ionic contaminants such as Cr(VI) pose a challenge for water purification using membrane-based processes. However, existing membranes have low permeability and selectivity for Cr(VI). Therefore, in this study, we prepared an electrically controlled adsorptive membrane (ECAM-L) by coating a loose Cl-doped polypyrrole layer on a carbon nanotube substrate, and we evaluated the performance of ECAM-L for Cr(VI) separation from water.

Preclinical evaluation of manufacturable SARS-CoV-2 spike virus-like particles produced in Chinese Hamster Ovary cells.

Background: As the COVID-19 pandemic continues to evolve, novel vaccines need to be developed that are readily manufacturable and provide clinical efficacy against emerging SARS-CoV-2 variants. Virus-like particles (VLPs) presenting the spike antigen at their surface offer remarkable benefits over other vaccine antigen formats; however, current SARS-CoV-2 VLP vaccines candidates in clinical development suffer from challenges including low volumetric productivity, poor spike antigen density, expression platform-driven divergent protein glycosylation and complex upstream/downstream processing requirements. Despite their extensive use for therapeutic protein manufacturing and proven ability to produce enveloped VLPs, Chinese Hamster Ovary (CHO) cells are rarely used for the commercial production of VLP-based vaccines.

Structural Engineering-Enabled Joule Heating Effect Cooperated with Capillary Effect Toward Fast Spreading of Droplets for High-Flux Separation of Viscous Emulsion.

Viscous emulsions with poor fluidity and high adhesion are extremely difficult to separate. Herein, high-flux separation of viscous emulsions is realized by developing structural engineered collagen fibers (CFs)-based composite membrane that featured 3D conductive hierarchical fiber structure with the spaced carbon nanofibers (CNFs) and activated carbon (AC) serving as conductive network and competitive adsorption-based demulsifying sites, respectively. The as-designed membrane structure boosts fast spreading of emulsion droplets on membrane surface aided by the synergistic effect of joule heat in situ generated by the spaced CNFs and the capillary effect derived from CFs, which guarantees the full contact of viscous emulsions with the spaced AC for achieving ultra-efficient demulsifying.

Treatment of Aniline Wastewater by Membrane Distillation and Crystallization.

Aniline is a highly toxic organic pollutant with "carcinogenic, teratogenic and mutagenesis" characteristics. In the present paper, a membrane distillation and crystallization (MDCr) process was proposed to achieve zero liquid discharge (ZLD) of aniline wastewater. Hydrophobic polyvinylidene fluoride (PVDF) membranes were used in the membrane distillation (MD) process.

One-Step Hydrothermal Strategy for Preparation of a Self-Cleaning TiO/SiO Fiber Membrane toward Oil-Water Separation in a Complex Environment.

Oil pollution caused by a large number of industrial activities and oil spill accidents has posed serious harm to the environment and human health. However, some challenges remain with the existing separation materials, such as poor stability and fouling resistance. Herein, a TiO/SiO fiber membrane (TSFM) was prepared by a one-step hydrothermal method for oil-water separation in acid, alkali, and salt environments.

Deep sampling of gRNA in the human genome and deep-learning-informed prediction of gRNA activities.

Life science studies involving clustered regularly interspaced short palindromic repeat (CRISPR) editing generally apply the best-performing guide RNA (gRNA) for a gene of interest. Computational models are combined with massive experimental quantification on synthetic gRNA-target libraries to accurately predict gRNA activity and mutational patterns. However, the measurements are inconsistent between studies due to differences in the designs of the gRNA-target pair constructs, and there has not yet been an integrated investigation that concurrently focuses on multiple facets of gRNA capacity.

Gumarontinib in patients with non-small-cell lung cancer harbouring exon 14 skipping mutations: a multicentre, single-arm, open-label, phase 1b/2 trial.

Background: Approximately 3-4% of patients with non-small-cell lung cancer (NSCLC) have exon 14 (ex14) skipping mutations. We report primary results from the phase 2 stage of a phase 1b/2 study of gumarontinib, a selective, potent, oral MET inhibitor, in patients with ex14 skipping mutation-positive (ex14-positive) NSCLC.

Methods: The single-arm, multicentre, open-label, phase 2 stage of the GLORY study was conducted at 42 centres across China and Japan.

Superhydrophobic aerogel blanket with magnetic and solar heating effect enables efficient continuous cleanup of highly viscous crude oil.

Rapid cleanup of highly-viscous oil spills the sea is eagerly desired while still remains a great challenge. Hydrophobic and lipophilic adsorbents are regarded as ideal candidate for oil spill remediation. However, traditional adsorbents are not suitable for viscous crude oil, which would block the porous structure and lead to poor adsorption efficiency.

One-stop assembly of adherent 3D retinal organoids from hiPSCs based on 3D-printed derived PDMS microwell platform.

The three-dimensional (3D) retinal organoids (ROs) derived from human induced pluripotent stem cells (hiPSCs), mimicking the growth and development of the human retina, is a promising model for investigating inherited retinal diseases. However, the efficient generation of homogenous ROs remains a challenge. Here we introduce a novel polydimethylsiloxane (PDMS) microwell platform containing 62 V-bottom micro-cavities for the ROs differentiation from hiPSCs.