FORCE platform overcomes barriers of oligonucleotide delivery to muscle and corrects myotonic dystrophy features in preclinical models.

Background: We developed the FORCE platform to overcome limitations of oligonucleotide delivery to muscle and enable their applicability to neuromuscular disorders. The platform consists of an antigen-binding fragment, highly specific for the human transferrin receptor 1 (TfR1), conjugated to an oligonucleotide via a cleavable valine-citrulline linker. Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by expanded CUG triplets in the DMPK RNA, which sequester splicing proteins in the nucleus, lead to spliceopathy, and drive disease progression.

Novel MRI-based Hyper-Fused Radiomics for Predicting Pathologic Complete Response to Neoadjuvant Therapy in Breast Cancer.

Rationale And Objectives: To propose a novel MRI-based hyper-fused radiomic approach to predict pathologic complete response (pCR) to neoadjuvant therapy (NAT) in breast cancer (BC).

Materials And Methods: Pretreatment dynamic contrast-enhanced (DCE) MRI and ultra-multi-b-value (UMB) diffusion-weighted imaging (DWI) data were acquired in BC patients who received NAT followed by surgery at two centers. Hyper-fused radiomic features (RFs) and conventional RFs were extracted from DCE-MRI or UMB-DWI.

Restriction Spectrum Imaging and Diffusion Kurtosis Imaging for Assessing Proliferation Status in Rectal Carcinoma.

Objectives: To investigate the application of the three-compartment restriction spectrum imaging (RSI) model, diffusion kurtosis imaging (DKI), and diffusion-weighted imaging (DWI) in predicting Ki-67 status in rectal carcinoma.

Methods: A total of 80 rectal carcinoma patients, including 47 high-proliferation (Ki-67 > 50%) cases and 33 low-proliferation (Ki-67 ≤ 50%) cases, underwent pelvic MRI were enrolled. Parameters derived from RSI (f, f, and f), DKI (MD and MK), and DWI (ADC) were calculated and compared between the two groups.

IBI310 (anti-CTLA-4 antibody) monotherapy or in combination with sintilimab in advanced melanoma or urothelial carcinoma.

IBI310 is a recombinant fully human IgG1 antibody against cytotoxic T lymphocyte antigen 4. This study was conducted to evaluate IBI310 monotherapy or combination therapy with sintilimab in the patients with advanced melanoma or urothelial carcinoma (UC). Patients in phase 1a received IBI310 at 0.

Cardiac MRI-derived Myocardial Fibrosis and Ventricular Dyssynchrony Predict Response to Cardiac Resynchronization Therapy in Patients with Nonischemic Dilated Cardiomyopathy.

Purpose: To determine the association of myocardial fibrosis and left ventricular (LV) dyssynchrony measured using cardiac MRI with late gadolinium enhancement (LGE) and feature tracking (FT), respectively, with response to cardiac resynchronization therapy (CRT) for nonischemic dilated cardiomyopathy (DCM).

Materials And Methods: This retrospective study included 98 patients (mean age, 59 years ± 10 [SD]; 54 men) who had nonischemic DCM, as assessed with LGE cardiac MRI before CRT. Cardiac MRI FT-derived dyssynchrony was defined as the SD of the time-to-peak strain (TTP-SD) of the LV segments in three directions (longitudinal, radial, and circumferential).

M2 Microglia Extracellular Vesicle miR-124 Regulates Neural Stem Cell Differentiation in Ischemic Stroke via AAK1/NOTCH.

Background: Small extracellular vesicles (sEVs) derived from M2 microglia (M2-microglia-derived small extracellular vesicles [M2-sEVs]) contribute to central nervous system repair, although the underlying mechanism remains unknown. In this study, we aimed to identify the mechanism through which microRNA-124 (miR-124) carried in sEVs promotes neural stem cell (NSC) proliferation and neuronal differentiation in the ischemic mouse brain.

Methods: M2-sEVs with or without miR-124 knockdown were injected intravenously for 7 consecutive days after transient middle cerebral artery occlusion surgery.

Single-frame deep-learning super-resolution microscopy for intracellular dynamics imaging.

Single-molecule localization microscopy (SMLM) can be used to resolve subcellular structures and achieve a tenfold improvement in spatial resolution compared to that obtained by conventional fluorescence microscopy. However, the separation of single-molecule fluorescence events that requires thousands of frames dramatically increases the image acquisition time and phototoxicity, impeding the observation of instantaneous intracellular dynamics. Here we develop a deep-learning based single-frame super-resolution microscopy (SFSRM) method which utilizes a subpixel edge map and a multicomponent optimization strategy to guide the neural network to reconstruct a super-resolution image from a single frame of a diffraction-limited image.

Computational mining of GeH-based Janus III-VI van der Waals heterostructures for solar cell applications.

The asymmetrical group III-VI monolayer Janus MXY (M = Al, Ga, In; X ≠ Y = S, Se, Te) have attracted widespread attention due to their significant optical absorption properties, which are the potential building blocks for van der Waals (vdW) heterostructure solar cells. In this study, we unraveled an InSTe/GeH vdW heterostructure as a candidate for solar cells by screening the Janus MXY and GeH monolayers on lattice mismatches and electronic band structures based on first-principles calculations. The results highlight that the InSTe/GeH vdW heterostructure exhibits a type-II band gap of 1.

Dual hydrogen production from electrocatalytic water reduction coupled with formaldehyde oxidation via a copper-silver electrocatalyst.

The broad employment of water electrolysis for hydrogen (H) production is restricted by its large voltage requirement and low energy conversion efficiency because of the sluggish oxygen evolution reaction (OER). Herein, we report a strategy to replace OER with a thermodynamically more favorable reaction, the partial oxidation of formaldehyde to formate under alkaline conditions, using a CuAg electrocatalyst. Such a strategy not only produces more valuable anodic product than O but also releases H at the anode with a small voltage input.

VV116 versus Nirmatrelvir-Ritonavir for Oral Treatment of Covid-19.

Background: Nirmatrelvir-ritonavir has been authorized for emergency use by many countries for the treatment of coronavirus disease 2019 (Covid-19). However, the supply falls short of the global demand, which creates a need for more options. VV116 is an oral antiviral agent with potent activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Left Bundle Branch Pacing Versus Biventricular Pacing for Acute Cardiac Resynchronization in Patients With Heart Failure.

Background: Left bundle branch pacing (LBBP) has emerged as an alternative to biventricular pacing (BVP) for delivering cardiac resynchronization therapy. We sought to compare the acute improvement of electrical and mechanical synchrony, and hemodynamics between LBBP and BVP in patients with heart failure and left bundle branch block.

Methods: LBBP and BVP were performed and compared in a crossover fashion in patients with heart failure and left bundle branch block undergoing cardiac resynchronization therapy implantation.

Modulation of intracellular kinase signaling to improve TIL stemness and function for adoptive cell therapy.

Introduction: Adoptive cellular therapy with tumor-infiltrating lymphocytes (TIL) has demonstrated promising clinical benefits in several solid tumors, but the efficacy of this therapy might be compromised by the "prone-to-exhaustion" phenotype of TIL and poor persistence in vivo. This calls for a robust expansion process to produce a large number of cells for clinical usage while at the same time maintaining favorable anti-tumor function and memory phenotype. Previous studies showed that the PI3K-AKT signaling pathway plays a key role in the regulation of T cell activation, differentiation and memory formation.

Towards practical and robust DNA-based data archiving using the yin-yang codec system.

DNA is a promising data storage medium due to its remarkable durability and space-efficient storage. Early bit-to-base transcoding schemes have primarily pursued information density, at the expense of introducing biocompatibility challenges or decoding failure. Here we propose a robust transcoding algorithm named the yin-yang codec, using two rules to encode two binary bits into one nucleotide, to generate DNA sequences that are highly compatible with synthesis and sequencing technologies.

Analysis of thermal decomposition of acidified sediments in gold plants and harmless disposal of it.

In the present work, thermal decomposition of ASs in air was characterized by a combination of TG-DSC, XRD, and TG-FTIR. The treatment of generated toxic (CN) gas was investigated as well. The result showed that the decomposition of ZnFe(CN) in ASs preferentially reacted with CuSCN leading to the early decomposition of ASs, in which a part of CuSCN decomposed into CuFeS or CuS followed by being oxidized to sulfates and oxides as the temperature increased to 420 °C.

Clinical and biomarker analyses of sintilimab versus chemotherapy as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma: a randomized, open-label phase 2 study (ORIENT-2).

This randomized, open-label, multi-center phase 2 study (NCT03116152) assessed sintilimab, a PD-1 inhibitor, versus chemotherapy in patients with esophageal squamous cell carcinoma after first-line chemotherapy. The primary endpoint was overall survival (OS), while exploratory endpoint was the association of biomarkers with efficacy. The median OS in the sintilimab group was significantly improved compared with the chemotherapy group (median OS 7.

Resolvin E1 Attenuates Pulmonary Hypertension by Suppressing Wnt7a/β-Catenin Signaling.

[Figure: see text].

Smooth Muscle Overexpression of PGC1α Attenuates Atherosclerosis in Rabbits.

[Figure: see text].

Multivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers.

SARS-CoV-2, the virus responsible for COVID-19, has caused a global pandemic. Antibodies can be powerful biotherapeutics to fight viral infections. Here, we use the human apoferritin protomer as a modular subunit to drive oligomerization of antibody fragments and transform antibodies targeting SARS-CoV-2 into exceptionally potent neutralizers.

Pharmacokinetics, Safety, and Tolerability of Single- and Multiple-Dose Once-Daily Baricitinib in Healthy Chinese Subjects: A Randomized Placebo-Controlled Study.

The objective of this phase 1 study was to evaluate the pharmacokinetics, safety, and tolerability of baricitinib after single and multiple doses in healthy Chinese adults. Eligible subjects received a once-daily dose of baricitinib 2, 4, or 10 mg or placebo on day 1 (single dose) and days 4 through 10 for 7 consecutive days (multiple doses). Plasma pharmacokinetic samples were collected up to 48 hours after dosing on days 1 and 10, with predose samples collected before dosing on day 1 and days 4 through 10.

Long noncoding RNA LUCAT1 promotes migration and invasion of prostate cancer cells by inhibiting KISS1 expression.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA LUCAT1 promotes migration and invasion of prostate cancer cells by inhibiting KISS1 expression, by C. Liu, L. Wang, Y.

Blood Pressure Classification of 2017 Associated With Cardiovascular Disease and Mortality in Young Chinese Adults.

The American College of Cardiology/American Heart Association introduced new guidelines for blood pressure (BP) classification in 2017. We explored associations between the newly defined categories and eventual cardiovascular disease (CVD) events, stroke, and all-cause mortality in young Chinese adults. In the community-based Kailuan Study, 16 006 participants aged 18 to 40 years and examined at baseline in 2006/2007 underwent 2-yearly follow-up examinations up to 2016 to 2017.