Safety and Efficacy of Remote Ischemic Conditioning in Patients With Intravenous Thrombolysis: The SERIC-IVT Trial.

Background: Approximately half of the patients with acute ischemic stroke who receive intravenous thrombolysis (IVT) do not achieve an excellent outcome. Remote ischemic conditioning (RIC) as a promising neuroprotective treatment may improve clinical outcomes in this population. This study aimed to assess the efficacy and safety of RIC in patients with IVT.

Facile synthesis of nanoporous Mg crystalline structure by organic solvent-based reduction for solid-state hydrogen storage.

Nanoporous metals have unique potentials for energy applications with a high surface area despite the percolating structure. Yet, a highly corrosive environment is required for the synthesis of porous metals with conventional dealloying methods, limiting the large-scale fabrication of porous structures for reactive metals. In this study, we synthesize a highly reactive Mg nanoporous system through a facile organic solution-based approach without any harsh etching.

A Dual-Functional Sulfur-Rich Copolymers for Stable Anchoring and Enhanced Conversion of Polysulfide in Lithium-Sulfur Batteries.

Sulfur-rich copolymers have gained a great deal of attention as promising cathode materials in Li-S batteries due to their low cost and naturally uniform sulfur dispersion. However, the poor electrical conductivity and shuttle effect cause rapid capacity decay and low sulfur utilization especially under high sulfur loading and low electrolyte/sulfur ratio. Herein, the FeS/C dispersed and Se-containing sulfur-rich copolymer (FSP) was synthesized by one-pot reaction of ferrocene, trithiocyanuric acid with SeS.

Delivery of therapeutic RNA by extracellular vesicles derived from Saccharomyces cerevisiae for medicine applications.

Employing small extracellular vesicles (EVs) as drug delivery vehicles presents a plethora of advantages over conventional drug delivery methods, including biological compatibility, engineering versatility for targeted delivery, and biodegradability. Therefore, strategies aimed at amplifying their therapeutic potential involve developing efficient, tissue-specific, and non-immunogenic delivery approaches. Despite rapid advancements in the realm of EVs as drug delivery systems in recent years, the availability of a high-yield, reproducible, and cost-effective source for EVs production and isolation remains a limiting factor for practical application.

Herbicide-resistant plants produced by precision adenine base editing in plastid DNA.

CRISPR-free, protein-only cytosine base editors (CBEs) or adenine base editors, composed of DNA-binding proteins such as zinc finger proteins or transcription activator-like effectors (TALEs) and nucleobase cytosine or adenine deaminases, respectively, enable organellar DNA editing in cultured cells, animals and plants. TALE-linked double-stranded DNA deaminase toxin A (DddA)-derived CBEs (DdCBEs) and TALE-linked adenine deaminases (TALEDs) install C-to-T and A-to-G single-nucleotide conversions, respectively, in mitochondria and chloroplasts. Interestingly, whereas TALEDs exclusively induce A-to-G conversions without C-to-T conversions in mammalian mitochondrial DNA, they often install unwanted C-to-T edits in addition to intended A-to-G edits in plastid DNA.

Progression Patterns and Risk Factors of Axial Elongation in Young Adults With Nonpathologic High Myopia: Three-Year Large Longitudinal Cohort Follow-Up.

Purpose: To investigate the progression patterns and risk factors of axial elongation in young adults with nonpathologic high myopia.

Design: Prospective, clinical observational cohort study with 2- to 4-year follow-up.

Methods: A total of 1043 eyes of 563 participants (3515 medical records) aged 18 to 50 years with nonpathologic high myopia (axial length [AL] ≥ 26 mm; myopic maculopathy < diffuse chorioretinal atrophy; without posterior staphyloma) were included from 1546 participants (6318 medical records).

Isomeric Effects of Au(S--CH) Nanoclusters on Photoluminescence: Roles of Electron-Vibration Coupling and Higher Triplet State.

The exploration of near-infrared photoluminescence (PL) from atomically precise nanoclusters is currently a prominent area of interest owing to its importance in both fundamental research and diverse applications. In this work, we investigate the near-infrared (NIR) photoluminescence mechanisms of two structural isomers of atomically precise gold nanoclusters of 28 atoms protected by cyclohexanethiolate (CHT) ligands, i.e.

Strict glucose control and elimination of NLRP3-induced inflammation prevents diabetic bladder dysfunction in the female Akita mouse model.

Purpose: Diabetic bladder dysfunction (DBD) is the most common diabetic complication. Logically, regulation of blood glucose should reverse dysfunction, but the Epidemiology of Diabetes Interventions and Complications study found strict control ineffective. However, it is possible that strict control may prevent DBD if initiated before symptoms appear.

Atezolizumab plus bevacizumab as first-line systemic therapy for hepatocellular carcinoma: a multi-institutional cohort study.

Background: Atezolizumab plus bevacizumab is the standard of care for advanced hepatocellular carcinoma (HCC) in the first-line setting, although was only evaluated in patients with Child-Pugh (CP) A liver function in the IMbrave150 trial. We sought to determine the outcomes of these patients based on CP score and ALBI grade in the US population.

Methods: This multicenter cohort study included patients with HCC who received atezolizumab with bevacizumab as first-line systemic therapy between March 2018 and November 2023.

Palladium-Catalyzed/Copper-Mediated Decarbonylative Cross-Coupling of -Pyrimidyl Thioesters for Biaryl Synthesis.

A palladium-catalyzed/copper-mediated cross-coupling of -pyrimidinyl thioesters with arylboronic acids to yield biaryls is described. The reaction is likely to proceed via cleavage of the S-C(O) bond and subsequent release of CO, rather than via cleavage of the S-C(pyrimidine) bond and release of SCO, as supported by the results of both experimental and computational studies. The investigation of the reaction scope with various -pyrimidinyl thioesters and arylboronic acids showed that the reaction is significantly affected by the substituent of the thioester and the presence of a chelatable substituent was found to increase reaction efficiency.

An aptamer-mediated base editing platform for simultaneous knockin and multiple gene knockout for allogeneic CAR-T cells generation.

Gene editing technologies hold promise for enabling the next generation of adoptive cellular therapies. In conventional gene editing platforms that rely on nuclease activity, such as clustered regularly interspaced short palindromic repeats CRISPR-associated protein 9 (CRISPR-Cas9), allow efficient introduction of genetic modifications; however, these modifications occur via the generation of DNA double-strand breaks (DSBs) and can lead to unwanted genomic alterations and genotoxicity. Here, we apply a novel modular RNA aptamer-mediated Pin-point base editing platform to simultaneously introduce multiple gene knockouts and site-specific integration of a transgene in human primary T cells.

Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias.

The interaction between menin and histone-lysine N-methyltransferase 2A (KMT2A) is a critical dependency for KMT2A- or nucleophosmin 1 (NPM1)-altered leukemias and an emerging opportunity for therapeutic development. JNJ-75276617 (bleximenib) is a novel, orally bioavailable, potent, and selective protein-protein interaction inhibitor of the binding between menin and KMT2A. In KMT2A-rearranged (KMT2A-r) and NPM1-mutant (NPM1c) acute myeloid leukemia (AML) cells, JNJ-75276617 inhibited the association of the menin-KMT2A complex with chromatin at target gene promoters, resulting in reduced expression of several menin-KMT2A target genes, including MEIS1 and FLT3.

Conformal frequency selective rasorber in S, C, X-band with low backward-scattering.

In this paper, a polarization-insensitive high transmittance bandpass filter with low radar cross section (RCS) in both S- and X-band is proposed. This is the first study to use the partition layout loading approach for conformal structures with transmissive windows, reducing the operating band RCS. Curved structures have stronger radiation at a smaller angle to the incident wave, and that is how their scattering differs from uniform scattering from flat structures.

Frequency of Common and Uncommon Alterations among Colorectal and Non-Colorectal Gastrointestinal Malignancies.

Background: The predictive and prognostic role of alterations has been evaluated in colorectal cancer (CRC); however, alterations have not been fully characterized in non-CRC gastrointestinal (GI) malignancies. In the present study, we report the frequency and spectrum of alterations among patients with non-CRC GI malignancies.

Methods: Patients with CRC and non-CRC GI malignancies who underwent somatic tumor profiling via a tissue-based or liquid-based assay were included in this study.

The ratio of skeletal muscle mass to body mass index combined with inflammatory immune markers to stratify survival of pancreatic cancer after pancreatoduodenectomy.

Background: We sought to combine skeletal muscle index and inflammatory immune markers to stratify long-term survival in patients with pancreatic cancer after pancreatoduodenectomy (PD).

Methods: A total of 581 patients with pancreatic cancer underwent PD were included, and divided into the training and validation cohort. Image analysis of computed tomography scans was used to calculate the ratio of skeletal muscle (SM) area to body mass index (BMI).

Coupling of Slack and Na1.6 sensitizes Slack to quinidine blockade and guides anti-seizure strategy development.

Quinidine has been used as an anticonvulsant to treat patients with KCNT1-related epilepsy by targeting gain-of-function KCNT1 pathogenic mutant variants. However, the detailed mechanism underlying quinidine's blockade against KCNT1 (Slack) remains elusive. Here, we report a functional and physical coupling of the voltage-gated sodium channel Na1.

Fractal Analysis of Left Ventricular Trabeculae in Patients with End-Stage Renal Disease: A Random Survival Tree Analysis.

Background: The complexity of left ventricular (LV) trabeculae is related to the prognosis of several cardiovascular diseases.

Purpose: To evaluate the prognostic value of LV trabecular complexity in patients with end-stage renal disease (ESRD).

Study Type: Prospective outcome study.

Impaired kidney function and the risk of all-cause mortality and cardiovascular disease among Chinese hypertensive adults: Using three different equations to estimate the glomerular filtration rate.

Objectives: We aimed to seek accurate assessments of the glomerular filtration rate (GFR) in a Chinese hypertensive population to identify individuals at high risk for chronic kidney disease (CKD) progression. Then, the risk of cardiovascular disease (CVD) and all-cause death due to kidney injury were further investigated under appropriate GFR-estimation equations.

Methods: In this prospective follow-up cohort study of 10,171 hypertensive patients, we compared the discrimination power of a trio of GFR-estimation equations using Harrell's C-index, measuring the model fit by calculating the Akaike information criterion.

Dithiine-linked metalphthalocyanine framework with undulated layers for highly efficient and stable HO electroproduction.

Realization of stable and industrial-level HO electroproduction still faces great challenge due large partly to the easy decomposition of HO. Herein, a two-dimensional dithiine-linked phthalocyaninato cobalt (CoPc)-based covalent organic framework (COF), CoPc-S-COF, was afforded from the reaction of hexadecafluorophthalocyaninato cobalt (II) with 1,2,4,5-benzenetetrathiol. Introduction of the sulfur atoms with large atomic radius and two lone-pairs of electrons in the C-S-C linking unit leads to an undulated layered structure and an increased electron density of the Co center for CoPc-S-COF according to a series of experiments in combination with theoretical calculations.

Self-adjuvant Astragalus polysaccharide-based nanovaccines for enhanced tumor immunotherapy: a novel delivery system candidate for tumor vaccines.

The study of tumor nanovaccines (NVs) has gained interest because they specifically recognize and eliminate tumor cells. However, the poor recognition and internalization by dendritic cells (DCs) and insufficient immunogenicity restricted the vaccine efficacy. Herein, we extracted two molecular-weight Astragalus polysaccharides (APS, 12.

Olgotrelvir, a dual inhibitor of SARS-CoV-2 M and cathepsin L, as a standalone antiviral oral intervention candidate for COVID-19.

Background: Oral antiviral drugs with improved antiviral potency and safety are needed to address current challenges in clinical practice for treatment of COVID-19, including the risks of rebound, drug-drug interactions, and emerging resistance.

Methods: Olgotrelvir (STI-1558) is designed as a next-generation antiviral targeting the SARS-CoV-2 main protease (M), an essential enzyme for SARS-CoV-2 replication, and human cathepsin L (CTSL), a key enzyme for SARS-CoV-2 entry into host cells.

Findings: Olgotrelvir is a highly bioavailable oral prodrug that is converted in plasma to its active form, AC1115.

Cross-shelf processes of terrigenous organic matter drive mercury speciation on the east siberian shelf in the Arctic Ocean.

The cross-shelf distributions of total mercury (THg), methylmercury (MeHg) and organic and inorganic matter, as well as the presence of the hgcA gene were investigated on the East Siberian Shelf (ESS) to understand the processes underlying the speciation of sedimentary Hg. Samples were collected from 12 stations grouped into four zones based on water depth: inner shelf (5 stations), mid-shelf (3 stations), outer shelf (2 stations), and slope (2 stations). The THg concentration in the surface sediment increased from the inner shelf (0.