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.

Radiomics of multimodal ultrasound for early prediction of pathologic complete response to neoadjuvant chemotherapy in breast cancer.

Rationale And Objectives: To construct and validate a clinical-radiomics model based on radiomics features extracted from two-stage multimodal ultrasound and clinicopathologic information for early predicting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients treated with NAC.

Materials And Methods: Consecutive women with biopsy-proven breast cancer undergoing multimodal US pretreatment and after two cycles of NAC and followed by surgery between January 2014 and November 2023 were retrospectively collected for clinical-radiomics model construction (n = 274) and retrospective test (n = 134). The predictive performance of it was further tested in a subsequent prospective internal test set recruited between January 2024 to July 2024 (n = 76).

Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease.

Background And Objectives: Nicotinamide is a coenzyme involved in cellular oxidation-reduction reactions that can inhibit Class III histone deacetylases (HDACs) or sirtuins. HDAC inhibition can affect numerous therapeutic pathways, including tau phosphorylation. We tested the hypothesis that nicotinamide treatment could reduce tau phosphorylation in early Alzheimer disease (AD).

Effect of Imaging Selection Paradigms on Endovascular Thrombectomy Outcomes in Patients With Acute Ischemic Stroke.

Background: The effect of imaging selection paradigms on endovascular thrombectomy outcomes in patients with acute ischemic stroke with large vessel occlusion remains uncertain. The study aimed to assess the effect of basic imaging (noncontrast computed tomography with or without computed tomographic angiography) versus advanced imaging (magnetic resonance imaging or computed tomography perfusion) on clinical outcomes following thrombectomy in patients with stroke with large vessel occlusion in the early and extended windows using a pooled analysis of patient-level data from 2 pivotal randomized clinical trials done in China.

Methods: This post hoc analysis used data from 1182 patients included in 2 multicenter, randomized controlled trials in China that evaluated adjunct therapies to endovascular treatment for acute ischemic stroke (Direct Endovascular Treatment for Large Artery Anterior Circulation Stroke performed from May 20, 2018, through May 2, 2020, and Intravenous Tirofiban Before Endovascular Treatment in Stroke from October 10, 2018, through October 31, 2021).

An immunogenic and oncogenic feature-based classification for chemotherapy plus PD-1 blockade in advanced esophageal squamous cell carcinoma.

Although chemotherapy plus PD-1 blockade (chemo+anti-PD-1) has become the standard first-line therapy for advanced esophageal squamous cell carcinoma (ESCC), reliable biomarkers for this regimen are lacking. Here we perform whole-exome sequencing on tumor samples from 486 patients of the JUPITER-06 study and develop a copy number alteration-corrected tumor mutational burden that depicts immunogenicity more precisely and predicts chemo+anti-PD-1 efficacy. We identify several other favorable immunogenic features (e.

Tilavonemab in early Alzheimer's disease: results from a phase 2, randomized, double-blind study.

Tau accumulation in patients with Alzheimer's disease tracks closely with cognitive decline and plays a role in the later stages of disease progression. This phase 2 study evaluated the safety and efficacy of tilavonemab, an anti-tau monoclonal antibody, in patients with early Alzheimer's disease. In this 96-week, randomized, double-blind, placebo-controlled study (NCT02880956), patients aged 55-85 years meeting clinical criteria for early Alzheimer's disease with a Clinical Dementia Rating-Global Score of 0.

Blocking MG53 Phosphorylation Protects Diabetic Heart From Ischemic Injury.

Background: As an integral component of cell membrane repair machinery, MG53 (mitsugumin 53) is important for cardioprotection induced by ischemia preconditioning and postconditioning. However, it also impairs insulin signaling via its E3 ligase activity-mediated ubiquitination-dependent degradation of IR (insulin receptor) and IRS1 (insulin receptor substrate 1) and its myokine function-induced allosteric blockage of IR. Here, we sought to develop MG53 into a cardioprotection therapy by separating its detrimental metabolic effects from beneficial actions.

Trophoblast-Derived Extracellular Vesicles Promote Preeclampsia by Regulating Macrophage Polarization.

Background: Systemic inflammation caused by dysfunctional macrophages is a crucial pathogenetic event in preeclampsia (PE). Trophoblast-derived extracellular vesicles (T-EVs) are potent immune cell signaling modulators in pregnancy. Herein, we aimed to investigate T-EVs' effect and mechanism on macrophage polarization and its role in PE pathogenesis, which remain unclear.

Brain Perfusion Alterations on 3D Pseudocontinuous Arterial Spin-Labeling MR Imaging in Patients with Autoimmune Encephalitis: A Case Series and Literature Review.

Autoimmune encephalitis is a heterogeneous group of newly identified disorders that are being diagnosed with increasing frequency. Early recognition and treatment of autoimmune encephalitis are crucial for patients, but diagnosis remains challenging and time-consuming. In this retrospective case series, we describe the findings of conventional MR imaging and 3D pseudocontinuous arterial spin-labeling in patients with autoimmune encephalitis confirmed by antibody testing.

A self-assembling nanoparticle vaccine targeting the conserved epitope of influenza virus hemagglutinin stem elicits a cross-protective immune response.

Various vaccine strategies have been developed to provide broad protection against diverse influenza viruses. The hemagglutinin (HA) stem is the major potential target of these vaccines. Enhancing immunogenicity and eliciting cross-protective immune responses are critical for HA stem-based vaccine designs.

Distinct Fold-Mode Formation of Crystalline Cu(I) Helical Coordination Polymers with Alternation of the Solid-State Emission Using Shape of the Counter Anions.

One-dimensional cationic coordination polymers have been a promising platform for designing solid-state physical properties through diverse coordination geometries. In particular, the folding mode of the coordination polymers that form a helical structure directly determines the metal-centered coordination environment. Herein, we report -heterocyclic carbene (NHC) Cu(I) cationic coordination polymers with pyrazine as the linker, which construct a 4-fold or 3-fold helical column in luminescent crystals using octahedral anions (SbF and PF) or a tetrahedral anion (BF), respectively.

Identification of copy number variation-driven molecular subtypes informative for prognosis and treatment in pancreatic adenocarcinoma of a Chinese cohort.

Background: Pancreatic adenocarcinoma (PAAD) is one of the most lethal carcinomas, and the current histopathological classifications are of limited use in clinical decision-making. There is an unmet need to identify new biomarkers for prognosis-informative molecular subtyping and ultimately for precision medicine.

Methods: We profiled genomic alterations for 608 PAAD patients in a Chinese cohort, including somatic mutations, pathogenic germline variants and copy number variations (CNV).

Structure of the full-length Clostridium difficile toxin B.

Clostridium difficile is an opportunistic pathogen that establishes in the colon when the gut microbiota are disrupted by antibiotics or disease. C. difficile infection (CDI) is largely caused by two virulence factors, TcdA and TcdB.

Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue.

Brown adipose tissue (BAT) is an exclusive tissue of nonshivering thermogenesis. It is fueled by lipids and glucose and involved in energy and metabolic homeostasis. Intrauterine exposure to hyperglycemia during gestational diabetes mellitus may result in abnormal fetal development and metabolic phenotypes in adulthood.

Theoretical and conceptual DFT study of pnicogen- and halogen-bonded complexes of PHX---BrCl.

The pnicogen and halogen bonding interactions in the PHX---BrCl(X = H, F, OH, OCH and CH) complexes have been studied at the MP2/aug-cc-pVTZ level. Analysis of interaction energies shows that the pnicogen-bonded structures are less stable than the corresponding halogen-bonded structures. The pnicogen and halogen bonds were also studied by conceptual DFT reactivity indices.

Inhibitory Effects of Sulfur Dioxide on Rat Myocardial Fibroblast Proliferation and Migration.

Background: Myocardial fibrosis is an important pathological change in many heart diseases, but its pathogenesis is very complex and has not yet been fully elucidated. The study was designed to examine whether endogenous sulfur dioxide (SO) is a novel myocardial fibroblast proliferation and migration inhibitor.

Methods: Primary rat myocardial fibroblasts were isolated and transfected with aspartate aminotransferase (AAT1 and AAT2) knockdown lentivirus or empty lentivirus.

The metallic state in neutral radical conductors: dimensionality, pressure and multiple orbital effects.

Pressure-induced changes in the solid-state structures and transport properties of three oxobenzene-bridged bisdithiazolyl radicals 2 (R = H, F, Ph) over the range 0-15 GPa are described. All three materials experience compression of their π-stacked architecture, be it (i) 1D ABABAB π-stack (R = Ph), (ii) quasi-1D slipped π-stack (R = H), or (iii) 2D brick-wall π-stack (R = F). While R = H undergoes two structural phase transitions, neither of R = F, Ph display any phase change.

Small-conductance, calcium-activated potassium channel 3 (SK3) is a modulator of endometrial remodeling during endometrial growth.

Background: Small-conductance, Ca(2+)-activated K(+) channel 3 (SK3) has been shown to be expressed in porcine endometrium. However, the roles of SK3 in human endometrium during the menstrual cycle and early pregnancy are unknown.

Objective: The objective of the study was to investigate the expression and function of SK3 in human endometrium and the mechanism involved.

High maternal serum estradiol environment in the first trimester is associated with the increased risk of small-for-gestational-age birth.

Context: There are increasing concerns that a disrupted endocrine environment may disturb the growth of the fetus. Assisted reproductive technology (ART) situates gamete/embryo in a supraphysiological estradiol (E2) environment and, thus, provides an ideal model to investigate this problem.

Objective: Our objective was to investigate whether the maternal high-E2 environment in the first trimester increases the risks of low birth weight (LBW) and small-for-gestational-age (SGA) birth.

Antiviral activity and mechanism of action of novel thiourea containing chiral phosphonate on tobacco mosaic virus.

Using half-leaf method O,O'-diisopropyl (3-(L-1-(benzylamino)-1-oxo-3- phenylpropan-2-yl)thioureido)(phenyl)methyl phosphonate (2009104) was studied for its activity on tobacco mosaic virus (TMV). It showed good curative activity in vivo and the curative activity at 500 μg/mL was found to be 53.3%.

Codoping synergistic effects in N-doped SrTiO(3) for higher energy conversion efficiency.

To understand the codoping synergistic effects in metal oxide semiconductors with wide band gaps as photocatalysts, we chose N-doped SrTiO(3) as a host to determine the effects of some nonmetal and metal codopants on it by performing the first-principles calculations for N/H-, N/X- (X = F, Cl, Br, I), N/M(1)- (M(1) = V, Nb, Ta) and N/M(2)- (M(2) = Sc, Y, La) codoped SrTiO(3). Our study shows that the codoping of N with nonmetal atoms H, F and all metal atoms except Ta can reduce the energy cost of N doping and thus improve the solubility of N in SrTiO(3). Octahedra in codoped SrTiO(3) suffer from a relative larger distortion than that of N-doped SrTiO(3) and the distorted octahedra can generate a more efficient internal field, which can promote the separation and reduce the recombination of electron-hole pairs, due to the nonzero dipole moment of distorted octahedra.