A neural network for long-term super-resolution imaging of live cells with reliable confidence quantification.

Super-resolution (SR) neural networks transform low-resolution optical microscopy images into SR images. Application of single-image SR (SISR) methods to long-term imaging has not exploited the temporal dependencies between neighboring frames and has been subject to inference uncertainty that is difficult to quantify. Here, by building a large-scale fluorescence microscopy dataset and evaluating the propagation and alignment components of neural network models, we devise a deformable phase-space alignment (DPA) time-lapse image SR (TISR) neural network.

Conglomerated Imiquimod and Metronidazole Incorporated Biodegradable Nanofibrous Mats for Potential Therapy of Cervical Cancer.

Background: In clinical practice, imiquimod is used to treat Human Papillomavirus (HPV)-related lesions, such as condyloma and Cervical Intraepithelial Neoplasia (CIN). Metronidazole is the most commonly prescribed antibiotic for bacterial vaginosis. The study developed biodegradable imiquimod- and metronidazole-loaded nanofibrous mats and assessed their effectiveness for the topical treatment of cervical cancer, a type of HPV-related lesion.

Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.

First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial.

Programmed cell death protein-1 (PD-1) inhibitors plus chemotherapy have been the standard of care in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma; however, the survival benefits are modest in patients with low programmed death ligand 1 (PD-L1) expression. Here we investigated the efficacy and safety of cadonilimab (PD-1/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody) plus chemotherapy as first-line treatment in G/GEJ adenocarcinoma. The prespecified interim analysis is reported here.

iDIA-QC: AI-empowered data-independent acquisition mass spectrometry-based quality control.

Quality control (QC) in mass spectrometry (MS)-based proteomics is mainly based on data-dependent acquisition (DDA) analysis of standard samples. Here, we collect 2754 files acquired by data independent acquisition (DIA) and paired 2638 DDA files from mouse liver digests using 21 mass spectrometers across nine laboratories over 31 months. Our data demonstrate that DIA-based LC-MS/MS-related consensus QC metrics exhibit higher sensitivity compared to DDA-based QC metrics in detecting changes in LC-MS status.

Enhancement of photocatalytic CO reduction in BiOBr through chirality-induced electron spin polarization regulation.

Severe photogenerated charge carrier recombination involved in photocatalytic CO reduction leads to low photocatalytic efficiency. Here we demonstrate that a chiral hierarchical structure could facilitate charge separation in BiOBr, thus suppressing charge recombination and enhancing photocatalytic performance. Chiral helical flower-like BiOBr nanospheres were prepared a D/L-sorbitol-assisted hydrothermal process, exhibiting a 1.

High clinical utility of long-read sequencing for precise diagnosis of congenital adrenal hyperplasia in 322 probands.

Background: The molecular genetic diagnosis of congenital adrenal hyperplasia (CAH) is very challenging due to the high homology between the CYP21A2 gene and its pseudogene CYP21A1P.

Methodology: This study aims to assess the clinical efficacy of targeted long-read sequencing (T-LRS) by comparing it with a control method based on the combined assay (NGS, Multiplex ligation-dependent probe amplification and Sanger sequencing) and to introduce T-LRS as a first-tier diagnostic test for suspected CAH patients to improve the precise diagnosis of CAH.

Results: A large cohort of 562 participants including 322 probands and 240 family members was enrolled for the perspective (96 probands) and prospective study (226 probands).

Early Versus Delayed Antihypertensive Treatment After Acute Ischemic Stroke by Hypertension History.

Background: We performed a prespecified subgroup analysis of the CATIS-2 trial (China Antihypertensive Trial in Acute Ischemic Stroke II) to compare the effect of early versus delayed antihypertensive treatment on death and disability in patients with and without medical history of hypertension.

Methods: CATIS-2 is a multicenter randomized clinical trial conducted in 106 hospitals in China. The trial randomized 4810 patients with acute ischemic stroke within 24 to 48 hours of symptom onset and elevated systolic blood pressure between 140 and <220 mm Hg to receive antihypertensive treatment immediately after randomization or to discontinue antihypertensive medications for 7 days and then receive treatment on day 8.

Simultaneous determination of the monosaccharide types and their absolute configurations in polysaccharides based on UPLC-MS/MS.

Analysing monosaccharide composition is an essential step in deciphering polysaccharide structures. However, it presents significant challenges due to the pronounced hydrophilicity and the vast array of monosaccharide isomers. Gas/liquid chromatography, coupled with an aldononitrile acetate derivatisation, has been widely used for monosaccharide composition analysis.

Functionalized Periosteum-Derived Microsphere-Hydrogel with Sequential Release of E7 Short Peptide/miR217 for Large Bone Defect Repairing.

Large bone defects are still a persistent challenge in orthopedics. The availability limitations and associated complications of autologous and allogeneic bone have prompted an increasing reliance on tissue engineering and regenerative medicine. In this study, we developed an injectable scaffold combining an acellular extracellular periosteal matrix hydrogel with poly(d,l-lactate--glycol-acetate) microspheres loaded with the E7 peptide and miR217 (miR217/E7@MP-GEL).

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.

A Preclinical Immunogenicity Study of the Recombinant Human Papillomavirus Nine-Valent Virus-like Particle Vaccine.

Background: Cervical cancer is associated with persistent infection of high-risk human papillomaviruses (HPVs). Prophylactic HPV vaccines have been recommended and have significant efficacy in preventing cervical cancer. Multivalent HPV vaccines have a better preventative effect on HPV-related diseases.

Prevention of Stroke in Intracerebral Haemorrhage Survivors with Atrial Fibrillation: Rationale and Design for PRESTIGE-AF Trial.

Adequate secondary prevention in survivors of intracerebral hemorrhage (ICH) who also have atrial fibrillation (AF) is a long-standing clinical dilemma because these patients are at increased risk of recurrent ICH as well as of ischemic stroke. The efficacy and safety of oral anticoagulation, the standard preventive medication for ischemic stroke patients with AF, in ICH patients with AF are uncertain. PRESTIGE-AF is an international, phase 3b, multi-center, randomized, open, blinded end-point assessment (PROBE) clinical trial that compared the efficacy and safety of direct oral anticoagulants (DOACs) with no DOAC (either no antithrombotic treatment or any antiplatelet drug).

Primary Cilia Regulate the Homeostasis and Regeneration of the Stem Cell Niche in the Tooth.

Primary cilia, functioning as crucial hubs for signal sensing and transduction, are integral to the development and maintenance of homeostasis across various organs. However, their roles in tooth homeostasis and repair remain inadequately understood. In this study, we reveal an indispensable role for primary cilia in regulating the homeostasis and regeneration of teeth, primarily through the regulation of cell proliferation.

Development of a RIPK1 degrader to enhance antitumor immunity.

The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and emerges as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain of RIPK1, here we harness proteolysis targeting chimera (PROTAC) technology to develop a RIPK1 degrader, LD4172. LD4172 exhibits potent and selective RIPK1 degradation both in vitro and in vivo.

Considerations for building and using integrated single-cell atlases.

The rapid adoption of single-cell technologies has created an opportunity to build single-cell 'atlases' integrating diverse datasets across many laboratories. Such atlases can serve as a reference for analyzing and interpreting current and future data. However, it has become apparent that atlasing approaches differ, and the impact of these differences are often unclear.

Systematic review and meta-analysis of the impact of the refreezing and rebiopsy embryos on reproductive outcomes in patients undergoing freeze-thaw embryo transfer.

Objective: To explore whether refreezing and rebiopsy affect reproductive outcomes.

Design: Systematic review and meta-analysis.

Setting: Not applicable.

Unraveling the Growth Mechanism of Chiral Inorganic Nanocrystals via High-Resolution Electron Microscopy.

Chiral inorganic nanomaterials have attracted broad interest due to their intriguing chirality-dependent performances. However, there is a lack of experimental studies and atomic-level evidence on their growth mechanism. Herein, high-crystalline chiral tellurium nanowires were synthesized in an alkali solution by using tellurium oxide as an inorganic source and hydrazine hydrate as a reductant.

DCBLD1 Modulates Angiogenesis by Regulation of the VEGFR-2 Endocytosis in Endothelial Cells.

Background: Unwanted angiogenesis is involved in the progression of various malignant tumors and cardiovascular diseases, and the factors that regulate angiogenesis are potential therapeutic targets. We tested the hypothesis that DCBLD1 (discoidin, CUB, and LCCL domain-containing protein 1) is a coreceptor of VEGFR-2 (vascular endothelial growth factor receptor-2) and modulates angiogenesis in endothelial cells.

Methods: A carotid artery ligation model and retinal angiogenesis assay were used to study angiogenesis using globe knockout or endothelial cell-specific conditional knockout mice in vivo.

Efficient non-viral immune cell engineering using circular single-stranded DNA-mediated genomic integration.

The use of adeno-associated viruses (AAVs) as donors for homology-directed repair (HDR)-mediated genome engineering is limited by safety issues, manufacturing constraints and restricted packaging limits. Non-viral targeted genetic knock-ins rely primarily on double-stranded DNA (dsDNA) and linear single-stranded DNA (lssDNA) donors. dsDNA is known to have low efficiency and high cytotoxicity, while lssDNA is challenging for scaled manufacture.

Serum GFAP and UCH-L1 Levels for the Assessment of the Absence of Hemorrhagic Transformation: A Multicenter Prospective Cohort Study.

Background: Currently, validated biomarkers for assessing hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) are lacking. We aimed to validate a test combining GFAP (glial fibrillary acidic protein) and UCH-L1 (ubiquitin C-terminal hydrolase-L1) to indicate the absence of HT after IVT.

Methods: We prospectively enrolled consecutive patients with stroke treated with IVT from 16 hospitals.

Virtual MR Elastography and Multi-b-value DWI Models for Predicting Microvascular Invasion in Solitary BCLC Stage A Hepatocellular Carcinoma.

Rationale And Objectives: To evaluate the performance of virtual MR elastography (vMRE) for predicting microvascular invasion (MVI) in Barcelona Clinic Liver Cancer (BCLC) stage A (≤ 5.0 cm) hepatocellular carcinoma (HCC) and to construct a combined nomogram based on vMRE, multi-b-value DWI models, and clinical-radiological (CR) features.

Methods: Consecutive patients with suspected HCC who underwent multi-b-value DWI examinations were prospectively collected.

[Spatial Distribution Characteristics and Ecological Risks of Typical Drugs in the Yongjiang River Basin].

In recent years, due to large-scale production and widespread use, drugs have posed a potential threat to biological and human health and have received increasing attention. The occurrence and distribution of drugs in urban rivers are influenced by various factors, such as urbanization level, population density, regional geographical and climatic characteristics, and drug consumption habits. In October 2022, the Yongjiang River Basin was divided into four sub-basins： upstream, midstream, tributaries, and downstream.

Spatial omics-based machine learning algorithms for the early detection of hepatocellular carcinoma.

Background: Worldwide, hepatocellular carcinoma (HCC) is the second most lethal cancer, although early-stage HCC is amenable to curative treatment and can facilitate long-term survival. Early detection has proved difficult, as proteomics, transcriptomics, and genomics have been unable to discover suitable biomarkers.

Methods: To find new biomarkers of HCC, we utilized a spatial omics N-glycan imaging method to identify altered glycosylation in cancer tissue (n = 53) and in paired serum of individuals with HCC (n = 23).

Peli1 Deficiency in Macrophages Attenuates Pulmonary Hypertension by Enhancing Foxp1-Mediated Transcriptional Inhibition of IL-6.

Background: The infiltration of macrophages into the lungs is a common characteristic of perivascular inflammation, contributing to vascular remodeling in pulmonary hypertension (PH). Peli1 (pellino E3 ubiquitin-protein ligase 1) plays a critical role in regulating the production of proinflammatory cytokines and the polarization of macrophages in various diseases. However, the role of Peli1 in PH remains to be investigated.