Multiplexed spatial mapping of chromatin features, transcriptome and proteins in tissues.

The phenotypic and functional states of cells are modulated by a complex interactive molecular hierarchy of multiple omics layers, involving the genome, epigenome, transcriptome, proteome and metabolome. Spatial omics approaches have enabled the study of these layers in tissue context but are often limited to one or two modalities, offering an incomplete view of cellular identity. Here we present spatial-Mux-seq, a multimodal spatial technology that allows simultaneous profiling of five different modalities: two histone modifications, chromatin accessibility, whole transcriptome and a panel of proteins at tissue scale and cellular level in a spatially resolved manner.

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.

Glecirasib in KRAS-mutated nonsmall-cell lung cancer: a phase 2b trial.

Glecirasib (JAB-21822) is a new covalent oral KRAS-G12C inhibitor. This multicenter, single-arm phase 2b study assessed the efficacy and safety of glecirasib administered orally at 800 mg daily in patients with locally advanced or metastatic KRAS-mutated nonsmall-cell lung cancer. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC).

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.

Single-cell data-driven design of armed oncolytic virus to boost cooperative innate-adaptive immunity against cancer.

Oncolytic viruses have been considered promising cancer immunotherapies. However, oncovirotherapy agents impart durable responses in only a subset of cancer patients. Thus, exploring the cellular and molecular mechanisms underlying the heterogeneous responses in patients can provide guidance to develop more effective oncolytic virus therapies.

Fat fraction quantification by MRI predicts diagnosis and prognosis of HBV-related steatohepatitic hepatocellular carcinoma.

Objectives: This study explored the clinical prognosis and lipidomics of hepatitis B virus steatohepatitic hepatocellular carcinoma (HBV-SHHCC) and aimed to identify a noninvasive and convenient method to diagnose this phenotype and guide treatment using MRI.

Methods: A total of 433 HBV-infected HCC patients were enrolled in this retrospective study. Survival data were analyzed using Cox regression analyses, and lipidomics was used to study HCC tissue composition.

Upregulated let-7 expression in the follicular fluid of patients with endometriomas leads to dysfunction of granulosa cells through targeting of IGF1R.

Study Question: What molecular mechanisms underlie the decline in ovarian reserve as the number and quality of oocytes decrease in patients with ovarian endometriomas (OEM)?

Summary Answer: Elevated expression of the let-7 micro(mi)RNAs in the follicular microenvironment of OEM-affected ovaries targets the expression of type 1 insulin-like growth factor receptor (IGF1R) in granulosa cell (GC) and disrupts their proliferation, steroid hormone secretion levels, adenosine triphosphate (ATP) energy metabolism, and reactive oxygen species (ROS) oxidative stress levels.

What Is Known Already: Patients with OEM exhibit diminished ovarian reserve, characterized by reduced oocyte quantity and quality. Fibrotic changes in the ovarian tissue surrounding the OEM create a disruptive microenvironment for follicular growth and development.

Construction of a lung cancer 3D culture model based on alginate/gelatin micro-beads for drug evaluation.

Background: Lung cancer is one of the most common malignant tumors worldwide. Despite advances in lung cancer treatment, patients still face challenges related to drug resistance and recurrence. Current methods for evaluating anti-cancer drug activity are insufficient, as they rely on two-dimensional (2D) cell culture and animal models.

Multiplexed spatial mapping of chromatin features, transcriptome, and proteins in tissues.

The phenotypic and functional states of a cell are modulated by a complex interactive molecular hierarchy of multiple omics layers, involving the genome, epigenome, transcriptome, proteome, and metabolome. Spatial omics approaches have enabled the capture of information from different molecular layers directly in the tissue context. However, current technologies are limited to map one to two modalities at the same time, providing an incomplete representation of cellular identity.

BMI variability and cardiovascular outcomes within clinical trial and real-world environments in type 2 diabetes: an IMI2 SOPHIA study.

Background: BMI variability has been associated with increased cardiovascular disease risk in individuals with type 2 diabetes, however comparison between clinical studies and real-world observational evidence has been lacking. Furthermore, it is not known whether BMI variability has an effect independent of HbA1c variability.

Methods: We investigated the association between BMI variability and 3P-MACE risk in the Harmony Outcomes trial (n = 9198), and further analysed placebo arms of REWIND (n = 4440) and EMPA-REG OUTCOME (n = 2333) trials, followed by real-world data from the Tayside Bioresource (n = 6980) using Cox regression modelling.

Effect of Acupuncture for Methadone Reduction : A Randomized Clinical Trial.

Background: Methadone maintenance treatment (MMT) is effective for managing opioid use disorder, but adverse effects mean that optimal therapy occurs with the lowest dose that controls opioid craving.

Objective: To assess the efficacy of acupuncture versus sham acupuncture on methadone dose reduction.

Design: Multicenter, 2-group, randomized, sham-controlled trial.

Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors.

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841).

Exploring the microRNA-mRNA regulatory network associated with solasonine in bladder cancer.

Background: Solasonine has been demonstrated to exert an inhibitory effect on bladder cancer (BC), but the potential mechanisms remain unclear. Therefore, the aim of this study is to explore the association between microRNAs (miRNAs)-mediated regulation and the anti-tumor activities of solasonine in BC.

Methods: MiRNA sequencing was performed to identify the differentially expressed microRNAs (DE-miRNAs) associated with solasonine in BC cells.

IRE1α Mediates the Hypertrophic Growth of Cardiomyocytes Through Facilitating the Formation of Initiation Complex to Promote the Translation of TOP-Motif Transcripts.

Background: Cardiomyocyte growth is coupled with active protein synthesis, which is one of the basic biological processes in living cells. However, it is unclear whether the unfolded protein response transducers and effectors directly take part in the control of protein synthesis. The connection between critical functions of the unfolded protein response in cellular physiology and requirements of multiple processes for cell growth prompted us to investigate the role of the unfolded protein response in cell growth and underlying molecular mechanisms.

Recurrence Characteristics on Optical Coherence Tomography and Treatments of Reis-Bücklers Corneal Dystrophy After Phototherapeutic Keratectomy or Penetrating Keratoplasty.

Purpose: To evaluate the recurrence characteristics on optical coherence tomography and clinical outcomes after phototherapeutic keratectomy (PTK) or penetrating keratoplasty (PKP) in patients with Reis-Bücklers corneal dystrophy (RBCD).

Design: Retrospective interventional case series.

Methods: Seventeen patients with RBCD (31 eyes, including 6 surgery-naïve eyes and 25 surgical eyes) received 44 surgical interventions from 1996 through 2022.

Efficacy of Polyethylene Glycol Electrolyte Powder Combined With Linaclotide for Colon Cleansing in Patients With Chronic Constipation Undergoing Colonoscopy: A Multicenter, Single-Blinded, Randomized Controlled Trial.

Introduction: Constipation is an independent risk factor for poor bowel preparation. This study aimed to evaluate the bowel cleansing efficacy and safety of polyethylene glycol (PEG) combined with linaclotide (lin) for colonoscopy in patients with chronic constipation (CC).

Methods: This single-blinded, randomized, controlled, and multicenter study was conducted from July 2021 to December 2022 at 7 hospitals.