Addition of SHR-1701 to first-line capecitabine and oxaliplatin (XELOX) plus bevacizumab for unresectable metastatic colorectal cancer.

This phase 2/3 trial (NCT04856787) assessed the efficacy and safety of SHR-1701, a bifunctional protein targeting PD-L1 and TGF-β, in combination with BP102 (a bevacizumab biosimilar) and XELOX (capecitabine plus oxaliplatin) as a first-line treatment for unresectable metastatic colorectal cancer (mCRC). In this phase 2 study, a total of 62 patients with untreated, histologically confirmed colorectal adenocarcinoma and no prior systemic therapy for metastatic disease were enrolled. Patients received SHR-1701 (30 mg/kg), bevacizumab (7.

Individually addressed entangling gates in a two-dimensional ion crystal.

Two-dimensional (2D) ion crystals may represent a promising path to scale up qubit numbers for ion trap quantum information processing. However, to realize universal quantum computing in this system, individually addressed high-fidelity two-qubit entangling gates still remain challenging due to the inevitable micromotion of ions in a 2D crystal as well as the technical difficulty in 2D addressing. Here we demonstrate two-qubit entangling gates between any ion pairs in a 2D crystal of four ions.

Structural investigation of the docking domain assembly from trans-AT polyketide synthases.

Docking domains (DDs) located at the C- and N-termini of polypeptides play a crucial role in directing the assembly of polyketide synthases (PKSs), which are multienzyme complexes. Here, we determined the crystal structure of a complex comprising the C-terminal DD (DD) and N-terminal DD (DD) of macrolactin trans-acyltransferase (AT) PKS that were fused to a functional enzyme, AmpC EC2 β-lactamase. Interface analyses of the DD/DD complex revealed the molecular intricacies in the core section underpinning the precise DD assembly.

Enteropathy and intestinal malabsorption in patients treated with antihypertensive drugs. .

Objectives: To investigate differences in the incidence of enteropathy or intestinal malabsorption in patients taking angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitor (ACEI), calcium channel blocker (CCB), and beta blockers (BBs) at a single center in Korea.

Methods: In this retrospective study, we utilized data from the Yangsan electronic medical records to identify 129,169 patients. These individuals were prescribed olmesartan, other ARBs, ACEI, CCB, and BBs between November 2008 and February 2021.

Skin derived precursors induced Schwann cells mediated tissue engineering-aided neuroregeneration across sciatic nerve defect.

A central question in neural tissue engineering is how the tissue-engineered nerve (TEN) translates detailed transcriptional signals associated with peripheral nerve regeneration into meaningful biological processes. Here, we report a skin-derived precursor-induced Schwann cell (SKP-SC)-mediated chitosan/silk fibroin-fabricated tissue-engineered nerve graft (SKP-SCs-TEN) that can promote sciatic nerve regeneration and functional restoration nearly to the levels achieved by autologous nerve grafts according to behavioral, histological, and electrophysiological evidence. For achieving better effect of neuroregeneration, this is the first time to jointly apply a dynamic perfusion bioreactor and the ascorbic acid to stimulate the SKP-SCs secretion of extracellular matrix (ECM).

Lifetime Cumulative Effect of Reproductive Factors on Stroke and Its Subtypes in Postmenopausal Chinese Women: A Prospective Cohort Study.

Background And Objectives: Multiple reproductive factors are associated with stroke. Little is known about the cumulative effects of reproductive factors during a reproductive life course on stroke and its subtypes, especially among female Chinese individuals. The objective of this study was to assess the associations of lifetime cumulative estrogen exposure due to reproductive factors with stroke and its etiologic subtypes among postmenopausal Chinese women.

An anti-influenza A virus microbial metabolite acts by degrading viral endonuclease PA.

The emergence of new highly pathogenic and drug-resistant influenza strains urges the development of novel therapeutics for influenza A virus (IAV). Here, we report the discovery of an anti-IAV microbial metabolite called APL-16-5 that was originally isolated from the plant endophytic fungus Aspergillus sp. CPCC 400735.

Inflammatory Endotype-Associated Airway Resistome in Chronic Obstructive Pulmonary Disease.

Antimicrobial resistance is a global concern in chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD). The collection of antibiotic resistance genes or resistome in human airways may underlie the resistance. COPD is heterogeneous, and understanding the airway resistome in relation to patient phenotype and endotype may inform precision antibiotic therapy.

Comparison of Overall Survival between Surgical Resection and Radiofrequency Ablation for Hepatitis B-Related Hepatocellular Carcinoma.

It remains controversial whether surgical resection, compared to radiofrequency ablation (RFA), improves overall survival (OS) in patients with early hepatocellular carcinoma (HCC). This study aimed to compare OS after RFA with that after resection for HCC. This retrospective study included patients who underwent RFA or surgical resection as initial treatment for hepatitis B virus (HBV)-related HCC at a very early or early stage.

RBD-homodimer, a COVID-19 subunit vaccine candidate, elicits immunogenicity and protection in rodents and nonhuman primates.

The pandemic of COVID-19 caused by SARS-CoV-2 has raised a new challenges to the scientific and industrious fields after over 1-year spread across different countries. The ultimate approach to end the pandemic is the timely application of vaccines to achieve herd immunity. Here, a novel SARS-CoV-2 receptor-binding domain (RBD) homodimer was developed as a SARS-CoV-2 vaccine candidate.

Serum albumin and beta-amyloid deposition in the human brain.

Objectives: To investigate the relationships of serum albumin with in vivo Alzheimer disease (AD) pathologies, including cerebral β-amyloid (Aβ) protein deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMH), in the human brain.

Methods: A total of 396 older adults without dementia underwent comprehensive clinical assessments, measurement of serum albumin level, and multimodal brain imaging, including [C] Pittsburgh compound B-PET, F-fluorodeoxyglucose-PET, and MRI. Serum albumin was categorized as follows: <4.

Deep sequencing of circulating tumor DNA detects molecular residual disease and predicts recurrence in gastric cancer.

Identifying locoregional gastric cancer patients who are at high risk for relapse after resection could facilitate early intervention. By detecting molecular residual disease (MRD), circulating tumor DNA (ctDNA) has been shown to predict post-operative relapse in several cancers. Here, we aim to evaluate MRD detection by ctDNA and its association with clinical outcome in resected gastric cancer.

Advances in Analysis of Biodistribution of Exosomes by Molecular Imaging.

Exosomes are nano-sized membranous vesicles produced by nearly all types of cells. Since exosome-like vesicles are produced in an evolutionarily conserved manner for information and function transfer from the originating cells to recipient cells, an increasing number of studies have focused on their application as therapeutic agents, drug delivery vehicles, and diagnostic targets. Analysis of the in vivo distribution of exosomes is a prerequisite for the development of exosome-based therapeutics and drug delivery vehicles with accurate prediction of therapeutic dose and potential side effects.

Comparison of Models for Tumor Recurrence after Liver Transplantation for the Patients with Hepatocellular Carcinoma: A Multicenter Long-Term Follow-Up Study.

Background And Aims: Several models have been developed to predict tumor the recurrence of hepatocellular carcinoma (HCC) after liver transplantation besides the conventional Milan criteria (MC), including the MoRAL score. This study aimed to compare the prognostication power of the MoRAL score to most models designed so far in the Eastern and Western countries.

Methods: This study included 564 patients who underwent living donor liver transplantation (LDLT) in three large-volume hospitals in Korea.

Nanoformulation of Brain-Derived Neurotrophic Factor with Target Receptor-Triggered-Release in the Central Nervous System.

Brain-derived neurotrophic factor (BDNF) is identified as a potent neuroprotective and neuroregenerative agent for many neurological diseases. Regrettably, its delivery to the brain is hampered by poor serum stability and rapid brain clearance. Here, a novel nanoformulation is reported composed of a bio-compatible polymer, poly(ethylene glycol)--poly(L-glutamic acid) (PEG-PLE), that hosts the BDNF molecule in a nanoscale complex, termed here Nano-BDNF.

Moderating effect of ε4 on the relationship between sleep-wake cycle and brain β-amyloid.

Objectives: To clarify the relationships between sleep-wake cycle and cerebral β-amyloid (Aβ) deposition in cognitively normal (CN) older adults, focusing primarily on the moderating effects of the ε4 allele.

Methods: The present study included 133 CN older adults who participated in the Korean Brain Aging Study for Early Diagnosis & Prediction of Alzheimer's Disease cohort. All participants underwent [C] Pittsburgh compound B-PET imaging to quantify Aβ deposition in the brain and blood sampling for genotyping.

First-Line Use of Core Needle Biopsy for High-Yield Preliminary Diagnosis of Thyroid Nodules.

Background And Purpose: Although core needle biopsy was introduced as a diagnostic alternative to fine-needle aspiration, the utility and safety of core needle biopsy for thyroid nodules in a large population has yet to be studied comprehensively. We evaluate core needle biopsy yields on a large-scale basis to investigate its potential in the preliminary diagnosis of thyroid nodules.

Materials And Methods: Between March 2005 and December 2013, 2448 initially detected thyroid nodules from 2120 consecutive patients who underwent core needle biopsy were retrospectively evaluated.

Interferon-γ-mediated allograft rejection exacerbates cardiovascular disease of hyperlipidemic murine transplant recipients.

Rationale: Transplantation, the most effective therapy for end-stage organ failure, is markedly limited by early-onset cardiovascular disease (CVD) and premature death of the host. The mechanistic basis of this increased CVD is not fully explained by known risk factors.

Objective: To investigate the role of alloimmune responses in promoting CVD of organ transplant recipients.

Stemness characteristics of human corneal endothelial cells cultured in various media.

Purpose: To investigate stemness characteristics of human corneal endothelial cells (HCECs) cultured in various media.

Methods: Human corneal endothelial cells were isolated using a sphere-forming assay. Cells were allowed to attach to the bottom of culture plates and were cultured in different media designated as medium A (Opti-MEM I with 8% fetal bovine serum), medium B (DMEM/F12 with B27 supplement), medium E (DMEM/F12 with epidermal growth factor [EGF]), and medium BE (DMEM/F12 with B27 supplement and EGF), respectively.

Up-regulation of programmed cell death 1 ligand 1 on neutrophils may be involved in sepsis-induced immunosuppression: an animal study and a prospective case-control study.

Background: Recent studies have shown that neutrophils may display an antigen-presenting function and inhibit lymphocyte proliferation by expressing programmed cell death 1 ligand 1 (PD-L1). The current study was performed to investigate the effect of neutrophils and their pathophysiological significance during sepsis.

Methods: Neutrophil PD-L1 expression was determined in both septic mice (n = 6) and patients (n = 41).

MicroRNA profiling in Chinese patients with primary Sjögren syndrome reveals elevated miRNA-181a in peripheral blood mononuclear cells.

Objective: Characterized by chronic inflammation, dysfunction of exocrine glands, and systemic autoimmunity, primary Sjögren syndrome (pSS) is a common autoimmune disease in elderly women. Our study was performed to explore the potential involvement of microRNA (miRNA) in Chinese patients with pSS.

Methods: Using microarrays, miRNA expression in peripheral blood mononuclear cells (PBMC) was profiled in 4 female patients with pSS and 3 healthy participants, followed by a large-scale study of 33 patients and 10 healthy individuals.

Therapeutic potential of Dickkopf-1 in wild-type BRAF papillary thyroid cancer via regulation of β-catenin/E-cadherin signaling.

Background: Aberrant activation of the Wnt/β-catenin pathway is a common pathogenesis of various human cancers. We investigated the role of the Wnt inhibitor, Dkk-1, in papillary thyroid cancer (PTC).

Methods: Immunohistochemical β-catenin staining was performed in tissue microarray containing 148 PTCs and five normal thyroid tissues.

A Functional Antagonistic Relationship between Auxin and Mitochondrial Retrograde Signaling Regulates Alternative Oxidase1a Expression in Arabidopsis.

The perception and integration of stress stimuli with that of mitochondrion function are important during periods of perturbed cellular homeostasis. In a continuous effort to delineate these mitochondrial/stress-interacting networks, forward genetic screens using the mitochondrial stress response marker alternative oxidase 1a (AOX1a) provide a useful molecular tool to identify and characterize regulators of mitochondrial stress signaling (referred to as regulators of alternative oxidase 1a [RAOs] components). In this study, we reveal that mutations in genes coding for proteins associated with auxin transport and distribution resulted in a greater induction of AOX1a in terms of magnitude and longevity.