An immobilized antibody-based affinity grid strategy for on-grid purification of target proteins enables high-resolution cryo-EM.

In cryo-electron microscopy (cryo-EM), sample preparation poses a critical bottleneck, particularly for rare or fragile macromolecular assemblies and those suffering from denaturation and particle orientation distribution issues related to air-water interface. In this study, we develop and characterize an immobilized antibody-based affinity grid (IAAG) strategy based on the high-affinity PA tag/NZ-1 antibody epitope tag system. We employ Pyr-NHS as a linker to immobilize NZ-1 Fab on the graphene oxide or carbon-covered grid surface.

Microglial Activation Imaging Using F-DPA-714 PET/MRI for Detecting Autoimmune Encephalitis.

Background Translocator protein (TSPO) PET has been used to visualize microglial activation in neuroinflammation and is a potential imaging tool for detecting autoimmune encephalitis (AIE). Purpose To compare the detection rate between TSPO radioligand fluorine 18 (F) DPA-714 PET and conventional MRI and assess the relationship between F-DPA-714 uptake and clinical features in participants with AIE. Materials and Methods Healthy volunteers and patients with AIE were enrolled in this prospective study between December 2021 and April 2023.

New Loss-of-Function Mutations in PCSK9 Reduce Plasma LDL Cholesterol.

Background: Lower plasma levels of LDL (low-density lipoprotein) cholesterol (LDL-C) can reduce the risk of atherosclerotic cardiovascular disease. The loss-of-function mutations in (proprotein convertase subtilisin/kexin type 9) have been known to associate with low LDL-C in many human populations. PCSK9 genetic variants in Chinese Uyghurs who are at high risk of atherosclerotic cardiovascular disease due to their dietary habits have not been reported.

VV116 versus Nirmatrelvir-Ritonavir for Oral Treatment of Covid-19.

Background: Nirmatrelvir-ritonavir has been authorized for emergency use by many countries for the treatment of coronavirus disease 2019 (Covid-19). However, the supply falls short of the global demand, which creates a need for more options. VV116 is an oral antiviral agent with potent activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Inhibition of HIPK2 protects stress-induced pathological cardiac remodeling.

Background: Homeodomain-Interacting Protein Kinase 2 (HIPK2) has been reported to maintain basal cardiac function, however, its role in pathological cardiac remodeling remains unclear.

Methods: HIPK2 inhibitors (tBID and PKI1H) treated mice and two lines of HIPK2 mice were subjected to transverse aortic constriction (TAC). HIPK2 knockdown were performed in neonatal rat cardiomyocytes (NRCMs), neonatal rat cardiac fibroblasts (NRCFs), and human embryonic stem cell-derived cardiomyocytes (hESC-CMs).

Retraction Note: METTL3 promotes the progression of nasopharyngeal carcinoma through mediating M6A modification of EZH2.

The article "METTL3 promotes the progression of nasopharyngeal carcinoma through mediating M6A modification of EZH2, by Q.-Z. Meng, C.

Amide Proton Transfer Could Provide More Accurate Lesion Characterization in the Transition Zone of the Prostate.

Background: There is an overlap comparing transition zone prostate cancer (TZ PCa) and benign prostatic hyperplasia (BPH) on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), creating additional challenges for assessment of TZ tumors on MRI.

Purpose: To evaluate whether amide proton transfer-weighted (APTw) imaging provides new diagnostic ideas for TZ PCa.

Study Type: Prospective.

Sex Differences in Short-Term and Long-Term Outcomes Among Patients With Acute Ischemic Stroke in China.

Background: Sex differences in stroke outcomes are crucial to secondary prevention, but previous reports showed inconsistent results. We aimed to explore the sex differences in stroke outcomes in the Third China National Stroke Registry, a prospective multicenter registry study.

Methods: Among the 15 166 patients enrolled between 2015 and 2018, 9038 patients with acute ischemic stroke (AIS) were included.

CIRKIL Exacerbates Cardiac Ischemia/Reperfusion Injury by Interacting With Ku70.

Background: Ku70 participates in several pathological processes through mediating repair of DNA double-strand breaks. Our previous study has identified a highly conserved long noncoding RNA cardiac ischemia reperfusion associated Ku70 interacting lncRNA (CIRKIL) that was upregulated in myocardial infarction. The study aims to investigate whether CIRKIL regulates myocardial ischemia/reperfusion (I/R) through binding to Ku70.

Dietary Pattern and Long-Term Effects of Particulate Matter on Blood Pressure: A Large Cross-Sectional Study in Chinese Adults.

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Discovery of a new class of integrin antibodies for fibrosis.

Lung fibrosis, or the scarring of the lung, is a devastating disease with huge unmet medical need. There are limited treatment options and its prognosis is worse than most types of cancer. We previously discovered that MK-0429 is an equipotent pan-inhibitor of αv integrins that reduces proteinuria and kidney fibrosis in a preclinical model.

Rheb (Ras Homolog Enriched in Brain 1) Deficiency in Mature Macrophages Prevents Atherosclerosis by Repressing Macrophage Proliferation, Inflammation, and Lipid Uptake.

Objective: Macrophage foam cell formation is an important process in atherosclerotic plaque development. The small GTPase Rheb (Ras homolog enriched in brain 1) regulates endocytic trafficking that is critical for foam cell formation. However, it is unclear whether and how macrophage Rheb regulates atherogenesis, which are the focuses of the current study.

Toll-Like Receptor 4/MyD88-Mediated Signaling of Hepcidin Expression Causing Brain Iron Accumulation, Oxidative Injury, and Cognitive Impairment After Intracerebral Hemorrhage.

Background: Disturbance of brain iron metabolism after intracerebral hemorrhage (ICH) results in oxidative brain injury and cognition impairment. Hepcidin plays an important role in regulating iron metabolism, and we have reported that serum hepcidin is positively correlated with poor outcomes in patients with ICH. However, the roles of hepcidin in brain iron metabolism after ICH remain largely unknown.

Effects of an Isolated Complete Right Bundle Branch Block on Mechanical Ventricular Function.

Objectives: The purpose of this study was to investigate the effects of an isolated complete right bundle branch block on mechanical ventricular function.

Methods: Two groups of participants were enrolled in this study: a block group, consisting of 98 patients with isolated complete right bundle branch blocks without structural heart disease, and a control group, consisting of 92 healthy adults. The diameter, end-diastolic area, end-systolic area, and right ventricular (RV) fractional area change were obtained to evaluate morphologic and systolic function by 2-dimensional sonographic technology.

Contrast-Enhanced Sonography for Diagnosing Collateral Transformation of the Hepatic Artery After Liver Transplantation.

Objectives: To determine the contrast-enhanced sonographic features of hepatic artery collateral transformation in patients with hepatic artery complications after liver transplantation.

Methods: Ninety-nine liver transplant recipients who underwent contrast-enhanced sonography were recruited from April 2004 to May 2014. The reference standards were conventional angiography and computed tomographic angiography.

A Novel Partial Agonist of Peroxisome Proliferator-Activated Receptor γ with Excellent Effect on Insulin Resistance and Type 2 Diabetes.

Partial agonists of peroxisome proliferator-activated receptor γ (PPARγ) reportedly reverse insulin resistance in patients with type 2 diabetes mellitus. In this work, a novel non-thiazolidinedione-partial PPARγ ligand, MDCCCL1636 [N-(4-hydroxyphenethyl)-3-mercapto-2-methylpropanamide], was investigated. The compound displayed partial agonist activity in biochemical and cell-based transactivation assays and reversed insulin resistance.

Brown Adipose Tissue Transplantation Reverses Obesity in Ob/Ob Mice.

Increasing evidence indicates that brown adipose tissue (BAT) transplantation enhances whole-body energy metabolism in a mouse model of diet-induced obesity. However, it remains unclear whether BAT also has such beneficial effects on genetically obese mice. To address this issue, we transplanted BAT from C57/BL6 mice into the dorsal subcutaneous region of age- and sex-matched leptin deficient Ob/Ob mice.

Noninvasive evaluation of liver fibrosis using real-time tissue elastography and transient elastography (FibroScan).

Objectives: The purpose of this study was to assess liver fibrosis with real-time tissue elastography and to compare the results with those of transient elastographic (FibroScan; Echosens, Paris, France) measurements by using liver biopsy as the reference standard.

Methods: Real-time tissue elastography and percutaneous liver biopsy were performed in 166 patients with chronic hepatitis B (estimation group). The relationship between the parameters obtained via real-time tissue elastography and the hepatic fibrosis stage was evaluated by a stepwise multiple linear regression, and the regression equation was used to calculate the liver fibrosis index.