Integrated molecular and functional characterization of the intrinsic apoptotic machinery identifies therapeutic vulnerabilities in glioma.

Genomic profiling often fails to predict therapeutic outcomes in cancer. This failure is, in part, due to a myriad of genetic alterations and the plasticity of cancer signaling networks. Functional profiling, which ascertains signaling dynamics, is an alternative method to anticipate drug responses.

Characteristics and Significance of Tertiary Lymphoid Structures Based on Molecular Subtypes in Endometrial Cancer.

The purpose of this study is to investigate the characteristics and significance of tertiary lymphoid structures (TLSs) in endometrial cancer (EC) based on molecular subtypes. A total of 220 patients with EC were retrospectively enrolled, including 20 with polymerase epsilon ultramutated (POLE-mut), 63 with mismatch repair deficient, 32 with p53 abnormal, and 105 with no specific molecular profile. The presence and maturity of TLSs were determined by immunohistochemical markers (CD3, CD20, CD21, and Bcl6).

Analysis of growth pattern of temporal bone pneumatization using 3D reconstructed computed tomography.

Background: Temporal bone pneumatization (TBP) is influenced by age, sex, and race, and it seems to progress rapidly to puberty. However, the extent of TBP in childhood remains unclear.

Purpose: To investigate the progression of TBP in children aged 1-18 years via three-dimensional (3D) reconstruction of high-resolution computed tomography (CT) images.

First-Principles Study on Janus-Structured ScCX/ScCY (X, Y = F, Cl, Br) Heterostructures for Solar Energy Conversion.

Two-dimensional van der Waals heterostructures have good application prospects in solar energy conversion due to their excellent optoelectronic performance. In this work, the electronic structures of ScCF/ScCCl, ScCF/ScCBr, and ScCCl/ScCBr heterostructures, as well as their properties in photocatalysis and photovoltaics, have been comprehensively studied using the first-principles method. Firstly, both of the three thermodynamically and dynamically stable heterostructures are found to have type-II band alignment with band gap values of 0.

Implementation of a Clinical Vessel Wall MR Imaging Program at an Academic Medical Center.

Background And Purpose: The slow adoption of new advanced imaging techniques into clinical practice has been a long-standing challenge. Principles of implementation science and the reach, effectiveness, adoption, implementation, maintenance (RE-AIM) framework were used to build a clinical vessel wall imaging program at an academic medical center.

Materials And Methods: Six phases for implementing a clinical vessel wall MR imaging program were contextualized to the RE-AIM framework.

Therapeutic targeting nudix hydrolase 1 creates a MYC-driven metabolic vulnerability.

Tumor cells must rewire nucleotide synthesis to satisfy the demands of unbridled proliferation. Meanwhile, they exhibit augmented reactive oxygen species (ROS) production which paradoxically damages DNA and free deoxy-ribonucleoside triphosphates (dNTPs). How these metabolic processes are integrated to fuel tumorigenesis remains to be investigated.

A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models.

Idiopathic pulmonary fibrosis (IPF) is an aggressive interstitial lung disease with a high mortality rate. Putative drug targets in IPF have failed to translate into effective therapies at the clinical level. We identify TRAF2- and NCK-interacting kinase (TNIK) as an anti-fibrotic target using a predictive artificial intelligence (AI) approach.

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.

Author Correction: Experimental study on thioredoxin redox inhibitor 1-methylpropyl 2-imidazolyl disulfide promoting apoptosis of multiple myeloma cells in vitro and in vivo.

Correction to: European Review for Medical and Pharmacological Sciences 2022; 26 (4): 1283-1292. DOI: 10.26355/eurrev_202202_28121-PMID: 35253185-published online on December 15, 2022.

Heterozygous Mutations Cause Cerebral Small Vessel Diseases: Genetic, Clinical, and Pathologic Findings From 3 Chinese Pedigrees.

Background And Objectives: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a rare hereditary cerebrovascular disease caused by homozygous or compound heterozygous variations in the high-temperature requirement A serine peptidase 1 () gene. However, several studies in recent years have found that some heterozygous mutations also cause cerebral small vessel disease (CSVD). The current study aims to report the novel genotypes, phenotypes, and histopathologic results of 3 pedigrees of CSVD with heterozygous mutation.

Ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone in patients with previously untreated non-germinal centre B-cell-like diffuse large B-cell lymphoma: A Chinese subgroup analysis of the phase III PHOENIX trial.

In this post hoc subgroup analysis of 200 patients enrolled in China from the phase III PHOENIX trial (= 838, NCT01855750), addition of ibrutinib to rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) did not improve event-free survival (EFS) versus placebo+R-CHOP in the intent-to-treat (ITT;  = 200, hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0·509-1.349; = 0.

Species diversity, systematic revision and molecular phylogeny of (, ) with an emphasis on Chinese collections.

is one of the main families of macrofungi since species in the family are both ecologically and economically important. The double-walled basidiospores with ornamented endospore walls are the characteristic features of . It is a large and complex family; although many studies have focused on , the global diversity, geographic distribution, taxonomy and molecular phylogeny of still remained incompletely understood.

SHR1032, a novel STING agonist, stimulates anti-tumor immunity and directly induces AML apoptosis.

Stimulator of interferon genes (STING) activation induces type I interferons and pro-inflammatory cytokines which stimulate tumor antigen cross presentation and the adaptive immune responses against tumor. The first-generation of STING agonists, cyclic di-nucleotide (CDN), mimicked the endogenous STING ligand cyclic guanosine monophosphate adenosine monophosphate, and displayed limited clinical efficacy. Here we report the discovery of SHR1032, a novel small molecule non-CDN STING agonist.

Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine.

Peripheral neurons that sense glucose relay signals of glucose availability to integrative clusters of neurons in the brain. However, the roles of such signalling pathways in the maintenance of glucose homoeostasis and their contribution to disease are unknown. Here we show that the selective activation of the nerve plexus of the hepatic portal system via peripheral focused ultrasound stimulation (pFUS) improves glucose homoeostasis in mice and rats with insulin-resistant diabetes and in swine subject to hyperinsulinemic-euglycaemic clamps.

Suppression of toxicity of the mutant huntingtin protein by its interacting compound, desonide.

Identifying inhibitors of pathogenic proteins is the major strategy of targeted drug discoveries. This strategy meets challenges in targeting neurodegenerative disorders such as Huntington’s disease (HD), which is mainly caused by the mutant huntingtin protein (mHTT), an “undruggable” pathogenic protein with unknown functions. We hypothesized that some of the chemical binders of mHTT may change its conformation and/or stability to suppress its downstream toxicity, functioning similarly to an “inhibitor” under a broader definition.

Ablation of Plasma Prekallikrein Decreases Low-Density Lipoprotein Cholesterol by Stabilizing Low-Density Lipoprotein Receptor and Protects Against Atherosclerosis.

Background: High blood cholesterol accelerates the progression of atherosclerosis, which is an asymptomatic process lasting for decades. Rupture of atherosclerotic plaques induces thrombosis, which results in myocardial infarction or stroke. Lowering cholesterol levels is beneficial for preventing atherosclerotic cardiovascular disease.

Single-cell analysis of human primary prostate cancer reveals the heterogeneity of tumor-associated epithelial cell states.

Prostate cancer is the second most common malignancy in men worldwide and consists of a mixture of tumor and non-tumor cell types. To characterize the prostate cancer tumor microenvironment, we perform single-cell RNA-sequencing on prostate biopsies, prostatectomy specimens, and patient-derived organoids from localized prostate cancer patients. We uncover heterogeneous cellular states in prostate epithelial cells marked by high androgen signaling states that are enriched in prostate cancer and identify a population of tumor-associated club cells that may be associated with prostate carcinogenesis.

Halftone spatial frequency domain imaging enables kilohertz high-speed label-free non-contact quantitative mapping of optical properties for strongly turbid media.

The ability to quantify optical properties (i.e., absorption and scattering) of strongly turbid media has major implications on the characterization of biological tissues, fluid fields, and many others.

Blocking FcγRIIB in Smooth Muscle Cells Reduces Hypertension.

[Figure: see text].