Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) in China: a subgroup of ALPINE.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has different epidemiology in Chinese vs. Western patients, but there are few studies of CLL/SLL in large populations of Chinese patients. ALPINE is a global phase 3 trial investigating Bruton tyrosine kinase inhibitors zanubrutinib vs.

The construction and optimization of engineered yeast chassis for efficient biosynthesis of 8-hydroxygeraniol.

Microbial production of monoterpenoid indole alkaloids (MIAs) provides a sustainable and eco-friendly means to obtain compounds with high pharmaceutical values. However, efficient biosynthesis of MIAs in heterologous microorganisms is hindered due to low supply of key precursors such as geraniol and its derivative 8-hydroxygeraniol catalyzed by geraniol 8-hydroxylase (G8H). In this study, we developed a facile evolution platform to screen strains with improved yield of geraniol by using the SCRaMbLE system embedded in the Sc2.

Reverse metabolomics for the discovery of chemical structures from humans.

Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse metabolomics as a discovery strategy, whereby tandem mass spectrometry spectra acquired from newly synthesized compounds are searched for in public metabolomics datasets to uncover phenotypic associations. To demonstrate the concept, we broadly synthesized and explored multiple classes of metabolites in humans, including N-acyl amides, fatty acid esters of hydroxy fatty acids, bile acid esters and conjugated bile acids.

Histone Lactylation Boosts Reparative Gene Activation Post-Myocardial Infarction.

Background: Inflammation resolution and cardiac repair initiation after myocardial infarction (MI) require timely activation of reparative signals. Histone lactylation confers macrophage homeostatic gene expression signatures via transcriptional regulation. However, the role of histone lactylation in the repair response post-MI remains unclear.

Comparison of Computed Tomography Perfusion and Multiphase Computed Tomography Angiogram in Predicting Clinical Outcomes in Endovascular Thrombectomy.

Background: In patients with acute stroke who undergo endovascular thrombectomy, the relative prognostic power of computed tomography perfusion (CTP) parameters compared with multiphase CT angiogram (mCTA) is unknown. We aimed to compare the predictive accuracy of mCTA and CTP parameters on clinical outcomes.

Methods: We included patients with acute ischemic stroke who had anterior circulation large vessel occlusion within 24 hours of onset in Melbourne Brain Centre at the Royal Melbourne Hospital.

PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Triggers Vascular Smooth Muscle Cell Senescence and Apoptosis: Implication of Its Direct Role in Degenerative Vascular Disease.

Objective: PCSK9 (proprotein convertase subtilisin/kexin type 9) plays a critical role in cholesterol metabolism via the PCSK9-LDLR (low-density lipoprotein receptor) axis in the liver; however, evidence indicates that PCSK9 directly contributes to the pathogenesis of various diseases through mechanisms independent of its LDL-cholesterol regulation. The objective of this study was to determine how PCSK9 directly acts on vascular smooth muscle cells (SMCs), contributing to degenerative vascular disease. Approach and Results: We first examined the effects of PCSK9 on cultured human aortic SMCs.

Double-Negative α-Fetoprotein and Carbohydrate Antigen 19-9 Predict a Good Prognosis in Intrahepatic Cholangiocarcinoma: A Propensity Score Matching Analysis.

Introduction: Carbohydrate antigen 19-9 (CA19-9) and α-fetoprotein (AFP) are routinely tested in patients with liver malignancies before surgery. However, few reports have explored the relevance of the expression pattern of these 2 tumor markers regarding the prognosis of intrahepatic cholangiocarcinoma (ICC). We herein combined these 2 tumor markers to investigate the influence on ICC malignancy and patient prognosis.

Optimal Tissue Reperfusion Estimation by Computed Tomography Perfusion Post-Thrombectomy in Acute Ischemic Stroke.

Background And Purpose: Modified Thrombolysis in Cerebral Infarction score (mTICI) ≥2b is defined as successful reperfusion. However, mTICI has rarely been correlated with dynamic perfusion imaging postendovascular therapy for acute stroke. We aimed to study the proportion of tissue optimal reperfusion (TOR) postendovascular therapy across different grades of mTICI.

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Eliminating mesothelioma by AAV-vectored, PD1-based vaccination in the tumor microenvironment.

The potency of cancer vaccines is often compromised by a variety of immunoinhibitory mechanisms, including stimulation of the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint pathway. Here, to overcome inhibition, we determined the potential of recombinant adeno-associated virus (rAAV)-vectored, PD1-based vaccination in the tumor microenvironment (TME) to activate antigen-specific T cell responses in the immune-competent murine mesothelioma model. We found that our rAAV-soluble PD1 (sPD1)-TWIST1 vaccine elicited and maintained TWIST1-specific cytotoxic T lymphocyte (CTL) responses and the PD-1 blocker systemically against lethal mesothelioma challenge after intramuscular injection, which was more effective than rAAV-TWIST1 or rAAV-sPD1 alone.

Visualization of Macrophage Lytic Cell Death During Mycobacterial Infection in Zebrafish Embryos via Intravital Microscopy.

Zebrafish is an excellent model organism for studying innate immune cell behavior due to its transparent nature and reliance solely on its innate immune system during early development. The Zebrafish Mycobacterium marinum (M. marinum) infection model has been well-established in studying host immune response against mycobacterial infection.

Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage.

Recurrent miscarriage (RM) affects millions of couples globally, and half of them have no demonstrated etiology. Genome sequencing (GS) is an enhanced and novel cytogenetic tool to define the contribution of chromosomal abnormalities in human diseases. In this study we evaluated its utility in RM-affected couples.

A New Segmented Virus Associated with Human Febrile Illness in China.

Background: In 2017, surveillance for tickborne diseases in China led to the identification of a patient who presented to a hospital in Inner Mongolia with a febrile illness that had an unknown cause. The clinical manifestation of the illness was similar to that of tickborne encephalitis virus (TBEV) infection, but neither TBEV RNA nor antibodies against the virus were detected.

Methods: We obtained a blood specimen from the index patient and attempted to isolate and identify a causative pathogen, using genome sequence analysis and electron microscopy.

Effect of aprepitant administration on CINV caused by cisplatin multi-day chemotherapy and pharmacokinetics of docetaxel.

Purpose: To compare efficacy and safety of postponing administration of aprepitant and routine triple-antiemetic treatment for chemotherapy-induced nausea and vomiting in patients who received docetaxel and cisplatin multi-day chemotherapy treatment, and to evaluate the effect of aprepitant on docetaxel pharmacokinetics in the Chinese population.

Methods: A total of 24 cancer patients (including 5 females and 19 males, 22-74 years old) received two cycles of high-emetic DP (docetaxel 75 mg/m on day 1 + cisplatin 25 mg/m on days 1-3) regimen. A randomized, two-period and cross-over study was applied for prevention of chemotherapy-induced nausea and vomiting.

Crystal Chemistry and Thermoelectric Properties of Type-I Clathrate Ba₈NiSiGe ( = 0, 10, 20, 42.2).

Thermoelectric materials are actively considered for waste heat recovery applications. To improve the heat to electricity conversion efficiency, fundamental understanding on composition, crystal structure, and interrelation with the thermoelectric properties is necessary. Here, we report the chemical and thermoelectric properties of type-I clathrates Ba 8 Ni 3.

Tumor-penetrating Peptide-integrated Thermally Sensitive Liposomal Doxorubicin Enhances Efficacy of Radiofrequency Ablation in Liver Tumors.

Purpose To investigate the role of a tumor-penetrating peptide (internalizing CRGDRGPDC [iRGD])-integrated thermally sensitive liposomal (TSL) doxorubicin (DOX) in combination with radiofrequency (RF) ablation of liver tumors in an animal model. Materials and Methods Approval from the institutional animal care and use committee was obtained. Characterization of iRGD-TSL-DOX was performed in vitro.

Mnk1 (Mitogen-Activated Protein Kinase-Interacting Kinase 1) Deficiency Aggravates Cardiac Remodeling in Mice.

Identifying the key factor involved in cardiac remodeling is critically important for developing novel strategies to protect against heart failure. Here, the role of Mnk1 (mitogen-activated protein kinase-interacting kinase 1) in cardiac remodeling was clarified. Cardiac remodeling was induced by transverse aortic constriction in Mnk1-knockout mice and their wild-type control mice.

MicroRNA-424 protects against focal cerebral ischemia and reperfusion injury in mice by suppressing oxidative stress.

Background And Purpose: We previously showed that the microRNA miR-424 protects against permanent cerebral ischemic injury in mice by suppressing microglia activation. This study investigated the role of miR-424 in transient cerebral ischemia in mice with a focus on oxidative stress-induced neuronal injury.

Methods: Transient cerebral ischemia was induced in C57/BL6 mice by middle cerebral artery occlusion for 1 hour followed by reperfusion (ischemia/reperfusion).

Ischemic postconditioning relieves cerebral ischemia and reperfusion injury through activating T-LAK cell-originated protein kinase/protein kinase B pathway in rats.

Background And Purpose: Ischemic postconditioning (IPostC) protects against ischemic brain injury. To date, no study has examined the role of T-LAK-cell-originated protein kinase (TOPK) in IPostC-afforded neuroprotection. We explored the molecular mechanism related with TOPK in antioxidant effect of IPostC against ischemia/reperfusion.

Direct 4-D PET list mode parametric reconstruction with a novel EM algorithm.

The production of images of kinetic parameters is often the ultimate goal of positron emission tomography (PET) imaging. The indirect method of PET parametric imaging, also called the frame-based method (FM), is performed by fitting the time-activity curve (TAC) for each voxel with an appropriate compartment model after image reconstruction. The indirect method is simple and easily implemented, however, it usually leads to some loss of accuracy or precision, due to the use of two separate steps.

Direct 4D List Mode Parametric Reconstruction for PET with a Novel EM Algorithm.

We present a direct method for producing images of kinetic parameters from list mode PET data. The time-activity curve for each voxel is described by a one-tissue compartment, 2-parameter model. Extending previous EM algorithms, a new spatiotemporal complete data space was introduced to optimize the maximum likelihood function.