The de novo synthesis of GABA and its gene regulatory function control hepatocellular carcinoma metastasis.

The neurotransmitter gamma-aminobutyric acid (GABA) has been thought to be involved in the development of some types of cancer. Yet, the de novo synthesis of GABA and how it functions in hepatocellular carcinoma (HCC) remain unclear. Here, we report that SLC6A12 acts as a transporter of GABA, and that aldehyde dehydrogenase 9 family member A1 (ALDH9A1), not glutamate decarboxylase 1 (GAD1), generates GABA in human HCC.

Fine-Needle Portosystemic Pressure Gradient as a Reference for Portal Hypertension in Patients with Intrahepatic Venovenous Shunt: A Prospective Study.

Purpose: To evaluate the consistency and agreement between portal venous pressure measured by fine-needle (F), portal vein catheterization (D), and hepatic vein balloon-occlusion (W) in decompensated cirrhotic patients with intrahepatic venovenous shunts (IHVS).

Materials And Methods: 156 consecutive patients planning to receive transjugular intrahepatic portosystemic shunt in our center were screened for study participation. The F/D/W were assessed for consistency by Pearson coefficient (r), linear regression coefficient (R), and intraclass correlation coefficient (ICC), and for disagreement (error exceeding 20% of D) by Bland-Altman method.

The ability of virtual noncontrast images to remove intrinsic and external iodine from the thyroid via dual-layer spectral detector computed tomography.

Background: Virtual noncontrast (VNC) images generated by dual-layer spectral computed tomography (DLCT) remove iodine influence from enhanced images to simulate true noncontrast (TNC) images. Previous research has demonstrated the high comparability of abdominal VNC images with TNC images, suggesting their potential as substitutes. Given the thyroid's significant iodine content, this study evaluated the efficacy of VNC images for removing both intrinsic and extrinsic iodine through an analysis of computed tomography (CT) attenuation and iodine density in TNC and enhanced VNC thyroid images.

Consensus Recommendations for Studies of Outflow Facility and Intraocular Pressure Regulation Using Ex Vivo Perfusion Approaches.

Intraocular pressure (IOP) elevation is the primary risk factor and currently the main treatable factor for progression of glaucomatous optic neuropathy. In addition to direct clinical and living animal in vivo studies, ex vivo perfusion of anterior segments and whole eyes is a key technique for studying conventional outflow function as it is responsible for IOP regulation. We present well-tested experimental details, protocols, considerations, advantages, and limitations of several ex vivo model systems for studying IOP regulation.

Genome-wide single-cell and single-molecule footprinting of transcription factors with deaminase.

Decades of research have established that mammalian transcription factors (TFs) bind to each gene's regulatory regions and cooperatively control tissue specificity, timing, and intensity of gene transcription. Mapping the combination of TF binding sites genome wide is critically important for understanding functional genomics. Here, we report a technique to measure TFs' binding sites on the human genome with a near single-base resolution by footprinting with deaminase (FOODIE) on a single-molecule and single-cell basis.

[Electroacupuncture inhibits inflammatory response through hexokinase 2 - mediated Warburg effect in rats with acute lung injury].

Objectives: To observe whether electroacupuncture (EA) can inhibit the inflammatory response via down-regulating hexokinase 2 (HK2) mediated Warburg effect in rats with acute lung injury (ALI).

Methods: Male Sprague-Dawley rats were randomly divided into control, model and EA groups, with 12 rats in each group. The ALI model was established by injection of lipopolysaccharides (LPS, 5 mg/mL, 1 mL/kg) into the tail vein.

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.

Weight loss with atogepant during the preventive treatment of migraine: A pooled analysis.

Background: Migraine is associated with obesity. These analyses evaluated weight change with atogepant used as a preventive migraine treatment.

Methods: Five atogepant clinical trials in adults with migraine (one phase 2b/3; four phase 3) were included: Three 12-week, randomized, placebo-controlled trials (episodic migraine: two; chronic migraine: one); one 40-week, open-label extension trial and one 52-week, standard care, randomized, long-term safety trial in episodic migraine.

Effect of emodin on acute lung injury: a meta-analysis of preclinical trials.

Background: Emodin has protective effects on acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). This meta-analysis intended to illustrate the efficacy of emodin on ALI/ARDS animal models.

Methods: Relevant preclinical studies were searched on PubMed, EMBASE, and Web of Science.

Small Extracellular Vesicle-Associated MiRNAs in Polarized Retinal Pigmented Epithelium.

Purpose: Oxidative stress in the retinal pigmented epithelium (RPE) has been implicated in age-related macular degeneration by impacting endocytic trafficking, including the formation, content, and secretion of extracellular vesicles (EVs). Using our model of polarized primary porcine RPE (pRPE) cells under chronic subtoxic oxidative stress, we tested the hypothesis that RPE miRNAs packaged into EVs are secreted in a polarized manner and contribute to maintaining RPE homeostasis.

Methods: Small EVs (sEVs) enriched for exosomes were isolated from apical and basal conditioned media from pRPE cells grown for up to four weeks with or without low concentrations of hydrogen peroxide using two sEV isolation methods, leading to eight experimental groups.

A randomized, placebo-controlled first-in-human study of oral TQS-168 in healthy volunteers: Assessment of safety, tolerability, pharmacokinetics, pharmacodynamics, and food effect.

TQS-168, a first-in-class small-molecule inducer of peroxisome proliferator-activated receptor gamma coactivator 1-alpha gene expression, is in development for the treatment of amyotrophic lateral sclerosis. A single-ascending-dose (SAD) and multiple-ascending-dose (MAD) study of TQS-168 was carried out in healthy male subjects to investigate safety, tolerability, pharmacokinetics (PK), food effect, and preliminary pharmacodynamic effects (PD). Since solubility enhancement could be beneficial, assessment of three formulations was incorporated into the study using an integrated rapid manufacturing and clinical testing approach.

The polysaccharide from purple sweet potato (Ipomoea batatas (L.) Lam) alleviates lipopolysaccharide-induced acute lung injury in mice via the VIP/cAMP/PKA/AQPs signaling pathway.

Background: The polysaccharide (PSP) from purple sweet potato has great potential for regulating apoptosis, but its regulatory role in acute lung injury (ALI) is unknown.

Methods: The objective of this study was to investigate the protective effect of PSP on lipopolysaccharide (LPS)-induced ALI in mice and lung epithelial A549 cells and its mechanism. Moreover, subacute toxicity evaluation of PSP was carried out on ICR mice.

Short- and mid-term outcomes of the aortic root repair versus root replacement in acute type A aortic dissection.

Background: In patients with acute acute type A aortic dissection (ATAAD) requiring emergency surgery, the use of aortic root repair or replacement remains a topic of controversy. The purpose of this study was to evaluate the early and mid-term clinical outcomes after aortic root repair or replacement, and to provide a theoretical basis for such patients.

Methods: The study included 442 consecutive patients with ATAAD who underwent aortic root repair [n=227, repair group (RG)] or the Bentall procedure [n=215, Bentall group (BG)] at our hospital between December 2018 and December 2021.

Customizing Bonding Affinity with Multi-Intermediates via Interfacial Electron Capture to Boost Hydrogen Evolution in Alkaline Water Electrolysis.

Developing efficient and earth-abundant alkaline HER electrocatalysts is pivotal for sustainable energy, but co-regulating its intricate multi-step process, encompassing water dissociation, OH desorption, and hydrogen generation, is still a great challenge. Herein, we tackle these obstacles by fabricating a vertically integrated electrode featuring a nanosheet array with prominent dual-nitride metallic heterostructures characterized by impeccable lattice matching and excellent conductivity, functioning as a multi-purpose catalyst to fine-tune the bonding affinity with alkaline HER intermediates. Detailed structural characterization and theoretical calculation elucidate that charge redistribution at the heterointerface reduces the O p-W d and H s-W d interactions vs.

Extract of Nanhaia speciosa J. Compton & Schrire alleviates LPS-induced acute lung injury via the NF-κB/Nrf2/AQPs pathway.

Ethnopharmacological Relevance: Nanhaia speciosas J. Compton & Schrire (the name Nanhaia speciosas J. Compton & Schrire has been accepted by the World Checklist of Vascular Plants https://www.

Oral administration of Lactobacillus plantarum expressing aCD11c modulates cellular immunity alleviating inflammatory injury due to Klebsiella pneumoniae infection.

Background: Klebsiella pneumoniae (KP), responsible for acute lung injury (ALI) and inflammation of the gastrointestinal tract, is a zoonotic pathogen that poses a threat to livestock farming worldwide. Nevertheless, there is currently no validated vaccine to prevent KP infection. The development of mucosal vaccines against KP using Lactobacillus plantarum (L.

Wedelolactone inhibits ferroptosis and alleviates hyperoxia-induced acute lung injury via the Nrf2/HO-1 signaling pathway.

Hyperoxia-induced acute lung injury (HALI) is a complication of oxygen therapy. Ferroptosis is a vital factor in HALI. This paper was anticipated to investigate the underlying mechanism of wedelolactone (WED) on ferroptosis in HALI.

A Light-Driven In Vitro Enzymatic Biosystem for the Synthesis of α-Farnesene from Methanol.

Terpenoids of substantial industrial interest are mainly obtained through direct extraction from plant sources. Recently, microbial cell factories or in vitro enzymatic biosystems have emerged as promising alternatives for terpenoid production. Here, we report a route for the synthesis of α-farnesene based on an in vitro enzyme cascade reaction using methanol as an inexpensive and renewable C1 substrate.

Cyanidin-3-O-glucoside attenuates LPS-induced endometritis in mice via regulating PPARγ activation.

Endometritis is a common disease that endangers human and animal health. Cyanidin-3-O-glucoside (C3G), a kind of anthocyanin, exists in a variety of plants and shows many biological activities. Here, we investigated the effect and mechanism of C3G on LPS-induced endometritis in mice.