Retraction note to: Shugan Jieyu capsule effects on peripheral blood micro-124, micro-132, and brain-derived neurotrophic factor in patients with mild to moderate depression.

[This retracts the article on p. 1354 in vol. 14, PMID: 39319232.

Influence of YO Nano-Dispersoids on the Characteristics of AlCoCrFeNi-Reinforced Tungsten Alloys via Mechanical Alloying and Low-Temperature Sintering.

This study investigates the effects of nano-oxide dispersoids on microstructural evolution, phase formation, and mechanical properties of W-Mo-Ti alloys reinforced with AlCoCrFeNi during mechanical alloying. An EBSD/EDS analysis confirmed the formation of different phases, including the tungsten matrix, FCC reinforcement phase, AlO, and (Al,Cr) oxide. YO particles played a crucial role in refining the microstructure, promoting a uniform dispersion of the reinforcement phase and oxide particles in the tungsten model alloys.

Tat-Beclin-1 Peptide Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease by Enhancing Hepatic Autophagy.

Autophagy plays a crucial role in hepatic lipid metabolism, making it a key therapeutic target for addressing metabolic dysfunction-associated steatotic liver disease (MASLD). This study evaluates the efficacy of the Tat-Beclin-1 (TB-1) peptide, a specific autophagy inducer, in mitigating MASLD. Initially, we examined the impact of the TB-1 peptide on autophagic activity and intracellular lipid metabolism in HepG2 cells treated with oleic acid, using a Tat scrambled (TS) control peptide for comparison.

Identification of a 5-gene signature panel for the prediction of prostate cancer progression.

Background: Despite nearly 100% 5-year survival for localised prostate cancer, the survival rate for metastatic prostate cancer significantly declines to 32%. Thus, it is crucial to identify molecular indicators that reflect the progression from localised disease to metastatic prostate cancer.

Methods: To search for molecular indicators associated with prostate cancer metastasis, we performed proteomic analysis of rapid autopsy tissue samples from metastatic prostate cancer (N = 8) and localised prostate cancer (N = 2).

Serum metabolomics analysis of malnutrition in patients with gastric cancer: a cross sectional study.

Background: Although malnutrition is common in cancer patients, its molecular mechanisms has not been fully clarified. This study aims to identify significantly differential metabolites, match the corresponding metabolic pathways, and develop a predictive model of malnutrition in patients with gastric cancer.

Methods: In this cross-sectional study, we applied non-targeted metabolomics using liquid chromatography-mass spectrometry to explore the serum fingerprinting of malnutrition in patients with gastric cancer.

Shugan Jieyu capsule effects on peripheral blood micro-124, micro-132, and brain-derived neurotrophic factor in patients with mild to moderate depression.

Background: To assess the effectiveness of Shugan Jieyu capsules on peripheral blood miR-124, miR-132, and brain-derived neurotrophic factor (BDNF) levels in patients with mild to moderate depression following coronary artery intervention [percutaneous coronary intervention (PCI)] for coronary heart disease.

Aim: To evaluate the therapeutic efficacy of Shugan Jieyu capsules and their effects on the peripheral blood levels of miR-124, miR-132, and BDNF in patients with mild to moderate depression following PCI for coronary heart disease.

Methods: Patients with mild-to-moderate depression of the liver-qi stagnation type after PCI for coronary heart disease at the 305 Hospital of the People's Liberation Army were enrolled from June 2022 to November 2023 and randomly assigned to two groups: Experimental (treated with Shugan Jieyu capsules) and control (treated with escitalopram oxalate tablets).

Structural and dynamic changes in P-Rex1 upon activation by PIP and inhibition by IP.

PIP-dependent Rac exchanger 1 (P-Rex1) is abundantly expressed in neutrophils and plays central roles in chemotaxis and cancer metastasis by serving as a guanine-nucleotide exchange factor (GEF) for Rac. The enzyme is synergistically activated by PIP and heterotrimeric Gβγ subunits, but mechanistic details remain poorly understood. While investigating the regulation of P-Rex1 by PIP, we discovered that Ins(1,3,4,5)P (IP) inhibits P-Rex1 activity and induces large decreases in backbone dynamics in diverse regions of the protein.

Structure of adenylyl cyclase 5 in complex with Gβγ offers insights into ADCY5-related dyskinesia.

The nine different membrane-anchored adenylyl cyclase isoforms (AC1-9) in mammals are stimulated by the heterotrimeric G protein, Gα, but their response to Gβγ regulation is isoform specific. In the present study, we report cryo-electron microscope structures of ligand-free AC5 in complex with Gβγ and a dimeric form of AC5 that could be involved in its regulation. Gβγ binds to a coiled-coil domain that links the AC transmembrane region to its catalytic core as well as to a region (C) that is known to be a hub for isoform-specific regulation.

Molecular basis for Gβγ-mediated activation of phosphoinositide 3-kinase γ.

The conversion of phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-triphosphate by phosphoinositide 3-kinase γ (PI3Kγ) is critical for neutrophil chemotaxis and cancer metastasis. PI3Kγ is activated by Gβγ heterodimers released from G protein-coupled receptors responding to extracellular signals. Here we determined cryo-electron microscopy structures of Sus scrofa PI3Kγ-human Gβγ complexes in the presence of substrates/analogs, revealing two Gβγ binding sites: one on the p110γ helical domain and another on the p101 C-terminal domain.

Ex vivo drug testing of patient-derived lung organoids to predict treatment responses for personalized medicine.

Lung cancer is the leading cause of global cancer-related mortality resulting in ∼ 1.8 million deaths annually. Systemic, molecular targeted, and immune therapies have provided significant improvements of survival outcomes for patients.

Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination.

While macrophage phagocytosis is an immune defense mechanism against invading cellular organisms, cancer cells expressing the CD47 ligand send forward signals to repel this engulfment. Here we report that the reverse signaling using CD47 as a receptor additionally enhances a pro-survival function of prostate cancer cells under phagocytic attack. Although low CD47-expressing cancer cells still allow phagocytosis, the reverse signaling delays the process, leading to incomplete digestion of the entrapped cells and subsequent tumor hybrid cell (THC) formation.

Effects of Alloying Elements and Mechanical Alloying on Characteristics of WVTaTiCr Refractory High-Entropy Alloys.

Refractory high-entropy alloys (RHEAs) are among the promising candidates for the design of structural materials in advanced nuclear energy systems. The effects of Cr, V, Ta, and Ti elements and ball milling on the microstructural evolution and mechanical properties of model RHEAs were investigated. The results show that W-rich BCC1 and Ta-rich BCC2 solid solution phases were generated after a long milling duration.

Isoform Specific Regulation of Adenylyl Cyclase 5 by Gβγ.

The nine different membrane-anchored adenylyl cyclase isoforms (AC1-9) in mammals are stimulated by the heterotrimeric G protein Gα, but their response to Gβγ regulation is isoform-specific. For example, AC5 is conditionally activated by Gβγ. Here, we report cryo-EM structures of ligand-free AC5 in complex with Gβγ and of a dimeric form of AC5 that could be involved in its regulation.

Molecular basis for Gβγ-mediated activation of phosphoinositide 3-kinase γ.

The conversion of PIP2 to PIP3 by phosphoinositide 3-kinase γ (PI3Kγ) is a critical step in neutrophil chemotaxis and is essential for metastasis in many types of cancer. PI3Kγ is activated via directed interaction with Gβγ heterodimers released from cell-surface G protein-coupled receptors (GPCRs) responding to extracellular signals. To resolve how Gβγ activates PI3Kγ, we determined cryo-EM reconstructions of PI3Kγ-Gβγ complexes in the presence of various substrates/analogs, revealing two distinct Gβγ binding sites, one on the p110γ helical domain and one on the C-terminal domain of the p101 subunit.

N-Formimidoylation/-iminoacetylation modification in aminoglycosides requires FAD-dependent and ligand-protein NOS bridge dual chemistry.

Oxidized cysteine residues are highly reactive and can form functional covalent conjugates, of which the allosteric redox switch formed by the lysine-cysteine NOS bridge is an example. Here, we report a noncanonical FAD-dependent enzyme Orf1 that adds a glycine-derived N-formimidoyl group to glycinothricin to form the antibiotic BD-12. X-ray crystallography was used to investigate this complex enzymatic process, which showed Orf1 has two substrate-binding sites that sit 13.

KLRF1, a novel marker of CD56 NK cells, predicts improved survival for patients with locally advanced bladder cancer.

Background: Bladder tumor-infiltrating CD56 NK cells are more tumor cytotoxic than their CD56 counterparts. Identification of NK cell subsets is labor-intensive and has limited utility in the clinical setting. Here, we sought to identify a surrogate marker of bladder CD56 NK cells and to test its prognostic significance.

Autophagy Dysregulation in Metabolic Associated Fatty Liver Disease: A New Therapeutic Target.

Metabolic associated fatty liver disease (MAFLD) is one of the most common causes of chronic liver disease worldwide. To date, there is no FDA-approved treatment, so there is an urgent need to determine its pathophysiology and underlying molecular mechanisms. Autophagy is a lysosomal degradation pathway that removes damaged organelles and misfolded proteins after cell injury through endoplasmic reticulum stress or starvation, which inhibits apoptosis and promotes cell survival.

Pathogenic effects of Desulfovibrio in the gut on fatty liver in diet-induced obese mice and children with obesity.

Background: Although we know the key role of gut dysbiosis in nonalcoholic fatty liver disease (NAFLD), it remains unclear what microbe(s) are responsible. This study aims to identify the microbes that cause NAFLD.

Methods: C57BL/6JNarl male mice fed a high-fat diet (HFD) were orally administered Lactobacillus reuteri (L.

Cryo-EM structures of alphavirus conformational intermediates in low pH-triggered prefusion states.

Alphaviruses can cause severe human arthritis and encephalitis. During virus infection, structural changes of viral glycoproteins in the acidified endosome trigger virus-host membrane fusion for delivery of the capsid core and RNA genome into the cytosol to initiate virus translation and replication. However, mechanisms by which E1 and E2 glycoproteins rearrange in this process remain unknown.

Structural/functional studies of Trio provide insights into its configuration and show that conserved linker elements enhance its activity for Rac1.

Trio is a large and highly conserved metazoan signaling scaffold that contains two Dbl family guanine nucleotide exchange factor (GEF) modules, TrioN and TrioC, selective for Rac and RhoA GTPases, respectively. The GEF activities of TrioN and TrioC are implicated in several cancers, especially uveal melanoma. However, little is known about how these modules operate in the context of larger fragments of Trio.

Utility and Safety of Perampanel in Pediatric FIRES and Other Drug-Resistant Epilepsies.

Perampanel is a novel antiepileptic drug, which antagonises AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) glutamate receptor. We describe perampanel as an adjunctive treatment for FIRES (febrile infection-related epilepsy syndrome) and other drug-resistant epilepsies. A single-centre, observational, retrospective study involving 20 pediatric patients was conducted.

Unique Severe HyperEkplexia-Like Apneic Events (SHELAE) Improved by High-Dose Piracetam.

Breath-holding spells are common non-epileptic events with onset between 6 months and 18 months of age that are usually triggered by minor painful events or strong emotions. Symptomatic treatments for breath-holding spells include iron supplementation, glycopyrrolate and piracetam. Hyperekplexia is a rare non-epileptic disorder characterized by generalized hypertonia and exaggerated startle.