pERK transition-induced directional mode switching promotes epithelial tumor cell migration.

Increasing evidence suggests that tumor cells exhibit extreme plasticity in migration modes in order to adapt to microenvironments. However, the underlying mechanism for governing the migration mode switching is still unclear. Here, we revealed that epithelial tumor cells could develop a stable directional mode driven by hyperactivated ERK activity.

Medicinal cannabis oil improves anxiety-like and depressive-like behaviors in CCS mice via the BDNF/TRPC6 signaling pathway.

Background: Post-traumatic stress disorder (PTSD) refers to a chronic impairing psychiatric disorder occurring after exposure to the severe traumatic event. Studies have demonstrated that medicinal cannabis oil plays an important role in neuroprotection, but the mechanism by which it exerts anti-PTSD effects remains unclear.

Methods: The chronic complex stress (CCS) simulating the conditions of long voyage stress for 4 weeks was used to establish the PTSD mice model.

Delayed Reaction of Radiation on the Central Nervous System and Bone System in C57BL/6J Mice.

The aim of this study was to provide a suitable mouse model of radiation-induced delayed reaction and identify potential targets for drug development related to the prevention and treatment of radiation injury. C57BL/6J mice were subjected to singular (109 cGy/min, 5 Gy*1) and fractional (109 cGy/min, 5 Gy*2) total body irradiation. The behavior and activity of mice were assessed 60 days after ionizing radiation (IR) exposure.

Effects of bilateral repetitive transcranial magnetic stimulation on prospective memory in patients with schizophrenia: A double-blind randomized controlled clinical trial.

Aims: To investigate effects of repetitive transcranial magnetic stimulation (rTMS) on the prospective memory (PM) in patients with schizophrenia (SCZ).

Methods: Fifty of 71 patients completed this double-blind placebo-controlled randomized trial and compared with 18 healthy controls' (HCs) PM outcomes. Bilateral 20 Hz rTMS to the dorsolateral prefrontal cortex at 90% RMT administered 5 weekdays for 4 weeks for a total of 20 treatments.

Network pharmacology analysis of the active ingredients of Corydalis hendersonii Hemsl. and their effects on eliminating neuroinflammation and improving motor functions in MPTP-intoxicated mice.

Ethnopharmacological Relevance: Corydalis hendersonii Hemsl. (CH), is a traditional Tibetan medicine used in highland areas for the treatment of alpine polycythemia, ulcers and various inflammatory diseases. Its antioxidant and anti-inflammatory effects have been demonstrated in experimental mice.

Boosting variant-calling performance with multi-platform sequencing data using Clair3-MP.

Background: With the continuous advances in third-generation sequencing technology and the increasing affordability of next-generation sequencing technology, sequencing data from different sequencing technology platforms is becoming more common. While numerous benchmarking studies have been conducted to compare variant-calling performance across different platforms and approaches, little attention has been paid to the potential of leveraging the strengths of different platforms to optimize overall performance, especially integrating Oxford Nanopore and Illumina sequencing data.

Results: We investigated the impact of multi-platform data on the performance of variant calling through carefully designed experiments with a deep learning-based variant caller named Clair3-MP (Multi-Platform).

Repetitive transcranial magnetic stimulation for psychiatric symptoms in long-term hospitalized veterans with schizophrenia: A randomized double-blind controlled trial.

Unlabelled: Multiple lines of evidence demonstrate that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve clinical outcomes in patients with schizophrenia (SCZ). However, the efficacy of HF-rTMS on psychiatric symptoms remains unknown in veterans with SCZ. This study aimed to investigate whether HF-rTMS was beneficial in alleviating the clinical symptoms in veterans with SCZ.

Ginsenoside Rb1 Ameliorated Bavachin-Induced Renal Fibrosis via Suppressing Bip/eIF2α/CHOP Signaling-Mediated EMT.

The nephrotoxicity of , an effective traditional Chinese medicine for vitiligo treatment, has been reported. As one of the main toxic components in , bavachin (BV) was considered to be related to -caused adverse outcomes, but the direct evidence and molecular mechanism underlying BV-induced nephrotoxicity are not well elucidated. Therefore, this study was designed to confirm whether BV would cause toxic effects on the kidney and explore the possible mode of action.

A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants.

BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 μg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 μg of UB-612 approximately 7 to 9 months after the second dose.

Detecting structural variations with precise breakpoints using low-depth WGS data from a single oxford nanopore MinION flowcell.

Structural variation (SV) is a major cause of genetic disorders. In this paper, we show that low-depth (specifically, 4×) whole-genome sequencing using a single Oxford Nanopore MinION flow cell suffices to support sensitive detection of SV, particularly pathogenic SV for supporting clinical diagnosis. When using 4× ONT WGS data, existing SV calling software often fails to detect pathogenic SV, especially in the form of long deletion, terminal deletion, duplication, and unbalanced translocation.

Targeting Mitochondrial Metabolism and RNA Polymerase POLRMT to Overcome Multidrug Resistance in Cancer.

Clinically, the prognosis of tumor therapy is fundamentally affected by multidrug resistance (MDR), which is primarily a result of enhanced drug efflux mediated by channels in the membrane that reduce drug accumulation in tumor cells. How to restore the sensitivity of tumor cells to chemotherapy is an ongoing and pressing clinical issue. There is a prevailing view that tumor cells turn to glycolysis for energy supply due to hypoxia.

Enterococcus faecalis contributes to hypertension and renal injury in Sprague-Dawley rats by disturbing lipid metabolism.

Objective: Increasing studies have demonstrated that gut microbiota play vital roles in the development of hypertension. However, the underlying mechanism is not fully understood.

Methods: The relative abundance of Enterococcus faecalis was determined in the faecal samples of angiotensin II or deoxycorticosterone acetate/salt-induced hypertensive rats.

LARP7 Protects Against Heart Failure by Enhancing Mitochondrial Biogenesis.

Background: Heart failure (HF) is among the leading causes of morbidity and mortality, and its prevalence continues to rise. LARP7 (La ribonucleoprotein domain family member 7) is a master regulator that governs the DNA damage response and RNAPII (RNA polymerase II) pausing pathway, but its role in HF pathogenesis is incompletely understood.

Methods: We assessed LARP7 expression in human HF and in nonhuman primate and mouse HF models.

L ARP7 Is a BRCA1 Ubiquitinase Substrate and Regulates Genome Stability and Tumorigenesis.

Attenuated DNA repair leads to genomic instability and tumorigenesis. BRCA1/BARD1 are the best-known tumor suppressors that promote homology recombination (HR) and arrest cell cycle. However, it remains ambiguous whether and how their E3 ligase activity regulates HR.

Gut dysbiosis contributes to high fructose-induced salt-sensitive hypertension in Sprague-Dawley rats.

Objectives: Although it is known that high fructose intake causes salt-sensitive hypertension, the underlying mechanism remains unclear. The aim of this study was to determine whether chronic intake of high fructose coupled with salt (HFS) might alter the structure of the gut microbiota, which contributes to elevated blood pressure.

Methods: For 8 wk, Sprague-Dawley rats were given 20% fructose in drinking water and 4% sodium chloride in their diet to induce hypertension.

Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis.

The bivalent domain (BD) at promoter region is an unique epigenetic feature poised for activation or repression during cell differentiation in embryonic stem cell. However, the function of BDs in already differentiated cells remains exclusive. By profiling the epigenetic landscape of endothelial cells during VEGFA (vascular endothelial growth factor A) stimulation, we discovered that BDs are widespread in endothelial cells and preferentially marked genes responsive to VEGFA.

A dynamic and integrated epigenetic program at distal regions orchestrates transcriptional responses to VEGFA.

Cell behaviors are dictated by epigenetic and transcriptional programs. Little is known about how extracellular stimuli modulate these programs to reshape gene expression and control cell behavioral responses. Here, we interrogated the epigenetic and transcriptional response of endothelial cells to VEGFA treatment and found rapid chromatin changes that mediate broad transcriptomic alterations.

A novel signal amplification strategy of an electrochemical aptasensor for kanamycin, based on thionine functionalized graphene and hierarchical nanoporous PtCu.

An ultrasensitive electrochemical aptasensor for the quantitative detection of kanamycin antibiotic was fabricated based on a novel signal amplification strategy. This aptasensor was developed using thionine functionalized graphene (GR-TH) and hierarchical nanoporous (HNP) PtCu alloy as biosensing substrates for the first time. HNP-PtCu alloy with controllable bimodal ligament/pore distributions was successfully prepared by two-step dealloying of a well-designed PtCuAl precursor alloy combined with an annealing operation.