Geostress-Adaptive Charge Structure Design and Field Validation for Machinery Room Excavation.

The application of blasting in modern engineering construction is prized for its speed, efficiency, and cost-effectiveness. However, the resultant vibrations can have significant adverse effects on surrounding buildings and residents. The challenge of optimizing blasting procedures to satisfy excavation needs while minimizing vibration impacts is a critical concern in blasting excavation.

[miR-2110 Affects the Biological Behaviors of Lung Adenocarcinoma by Regulating CDT1].

Objective: To investigate the effect of miR-2110 on the biological behaviors, such as cell proliferation, apoptosis, and metastasis, of lung adenocarcinoma (LUAD) cells by means of cell and animal experiments.

Methods: Bioinformatics websites, including ENCORI, TargetScan, miRTarBase, and Tarbase, were used to analyze the changes in the expression of miR-2110 in LUAD samples and to predict miR-2110 target. LUAD tissue samples and cells were collected and the changes in the expression of miR-2110 were verified through PCR technology.

Tyrosine hydroxylase-positive neurons in the rostral ventrolateral medulla mediate sympathetic activation in sepsis.

Aim: Sepsis results in high mortality and is associated with organ dysfunction caused by infection. The present study aimed to elucidate whether early-stage sympathetic activation is associated with the prognosis of sepsis and its possible mechanisms.

Methods: Patients with sepsis and healthy controls were included.

Electroacupuncture at different intensities inhibits nociceptive discharges of wide dynamic range neurons in spinal dorsal horn of rats.

Objectives: To observe the effect of electroacupuncture (EA) at different intensities on nociceptive discharges of wide dynamic range (WDR) neurons in the spinal dorsal horns (DHs) of rats, so as to explore its regulatory characteristics on nociceptive signals at the spinal level.

Methods: A total of 25 male SD rats were used in the present study. A microelectrode array was used to record the discharge activity of WDR neurons in the lumbar spinal DHs of normal rats.

Trimethylamine-N-oxide aggravated the sympathetic excitation in D-galactose induced aging rats by down-regulating P2Y12 receptor in microglia.

This study aimed to determine whether trimethylamine N-oxide (TMAO) was involved in sympathetic activation in aging and the underlying mechanisms. Our hypothesis is TMAO reduces P2Y12 receptor (P2Y12R) and induces microglia-mediated inflammation in the paraventricular nucleus (PVN), then leading to sympathetic activation in aging. This study involved 18 young adults and 16 old adults.

AURKA knockdown inhibits esophageal squamous cell carcinoma progression through ferroptosis.

Aurora kinase A, as a pro-carcinogenic in gastric cancer and glioma kinase, is enhanced in several human tumors. However, it's regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remains unclear. Thus, this study aimed to investigate the expression status, functional roles, and molecular mechanisms of AURKA in ESCC development.

Water-soluble single molecular probe for simultaneous detection of viscosity and hydrazine.

Hydrazine (NH) can cause serious damage to human health, while intracellular viscosity is highly associated with many diseases and cellular dysfunctions. Herein, we report the synthesis of a dual-responsive organic molecule-based fluorescent probe with excellent water solubility being capable of detection of NH and viscosity through dual-fluorescence channels in "turn on" manner for both. Besides sensitive detection of NH in aqueous solution with detection limit of 0.

Hydrogen Sulfide Inhibited Sympathetic Activation in D-Galactose-Induced Aging Rats by Upregulating Klotho and Inhibiting Inflammation in the Paraventricular Nucleus.

The present study aimed to explore the central relationship between cardiovascular conditions and aging. D-galactose (D-gal) was utilized to induce an accelerated aging model and to evaluate the effects of hydrogen sulfide (HS) on aging-related cardiovascular risk factors and mechanisms. Eight-week-old Sprague Dawley rats were given an intraperitoneal injection of 250 mg/kg D-gal every day with or without HS (56 μmol/kg) for 12 weeks.

Dual-responsive ratiometric fluorescent sensor for tetracyclines detection based on europium-decorated copper nanoclusters.

Development of accurate and efficient TCs residue analysis methods is of great significance for the protection of environment, food safety and public health. Herein, a dual-responsive ratiometric fluorescence sensor being capable of simple and sensitive detection of tetracycline (TC) was presented, which was constructed by immobilizing europium ions (Eu) onto the mercaptopropionic acid stabilized copper nanoclusters (MPA-Cu NCs). In the presence of TC, the red fluorescence of Eu was enhanced through antenna effect (AE), while the green fluorescence of MPA-Cu NCs was quenched through internal filter effect (IFE), leading to an obvious fluorescence color evolution from green to red for the probe solution.

Europium-modified carbon nitride nanosheets for smartphone-based fluorescence sensitive recognition of anthrax biomarker dipicolinic acid.

Development of selective and sensitive methods for the detection of 2, 6-dipicolinic acid (DPA), a biomarker produced by bacterial spores, is of great significance for maintaining public health and food safety. Herein, a ratiometric fluorescence strategy using graphene carbon nitride (g-CN) coupled with Eu is designed for the assay of DPA. As the concentration of DPA increases, the emission intensity of g-CN kept constant which acted as a stable internal reference, while the fluorescence of Eu was enhanced obviously due to the antenna effect.

Discovery of the Clinical Candidate MAK683: An EED-Directed, Allosteric, and Selective PRC2 Inhibitor for the Treatment of Advanced Malignancies.

Polycomb Repressive Complex 2 (PRC2) plays an important role in transcriptional regulation during animal development and in cell differentiation, and alteration of PRC2 activity has been associated with cancer. On a molecular level, PRC2 catalyzes methylation of histone H3 lysine 27 (H3K27), resulting in mono-, di-, or trimethylated forms of H3K27, of which the trimethylated form H3K27me3 leads to transcriptional repression of polycomb target genes. Previously, we have shown that binding of the low-molecular-weight compound EED226 to the H3K27me3 binding pocket of the regulatory subunit EED can effectively inhibit PRC2 activity in cells and reduce tumor growth in mouse xenograft models.

Robotic and video-assisted lobectomy/segmentectomy for non-small cell lung cancer have similar perioperative outcomes: a systematic review and meta-analysis.

Background: At present, the clinical conclusion that robotic-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS), which is better for patients with non-small cell lung cancer (NSCLC) is not clear. Therefore, this meta-analysis aimed to compare the perioperative outcomes between RATS and VATS for NSCLC.

Methods: The Population, Interventions, Comparators, Outcomes, and Study design (PICOS) framework was employed to develop the search strategy, and the findings was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

The HNF1A-AS1/miR-92a-3p axis affects the radiosensitivity of non-small cell lung cancer by competitively regulating the JNK pathway.

Background: It has been widely reported that long non-coding RNAs (lncRNAs) could affect the varieties of tumor response to radiotherapy. LncRNA HNF1A-AS1 is transcribed from HNF1A gene cluster's antisense strand. This work focused on the mechanism of how HNF1A-AS1 participated in the radiosensitivity of non-small cell lung cancer (NSCLC).

Clinicopathological and prognostic value of circulating tumor cells in esophageal carcinoma: a meta-analysis.

Background: The associations between circulating tumor cells (CTCs) in peripheral blood and prognosis of patients with esophageal carcinoma (EC) have been investigated by a number of studies, but the results are not consistent. Therefore, this study aimed to explore this controversial subject.

Methods: A literature database search was performed according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement.

Osimertinib for EGFR-mutant lung cancer with central nervous system metastases: a meta-analysis and systematic review.

Background: Osimertinib, a third-generation tyrosine kinase inhibitor (TKI), is the only Food and Drug Administration-approved third-generation epidermal growth factor receptor (EGFR)TKI. Osimertinib is a cancer medicine that interferes with the growth and spread of cancer cells in the body. Osimertinib is used to treat a certain type of non-small cell lung cancer.

Nanostructuring Bridges Semiconductor-Cocatalyst Interfacial Electron Transfer: Realizing Light-Intensity-Independent Energy Utilization and Efficient Sunlight-Driven Photocatalysis.

Despite thermodynamic feasibility, the high activation energy originating from potential barriers and trap states kinetically prevents the interfacial transfer of electrons from semiconductor nanostructures to reduction cocatalysts, resulting in a lowered utilization of photogenerated charge carriers in photocatalysis. Nanostructuring-induced narrowing of potential barriers offers a rational solution to kinetically facilitate interfacial electron transfer by tunneling. Here, inspired by theoretical simulation, we manage to promote the separation of photogenerated charge carriers by coating the semiconductor nanostructures with a homogeneous interlayer.

Light-Intensity-Dependent Semiconductor-Cocatalyst Interfacial Electron Transfer: A Dilemma of Sunlight-Driven Photocatalysis.

In photocatalytic reactions, the interfacial transfer of electrons from semiconductor nanostructures to cocatalysts is the key step that determines the utilization of photogenerated charges and is sensitively influenced by the behaviors of this electronic process. Under weak illumination, photocatalytic reaction rates deviate from linearity to incident light intensity ( = ·, with α → 0.5), because charge recombination predominates interfacial transfer.

Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy.

Overexpression and somatic heterozygous mutations of EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), are associated with several tumor types. EZH2 inhibitor, EPZ-6438 (tazemetostat), demonstrated clinical efficacy in patients with acceptable safety profile as monotherapy. EED, another subunit of PRC2 complex, is essential for its histone methyltransferase activity through direct binding to trimethylated lysine 27 on histone 3 (H3K27Me3).

Discovery and Molecular Basis of a Diverse Set of Polycomb Repressive Complex 2 Inhibitors Recognition by EED.

Polycomb repressive complex 2 (PRC2), a histone H3 lysine 27 methyltransferase, plays a key role in gene regulation and is a known epigenetics drug target for cancer therapy. The WD40 domain-containing protein EED is the regulatory subunit of PRC2. It binds to the tri-methylated lysine 27 of the histone H3 (H3K27me3), and through which stimulates the activity of PRC2 allosterically.

Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator.

A novel series of alkoxyimino derivatives as S1P1 agonists were discovered through de novo design using FTY720 as the chemical starting point. Extensive structure-activity relationship studies led to the discovery of (E)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl)-2-ethylbenzyl)azetidine-3-carboxylic acid (32, BAF312, Siponimod), which has recently completed phase 2 clinical trials in patients with relapsing-remitting multiple sclerosis.

Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation.

Ezh2 (Enhancer of zeste homolog 2) protein is the enzymatic component of the Polycomb repressive complex 2 (PRC2), which represses gene expression by methylating lysine 27 of histone H3 (H3K27) and regulates cell proliferation and differentiation during embryonic development. Recently, hot-spot mutations of Ezh2 were identified in diffused large B-cell lymphomas and follicular lymphomas. To investigate if tumor growth is dependent on the enzymatic activity of Ezh2, we developed a potent and selective small molecule inhibitor, EI1, which inhibits the enzymatic activity of Ezh2 through direct binding to the enzyme and competing with the methyl group donor S-Adenosyl methionine.

Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models.

Neurotrophins and their receptors (TRKs) play key roles in the development of the nervous system and the maintenance of the neural network. Accumulating evidence points to their role in malignant transformations, chemotaxis, metastasis, and survival signaling and may contribute to the pathogenesis of a variety of tumors of both neural and non-neural origin. By screening the GNF kinase collection, a series of novel oxindole inhibitors of TRKs were identified.