Polarization smoothing based on full Poincaré beams modulated by stress-engineered optics.

In laser-driven inertial confinement fusion (ICF) facilities, nonuniform laser irradiation can cause significant challenges, such as hydrodynamics instability and laser plasma instability, which hinder the success of fusion. This article presents a new idea for improving the uniformity of far-field laser irradiation through a method of single-beam polarization smoothing. The method involves modulating full Poincaré beams using stress-engineered optics made from fused silica. We designed a stress birefringence system and conducted opto-mechanical modeling and analysis on it. The article elaborates on the mechanism and principles of generating large-aperture full Poincaré beams by stress birefringence, as well as the mechanism of polarization smoothing by full Poincaré beams. Near-field polarization measurements were conducted to verify these mechanisms, and the effectiveness of this method in improving the uniformity of laser irradiation in the target area was evaluated through far-field optical tests.

Performance of the neural network-based prediction model in closed-loop adaptive optics.

Adaptive optics (AO) technology is an effective means to compensate for atmospheric turbulence, but the inherent delay error of an AO system will cause the compensation phase of the deformable mirror (DM) to lag behind the actual distortion, which limits the correction performance of the AO technology. Therefore, the feed-forward prediction of atmospheric turbulence has important research value and application significance to offset the inherent time delay and improve the correction bandwidth of the AO system. However, most prediction algorithms are limited to an open-loop system, and the deployment and the application in the actual AO system are rarely reported, so its correction performance improvement has not been verified in practice. We report, to our knowledge, the first successful test of a deep learning-based spatiotemporal prediction model in an actual 3 km laser atmospheric transport AO system and compare it with the traditional closed-loop control methods, demonstrating that the AO system with the prediction model has higher correction performance.

Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of digestive system tumor related death in the world. Unfortunately, effective chemopreventive agent is lack for patients with ESCC in clinical practice, which leads to the extremely high mortality rate. METHODS: A library of prescribed drugs was screened for finding critical anti-tumor properties in ESCC cells. The phosphoproteomics, kinase array, pulldown assay and drug affinity responsive target stabilization assay (DARTS) were applied to explore mechanisms and searched for synergistic targets. Established models of PDX in mice were used to determine the therapeutic effect of domperidone. RESULTS: After screening a library of prescribed drugs, we discovered that domperidone has anti-tumor properties. Domperidone, acting as a gastroprokinetic agent, has been widely used in clinic for gastrointestinal motility disorders. Despite limited research, there are indications that domperidone may have anti-tumor properties. In this study, we determined that domperidone significantly inhibited ESCC proliferation in vitro and in vivo. We employed phosphoproteomics to reveal p-ERK, and p-SMAD3 down-regulation upon domperidone treatment. Then, the results of kinase assay and pulldown assay further validated that domperidone directly combined with MEK1/2 and CDK4, leading to the inhibition of their kinase activity. Furthermore, our results revealed that MEK/ERK and CDK4/SMAD3 signal pathway were major pathways in domperidone against ESCC. CONCLUSION: Collectively, these findings suggest that domperidone serves as an effective "multi-target" inhibitor of MEK1/2 and CDK4, offering potential benefits for the chemoprevention of ESCC.

Crystalline-Amorphous Heterophase PdMoCrW Tetrametallene: Highly Efficient Oxygen Reduction Electrocatalysts for a Long-Term Zn-Air Battery.

Metallenes have received sustained attention owing to their unique microstructure characteristics and compelling catalytic applications, but the synthesis of multielement crystalline-amorphous metallenes remains a formidable challenge. Herein, we report a one-step wet chemical reduction method to synthesize composition-tunable crystalline-amorphous heterophase PdMoCrW tetrametallene. As-synthesized PdMoCrW tetrametallene is composed of approximately six to seven atomic layers and has flexible crimpiness, a crystalline-amorphous heterophase structure, and high-valence metal species. Time-dependent experiments show that PdMoCrW tetrametallene follows a three-step growth mechanism that includes nucleation, lateral growth, and atom diffusion, respectively. The novel ultrathin structure, optimized Pd electronic structure, and hydrophilic surface together greatly promote the activity and stability of PdMoCrW tetrametallene in the alkaline oxygen reduction reaction. Pd75.9Mo9.4Cr8.9W5.8/C exhibits excellent mass and specific activities of 2.81 A mgPd-1 and 4.05 mA cm-2, which are 20.07/14.46 and 23.42/16.20 times higher than those of commercial Pt/C and Pd/C, respectively. Furthermore, a Zn-air battery assembled using Pd75.9Mo9.4Cr8.9W5.8/C as a cathode catalyst achieves a peak power density of 156 mW cm-2 and an ultralong durability of 329 h. This study reports an effective strategy for constructing crystalline-amorphous quaternary metallenes to advance non-Pt electrocatalysts toward oxygen reduction reaction (ORR) performance and for a Zn-air battery.

Long-term efficacy of microwave ablation for multifocal papillary thyroid microcarcinoma: a 5-year follow-up study.

OBJECTIVES: Microwave ablation (MWA) has achieved excellent long-term efficacy in treating unifocal papillary thyroid microcarcinoma (UPTMC). The therapeutic effect of this treatment on multifocal papillary thyroid microcarcinoma (MPTMC) is unknown. Therefore, we evaluated the long-term efficacy of MWA for low-risk MPTMC and to provide evidence-based medicine for the revision of clinical guidelines. METHODS: This study included 66 MPTMC patients with a total of 158 lesions, all of whom received MWA. We collected and retrospectively analyzed the patients' follow-up data before MWA, at 1, 3, 6, and 12 months posttreatment and every 6 months thereafter until 5 years posttreatment. We evaluated the MWA complication rate, technical success rate (TSR), lesion volume reduction rate (VRR), and complete disappearance rate (CDR) during follow-up and in those patients with tumor progression and delayed surgery. RESULTS: After 60 months of follow-up, all 158 lesions disappeared in 66 patients, and the volume was reduced from 43.82 mm3 to 0.00 mm3. The TSR and VRR were both 100%. The CDRs at 1 year, 2 years, and 3 years were 57.59%, 93.67%, and 100%, respectively. The complication rate was 3.03% (2/66), and the incidence of tumor progression was 3.03% (2/66), including one new intrathyroidal lesion and one cervical lymph node metastasis (LNM). These lesions were retreated with MWA, and the lesions disappeared during the follow-up period. CONCLUSIONS: Ultrasound-guided MWA for low-risk MPTMC is safe and effective and may serve as an alternative option for patients who refuse surgery or active surveillance (AS). CLINICAL RELEVANCE STATEMENT: This study concludes that ultrasound-guided microwave ablation for low-risk multifocal papillary thyroid microcarcinoma is safe and effective and may serve as an alternative option for patients who refuse surgery or active surveillance. KEY POINTS: • Ultrasound-guided microwave ablation for low-risk multifocal papillary thyroid microcarcinoma is safe and effective. • During 5 years of follow-up, multifocal papillary thyroid microcarcinoma patients treated with microwave ablation had a favorable prognosis. • To provide evidence-based medicine for the revision of clinical guidelines.

The clinical trajectory of peripheral blood immune cell subsets, T-cell activation, and cytokines in septic patients.

OBJECTIVE AND DESIGN: Changes in the immune status of patients with sepsis may have a major impact on their prognosis. Our research focused on changes in various immune cell subsets and T-cell activation during the progression of sepsis. METHODS AND SUBJECTS: We collected data from 188 sepsis patients at the First Affiliated Hospital of Zhejiang University School of Medicine. The main focus was on the patient's immunocyte subset typing, T-cell activation/Treg cell analysis, and cytokine assay, which can indicate the immune status of the patient. RESULTS: The study found that the number of CD4+ T cells, CD8+ T cells, NK cells, and B cells decreased early in the disease, and the decrease in CD4+ and CD8+ T cells was more pronounced in the death group. T lymphocyte activation was inhibited, and the number of Treg cells increased as the disease progressed. T lymphocyte inhibition was more significant in the death group, and the increase in IL-10 was more significant in the death group. Finally, we used patients' baseline conditions and immunological detection indicators for modeling and found that IL-10, CD4+ Treg cells, CD3+HLA-DR+ T cells, and CD3+CD69+ T cells could predict patients' prognosis well. CONCLUSION: Our study found that immunosuppression occurs in patients early in sepsis. Early monitoring of the patient's immune status may provide a timely warning of the disease.

Mesenchymal stem cell-based therapy for paraquat-induced lung injury.

Paraquat poisoning results in significant pulmonary damage, but current treatments are only minimally effective in repairing the injured lung tissues. Recent research has highlighted the promise of using stem cell therapy, namely mesenchymal stem cells, as a new method for treating paraquat toxicity. These cells have shown effectiveness in decreasing inflammation, apoptosis, and fibrosis in the mice lungs subjected to paraquat. The therapeutic implications of mesenchymal stem cells are believed to arise from their release of bioactive proteins and their capacity to regulate inflammatory responses. However, additional clinical study is required to validate these therapies' efficacy. This review thoroughly explores the pathophysiology of paraquat poisoning and the properties of mesenchymal stem cells. Additionally, it critically assesses the long-term safety and effectiveness of mesenchymal stem cell therapies, which is crucial for developing more dependable and effective treatment protocols. In summary, although mesenchymal stem cells offer promising prospects for treating lung injuries, more investigations are required to optimize their therapeutic promise and ensure their safe clinical application in the context of paraquat poisoning.

HIV infection increases the risk of inflammatory bowel disease: a systematic review and meta-analysis.

OBJECTIVE: In order to synthesize available results regarding human immunodeficiency virus (HIV) infection and inflammatory bowel disease (IBD), we conducted a systematic review and meta-analysis to provide quantitative estimates of associated risk. METHODS: A systematic search of four scientific databases, PubMed, the Cochrane Library, EMBASE, and Scopus, was performed. The overall odds ratio (OR) with the corresponding 95% CI was calculated via a random effects model. Sensitivity analyses and tests for publication bias were then performed. RESULTS: Of the 3046 articles retrieved, seven studies with a cumulative sample size greater than 57,000,000 were included in our analysis. A subsequent meta-analysis based on a random effects model (heterogeneity test, I2 = 99.9) revealed an association between HIV infection and IBD: OR = 2.68 (95% CI: 1.17, 6.13). The funnel plot of this meta-analysis was asymmetric (Egger's test: P = 0.01), and significant publication bias was found. Sensitivity analysis of the 3 dimensions revealed that the results of this meta-analysis were relatively stable. CONCLUSIONS: A significant correlation may exist between HIV infection and intestinal disease, and more large-scale studies are needed to draw firm conclusions. It is recommended that HIV patients be screened for intestinal diseases.

Mid-to-late stage diquat accumulation in the central nervous system: A severe case of oral poisoning.

A 54-year-old woman in good health was admitted to our hospital with diquat poisoning. The patient drank an unknown dose of diquat, and acute kidney injury developed early. However, there were no obvious pulmonary abnormalities and no signs of central nervous system toxicity in the early stage. The woman underwent active treatment, which resulted in a significant decrease in blood diquat levels, but her lung condition progressively worsened and neurological symptoms developed. Fortunately, the patient survived after intensive hemoperfusion combined with continuous renal replacement therapy (CRRT), intracranial pressure reduction, and anti-infective treatment. This case report highlights the importance of being aware of the development of delayed pulmonary symptoms and neurologic complications when caring for patients poisoned with diquat, even in those with low diquat blood concentrations. Interestingly, we also detected the concentration of diquat in the cerebrospinal fluid (CSF) of patients with diquat poisoning, and found that the rate of decrease of diquat concentration in the CSF was considerably slower than that in the blood.Notably, a specific correlation was observed between the concentration of diquat in the CSF, rather than in the blood, and both the intracranial pressure (ICP) and the severity of cerebral edema in this patient.

Structural basis of AlpA-dependent transcription antitermination.

AlpA positively regulates a programmed cell death pathway linked to the virulence of Pseudomonas aeruginosa by recognizing an AlpA binding element within the promoter, then binding RNA polymerase directly and allowing it to bypass an intrinsic terminator positioned downstream. Here, we report the single-particle cryo-electron microscopy structures of both an AlpA-loading complex and an AlpA-loaded complex. These structures indicate that the C-terminal helix-turn-helix motif of AlpA binds to the AlpA binding element and that the N-terminal segment of AlpA forms a narrow ring inside the RNA exit channel. AlpA was also revealed to render RNAP resistant to termination signals by prohibiting RNA hairpin formation in the RNA exit channel. Structural analysis predicted that AlpA, 21Q, λQ and 82Q share the same mechanism of transcription antitermination.

Early Intraventricular Antibiotic Therapy Improved In-Hospital-Mortality in Neurocritical Patients with Multidrug-Resistant Bacterial Nosocomial Meningitis and Ventriculitis.

BACKGROUND: Hospital-acquired multidrug-resistant (MDR) bacterial meningitis and/or ventriculitis (MEN) is a severe condition associated with high mortality. The risk factors related to in-hospital mortality of patients with MDR bacterial MEN are unknown. We aimed to examine factors related to in-hospital mortality and evaluate their prognostic value in patients with MDR bacterial MEN treated in the neurointensive care unit. METHODS: This was a single-center retrospective cohort study of critically ill neurosurgical patients with MDR bacterial MEN admitted to our hospital between January 2003 and March 2021. Data on demographics, admission variables, treatment, time to start of intraventricular (IVT) therapy, and in-hospital mortality were analyzed. Both univariate and multivariable analyses were performed to identify determinants of in-hospital mortality. RESULTS: All 142 included patients received systemic antibiotic therapy, and 102 of them received concomitant IVT treatment. The median time to start of IVT treatment was 2 days (interquartile range 1-5 days). The time to start of IVT treatment had an effect on in-hospital mortality (hazard ratio 1.17; 95% confidence interval 1.02-1.34; adjusted p = 0.030). The cutoff time to initiate IVT treatment was identified at 3 days: patients treated within 3 days had a higher cerebrospinal fluid (CSF) sterilization rate (81.5%) and a shorter median time to CSF sterilization (7 days) compared with patients who received delayed IVT treatment (> 3 days) (48.6% and 11.5 days, respectively) and those who received intravenous antibiotics alone (42.5% and 10 days, respectively). CONCLUSIONS: Early IVT antibiotics were associated with superior outcomes in terms of the in-hospital mortality rate, time to CSF sterilization, and CSF sterilization rate compared with delayed IVT antibiotics and intravenous antibiotics alone.

Diquat exacerbates oxidative stress and neuroinflammation by blocking the autophagic flux of microglia in the hippocampus.

Diquat (DQ) is a widely utilized nonselective herbicide that is primarily used to control a wide range of weeds and crop residues. It also has significant environmental implications. DQ exposure can cause severe damage to the central nervous system (CNS), a critical symptom of acute poisoning that endangers patients. Despite its severity, the underlying mechanisms of DQ-induced toxic encephalopathy remain unclear, hindering the development of precise treatments. Our research demonstrated that acute DQ exposure in mice significantly increases oxidative stress and triggers neuroinflammation in the hippocampus. Furthermore, in vitro findings indicate that the detrimental effects of DQ are mediated by its disruption of autophagic processes, leading to exacerbated neural damage. DQ initially promotes autophagy in BV2 microglia for self-protection against oxidative stress and inflammation. However, this process is subsequently blocked, intensifying neural damage. Crucially, our results show that the activation of autophagy can reverse these adverse effects. This study not only sheds light on the intricate mechanisms of DQ neurotoxicity but also provides potential therapeutic targets for mitigating DQ-induced toxic encephalopathy.

Severe liver injury and clinical characteristics of occupational exposure to 2-amino-5-chloro-N,3-dimethylbenzamide: A case series.

BACKGROUND: The 2-amino-5-chloro-N,3-dimethylbenzamide is a key intermediate in the synthesis of pesticides and pharmaceuticals. However, no literature currently exists on 2-amino-5-chloro-N,3-dimethylbenzamide poisoning in humans. This study aimed to reveal the health hazard of this chemical for humans and summarize the clinical characteristics of patients with occupational 2-amino-5-chloro-N,3-dimethylbenzamide poisoning. METHODS: This observational study included four patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning from June 2022 to July 2022. The entire course of the incidents was described in detail. Blood 2-amino-5-chloro-N,3-dimethylbenzamide concentrations were detected by a mass spectrometer. Hematoxylin and eosin staining was performed to assess liver injury, and immunofluorescence was used to evaluate hepatic mitophagy. RESULTS: The 2-amino-5-chloro-N,3-dimethylbenzamide powder (99% purity) entered the human body mainly via the skin and respiratory tract due to poor personal protective measures. The typical course of 2-amino-5-chloro-N,3-dimethylbenzamide poisoning was divided into latency, rash, fever, organic damage, and recovery phases in accordance with the clinical evolution. Rash and fever may be the important premonitory symptoms for further organ injuries. The chemical was detected in the blood of all patients and caused multiple organ injuries, predominantly liver injury, including kidney, myocardium, and microcirculation. Three patients recovered smoothly after comprehensive treatments, including artificial liver therapy, continuous renal replacement therapy, glucocorticoids, and other symptomatic and supportive treatments. One patient survived by liver transplantation. The postoperative pathological findings of the removed liver showed acute liver failure, and immunofluorescence staining confirmed the abundance of mitophagy in residual hepatocytes. CONCLUSIONS: This study is the first to elaborate the clinical characteristics of patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning. The chemical enters the body through the respiratory tract and skin during industrial production. The 2-amino-5-chloro-N,3-dimethylbenzamide poisoning causes multiple-organ dysfunction with a predominance of liver injury. Liver transplantation may be an effective option for patients with severe liver failure. The mechanisms of liver injury induced by 2-amino-5-chloro-N,3-dimethylbenzamide might involve abnormal mitochondrial function and mitophagy.

Factors influencing TSH suppression efficacy in postoperative papillary thyroid carcinoma patients: a retrospective cohort study.

OBJECTIVES: While surgery plays a crucial role in treating papillary thyroid carcinoma (PTC), the potential effects of subsequent TSH suppression therapy on prognosis should not be overlooked. This study aims to investigate the factors that influence postoperative TSH suppression therapy in patients with PTC. METHODS: This study was a retrospective cohort study conducted at our hospital. It included 268 patients who underwent surgery and were pathologically diagnosed with PTC between February 2019 and February 2021. The selected patients received postoperative TSH suppression therapy. Based on the TSH level measured 12 months after surgery, the patients were divided into two groups: TSH level conforming group (n = 80) and non-conforming group (n = 188). We then compared the general clinical data, clinicopathological characteristics, preoperative laboratory test indicators, postoperative levothyroxine sodium tablet dosage, follow-up frequency, and thyroid function-related indicators between the two groups of patients. The correlation between the observed indicators and the success of TSH suppression therapy was further analyzed, leading to the identification of influencing factors for TSH suppression therapy. RESULTS: There were no statistically significant differences in general clinical data and clinicopathological characteristics between the two groups of patients (P > 0.05). The proportion of patients with preoperative TSH ≥ 2.0 mU/L was higher in the non-conforming group compared to the TSH level conforming group (P < 0.05), and the ROC curve analysis indicated that the area under the curve for the preoperative TSH index was 0.610 (P < 0.05). The proportion of patients in the TSH level conforming group who took oral levothyroxine sodium tablets at a dose of ≥ 1.4 µg/kg·d after surgery was higher (P < 0.05). The postoperative levels of FT3 and FT4 were higher in the TSH level conforming group (P < 0.05). The results of binary logistic regression analysis indicated that factors "Postoperative TSH level ≥ 2 mU/L", "Levothyroxine sodium tablet dose<1.4 µg/kg·d", and "Combined with Hashimoto thyroiditis" were significantly associated with an elevated risk of postoperative TSH levels failing to reach the target (P < 0.05). CONCLUSION: Optimal thyroid function in patients with PTC post-surgery is best achieved when adjusting the dose of levothyroxine sodium in a timely manner to reach the target TSH level during follow-up visits.

Overview of Health-Monitoring Technology for Long-Distance Transportation Pipeline and Progress in DAS Technology Application.

There are various health issues associated with the different stages of long-distance pipeline transportation. These issues pose potential risks to environmental pollution, resource waste, and the safety of human life and property. It is essential to have real-time knowledge of the overall health status of pipelines throughout their entire lifecycle. This article investigates various health-monitoring technologies for long-distance pipelines, providing references for addressing potential safety issues that may arise during long-term transportation. This review summarizes the factors and characteristics that affect pipeline health from the perspective of pipeline structure health. It introduces the principles of major pipeline health-monitoring technologies and their respective advantages and disadvantages. The review also focuses on the application of Distributed Acoustic Sensing (DAS) technology, specifically time and space continuous monitoring technology, in the field of pipeline structure health monitoring. This paper discusses the process of commercialization development of DAS technology, the main research progress in the experimental field, and the open research issues. DAS technology has broad application prospects in the field of long-distance transportation pipeline health monitoring.

Subnanoscale Dual-Site Pd-Pt Layers Make PdPtCu Nanocrystals CO-Tolerant Bipolar Effective Electrocatalysts for Alcohol Fuel Cell Devices.

Finding a high-performance low-Pt bipolar electrocatalyst in actual direct alcohol fuel cells (DAFCs) remains challenging and desirable. Here, we developed a crystalline PdPtCu@amorphous subnanometer Pd-Pt "dual site" layer core-shell structure for the oxygen reduction reaction (ORR) and alcohol (methanol, ethylene glycol, glycerol, and their mixtures) oxidation reaction (AOR) in an alkaline electrolyte (denoted D-PdPtCu). The prepared D-PdPtCu/C achieved a direct 4-electron ORR pathway, a full oxidation pathway for AOR, and high CO tolerance. The ORR mass activity (MA) of D-PdPtCu/C delivered a 52.8- or 59.3-fold increase over commercial Pt/C or Pd/C, respectively, and no activity loss after 20000 cycles. The D-PdPtCu/C also exhibited much higher AOR MA and stability than Pt/C or Pd/C. Density functional theory revealed the intrinsic nature of a subnanometer Pd-Pt "dual site" surface for ORR and AOR activity enhancement. The D-PdPtCu/C as an effective bipolar electrocatalyst yielded higher peak power densities than commercial Pt/C in actual DAFCs.

[Mechanism of Ganke Granules intervening acute lung injury based on network pharmacology and experimental verification].

This study aims to explore the potential mechanism of action in the intervention of acute lung injury(ALI) based on the blood entry components of Ganke Granules in rats and in conjunction with network pharmacology, molecular docking, and animal experimental validation. The blood entry components of Ganke Granules in rats were imported into the SwissTargetPrediction platform to predict drug targets, and ALI-related targets were collected from the disease database. Intersections were taken, and protein-protein interaction(PPI) networks were constructed to screen the core targets, followed by Gene Ontology(GO) functional and Kyoto encyclopedia of genes and gnomes(KEGG) pathway enrichment analyses. A "blood entry components-target-pathway-disease" network was constructed, and the core components for disease intervention based on their topological parameters were screened. Molecular docking was used to predict the binding ability of the core components to key targets. The key targets of Ganke Granules in the intervention of ALI were verified by the lipopolysaccharide(LPS)-induced ALI mouse model. Through PPI topological parameter analysis, the top six key targets of STAT3, SRC, HSP90AA1, MAPK3, HRAS, and MAPK1 related to ALI were obtained. GO functional analysis showed that it was mainly related to ERK1 and ERK2 cascade, inflammatory response, and response to LPS. KEGG analysis showed that the main enrichment pathways were MAPK, neutrophil extracellular trap(NET) formation, and so on. Six core components(schizantherin B, schisandrin, besigomsin, harpagoside, isotectorigenin, and trachelanthamine) were filtered out by the "blood entry components-target-pathway-disease" network based on the analysis of topological parameters. Molecular docking results showed that the six core components and Tectoridin with the highest content in the granules had a high affinity with the key targets of MAPK3, SRC, MAPK1, and STAT3. In vivo experiment results showed that compared with the model group, Ganke Granules could effectively alleviate LPS-induced histopathological injury in the lungs of mice and reduce the percentage of inflammatory infiltration. The total protein content, nitric oxide(NO) level, myeloperoxidase(MPO) content, tumor necrosis factor-α(TNF-α), gamma interferon(IFN-γ), interleukin-1ß(IL-1ß), interleukin-6(IL-6), vascular endothelial growth factor(VEGF), and chemokine(C-X-C motif) ligand 1(CXCL1) chemokines in bronchoalveolar lavage fluid(BALF) were decreased, and the expression levels of lymphocyte antigen 6G(Ly6G), citrullinated histones 3(Cit-H3), and phosphorylated proteins SRC, ERK1/2, and STAT3 in lung tissue were significantly down-regulated. In conclusion, Ganke Granules could effectively inhibit the inflammatory response of ALI induced by LPS, protect lung tissue, regulate the release of inflammatory factors, and inhibit neutrophil infiltration and NET formation, and the mechanism of action may be related to inhibiting the activation of SRC/ERK1/2/STAT3 signaling pathway.

[Advances in clinical management of neonatal sepsis]. / 新生儿败血症的临床管理进展.

Neonatal sepsis, as a significant cause of various complications and adverse outcomes in neonates, remains a serious health burden both domestically and internationally. Strategies such as antibiotic prophylaxis during delivery, the utilization of early-onset sepsis risk calculators, and quality improvement initiatives in neonatal wards are beneficial in alleviating the disease burden of neonatal sepsis. This paper provides a review of the epidemiology, risk factors, and recent advances in clinical management of neonatal sepsis.

Daurisoline suppresses esophageal squamous cell carcinoma growth in vitro and in vivo by targeting MEK1/2 kinase.

Esophageal squamous cell carcinoma (ESCC) accounts for 90% of esophageal cancers and has a high mortality rate worldwide. The 5-year survival rate of ESCC patients in developing countries is <20%. Hence, there is an urgent need for developing new and effective treatments that are based on newly-discovered emerging molecules and pathways to prevent ESCC occurrence and recurrence. We investigated the effects of Daurisoline, a bis-benzylisoquinoline alkaloid extracted from the rhizome of menisperum dauricum, on ESCC cell proliferation and elucidated the molecular mechanisms underlying its functions. To explore the effects of Daurisoline on ESCC growth in vitro and in vivo, cell proliferation assays and anchorage-independent growth assays were performed and a patient-derived xenograft (PDX) model was established. Subsequently, phosphoproteomics, molecular docking analysis, pull down assays, mutation experiments and in vitro kinase assay were performed to explore the mechanism of Daurisoline's function on ESCC. Daurisoline inhibited ESCC proliferation in vitro and reduced ESCC PDX exnograft growth in vivo by reducing ERK1/2 phosphorylation. Furthermore, it directly bound to MEK1 (at Asn78 and Lys97) and MEK2 (at Asp194 and Asp212) kinases to inactivate the ERK1/2 signaling pathway. Our results suggest that Daurisoline is a dual inhibitor of MEK1 and MEK2 and suppresses ESCC growth both in vitro and in vivo by inactivating the ERK1/2 signaling pathway. This is first report on the use of MEK inhibitor for ESCC and highlights its potential applications for ESCC treatment and prevention.

Onset of p53/NF-κB signaling crosstalk in human melanoma cells in response to anti-cancer theabrownin.

As a major tea component, theabrownin represents a promising anti-cancer candidate. However, its effect on the melanoma is unknown. To evaluate the in vitro and in vivo anti-melanoma efficacy of TB, we conducted cell viability, immunostaining, comet, and TUNEL assays on human A375 melanoma cells, and employed a zebrafish xenograft model of A375 cells. Real-time PCR (qPCR) and western blot were conducted to explore the molecular mechanisms of TB. In vitro, TB significantly inhibited the proliferation of A375 cells, and A375 cells showed the highest inhibitory rate among the other melanoma cell line (A875) and human dermal fibroblasts. TB triggered DNA damage and induced apoptosis of A375 cells and significantly inhibited the growth of A375 xenograft tumors in zebrafishes. Several key molecular events were activated by TB, including DNA damage-associated p53 and NF-κB pathways, through up-regulation of GADD45α, γ-H2A.X, phospho-ATM(p-ATM), phospho-ATR (p-ATR), phospho-p53 (p-p53), phospho-IKKα/ß (p-IKKα/ß), phospho-p65 (p-p65), etc. However, the TB-activated molecular events were counteracted by either knockdown of p53 or p65, and only dual knockdown of both p53 and p65 completed counteracted the anti-melanoma efficacy of TB. In conclusion, TB triggered DNA damage and thereby inhibited proliferation and induced cellular senescence and apoptosis of melanoma cells through mechanisms mediated by p53/NF-κB signaling crosstalk. This is the first report on the efficacy and mechanisms of TB on melanoma cells, making TB a promising candidate for anti-melanoma agent development.