PRMT6 methylation of RCC1 regulates mitosis, tumorigenicity, and radiation response of glioblastoma stem cells.

Aberrant cell proliferation is a hallmark of cancer, including glioblastoma (GBM). Here we report that protein arginine methyltransferase (PRMT) 6 activity is required for the proliferation, stem-like properties, and tumorigenicity of glioblastoma stem cells (GSCs), a subpopulation in GBM critical for malignancy. We identified a casein kinase 2 (CK2)-PRMT6-regulator of chromatin condensation 1 (RCC1) signaling axis whose activity is an important contributor to the stem-like properties and tumor biology of GSCs. CK2 phosphorylates and stabilizes PRMT6 through deubiquitylation, which promotes PRMT6 methylation of RCC1, which in turn is required for RCC1 association with chromatin and activation of RAN. Disruption of this pathway results in defects in mitosis. EPZ020411, a specific small-molecule inhibitor for PRMT6, suppresses RCC1 arginine methylation and improves the cytotoxic activity of radiotherapy against GSC brain tumor xenografts. This study identifies a CK2α-PRMT6-RCC1 signaling axis that can be therapeutically targeted in the treatment of GBM.

Chondroprotective effects of bone marrow mesenchymal stem cell-derived exosomes in osteoarthritis.

Chondrocyte ferroptosis constitutes a major cause of the development of osteoarthritis (OA). Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have a protective role against ferroptosis in various diseases. Hence, we aimed to determine whether BMSC-Exos alleviated chondrocyte ferroptosis and its effect on OA, and to dissect out the possible mechanisms. An OA rat chondrocyte model was established by interleukin-1ß (IL-1ß) exposure, and treated with BMSC-Exos/ferroptosis inhibitor Ferrostatin-1. Cell viability/ferroptosis-related index levels [reactive oxygen species (ROS)/malondialdehyde (MDA)/glutathione (GSH)]/cell death/ACSL4 mRNA and protein levels and METTL3 levels were assessed by MTT/kits/immunohistochemical method and TUNEL staining/RT-qPCR and Western blot. METTL3/ACSL4 were overexpressed in rat chondrocytes to evaluate their role in BMSC-Exo-produced repression on chondrocyte ferroptosis. Bioinformatics website predicted the presence of m6A modification sites on ACSL4 mRNA, with the m6A level enriched on it assessed by MeRIP/RT-qPCR. ACSL4 mRNA stability was detected by actinomycin D assay. A surgical destabilized medial meniscus rat OA model was also established, followed by injection with BMSC-Exos to verify their function. IL-1ß stimulation in rat chondrocytes inhibited cell viability, elevated Fe2+/ROS/MDA levels, declined GSH levels and increased TUNEL positive cell number and ACSL4 level, which were neutralized by BMSC-Exos. BMSC-Exos limited chondrocyte ferroptosis by down-regulating METTL3, with the effect abrogated by METTL3 overexpression. METTL3 regulated the m6A modification of ACSL4 mRNA, increasing ACSL4 mRNA stability and ACSL4 expression. BMSC-Exos reduced chondrocyte ferroptosis and prevented OA progression via disruption of the METTL3-m6A-ACSL4 axis. BMSC-Exos might exert a chondroprotective effect by attenuating chondrocyte ferroptosis and alleviate OA progression.

Synthesis and biological evaluation of novel 1,2,3,4-tetrahydro-ß-carboline derivatives as potential antibacterial agents.

The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-ß-carboline (THßC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THßC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THßC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs.

Can social support mediate stigma and perceived stress in people live with human immunodeficiency virus?

Stigma has heavily impacted People Living with HIV (PLWH). Limited studies report on how social support affects HIV-related stigma and perceived stress, especially in Myanmar. During first seven months of 2020, a random sample of 248 eligible PLWH were contacted from a private, closed Facebook group with more than 18,000 Myanmar people, where 90% of the members were PLWH. Variables collected included demographics data, perceived stress, social support, and HIV stigma. After controlling for the effects of demographic variables, the path from HIV stigma to perceived stress (direct effect ß = 0.40) and though the mediation of social support was significant (indirect effect ß = 0.014). However, the mediating effect of social support was non-significant between HIV stigma and perceived stress. This exploratory study shows that social support did not have the expected effect of decreasing perceived stress in PLWH in Myanmar. Interventions to reduce HIV stigma to decrease perceived stress should consider other strategies, e.g., spirituality-based practice, to reduce perceived stress in Myanmar PLWH.

Operational encoding enhances action knowledge integration: insights from event-related potential analysis.

In this study, we conducted an examination of knowledge integration concerning action information and assessed the impact of operational on this process. Additionally, we delved into the underlying mechanisms of how operational encoding influences the processing of knowledge integration of action information, utilizing the event-related potential technique. The results of our investigation revealed that operational encoding, encompassing the observed operational encoding and the imagined operational encoding, exhibited superior performance in the integration of action knowledge compared to verbal encoding. This distinction may be attributed to the greater efficiency of operant encoding in activating motor cortical areas, thereby inducing more robust brain activity. These findings suggest the potential advantages of operational encoding in facilitating the integration of knowledge related to movement information at both cognitive and neural levels, underscoring its significant role in the processing of such information. Future studies can further explore the applications of operational encoding in domains, such as motor learning, skill training, and rehabilitation therapy. Such investigations may offer novel insights into enhancing human behavior and motor control.

Design, synthesis, and evaluation of formylpiperazine analogs of Ferrostatin-1 as novel improved ferroptosis inhibitors.

In this study, a series of new formylpiperazine-derived ferroptosis inhibitors were designed and synthesized based on the structure of a known ferroptosis inhibitor, ferrostatin-1 (Fer-1). The anti-ferroptosis activity of these synthetic compounds in human umbilical vein endothelial cells (HUVECs) induced by Erastin was evaluated. It was found that some of the new compounds, especially compound 26, showed potent anti-ferroptosis activity, as evidenced by its ability to restore cell viability, reduce iron accumulation, scavenge reactive oxygen species, maintain mitochondrial membrane potential, increase GSH levels, decrease LPO and MDA content, and upregulate GPX4 expression. Moreover, compound 26 exhibited superior microsomal stability than Fer-1. The present results suggest that compound 26 is a promising lead compound for the development of new ferroptosis inhibitors for the treatment of vascular diseases.

Tailoring the Superatomic Characteristics and Optical Behavior of Metal-Free Boron Clusters via Ligand Engineering.

It is of great importance to understand how the number and type of ligands influence the properties of clusters through ligand engineering, as this knowledge is crucial for the rational design and optimization of functional materials. Herein, the geometrical structures, binding energies, and electronic properties of nonmetallic Bn (n = 20 and 40) clusters with CO, PEt3, F, NO2, and CN ligands are systematically explored based on density functional theory (DFT) calculations. Our findings demonstrate that the CO ligand acts as an electron donor when attached to these two boron clusters, in contrast to their role as electron acceptors in interactions with metal oxide and metal chalcogenide clusters. This emphasizes the necessity of considering the intrinsic properties of the host cluster when modifying with ligands. Moreover, it was observed that substituting PEt3 with F, NO2, or CN converted the B20 cluster from an electron acceptor to an electron donor, thereby demonstrating the versatility in tuning the redox characteristics of boron clusters by selecting appropriate ligands. Intriguingly, the attachment of the PEt3, F, NO2, and CN ligands to B20 can significantly modulate the electronic properties of B20 to realize the formation of metal-free superalkali (B20(PEt3)n, n = 3-5) and superhalogen (B20F, B20NO2, and B20CN) clusters. Furthermore, the structure, stability, and optical absorption of the charge transfer complex B20(PEt3)3+B20F were analyzed. This complex has been identified as an efficient material for harvesting visible light. Our findings provide insights into the effects of ligand variations on boron cluster functionalities, offering a new perspective for the design of advanced materials with tailored cluster properties through ligand engineering.

Unraveling the Solvent Regulation in the Heteroatom-Doped Endohedral Gold Clusters: A Theoretical Study on the Electronic Properties and O2 Activation.

Liquid-phase synthesis of atomically precise nanoclusters has experienced rapid development recently, where polar solvents are indispensable in such a process. However, the regulation effect of solvents on the structural and electronic properties of different metal clusters and cluster assembly materials is still not well understood. Herein, a comprehensive density functional theory calculation has been performed to explore the solvation effect on heteroatom-doped endohedral gold clusters that always have remarkable stabilities and tunable electronic structures. The solvation free energy of the M@Au12 clusters (M = Cr, Mo, W, Co, Rh, Ir, Cu, Ag, and Au) was found to be related to the charge distribution of the central doped-atom M and the outer Au12 cage. Moreover, the aqueous solvent was observed to be able to increase the adsorption capacity of M@Au12 to O2 following the activation of O2 through the charge transfer from M@Au12 to O2, in which the transferred electrons occupy the π antibonding orbital of O2. In addition, the water solvent can also improve the hydrogenation reaction of O2 to form OOH over M@Au12, where the activation energy barrier for this process is very low with the participation of the solvent. Considering the importance of solvents in the liquid-phase synthesis of atomically precise clusters, these findings highlighted here could provide valuable theoretical guidance in potential applications of functional gold nanoclusters, especially in the liquid-phase cluster catalysis.

Dual External Field Strategy in Regulating the Superhalogen Characteristics of the Non-Noble Metal Constituted Tantalum Oxide Clusters.

The identification of the non-noble metal constituted TaO cluster as a potential analogue to the noble metal Au is significant for the development of tailored materials. It leverages the superatom concept to engineer properties with precision. However, the impact of incrementally integrating TaO units on the electronic configurations and properties within larger TaO-based clusters remains to be elucidated. By employing the density functional theory calculations, the global minima and low-lying isomers of the TanOn (n = 2-5) clusters were determined, and their structural evolution was disclosed. In the cluster series, Ta5O5 was found to possess the highest electron affinity (EA) with a value of 2.14 eV, based on which a dual external field (DEF) strategy was applied to regulate the electronic property of the cluster. Initially, the electron-withdrawing CO ligand was affixed to Ta5O5, followed by the application of an oriented external electric field (OEEF). The CO ligation was found to be able to enhance the Ta5O5 cluster's electron capture capability by adjusting its electron energy levels, with the EA of Ta5O5(CO)4 peaking at 2.58 eV. Subsequently, the introduction of OEEF further elevated the EA of the CO-ligated cluster. Notably, OEEF, when applied along the +x axis, was observed to sharply increase the EA to 3.26 eV, meeting the criteria for superhalogens. The enhancement of EA in response to OEEF intensity can be quantified as a functional relationship. This finding highlights the advantage of OEEF over conventional methods, demonstrating its capacity for precise and continuous modulation of cluster EAs. Consequently, this research has adeptly transformed tantalum oxide clusters into superhalogen structures, underscoring the effectiveness of the DEF strategy in augmenting cluster EAs and its promise as a viable tool for the creation of superhalogens.

Global 30-day morbidity and mortality of surgery for perforated peptic ulcer: GRACE study.

BACKGROUND: There is little international data on morbidity and mortality of surgery for perforated peptic ulcer (PPU). This study aimed to understand the global 30-day morbidity and mortality of patients undergoing surgery for PPU and to identify variables associated with these. METHOD: We performed an international study of adults (≥ 18 years) who underwent surgery for PPU from 1st January 2022 to 30th June 2022. Patients who were treated conservatively or had an underlying gastric cancer were excluded. Patients were divided into subgroups according to age (≤ 50 and > 50 years) and time from onset of symptoms to hospital presentation (≤ 24 and > 24 h). Univariate and Multivariate analyses were carried out to identify factors associated with higher 30-day morbidity and mortality. RESULTS:  1874 patients from 159 centres across 52 countries were included. 78.3% (n = 1467) of the patients were males and the median (IQR) age was 49 years (25). Thirty-day morbidity and mortality were 48.5% (n = 910) and 9.3% (n = 174) respectively. Median (IQR) hospital stay was 7 (5) days. Open surgery was performed in 80% (n = 1505) of the cohort. Age > 50 years [(OR = 1.7, 95% CI 1.4-2), (OR = 4.7, 95% CI 3.1-7.6)], female gender [(OR = 1.8, 95% CI 1.4-2.3), (OR = 1.9, 95% CI 1.3-2.9)], shock on admission [(OR = 2.1, 95% CI 1.7-2.7), (OR = 4.8, 95% CI 3.2-7.1)], and acute kidney injury [(OR = 2.5, 95% CI 1.9-3.2), (OR = 3.9), 95% CI 2.7-5.6)] were associated with both 30-day morbidity and mortality. Delayed presentation was associated with 30-day morbidity [OR = 1.3, 95% CI 1.1-1.6], but not mortality. CONCLUSIONS: This study showed that surgery for PPU was associated with high 30-day morbidity and mortality rate. Age, female gender, and signs of shock at presentation were associated with both 30-day morbidity and mortality.

Discovery of Novel Marine-Derived Phidiandine/Lipoic Acid Hybrid as a Potential Anti-Atherosclerosis Agent: Design, Synthesis and in Vitro/in Vivo Evaluation.

In the present study, a novel derivative, IOP-LA, was prepared by hybridizing antioxidant lipoic acid (LA) and our recently reported antioxidative marine phidianidine B-inspired indole/1,2,4-oxadiazole derivative. Our results demonstrated that IOP-LA could protect vascular endothelial cells (VECs) from oxidized low-density lipoprotein (oxLDL)-induced oxidative stress by activating the Nrf2 pathway, inhibit the production of atherosclerotic plaque, and promote the stability of atherosclerotic plaque in apoE-/- mice. Moreover, the protective effect of IOP-LA was superior to LA at the same concentration. Mechanistic studies revealed that IOP-LA significantly inhibited the increase of reactive oxygen species (ROS) levels and the translocation of nuclear factor kappa-B (NF-κB) nuclear induced by oxLDL through the nuclear factor erythroid2-related factor 2 (Nrf2) pathway. In summary, the data demonstrate that IOP-LA, as a new antioxidant, protects VECs from oxLDL-induced oxidative stress by activating the Nrf2 pathway. It is worth noting that this study provides a promising lead compound for the prevention and treatment of atherosclerosis.

Dual strategy involving hospital-based study and community-based screening to eliminate hepatitis C in remote areas.

BACKGROUND: /Purpose: To achieve the World Health Organization goal of eliminating viral hepatitis by 2030, a key strategy in resource-limited areas is to identify the areas with high prevalence and to prioritize screening and treatment intervention. We hypothesized that a hospital-based laboratory database could be used to estimate the township- and village-specific anti-hepatitis C virus (HCV) prevalence. METHODS: Yunlin County Public Health Bureau has been collecting anti-HCV test data from eight major hospitals. Township- and village-specific screening testing rates and anti-HCV prevalence were calculated for residents 40 years or older. A township with a wide range of anti-HCV prevalence rates was selected for outreach universal screening and for validating the village-specific prevalence of anti-HCV in the analysis of the data from the hospitals. RESULTS: The overall anti-HCV screening testing rate in Yunlin County was 30.4 %, whereas the anti-HCV prevalence rate for persons 40 years or older was 15.4 %. The village-specific anti-HCV prevalence rates ranged from 3.8 % to 85.8 %. Community-based screening was conducted in Kouhu Township. The village-specific anti-HCV prevalence rates ranged from 0 % to 18.8 %. Three of the four villages had the highest village-specific anti-HCV prevalence in the community-based study and the hospital-based study. Additionally, 95.8 % of the new HCV cases detected by universal screening received anti-HCV therapy. CONCLUSION: The hospital-based database provided a framework for identifying the villages with high anti-HCV prevalence. Additionally, community-based universal screening should be prioritized for villages with high prevalence in hospital-based databases.

An interdisciplinary treatment to reshape upper anterior displaced teeth by using dynamic occlusal recording with an intraoral scanner.

OBJECTIVE: This article describes an interdisciplinary treatment that helped a patient with displaced upper anterior teeth. A gingivectomy, root canal therapies, digital smile design, digital wax-up, and guided tooth preparations were applied. CLINICAL CONSIDERATIONS: A patient with pathologically migrated teeth asked for treatment without orthodontic involvement due to a primary failed orthodontic treatment history. A smile photo was taken and superimposed with the dentition in a CAD software to accomplish a digital smile design. The jaw movements were recorded with two different methods, a mechanical articulator and an intraoral scanner with Patient-Specific-Motion function. The occlusal contacts during protrusive and lateral movements were compared and the digital wax-up was designed according to the later occlusal data. An aesthetic crown lengthening and pre-op root canal treatment were carried out in advance accordingly. After guided tooth preparation with a silicone index, the final fixed restorations were manufactured and cemented. A 2-year follow-up showed that our prosthesis functions well. CONCLUSIONS: This clinical report revealed that an intraoral scanner with Patient-Specific-Motion function can effectively record individual dynamic occlusal patterns and these data can be integrated into the CAD/CAM process to enhance the fulfillment of clinical requirements. CLINICAL SIGNIFICANCE: This clinical procedure with a 2-year follow-up demonstrated that a prosthodontic-based interdisciplinary treatment of pathologically migrated teeth using dynamic occlusal recording with an intraoral scanner could achieve satisfactory esthetics in a relatively short treatment period. The Patient Specific Motion module may be used to record a personalized functional movement and the data can be integrated into the design process of the final restorations.

Molecular identification and genetic diversity of biting midges (Diptera: Ceratopogonidae) in the tropical environment on Hainan Island, China.

BACKGROUND OBJECTIVES: Biting midges are hematophagous arthropods responsible for zoonotic infectious diseases and have a wide distribution in temperate and tropical latitudes of the world. METHODS: The genomic DNA of midge samples was extracted using the Chelex method and the ITS1gene was amplified by PCR to identify the midge species via BLAST. The sequence characteristics and the genetic diversity were analyzed using ClustalOmega, DnaSP, Arlequin, PopART, and TCS software tool. The validity of the ITS1 gene as a DNA barcode marker was evaluated using DAMBE. The phylogenetic relationship was established in the MEGA software. The ABGD web determined the species boundary and the SDT software visualized the pairwise sequence comparisons. RESULTS: A total of 39 midge samples possessed the range from 364 to 429 bp of the ITS1 sequences. The midge samples were identified as Culicoides imicola, Culicoides oxystoma, Culicoides peregrinus, Culicoides jacobsoni, Forcipomyia peregrinator, and Culicoides fulvus, respectively. The ITS1 sequences had 288 conserved sites (60.25%), 167 variable sites (34.94%), 141 parsimony-informative sites (29.50%), and 26 singleton sites (5.44%), with a considerable sequence variation with a high haplotype diversity. Populations in Lingao, Haikou, Tunchang were relatively independent, with a low level of gene flow. A separate population of Forcipomyia genus in Danzhou was observed. INTERPRETATION CONCLUSION: The biting midges in Hainan, a tropical island, had abundant genetic diversity. Timely surveillance is a crucial control measure for the spread of midge-borne diseases.

Retinal Vasculitis as an Ocular Manifestation in Atopic Dermatitis-Associated Retinal Detachment: A Case Report.

Atopic dermatitis is usually associated with various ocular complications. We report a 21-year-old Chinese male who presented to our ophthalmology clinic with bilateral retinal detachment and cataracts. The patient had a clear medical history of atopic dermatitis, which had been diagnosed eight years earlier and had been treated with loratadine and pimecrolimus. Cataract surgery was performed in both eyes, combined with scleral buckling in the right eye and pars plana vitrectomy in the left eye. During postoperative follow-up, fundus fluorescein angiography indicated retinal vasculitis in both eyes and macular edema in the left eye, which coincided with an exacerbation of atopic dermatitis. Macular edema improved after four months of regular dupilumab treatment in the dermatology department. The ocular condition remained stable three years postoperatively.

Atopic Dermatitis Associated Retinal Detachment and Retinal Vasculitis: A Case Report.

Atopic dermatitis is usually associated with various ocular complications. We report a 21-year-old Chinese male who presented to our ophthalmology clinic with bilateral retinal detachment and cataracts. The patient had a clear medical history of atopic dermatitis, which had been diagnosed eight years earlier and had been treated with loratadine and pimecrolimus. Cataract surgery was performed for both eyes, combined with scleral buckling for the right eye and pars plana vitrectomy for the left eye. During postoperative follow-up, fundus fluorescein angiography showed retinal vasculitis in both eyes and macular edema in the left eye, which coincided with an exacerbation of atopic dermatitis. Macular edema improved after four months of regular dupilumab treatment in the dermatology department. The ocular condition remained stable three years postoperatively.

Meta-analysis of the SARS-CoV-2 positivity rate in municipal wastewater.

The aim of this study is to conduct a systematic analysis of the SARS-CoV-2 levels in urban sewage and evaluate the associated positivity rates, thereby developing comprehensive insights into the epidemic situation and providing valuable inputs for the development of effective disease prevention and control strategies. The PubMed, Scopus, Embase, China National Knowledge Infrastructure, Wanfang Database, and VIP databases were systematically searched based on the predefined retrieval strategy. The literature published up to February 2023 was meticulously screened according to the predetermined inclusion and exclusion criteria, and the relevant data were extracted for subsequent integration. The quality assessment of the included studies adhered to the rigorous Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement guidelines. The meta-analysis was conducted using Stata 17.0 software. The meta-analysis included a total of 34 studies, encompassing 8429 municipal wastewater samples. A random effects model was employed for the analysis, revealing an overall SARS-CoV-2 positivity rate of 53.7% in the municipal wastewater samples. The subgroup analyses demonstrated significant regional variations in the SARS-CoV-2 positivity rate in municipal wastewater, with Africa exhibiting the highest rate at 62.5% (95% confidence interval [CI] 47.4 ~ 76.0%) and Oceania displaying the lowest at 33.3% (95% CI 22.0 ~ 46.3%). However, the subgroup analyses based on the sampling site, strain prevalence period, and laboratory testing method did not yield any statistically significant differences. The SARS-CoV-2 positivity rate in wastewater is relatively high globally, although it exhibits regional disparities. Regions with larger populations and lower economic levels demonstrate higher viral detection rates in sewage. Different types of wastewater sampling sites can be employed to monitor distinct aspects of the COVID-19 pandemic. Continuous surveillance of SARS-CoV-2 in wastewater plays a pivotal role in complementing clinical data, helping to track outbreak progression across diverse regions.

[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.

[Risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus]. / æœ‰è¡€æµåŠ¨åŠ›å­¦æ„ä¹‰çš„åŠ¨è„‰å¯¼ç®¡æœªé—­æ—©äº§å„¿å¸ƒæ´›èŠ¬æ²»ç–—å¤±è´¥çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA). METHODS: A retrospective collection of clinical data was conducted on preterm infants with a gestational age of <34 weeks who were diagnosed with hsPDA and treated at the Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, from January 2018 to June 2023. The subjects were divided into two groups based on the treatment approach: the ibuprofen group (95 cases) and the ibuprofen plus surgery group (44 cases). The risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA were identified by binary logistic regression analysis. RESULTS: The binary logistic regression analysis revealed that an increased diameter of the ductus arteriosus, a resistance index (RI) value of the middle cerebral artery ≥0.80, and prolonged total invasive mechanical ventilation time were risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). Receiver operating characteristic curve analysis showed that a ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days had significant predictive value for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). The combined predictive value of these three factors was the highest, with an area under the curve of 0.843, a sensitivity of 86.5%, and a specificity of 75.0% (P<0.05). CONCLUSIONS: A ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days are risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA, and they are of significant predictive value for the necessity of surgical treatment following the failure of ibuprofen treatment.

Electric Field Promoted Click Surface-Enhanced Raman Spectroscopy for Rapid and Specific Detection of DNA 2-Deoxyribose 5'-Aldehyde Oxidation Products in Plasma.

Rapid identification of DNA oxidative damage sites is of great significance for disease diagnosis. In this work, electric field-regulated click reaction surface-enhanced Raman spectroscopy (e-Click-SERS) was developed aiming at the rapid and specific analysis of furfural, the biomarker of oxidative damage to the 5-carbon site of DNA deoxyribose. In e-Click-SERS, cysteamine-modified porous Ag filaments (cys@p-Ag) were prepared and used as electrodes, amine-aldehyde click reaction sites, and SERS substrates. Cysteamine was controlled as an "end-on" conformation by setting the voltage of cys@p-Ag at -0.1 V, which ensures its activity in participating in the amine-aldehyde click reaction during the detection of furfural. Benefiting from this, the proposed e-Click-SERS method was found to be sensitive, rapid-responding, and interference-resistant in analyzing furfural from plasma. The method detection limits of furfural were 5 ng mL-1 in plasma, and the whole "extraction and detection" procedure was completed within 30 min with satisfactory recovery. Interference from 13 kinds of common plasma metabolites was investigated and found to not interfere with the analysis, according to the exclusive adaptation of the amine-aldehyde click reaction. Notably, the e-Click-SERS technique allows in situ analysis of biological samples, which offers great potential to be a point-of-care testing tool for detecting DNA oxidative damage.