Relationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes.

The rapid global distribution of COVID-19 vaccines, with over a billion doses administered, has been unprecedented. However, in comparison to most identified clinical determinants, the implications of individual genetic factors on antibody responses post-COVID-19 vaccination for breakthrough outcomes remain elusive. Here, we conducted a population-based study including 357,806 vaccinated participants with high-resolution HLA genotyping data, and a subset of 175,000 with antibody serology test results. We confirmed prior findings that single nucleotide polymorphisms associated with antibody response are predominantly located in the Major Histocompatibility Complex region, with the expansive HLA-DQB1*06 gene alleles linked to improved antibody responses. However, our results did not support the claim that this mutation alone can significantly reduce COVID-19 risk in the general population. In addition, we discovered and validated six HLA alleles (A*03:01, C*16:01, DQA1*01:02, DQA1*01:01, DRB3*01:01, and DPB1*10:01) that independently influence antibody responses and demonstrated a combined effect across HLA genes on the risk of breakthrough COVID-19 outcomes. Lastly, we estimated that COVID-19 vaccine-induced antibody positivity provides approximately 20% protection against infection and 50% protection against severity. These findings have immediate implications for functional studies on HLA molecules and can inform future personalised vaccination strategies.

Medium- to long-term clinical efficacy of total hip arthroplasty with structural bone grafting for dysplasia of the hip.

BACKGROUND: Patients with dysplasia of the hip (DDH) have different degrees of bone defects above and outside the acetabulum, and anatomically reconstructing the acetabular centre of rotation is difficult in primary total hip arthroplasty (THA). METHODS: From April 2012 to December 2022, 64 patients (64 hips) with DDH treated with THA with structural bone graft in the superolateral acetabulum were selected. The Oxford hip score(OHS), Barthel index (BI), leg length discrepancy, Wibegr central edge-angle(CE), gluteus medius muscle strength, vertical and horizontal distance of the hip rotation center, coverage rate of the bone graft and complications were used to evaluate the clinical effectiveness of the patients. RESULTS: All patients were followed up for an average of 7.3±1.9 years. The OHS improved significantly after the operation (P<0.001). The postoperative BI was significantly greater than that before operation (P<0.001). The postoperative leg length discrepancy was significantly lower than that before the operation (P<0.001). Postoperative bedside photography revealed that the height and horizontal distance to the hip rotation center were significantly lower after surgery than before surgery (P<0.001). The postoperative CE was significantly greater than that before surgery (P<0.001). No acetabular component loosening or bone graft resorption was found during the postoperative imaging examination. CONCLUSIONS: The use of biological acetabular cup combined with structural bone graft in the superolateral acetabulum in THA for DDH can obtain satisfactory medium and long-term clinical and radiological results.

The Role of FveAFB5 in Auxin-Mediated Responses and Growth in Strawberries.

Auxin is a crucial hormone that regulates various aspects of plant growth and development. It exerts its effects through multiple signaling pathways, including the TIR1/AFB-based transcriptional regulation in the nucleus. However, the specific role of auxin receptors in determining developmental features in the strawberry (Fragaria vesca) remains unclear. Our research has identified FveAFB5, a potential auxin receptor, as a key player in the development and auxin responses of woodland strawberry diploid variety Hawaii 4. FveAFB5 positively influences lateral root development, plant height, and fruit development, while negatively regulating shoot branching. Moreover, the mutation of FveAFB5 confers strong resistance to the auxinic herbicide picloram, compared to dicamba and quinclorac. Transcriptome analysis suggests that FveAFB5 may initiate auxin and abscisic acid signaling to inhibit growth in response to picloram. Therefore, FveAFB5 likely acts as an auxin receptor involved in regulating multiple processes related to strawberry growth and development.

New Indole Alkaloids from the Fungus Talaromyces assiutensis JTY2.

Three new indole alkaloids, named talatensindoids A-C (1-3), together with two known biogenetically related indole alkaloids tryptamine (4) and L-tryptophan (5) were isolated from the Talaromyces assiutensis JTY2 based on the guidance of OSMAC approach. The structures of these indole alkaloids were determined by comprehensive spectroscopic analyses. The absolute configuration of 3 was confirmed by X-ray crystallographic analysis. Compound 1 represent the rare example of a chlorine-substituted indole alkaloid from natural products. The inhibitory activity of compounds 1-5 against two phytopathogenic fungi and three phytopathogenic bacteria was evaluated. Compound 1 exhibited broad spectrum antibacterial activities.

Lipopolysaccharide promotes cancer cell migration and invasion through METTL3/PI3K/AKT signaling in human cholangiocarcinoma.

Purpose: As a major structural component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS) has been detected in the blood circulation and tissues in patients with chronic diseases and cancers, which plays a critical role in the tumor formation and progression. However, the biological role of LPS in human intrahepatic cholangiocarcinoma remains unclear. The aims of this study were to investigate the role of LPS in the malignant progression of intrahepatic cholangiocarcinoma. Methods: The cell migration and invasion capacities of cholangiocarcinoma cell lines were evaluated by Boyden chamber assays. Expression levels of the key molecules involved in the PI3K/AKT signaling and METTL3 were detected by qPCR and western blot. The molecular mechanism by which LPS promotes the malignant behaviors was investigated by using siRNAs, plasmids and small molecule inhibitors. Results: In vitro experiments showed that exogenous LPS treatment promoted cell migration and invasion capacities in both QBC939 and HUCCT1 cell lines, while did not affect cell proliferation and apoptosis. Mechanistically, exogenous LPS treatment had been proved to induce the increased expression of METTL3 and activate the downstream PI3K/AKTsignaling pathway. In addition, suppression of METTL3 expression reduced cell proliferation, migration and invasion capacities in both cell lines. Furthermore, inhibition of METTL3 expression or inhibition of PI3K/AKT signaling decreased LPS-induced cell migration and invasion capacities. Moreover, knockdown of METTL3 or inhibition of METTL3 significantly inhibited LPS-induced activation of the PI3K/AKT signaling. Conclusion: In general, these results suggest that the LPS-METTL3-PI3K/AKT signal axis promotes cell migration and invasion in ICC, which contributes to a reduced overall survival in patients with ICC. It may broaden the horizon of cancer therapy with potential therapeutic targets.

Impact of Immunomodulatory Therapy on COVID-19 Vaccine Response in Patients with Autoimmune Inflammatory Rheumatic Diseases.

Coronavirus disease 2019 (COVID-19) vaccination is essential for patients with autoimmune inflammatory rheumatic diseases (AIIRD) to reduce the risk of morbidity and mortality associated with serious COVID-19 infection. With endemicity, waning of vaccine- and infection-acquired immunity, and development of SARS-CoV-2 variants, the need for additional doses of vaccines against serious illness in high-risk immunocompromised persons remains imperative. This review examines how immunomodulatory therapies affect vaccine-induced immune response in patients with AIIRD. Glucocorticoids, methotrexate, azathioprine, calcineurin inhibitors, mycophenolate mofetil, tumor necrosis factor inhibitors, and abatacept have been shown to variably attenuate both humoral and cellular immune responses to vaccination. Janus kinase inhibitors reduce humoral immune response. In contrast, sulfasalazine, leflunomide, belimumab, interleukin (IL)-17, IL-12/23, IL-6, and IL-1 inhibitors appear favorable, with mild or no impact on vaccine response. Although rituximab is known to profoundly diminish humoral immune response, cellular immunity is relatively preserved. Administering a third and subsequent vaccine dose or temporally coordinating the dosing of immunomodulatory drugs may improve vaccine effectiveness. Further research is needed to personalise vaccination strategies for AIIRD patients, considering their specific immunomodulatory treatments.

PS2MS: A Deep Learning-Based Prediction System for Identifying New Psychoactive Substances Using Mass Spectrometry.

The rapid proliferation of new psychoactive substances (NPS) poses significant challenges to conventional mass-spectrometry-based identification methods due to the absence of reference spectra for these emerging substances. This paper introduces PS2MS, an AI-powered predictive system designed specifically to address the limitations of identifying the emergence of unidentified novel illicit drugs. PS2MS builds a synthetic NPS database by enumerating feasible derivatives of known substances and uses deep learning to generate mass spectra and chemical fingerprints. When the mass spectrum of an analyte does not match any known reference, PS2MS simultaneously examines the chemical fingerprint and mass spectrum against the putative NPS database using integrated metrics to deduce possible identities. Experimental results affirm the effectiveness of PS2MS in identifying cathinone derivatives within real evidence specimens, signifying its potential for practical use in identifying emerging drugs of abuse for researchers and forensic experts.

Scoring method of English composition integrating deep learning in higher vocational colleges.

Along with the progress of natural language processing technology and deep learning, the subjectivity, slow feedback, and long grading time of traditional English essay grading have been addressed. Intelligent English automatic scoring has been widely concerned by scholars. Given the limitations of topic relevance feature extraction methods and traditional automatic grading methods for English compositions, a topic decision model is proposed to calculate the topic relevance score of the topic richness in English composition. Then, based on the Score of Relevance Based on Topic Richness (TRSR) calculation method, an intelligent English composition scoring method combining artificial feature extraction and deep learning is designed. From the findings, the Topic Decision (TD) model achieved the best effect only when it was iterated 80 times. The corresponding accuracy, recall and F1 value were 0.97, 0.93 and 0.95 respectively. The model training loss finally stabilized at 0.03. The Intelligent English Composition Grading Method Integrating Deep Learning (DLIECG) method has the best overall performance and the best performance on dataset P. To sum up, the intelligent English composition scoring method has better effectiveness and reliability.

The Influence of Mindful Parenting on Children's Creative Tendencies: The Chain Mediating Effect of Parent-Child Intimacy and Connectedness to Nature.

(1) Objectives: The aim of this study was to examine the relationship between mindful parenting and children's creative tendencies and to investigate the mediating role of parent-child intimacy and connectedness to nature in the relationship between mindful parenting and children's creative tendencies. (2) Methods: In this cross-sectional study, nearly 800 mothers of children aged 3-6 were enrolled. General sociodemographic data, the Mindfulness in Parenting Questionnaire (MIPQ), the Creativity Assessment Packet (CAP), the Child-Parent Relationship Scale-Short Form (CPRS-SF), and the Connectedness to Nature Index-Parents of Preschool Children (CNI-PPC) were all included in the questionnaire survey. (3) Results: There were significant positive correlations among mindful parenting, parent-child intimacy, connectedness to nature, and children's creative tendencies. Mindful parenting had a positive predictive effect on children's creative tendencies. Parent-child intimacy played a mediating role between mindful parenting and children's creative tendencies. Connectedness to nature played a mediating role between mindful parenting and children's creative tendencies. The correlation between mindful parenting and children's creative tendencies may be impacted by the chain mediation effects of parent-child intimacy and connectedness to nature. (4) Conclusions: By promoting parent-child intimacy and connectedness to nature, and by utilizing the chain mediating effects of both, mindful parenting positively impacted children's creative tendencies.

Nomogram for predicting surgical site infections in elderly patients after open lumbar spine surgery: A retrospective study.

The aim of this study is to develop a nomogram to assess the risk of surgical site infection in elderly patients undergoing open lumbar spine surgery and explore related risk factors. We reviewed the records of 578 elderly patients who had undergone open lumbar spine surgery. The clinical parameters were subjected to lasso regression and logistic regression analyses. Subsequently, a nomogram was constructed to predict the risk of postoperative surgical site infection and validated using bootstrap resampling. A total of 578 patients were included in the analysis, of which 17 were diagnosed as postoperative surgical site infection. Following the final logistic regression analysis, obesity, hypoalbuminemia and drinking history were identified as independent risk factors and subsequently incorporated into the nomogram. The nomogram demonstrated excellent discrimination, with an area under the receiver-operating characteristic curve of 0.879 (95% CI 0.769 ~ 0.989) after internal validation. The calibration curve exhibited a high level of consistency. Decision curve analysis revealed that this nomogram had greater clinical value when the risk threshold for surgical site infection occurrence was >1% and <89%. We had developed a nomogram for predicting the risk of postoperative surgical site infection in elderly patients who had undergone open lumbar spine surgery. Validation using bootstrap resampling demonstrated excellent discrimination and calibration, indicating that the nomogram may hold potential clinical utility as a simple predictive tool for healthcare professionals.

Abnormal levels of expression of microRNAs in peripheral blood of patients with traumatic brain injury are induced by microglial activation and correlated with severity of injury.

BACKGROUND: Microglia play a crucial role in regulating the progression of traumatic brain injury (TBI). In specific, microglia can self-activate and secrete various substances that exacerbate or alleviate the neuroimmune response to TBI. In addition, microRNAs (miRNAs) are involved in the functional regulation of microglia. However, molecular markers that reflect the dynamics of TBI have not yet been found in peripheral tissues. METHODS: Paired samples of peripheral blood were collected from patients with TBI before and after treatment. Next-generation sequencing and bioinformatics analysis were used to identify the main pathways and biological functions of TBI-related miRNAs in the samples. Moreover, lipopolysaccharide-treated human microglia were used to construct a cellular immune-activation model. This was combined with analysis of peripheral blood samples to screen for highly expressed miRNAs derived from activated microglia after TBI treatment. Quantitative reverse-transcriptase polymerase chain reaction was used to determine the expression levels of these miRNAs, allowing their relationship with the severity of TBI to be examined. Receiver operating characteristic (ROC) curves were constructed to analyse the clinical utility of these miRNAs for determining the extent of TBI. RESULTS: Sequencing results showed that 37 miRNAs were differentially expressed in peripheral blood samples from patients with TBI before and after treatment, with 17 miRNAs being upregulated and 20 miRNAs being downregulated after treatment. The expression profiles of these miRNAs were verified in microglial inflammation models and in the abovementioned peripheral blood samples. The results showed that hsa-miR-122-5p and hsa-miR-193b-3p were highly expressed in the peripheral blood of patients with TBI after treatment and that the expression levels of these miRNAs were correlated with the patients' scores on the Glasgow Coma Scale. ROC curve analysis revealed that abnormally high levels of expression of hsa-miR-122-5p and hsa-miR-193b-3p in peripheral blood have some clinical utility for distinguishing different extents of TBI and thus could serve as biomarkers of TBI. CONCLUSION: Abnormally high levels of expression of hsa-miR-122-5p and hsa-miR-193b-3p in the peripheral blood of patients with TBI were due to the activation of microglia and correlated with the severity of TBI. This discovery may help to increase understanding of the molecular pathology of TBI and guide the development of new strategies for TBI therapy based on microglial function.

Cultivation of microalgae-bacteria consortium by waste gas-waste water to achieve CO2 fixation, wastewater purification and bioproducts production.

The cultivation of microalgae and microalgae-bacteria consortia provide a potential efficient strategy to fix CO2 from waste gas, treat wastewater and produce value-added products subsequently. This paper reviews recent developments in CO2 fixation and wastewater treatment by single microalgae, mixed microalgae and microalgae-bacteria consortia, as well as compares and summarizes the differences in utilizing different microorganisms from different aspects. Compared to monoculture of microalgae, a mixed microalgae and microalgae-bacteria consortium may mitigate environmental risk, obtain high biomass, and improve the efficiency of nutrient removal. The applied microalgae include Chlorella sp., Scenedesmus sp., Pediastrum sp., and Phormidium sp. among others, and most strains belong to Chlorophyta and Cyanophyta. The bacteria in microalgae-bacteria consortia are mainly from activated sludge and specific sewage sources. Bioengineer in CBB cycle in microalgae cells provide effective strategy to achieve improvement of CO2 fixation or a high yield of high-value products. The mechanisms of CO2 fixation and nutrient removal by different microbial systems are also explored and concluded, the importance of microalgae in the technology is proven. After cultivation, microalgae biomass can be harvested through physical, chemical, biological and magnetic separation methods and used to produce high-value by-products, such as biofuel, feed, food, biochar, fertilizer, and pharmaceutical bio-compounds. Although this technology has brought many benefits, some challenging obstacles and limitation remain for industrialization and commercializing.

Chromosome-scale genome assembly of Lepus oiostolus (Lepus, Leporidae).

Lepus oiostolus (L. oiostolus) is a species endemic to the Qinghai-Tibet Plateau. However, the absence of a reference genome limits genetic studies. Here, we reported a high-quality L. oiostolus genome assembly, with scaffolds anchored to 24 chromosomes and a total assembled length of 2.80 Gb (contig N50 = 64.25 Mb). Genomic annotation uncovered 22,295 protein-coding genes and identified 49.84% of the sequences as transposable elements. Long interspersed nuclear elements (LINEs) constitute a high proportion of the genome. Our study is at the first time to report the chromosome-scale genome for the species of the L. oiostolus. It provides a valuable genomic resource for future research on the evolution of the Leporidae.

Identification of potential crucial genes shared in psoriasis and ulcerative colitis by machine learning and integrated bioinformatics.

BACKGROUND: Mounting evidence suggest that there are an association between psoriasis and ulcerative colitis (UC), although the common pathogeneses are not fully understood. Our study aimed to find potential crucial genes in psoriasis and UC through machine learning and integrated bioinformatics. METHODS: The overlapping differentially expressed genes (DEGs) of the datasets GSE13355 and GSE87466 were identified. Then the functional enrichment analysis was performed. The overlapping genes in LASSO, SVM-RFE and key module in WGCNA were considered as potential crucial genes. The receiver operator characteristic (ROC) curve was used to estimate their diagnostic confidence. The CIBERSORT was conducted to evaluate immune cell infiltration. Finally, the datasets GSE30999 and GSE107499 were retrieved to validate. RESULTS: 112 overlapping DEGs were identified in psoriasis and UC and the functional enrichment analysis revealed they were closely related to the inflammatory and immune response. Eight genes, including S100A9, PI3, KYNU, WNT5A, SERPINB3, CHI3L2, ARNTL2, and SLAMF7, were ultimately identified as potential crucial genes. ROC curves showed they all had high confidence in the test and validation datasets. CIBERSORT analysis indicated there was a correlation between infiltrating immune cells and potential crucial genes. CONCLUSION: In our study, we focused on the comprehensive understanding of pathogeneses in psoriasis and UC. The identification of eight potential crucial genes may contribute to not only understanding the common mechanism, but also identifying occult UC in psoriasis patients, even serving as therapeutic targets in the future.

Spectra-Based Machine Learning for Predicting the Statistical Interaction Properties of CO Adsorbates on Surface.

Theoretical analyses of small-molecule adsorption on heterogeneous catalyst surfaces often rely on simplified models of molecular adsorption with the most favorable configuration. Given that real-world experimental tests frequently entail multiple molecules interacting with the surface, there is a pressing need for a comprehensive multimolecule adsorption model to bridge the gap between theory and experiment. Using machine learning, we predict the average values of important adsorption properties from conformationally averaged, calculated infrared and Raman spectra and compare these values to those theoretically derived from the conformationally averaged ensemble. Remarkably, our approach yields excellent predictions even when faced with large and indeterminate numbers of surface molecules. These quantitative spectra-averaged property relationships provide a theoretical framework for extracting key interaction properties from the spectra of real chemical environments.

Oropouche virus: A neglected global arboviral threat.

The Oropouche virus is an important arthropod-borne virus in the Peribunyaviridae family that can cause febrile illnesses, and it is widely distributed in tropical regions such as Central and South America. Since the virus was first identified, a large number of related cases are reported every year. No deaths have been reported to date, however, the virus can cause systemic infections, including the nervous and blood systems, leading to serious complications. The transmission of Oropouche virus occurs through both urban and sylvatic cycles, with the anthropophilic biting midge Culicoides paraensis serving as the primary vector in urban areas. Direct human-to-human transmission of Oropouche virus has not been observed. Oropouche virus consists of three segments, and the proteins encoded by the different segments enables the virus to replicate efficiently in the host and to resist the host's immune response. Phylogenetic analyses showed that Oropouche virus sequences are geographically distinct and have closer homologies with Iquitos virus and Perdoes virus, which belong to the family Peribunyaviridae. Despite the enormous threat it poses to public health, there are currently no licensed vaccines or specific antiviral treatments for the disease it causes. Recent studies have utilised imJatobal virusmunoinformatics approaches to develop epitope-based peptide vaccines, which have laid the groundwork for the clinical use of vaccines. The present review focuses on the structure, epidemiology, immunity and phylogeny of Oropouche virus, as well as the progress of vaccine development, thereby attracting wider attention and research, particularly with regard to potential vaccine programs.

Effects of admission hyperglycemia and intravenous thrombolysis allocation in acute basilar artery occlusion after endovascular treatment: Analysis of the ATTENTION registry.

This study was to investigate the admission hyperglycemia and modified effect of intravenous thrombolysis (IVT) on clinical outcomes in acute basilar artery occlusion (BAO) patients receiving endovascular treatment (EVT). We prospectively recruited acute BAO patients from 48 stroke centers across 22 Chinese provinces in the ATTENTION registry from 2017 to 2021. Hyperglycemia on admission was defined as glucose ≥7.8 â€‹mmol/L. We performed multivariable logistic regression analysis to evaluate the correlation of hyperglycemia on admission with the primary outcome defined as a modified Rankin scale (mRS) score of <4 â€‹at 90 days, and the secondary outcomes defined as successful recanalization, mRS 0-1 and 0-2 â€‹at 90 days. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and mortality within 90 days. There were 1195 patients with acute BAO treated with EVT of whom 519 had hyperglycemia on admission. Hyperglycemia on admission was inversely associated with favorable neurological outcomes (mRS 0-3: adjusted odd ratio [aOR] 0.69, 95 â€‹% confidence intervals [CI] 0.54-0.89, P â€‹= â€‹0.004; mRS 0-1: aOR 0.67, 95 â€‹% CI 0.50-0.90, P â€‹= â€‹0.008; mRS 0-2: aOR 0.73, 95 â€‹% CI 0.56-0.95; P â€‹= â€‹0.02). Hyperglycemia on admission was not correlated to sICH nor successful recanalization. In the subgroup of BAO patients treated with direct EVT, those with hyperglycemia on admission had a higher mortality rate, and overall worse clinical outcomes at 90 days than patients without hyperglycemia. A significant interaction was observed between IVT and hyperglycemia on admission (Pinteraction â€‹= â€‹0.017). In patients with acute BAO treated with EVT, hyperglycemia on admission was associated with worse functional outcomes at 90 days but was not correlated with sICH nor successful recanalization. The effect of admission hyperglycemia appears to be modified by IVT allocation. Unique identifier: ChiCTR2000041117.

Evaluating the Impact of the BioFire FilmArray in Childhood Meningitis: An Observational Cohort Study.

BACKGROUND: Multiplex polymerase chain reaction assays have the potential to reduce antibiotic use and shorten length of inpatient stay in children with suspected central nervous system infection by obtaining an early microbiological diagnosis. The clinical impact of the implementation of the BioFire FilmArray Meningitis/Encephalitis Panel on the management of childhood meningitis was evaluated at the John Radcliffe Hospital in Oxford and Children's Health Ireland at Temple Street in Dublin. METHODS: Children who had lumbar punctures performed as part of a septic screen were identified retrospectively through clinical discharge coding and microbiology databases from April 2017 to December 2018. Anonymized clinical and laboratory data were collected. Comparison of antibiotic use, length of stay and outcome at discharge was made with a historical cohort in Oxford (2012-2016), presenting before implementation of the FilmArray. RESULTS: The study included 460 children who had a lumbar puncture as part of an evaluation for suspected central nervous system infection. Twelve bacterial cases were identified on the FilmArray that were not detected by conventional bacterial culture. Bacterial culture identified one additional case of bacterial meningitis, caused by Escherichia coli , which had not been identified on the FilmArray. Duration of antibiotics was shorter in children when FilmArray was used than before its implementation; enterovirus meningitis (median: 4 vs. 5 days), human parechovirus meningitis (median: 4 vs. 4.5 days) and culture/FilmArray-negative cerebrospinal fluid (median: 4 vs. 6 days). CONCLUSIONS: The use of a FilmArray can identify additional bacterial cases of meningitis in children that had been negative by traditional culture methods. Children with viral meningitis and culture-negative meningitis received shorter courses of antibiotics and had shorter hospital stays when FilmArray was used. Large studies to evaluate the clinical impact and cost effectiveness of incorporating the FilmArray into routine testing are warranted.

The impact of EID policy and trade on the environmental effects of Chinese paper enterprises from the perspective of financial constraints.

Accompanying China's accession to the World Trade Organization, the rapid development of the Chinese economy has led to increasingly serious environmental issues. However, the inherent mechanisms underlying the impact of Environmental Information Disclosure (EID) policy and trade on the environmental effects of Chinese paper enterprises remain unclear in the context of the era's requirement for a resource-conserving and environmentally-friendly society. The pollution problem in the papermaking industry has received attention worldwide, and how to balance the environmental and development issues of papermaking enterprises is an urgent issue that needs to be solved in the academic community. This study explores the impact mechanisms of EID policy and trade on the environmental effects of enterprises from the perspective of financial constraints. Utilizing the PSM-DID model, the study investigates the moderating effects of financial constraints on the EID policy and import-export trade. The findings reveal that both external and internal financial constraints have negative, detrimental effects on the environmental effects of the EID policy and trade. These constraints impede research and development investment and technological upgrades, hinder productivity improvement, and hamper the realization of "regulatory and trade innovation effects". This study enriches our understanding of the mechanisms by which trade affects the environmental effects of Chinese paper enterprises and further identifies the impacts of Chinese EID policy and trade on pollution emissions by enterprises, providing a theoretical basis and practical foundation for the government in formulating financial, environmental, and trade policies.

Epidermal growth factor potentiates EGFR(Y992/1173)-mediated therapeutic response of triple negative breast cancer cells to cold atmospheric plasma-activated medium.

Cold atmospheric plasma (CAP) holds promise as a cancer-specific treatment that selectively kills various types of malignant cells. We used CAP-activated media (PAM) to utilize a range of the generated short- and long-lived reactive species. Specific antibodies, small molecule inhibitors and CRISPR/Cas9 gene-editing approaches showed an essential role for receptor tyrosine kinases, especially epidermal growth factor (EGF) receptor, in mediating triple negative breast cancer (TNBC) cell responses to PAM. EGF also dramatically enhanced the sensitivity and specificity of PAM against TNBC cells. Site-specific phospho-EGFR analysis, signal transduction inhibitors and reconstitution of EGFR-depleted cells with EGFR-mutants confirmed the role of phospho-tyrosines 992/1173 and phospholipase C gamma signaling in up-regulating levels of reactive oxygen species above the apoptotic threshold. EGF-triggered EGFR activation enhanced the sensitivity and selectivity of PAM effects on TNBC cells. The proposed approach based on the synergy of CAP and EGFR-targeted therapy may provide new opportunities to improve the clinical management of TNBC.