Allysine-Targeted Molecular MRI Enables Early Prediction of Chemotherapy Response in Pancreatic Cancer.

Neoadjuvant therapy (NAT) is routinely used in pancreatic ductal adenocarcinoma (PDAC), but not all tumors respond to this treatment. Current clinical imaging techniques are not able to precisely evaluate and predict the response to neoadjuvant therapies over several weeks. A strong fibrotic reaction is a hallmark of a positive response, and during fibrogenesis allysine residues are formed on collagen proteins by the action of lysyl oxidases (LOX). Here we report the application of an allysine-targeted molecular magnetic resonance imaging (MRI) probe, MnL3, to provide an early, noninvasive assessment of treatment response in PDAC. Allysine increased 2- to 3-fold after one dose of NAT with FOLFIRINOX in sensitive human PDAC xenografts in mice. Molecular MRI with MnL3 could specifically detect and quantify fibrogenesis in PDAC xenografts. Comparing the MnL3 signal before and 3 days after one dose of FOLFIRINOX predicted subsequent treatment response. The MnL3 tumor signal increased by 70% from day 0 to day 3 in mice that responded to subsequent doses of FOLFIRINOX, while no signal increase was observed in FOLFIRINOX-resistant tumors. This study indicates the promise of allysine-targeted molecular MRI as a noninvasive tool to predict chemotherapy outcomes.

Microcystin-LR (MC-LR) inhibits green algae growth by regulating antioxidant and photosynthetic systems.

Microcystins release from bloom-forming cyanobacteria is considered a way to gain competitive advantage in Microcystis populations, which threaten water resources security and aquatic ecological balance. However, the effects of microcystins on microalgae are still largely unclear. Through simulated culture experiments and the use of UHPLC-MS-based metabolomics, the effects of two microcystin-LR (MC-LR) concentrations (400 and 1,600 µg/L) on the growth and antioxidant properties of three algae species, the toxic Microcystis aeruginosa, a non-toxic Microcystis sp., and Chlorella vulgaris, were studied. The MC-LR caused damage to the photosynthetic system and activated the protective mechanism of the photosynthetic system by decreasing the chlorophyll-a and carotenoid concentrations. Microcystins triggered oxidative stress in C. vulgaris, which was the most sensitive algae species studied, and secreted more glycolipids into the extracellular compartment, thereby destroying its cell structure. However, C. vulgaris eliminated reactive oxygen species (ROS) by secreting terpenoids, thereby resisting oxidative stress. In addition, two metabolic pathways, the vitamin B6 and the sphingolipid pathways, of C. vulgaris were significantly disturbed by microcystins, contributing to cell membrane and mitochondrial damage. Thus, both the low (400 µg/L) and the high (1,600 µg/L) MC-LR concentration inhibited algae growth within 3 to 7 days, and the inhibition rates increased with the increase in the MC-LR concentration. The above results indicate that the toxin-producing Microcystis species have a stronger toxin tolerance under longer-term toxin exposure in natural water environments. Thus, microcystins participates in interspecific interaction and phytoplankton population regulation and creates suitable conditions for the toxin-producing M. aeruginosa to become the dominant species in algae blooms.

A novel copper ion enhanced electrochemical DNA biosensor for the determination of epinephrine.

A novel electrochemical biosensor was developed for the detection of epinephrine (EP) by immobilizing double-strand DNA (dsDNA) bound with copper ions on a gold electrode (Cu2+/dsDNA/MCH/AuE). The electrochemical behavior of EP at Cu2+/dsDNA/MCH/AuE was examined, and the results demonstrated a significant enhancement in the electrocatalytic oxidation peak current of EP due to the formation of a stable G-Cu(II)-G sandwich structure between Cu2+ and guanine at the modified electrode. The modification process of the electrode was characterized by scanning electron microscopy, infrared spectroscopy, electrochemical impedance spectroscopy, and differential pulse voltammetry. A study on the effect of pH in phosphate buffer solution on the electrochemical oxidation of EP indicated that the catalytic oxidation process was pH-dependent. A plot of catalytic current versus EP concentration exhibited a dual-linear relationship within two ranges: 1.0-12.5 µM and 12.5-1000.0 µM, with correlation coefficients of 0.995 and 0.997, respectively. The limit of detection was determined to be 47 nM (S/N = 3). According to the calculated Hill coefficient (0.99), it can be concluded that the electrocatalytic process followed the Michaelis-Menten kinetic mechanism. The maximum catalytic current Im was 25 µA, while the apparent Michaelis-Menten constant Km was 1.425 mM. These findings indicated excellent electrocatalytic activity of the modified electrode towards oxidation of EP. The developed biosensor successfully detected EP in spiked mouse serum as well as epinephrine hydrochloride injection with high selectivity, sensitivity, stability, and accuracy.

Relationship of long-term exposure to air pollutant mixture with metabolic-associated fatty liver disease and subtypes: A retrospective cohort study of the employed population of Southwest China.

BACKGROUND: While evidence suggests that PM2.5 is associated with overall prevalence of Metabolic (dysfunction)-Associated Fatty Liver Disease (MAFLD), effects of comprehensive air pollutant mixture on MAFLD and its subtypes remain unclear. OBJECTIVE: To investigate individual and joint effects of long-term exposure to comprehensive air pollutant mixture on MAFLD and its subtypes. METHODS: Data of 27,699 participants of the Chinese Cohort of Working Adults were analyzed. MAFLD and subtypes, including overweight/obesity, lean, and diabetes MAFLD, were diagnosed according to clinical guidelines. Concentrations of NO3-, SO42-, NH4+, organic matter (OM), black carbon (BC), PM2.5, SO2, NO2, O3 and CO were estimated as a weighted average over participants' residential and work addresses for the three years preceding outcome assessment. Logistic regression and weighted quantile sum regression were used to estimate individual and joint effects of air pollutant mixture on presence of MAFLD. RESULTS: Overall prevalence of MAFLD was 26.6 % with overweight/obesity, lean, and diabetes MAFLD accounting for 92.0 %, 6.4 %, and 1.6 %, respectively. Exposure to SO42-, NO3-, NH4+, BC, PM2.5, NO2, O3and CO was significantly associated with overall MAFLD, overweight/obesity MAFLD, or lean MAFLD in single pollutant models. Joint effects of air pollutant mixture were observed for overall MAFLD (OR = 1.10 [95 % CI: 1.03, 1.17]), overweight/obesity (1.09 [1.02, 1.15]), and lean MAFLD (1.63 [1.28, 2.07]). Contributions of individual air pollutants to joint effects were dominated by CO in overall and overweight/obesity MAFLD (Weights were 42.31 % and 45.87 %, respectively), while SO42- (36.34 %), SO2 (21.00 %) and BC (12.38 %) were more important in lean MAFLD. Being male, aged above 45 years and smoking increased joint effects of air pollutant mixture on overall MAFLD. CONCLUSIONS: Air pollutant mixture was associated with MAFLD, particularly the lean MAFLD subtype. CO played a pivotal role in both overall and overweight/obesity MAFLD, whereas SO42- were associated with lean MAFLD.

A strategy to enhance the water solubility of luminescent ß-diketonate-Europium(III) complexes for time-gated luminescence bioassays.

Luminescent ß-diketonate-europium(III) complexes have been found a wide range of applications in time-gated luminescence (TGL) bioassays, but their poor water solubility is a main problem that limits their effective uses. In this work we propose a simple and general strategy to enhance the water solubility of luminescent ß-diketonate-europium(III) complexes that permits facile synthesis and purification. By introducing the fluorinated carboxylic acid group into the structures of ß-diketone ligands, two highly water-soluble and luminescent Eu3+ complexes, PBBHD-Eu3+ and CPBBHD-Eu3+, were designed and synthesized. An excellent solubility exceeding 20 mg/mL for PBBHD-Eu3+ was found in a pure aqueous buffer, while it also displayed strong and long-lived luminescence (quantum yield φ = 26%, lifetime τ = 0.49 ms). After the carboxyl groups of PBBHD-Eu3+ were activated, the PBBHD-Eu3+-labeled streptavidin-bovine serum albumin (SA-BSA) conjugate was prepared, and successfully used for the immunoassay of human α-fetoprotein (AFP) and the imaging of an environmental pathogen Giardia lamblia under TGL mode, which demonstrated the practicability of PBBHD-Eu3+ for highly sensitive TGL bioassays. The carboxyl groups of PBBHD can also be easily derivatized with other reactive chemical groups, which enables PBBHD-Eu3+ to meet diverse requirements of biolabeling technique, to provide new opportunities for developing functional europium(III) complex biolabels serving for TGL bioassays.

Clinical study of enhanced recovery after surgery in laparoscopic appendectomy for acute appendicitis.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocol is a comprehensive management modality that promotes patient recovery, especially in the patients undergoing digestive tumor surgeries. However, it is less commonly used in the appendectomy. AIM: To study the application value of ERAS in laparoscopic surgery for acute appendicitis. METHODS: A total of 120 patients who underwent laparoscopic appendectomy due to acute appendicitis were divided into experimental group and control group by random number table method, including 63 patients in the experimental group and 57 patients in the control group. Patients in the experimental group were managed with the ERAS protocol, and those in the control group were received the traditional treatment. The exhaust time, the hospitalization duration, the hospitalization expense and the pain score between the two groups were compared. RESULTS: There was no significant difference in age, gender, body mass index and Sunshine Appendicitis Grading System score between the experimental group and the control group (P > 0.05). Compared to the control group, the patients in the experimental group had earlier exhaust time, shorter hospitalization time, less hospitalization cost and lower degree of pain sensation. The differences were statistically significant (P < 0.01). CONCLUSION: ERAS could significantly accelerate the recovery of patients who underwent laparoscopic appendectomy for acute appendicitis, shorten the hospitalization time and reduce hospitalization costs. It is a safe and effective approach.

Seeing Your Stories: Visualization for Narrative Medicine.

Importance: Narrative medicine (NM), in which patient stories play a crucial role in their diagnosis and treatment, can potentially support a more holistic approach to patient care than traditional scientific ones. However, there are some challenges in the implementation of narrative medicine, for example, differences in understanding illnesses between physicians and patients and physicians' increased workloads and overloaded schedules. This paper first presents a review to explore previous visualization research for narrative medicine to bridge the gap between visualization researchers and narrative medicine experts and explore further visualization opportunities. Highlights: The review is conducted from 2 perspectives: (a) the contexts and domains in which visualization has been explored for narrative medicine and (b) the forms and solutions applied in these studies. Four applied domains are defined, including understanding patients from narrative records, medical communication, medical conversation training in education, and psychotherapy and emotional wellness enhancement. Conclusions: A future work framework illustrates some opportunities for future research, including groups of specific directions and future points for the 4 domains and 3 technological exploration opportunities (combination of narrative and medical data visualization, task-audience-based visual storytelling, and user-centered interactive visualization). Specifically, 3 directions of future work in medical communication (asynchronous online physician-patient communication, synchronous face-to-face medical conversation, and medical knowledge dissemination) were concluded.

Serum Troponin I Assessments in 5- to 30-Year-Olds After BNT162b2 Vaccination.

INTRODUCTION: Rare myocarditis and pericarditis cases have occurred in coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine recipients. Troponin levels, a potential marker of myocardial injury, were assessed in healthy participants before and after BNT162b2 vaccination. METHODS: Vaccine-experienced 12- to 30-year-olds in phase 3 crossover C4591031 Substudy B (NCT04955626) who had two or three prior BNT162b2 30-µg doses were randomized to receive BNT162b2 30 µg followed by placebo, or placebo followed by BNT162b2 30 µg, 1 month apart. A participant subset, previously unvaccinated against COVID-19, in the phase 3 C4591007 study (NCT04816643) received up to three vaccinations (BNT162b2 10 µg or placebo [5- to 11-year-olds]) or open-label BNT162b2 30 µg (12- to 15-year-olds). Blood samples collected pre-vaccination, 4 days post-vaccination, and 1-month post-vaccination (C4591031 Substudy B only) were analyzed. Frequencies of elevated troponin I levels (male, > 35 ng/l; female, > 17 ng/l) were assessed. RESULTS: Percentages of 12- to 30-year-olds (n = 1485) in C4591031 Substudy B with elevated troponin levels following BNT162b2 or placebo receipt were 0.5% and 0.8% before vaccination, 0.7% and 1.0% at day 4, and 0.7% and 0.5% at 1 month, respectively. In Study C4591007 (n = 1265), elevated troponin I levels were observed in 0.2, 0.4, and 0.2% of 5- to 11-year-old BNT162b2 recipients at baseline and 4 days post-dose 2 and 3, respectively; corresponding values in 12- to 15-year-olds were 0.4, 0.4, and 0.7%. No 5- to 11-year-old placebo recipients had elevated troponin levels. No myocarditis or pericarditis cases or deaths were reported. CONCLUSIONS: Among 5- to < 30-year-olds in both studies, troponin levels were rarely elevated (≤ 1.0%) and similar before and post-vaccination; troponin levels were also similar between BNT162b2 and placebo in 12- to 30-year-old and 5- to 11-year-old recipients in the respective studies. No myocarditis or pericarditis cases were reported. These findings did not provide evidence that BNT162b2 causes troponin elevations. No utility of routine measurement of troponin levels in asymptomatic BNT162b2 recipients was identified.

Photochemical processes transform dissolved organic matter differently depending on its initial composition.

Dissolved organic matter (DOM) is one of the most important fluxes in the global carbon cycle but its response to light exposure remains unclear at a molecular-level. The chemical response of DOM to light should vary with its molecular composition and environmental conditions while some basic hypotheses are still unclear, such as the balance between photobleaching and photo-humification and the question of oxidative properties. Here we exposed aquatic DOM from diverse freshwaters impacted by different levels of anthropogenic activity and algal exudates to environmentally-realistic light conditions. We found that photobleaching occurred in DOM with relatively high initial humic content producing low H/C molecules, whereas DOM with low initial humic content was humified. DOM pools with relatively high initial saturation and low aromaticity were prone to transform towards more unsaturated molecular formulae and high H/C molecules with a distinct decrease of bioavailability. Photo-transformation was mainly influenced by reactive intermediates, with reactive oxygen species (ROS) playing a dominant role in humification when the initial humus content of DOM was high. In contrast, for algal DOM with high protein content, it was likely that the autoxidation of excited state DOM was more important than indirect oxidation involving ROS. Our results reveal how photo-transformation patterns depend on the initial composition of DOM and provide new insights into the role of photochemical processes in biogeochemical cycling of DOM.

Explore on the Mechanism of miRNA-146a/TAB1 in the Regulation of Cellular Apoptosis and Inflammation in Ulcerative Colitis Based on NF-κB Pathway.

OBJECTIVE: Ulcerative colitis (UC) is a chronic non-specific inflammatory disease of the rectum and colon with unknown etiology. A growing number of evidence suggest that the pathogenesis of UC is related to excessive apoptosis and production of inflammatory cytokines. However, the functions and molecular mechanisms associated with UC remain unclear. MATERIALS AND METHODS: The in vivo and in vitro models of UC were established in this study. MiRNA or gene expression was measured by qRT-PCR assay. ELISA, CCK-8, TUNEL, and flow cytometry assays were applied for analyzing cellular functions. The interactions between miR-146a and TAB1 were verified by luciferase reporter and miRNA pull-down assays. RESULTS: MiR-146a was obviously increased in UC patients, DSS-induced colitis mice, and TNF-ɑ-induced YAMC cells, when compared to the corresponding controls. MiR- 146a knockdown inhibited the inflammatory response and apoptosis in DSS-induced colitis mice and TNF-ɑ-induced YAMC cells. Mechanistically, we found that TAB1 was the target of miR-146a and miR-146a knockdown suppressed the activation of NF-κB pathway in UC. More importantly, TAB1 could overturn the inhibitory effect of antagomiR-146a on cell apoptosis and inflammation in UC. CONCLUSION: MiR-146a knockdown inhibited cell apoptosis and inflammation via targeting TAB1 and suppressing NF-κB pathway, suggesting that miR-146a may be a new therapeutic target for UC treatment.

Mortality risk of people living with HIV under hypothetical intervention scenarios of PM2.5 and HIV severity: a prospective cohort study.

This study estimated and compared mortality risks among people living with HIV (PLWH) under the real-world and hypothetical scenarios of PM2.5 concentrations and HIV severity. An open cohort from all PLWH receiving antiretroviral therapy in Sichuan during 2010-2019 was constructed, resulting in 541,515 person-years. Annual mean concentrations of PM2.5 were estimated and linked to PLWH by their residential address. The parametric g-formula were used to assess 3- and 5-year mortality risks under the real-world and hypothetical scenarios of PM2.5 (10-35, 35-50, 50-75 µg/m3) and CD4 concentrations (0-200, 200-500, 500-800, 800-1100 counts/µl). The estimated 3- and 5-year mortality risks among the PLWH were 14.43 % and 19.38 %, respectively, which would decrease substantially when annual PM2.5 concentration were reduced to between 10 and 35 µg/m3 (risk difference [RD] = -3.23 % and - 4.06 %) and would increase when PM2.5 concentration were elevated to between 50 and 75 µg/m3 (RD = 3.59 % and 5.04 %). The mortality risk would increase when CD4 concentration were reduced to <200 counts/µl (RD = 15.90 % and 20.27 %) and would decrease when CD4 concentration were ≥ 200 counts/µl, especially to between 800 and 1100 counts/µl (RD = -9.01 % and - 11.75 %). The elevated concentration of PM2.5 may disproportionately affect individuals with immune deficiency, especially those with more severity. The findings would serve as justifications for future intervention design and policy making to alleviate air pollution and improve environmental justice and health equity.

Network analysis of illness perception, stigma, and resilience with cognition in old people living with HIV.

OBJECTIVES: Old people living with HIV (PLWH) are highly susceptible to HIV-related psychological and neurocognitive disorders, which are multidimensional and inseparably intertwined. Despite this, few studies have investigated the interrelationship between these disorders. We aimed to estimate the detailed associations and identify potential intervention points between HIV-related psychological factors and cognitive function in old PLWH. METHODS: This cross-sectional study drew on the Older People with HIV Infections Cohort from 65 communities in Sichuan, China. Three HIV-related psychological factors, including illness perception, HIV stigma perception and resilience, were collected using a self-reported questionnaire. Cognitive function was measured using the MoCA-B scale. Network analysis was used to estimate the interrelationships between HIV-related psychological factors and cognitive function dimensions in old PLWH, and to identify factors that act as bridges in connecting these factors in the network. RESULTS: Of the 1587 old PLWH, 47.0% had mild or severe cognitive function impairment. Network analysis revealed that better visual perception was directly connected with poorer negative self-image (edge weight: 0.13), and poorer illness comprehensibility was connected with poor visual perception (-0.09) and executive functioning (-0.13). The cognitive illness perceptions (bridge strength: 0.41), illness comprehensibility (0.36) and negative self-image (0.39) were identified as bridges connecting HIV-related psychological and cognitive function. CONCLUSIONS: The interconnection of HIV-related illness perception, stigma perception, and resilience with cognition may be achieved through the links of negative self-image, illness comprehensibility and cognitive illness perceptions. These factors may serve as potential non-pharmaceutical action points to improve psychological and cognitive health among old PLWH.

[Research progress in mechanism of puerarin in treating vascular dementia].

Vascular dementia(VD) is a condition of cognitive impairment due to acute and chronic cerebral hypoperfusion. The available therapies for VD mainly focus on mitigating cerebral ischemia, improving cognitive function, and controlling mental behavior. Achievements have been made in the basic and clinical research on the treatment of VD with traditional Chinese medicine(TCM) active components, including Ginkgo leaf extract, puerarin, epimedium, tanshinone, and ginsenoside. Most of these components have anti-inflammatory, anti-apoptotic, anti-oxidant, and neuroprotective effects, and puerarin demonstrates excellent performance in mitigating cholinergic nervous system disorders and improving synaptic plasticity. Puerarin, ginkgetin, and epimedium are all flavonoids, while tanshinone is a diterpenoid. Puerariae Lobatae Radix, pungent in nature, can induce clear Yang to reach the cerebral orifices and has the wind medicine functions of ascending, dispersing, moving, and scurrying. Puerariae Lobatae Radix entering collaterals will dredge blood vessels to promote blood flow, and that entering the sweat pore will open the mind, which is in line with the TCM pathogenesis characteristics of VD. This study reviews the progress in the mechanism of puerarin, the main active component of Puerariae Lobatae Radix, in treating VD. Puerarin can ameliorate cholinergic nervous system disorders, reduce excitotoxicity, anti-inflammation, inhibit apoptosis, alleviate oxidative stress injury, enhance synaptic plasticity, up-regulate neuroprotective factor expression, promote cerebral circulation metabolism, and mitigate Aß injury. The pathways of action include activating nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE), vascular endothelial growth factor(VEGF), extracellular regulated protein kinases(ERK), phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), Janus-activating kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3), AMP-activated protein kinase(AMPK), as well as inhibiting the tumor necrosis factor α(TNF-α), transient receptor potential melastatin 2(TRPM2)/N-methyl-D-aspartate receptor(NMDAR), p38 mitogen-activated protein kinase(p38 MAPK), Toll-like receptor 4(TLR4)/nuclear factor-kappaB(NF-κB), early growth response 1(Egr-1), and matrix metalloproteinase 9(MMP-9). By reviewing the papers about the treatment of VD by puerarin published by CNKI, Wanfang, VIP, PubMed, and Web of Science in the last 10 years, this study aims to support the treatment and drug development for VD.

Establishment of a differential diagnosis method and an online prediction platform for AOSD and sepsis based on gradient boosting decision trees algorithm.

OBJECTIVE: The differential diagnosis between adult-onset Still's disease (AOSD) and sepsis has always been a challenge. In this study, a machine learning model for differential diagnosis of AOSD and sepsis was developed and an online platform was developed to facilitate the clinical application of the model. METHODS: All data were collected from 42 AOSD patients and 50 sepsis patients admitted to Affiliated Hospital of Xuzhou Medical University from December 2018 to December 2021. In addition, 5 AOSD patients and 10 sepsis patients diagnosed in our hospital after March 2022 were collected for external validation. All models were built using the scikit-learn library (version 1.0.2) in Python (version 3.9.7), and feature selection was performed using the SHAP (Shapley Additive exPlanation) package developed in Python. RESULTS: The results showed that the gradient boosting decision tree(GBDT) optimization model based on arthralgia, ferritin × lymphocyte count, white blood cell count, ferritin × platelet count, and α1-acid glycoprotein/creatine kinase could well identify AOSD and sepsis. The training set interaction test (AUC: 0.9916, ACC: 0.9457, Sens: 0.9556, Spec: 0.9578) and the external validation also achieved satisfactory results (AUC: 0.9800, ACC: 0.9333, Sens: 0.8000, Spec: 1.000). We named this discrimination method AIADSS (AI-assisted discrimination of Still's disease and Sepsis) and created an online service platform for practical operation, the website is http://cppdd.cn/STILL1/ . CONCLUSION: We created a method for the identification of AOSD and sepsis based on machine learning. This method can provide a reference for clinicians to formulate the next diagnosis and treatment plan.

Hybrid transfer learning strategy for cross-subject EEG emotion recognition.

Emotion recognition constitutes a pivotal research topic within affective computing, owing to its potential applications across various domains. Currently, emotion recognition methods based on deep learning frameworks utilizing electroencephalogram (EEG) signals have demonstrated effective application and achieved impressive performance. However, in EEG-based emotion recognition, there exists a significant performance drop in cross-subject EEG Emotion recognition due to inter-individual differences among subjects. In order to address this challenge, a hybrid transfer learning strategy is proposed, and the Domain Adaptation with a Few-shot Fine-tuning Network (DFF-Net) is designed for cross-subject EEG emotion recognition. The first step involves the design of a domain adaptive learning module specialized for EEG emotion recognition, known as the Emo-DA module. Following this, the Emo-DA module is utilized to pre-train a model on both the source and target domains. Subsequently, fine-tuning is performed on the target domain specifically for the purpose of cross-subject EEG emotion recognition testing. This comprehensive approach effectively harnesses the attributes of domain adaptation and fine-tuning, resulting in a noteworthy improvement in the accuracy of the model for the challenging task of cross-subject EEG emotion recognition. The proposed DFF-Net surpasses the state-of-the-art methods in the cross-subject EEG emotion recognition task, achieving an average recognition accuracy of 93.37% on the SEED dataset and 82.32% on the SEED-IV dataset.

Moderating effect of urban endowment factors on environmental regulations-productivity relationship in Beijing-Tianjin-Hebei region.

In this paper, six major cities in the Beijing-Tianjin-Hebei region of China are classified into two groups, namely core city (Beijing) and industrial cities. The objective is to analyze the moderating effect of urban endowments in different urban contexts on the environmental regulation-productivity relationship using an econometric model. The results are: As environmental regulation intensifies, production in Beijing's high-polluting industries rises after falling, showing "innovation compensation" and "inefficient exit" effects. In contrast, the high-polluting industries in the industrial cities exhibit a "compliance cost" effect. In Beijing, four urban endowment factors, including economic development, technological innovation, human capital, and government intervention, can provide supportive conditions for business development under environmental regulatory pressure, primarily by reducing the "compliance cost" effect and enhancing the "innovation compensation" effect. In industrial cities, on the other hand, urban endowment factors have not had a positive moderating effect, and government intervention has even had a negative effect. We argue that government intervention may be the more fundamental urban endowment factor, which may affect the moderating outcomes of other endowment factors. Based on these findings, we propose that governments should make greater use of guiding and incentive-based environmental policy instruments, while reducing administrative interventions. Appropriate policy instruments can activate the positive moderating role of urban endowments and thus provide a better supportive environment for firms' technological innovation.

Nondestructive Detection and Early Warning of Pavement Surface Icing Based on Meteorological Information.

Monitoring and warning of ice on pavement surfaces are effective means to improve traffic safety in winter. In this study, a high-precision piezoelectric sensor was developed to monitor pavement surface conditions. The effects of the pavement surface temperature, water depth, and wind speed on pavement icing time were investigated. Then, on the basis of these effects, an early warning model of pavement icing was proposed using an artificial neural network. The results showed that the sensor could detect ice or water on the pavement surface. The measurement accuracy and reliability of the sensor were verified under long-term vehicle load, temperature load, and harsh natural environment using test data. Moreover, pavement temperature, water depth, and wind speed had a significant nonlinear effect on the pavement icing time. The effect of the pavement surface temperature on icing conditions was maximal, followed by the effect of the water depth. The effect of the wind speed was moderate. The model with a learning rate of 0.7 and five hidden units had the best prediction effect on pavement icing. The prediction accuracy of the early warning model exceeded 90%, permitting nondestructive and rapid detection of pavement icing based on meteorological information.

Transcriptional Analysis of lncRNA and Target Genes Induced by Influenza A Virus Infection in MDCK Cells.

BACKGROUND: The MDCK cell line is the primary cell line used for influenza vaccine production. Using genetic engineering technology to change the expression and activity of genes that regulate virus proliferation to obtain high-yield vaccine cell lines has attracted increasing attention. A comprehensive understanding of the key genes, targets, and molecular mechanisms of viral regulation in cells is critical to achieving this goal, yet the post-transcriptional regulation mechanism involved in virus proliferation-particularly the effect of lncRNA on influenza virus proliferation-is still poorly understood. Therefore, this study used high-throughput RNA-seq technology to identify H1N1 infection-induced lncRNA and mRNA expression changes in MDCK cells and explore the regulatory relationship between these crucial lncRNAs and their target genes. RESULTS: In response to H1N1 infection in MDCK cells 16 h post-infection (hpi) relative to uninfected controls, we used multiple gene function annotation databases and initially identified 31,501 significantly differentially expressed (DE) genes and 39,920 DE lncRNAs (|log2FC| > 1, p < 0.05). Among these, 102 lncRNAs and 577 mRNAs exhibited predicted correlations with viral response mechanisms. Based on the magnitude of significant expression differences, related research, and RT-qPCR expression validation at the transcriptional level, we further focused on 18 DE mRNAs and 32 DE lncRNAs. Among these, the differential expression of the genes RSAD2, CLDN1, HCLS1, and IFIT5 in response to influenza virus infection was further verified at the protein level using Western blot technology, which showed results consistent with the RNA-seq and RT-qPCR findings. We then developed a potential molecular regulatory network between these four genes and their six predicted lncRNAs. CONCLUSIONS: The results of this study will contribute to a more comprehensive understanding of the molecular mechanism of host cell non-coding RNA-mediated regulation of influenza virus replication. These results may also identify methods for screening target genes in the development of genetically engineered cell lines capable of high-yield artificial vaccine production.

Phytoplankton interspecific interactions modified by symbiotic fungi and bacterial metabolites under environmentally relevant hydrogen peroxide concentrations stress.

Hydrogen peroxide (H2O2), which accumulates in water and triggers oxidative stress for aquatic microbes, has been shown to have profound impacts on planktonic microbial community dynamics including cyanobacterial bloom formation. Yet, potential effects of H2O2 on interspecific relationships of phytoplankton-microbe symbiotic interactions remain unclear. Here, we investigated effects of environmentally relevant H2O2 concentrations on interspecific microbial relationships in algae-microbe symbiosis. Microbes play a crucial role in the competition between M. aeruginosa and Chlorella vulgaris at low H2O2 concentrations (∼400 nM), in which fungi and bacteria protect Microcystis aeruginosa from oxidative stress. Moreover, H2O2 stimulated the synthesis and release of extracellular microcystin-LR from Microcystis aeruginosa, while intracellular microcystin-LR concentrations remained at a relatively constant level. In the presence of H2O2, loss of organoheterocyclic compounds, organic acids and ketones contributed to the growth of M. aeruginosa, but the reduction of vitamins inhibited it. Regulation of interspecific relationships by H2O2 is achieved by its action on fungal species and bacterial secretory metabolites. This study explored the response of phytoplankton interspecific relationships in symbiotic phytoplankton-microbe interactions to environmentally relevant H2O2 concentrations stress, providing a theoretical basis for understanding the formation of harmful-algae blooming and impact of photochemical properties of water on aquatic ecological safety and stability.

The causal association between polycystic ovary syndrome and susceptibility and severity of COVID-19: a bidirectional Mendelian randomization study using genetic data.

Introduction: Observational studies have reported an association between polycystic ovary syndrome (PCOS) and COVID-19, but a definitive causal relationship has not been established. This study aimed to assess this association using two-way two-sample Mendelian randomization (MR). Methods: A summary of PCOS characteristics was compiled using the PCOS summary statistics from the Apollo University of Cambridge Repository. COVID-19 susceptibility and severity statistics, including hospitalization and extremely severe disease, were obtained from genome-wide association studies from the COVID-19 Host Genetics Initiative. The primary analysis used the inverse variance-weighted method, supplemented by the weighted median, MR-Egger, and MR-PRESSO methods. Results: The forward MR analysis showed no significant impact of PCOS on COVID-19 susceptibility, hospitalization, or severity (OR = 0.983, 1.011, 1.014; 95% CI = 0.958-1.008, 0.958-1.068, 0.934-1.101; and p = 0.173, 0.68, 0.733; respectively). Similarly, reverse MR analysis found no evidence supporting COVID-19 phenotypes as risk or protective factors for PCOS (OR = 1.041, 0.995, 0.944; 95% CI = 0.657-1.649, 0.85-1.164, 0.843-1.058; and p = 0.864, 0.945, 0.323; respectively). Consequently, no significant association between any COVID-19 phenotype and PCOS was established. Conclusion: This MR study suggested that PCOS is not a causal risk factor for the susceptibility and severity of COVID-19. The associations identified in previous observational studies might be attributable to the presence of comorbidities in the patients.