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Ion mobility spectrometry (IMS) is a trace detection technique operating at atmospheric pressure. It is widely utilized in various fields, such as explosives and drug detection, chemical warfare agent detection, and biomedical applications, due to its fast response time and high sensitivity. The various of substances can be identified through analyzing the discrepancies in the drift time of charged particles in an electric field. Depending on the polarity of the charged particles, it can operate under either positive or negative ion mode. Currently, the majority of IMS operate in only one detection mode. For example, explosives detection operates under negative ion mode, while drug detection operates under positive ion mode. However, single detection mode system is prone to miss detections because some substances may differentially respond to positive and negative detection modes. Simultaneous detection under both positive and negative ion modes can further enhance detection accuracy. In this study, a dual-drift tube ion mobility spectrometry capable of simultaneously detecting positive and negative ions was constructed using corona discharge ionization source technology and a compact dual ion-gated pulse control circuit. The instrument parameters of IMS were optimized, while simultaneously determined hexogen, methamphetamine and the metabolite of trinitrotoluene (TNT)，2,4-diamino-6-nitrotoluene (2,4-DANT). The optimal experimental conditions were selected as follows: a drift gas flow rate of 600 mL/min, a carrier gas flow rate of 500 mL/min, a drift tube temperature of 100 ℃, and a thermal desorption temperature of 200 ℃. The reduced mobility values of 1.72 cm2/V·s and 1.44 cm2/V·s are obtained through the detection of explosive hexogen (RDX) and drug methamphetamine (MA), respectively. These values agree well with the reported values, thereby proving the reliability of the instrument’s detection. Finally, the performance of the developed instrument was evaluated using 2,4-DANT, this substance that can be detected under both positive and negative ion modes. Production peaks are observed in both modes, and the normalized mobility values for 2,4-DANT are reported as approximately 1.67 cm2/V·s and 1.33 cm2/V·s under positive and negative ion modes, respectively. Through exploring the detection limits for both positive and negative ions, it was revealed that the homemade dual ion mobility spectrometer is capable of simultaneous detection of both positive and negative ions, achieves the lowest detection limits of 200 pg and 260 pg for 2,4-DANT, respectively. Importantly, these detection limits are not significantly compromised by sample division, which underscores the broad applicability and value of the instrument, highlighting its potential in various fields.

Atmospheric organic aerosols consist of both gas-phase organic compounds and particle-phase organic compounds. The components of aerosol particles (solid or liquid droplets) can undergo exchange or chemical reactions with gas-phase components, influencing atmospheric physical and chemical processes and potentially impacting atmospheric environment, climate, and human health. Methods for detecting organic compounds in aerosol particle phase are classified into offline and online detection. Offline detection methods involve collecting aerosol samples for analysis using chromatography-mass spectrometry, which is time-consuming and limited sensitivity. Online detection methods involve enriching aerosols through aerodynamic lens and then detecting them using laser ablation or electron impact ionization techniques. However, these methods usually generate a large number of ion fragments, making mass spectrum analysis difficult. Therefore, it is necessary to develop an online detection method for aerosol particle-phase organic compounds with soft ionization and high sampling efficiency. In the present work, a set of aerodynamic lens sampling systems was designed and developed for online detection and analysis of organic compounds in aerosol particle phase. This sampling system consists of a gas-phase stripping module for removing gas-phase organic compounds, an aerodynamic lens module for particle focusing and enrichment, and a thermal desorption module for extracting particle-phase organic compounds. The efficiency of gas-phase organic compound removal and the particle transmission rate of the gas-phase stripping module were firstly investigated. The results showed that gas-phase stripping module achieves a removal efficiency of 98.89% for gas-phase organic compounds, and the particle transmission rate ranges from 75.16% to 91.15% for particles with the diameters between 295 and 375 nm. Subsequently, the effectiveness of the aerodynamic lens was studied through theoretical simulations. The simulation results indicated that the transmission rate of particles in the diameters of 0.36-6.0 μm is above 90% in the designed aerodynamic lens. Finally, The designed aerodynamic lens sampling system with a homemade proton transfer reaction mass spectrometer (PTR-MS) was integrated to develop an aerodynamic lens-PTR-MS device. This device was tested by detecting simulated aerosol samples containing reaction products of α-pinene and ozone. The mass spectrometry results demonstrated that the intensity changes of the examined ten ions are closely related to the presence of α-pinene, confirming that the device can achieve online detection of organic compounds in aerosols ranging from submicron to several micrometers.

The situation of coal as the stabilizer guarantee the energy safety in China cannot be changed in the short term, and it will continue to face the problems of coal resource protection and the low utilization rate of coal-based solid waste. Through innovative mining methods, improving the recovery rate of coal resources and the large-scale disposal of coal-based solid waste, a new path is being paved for the green and sustainable development of the coal industry. Based on the in-depth research on the development status of coal mining technology, a new roadway excavation method of “excavation-backfill-retention” is proposed. This paper systematically discusses the scientific problems and key technologies of the “excavation-backfill-retention” construction method from three aspects: rapid excavation, continuous and efficient backfilling and safe construction of large-section roadways. The research results show that ① aiming at the engineering problems such as the fast excavation of large section roadway and the stability control of surrounding rock of heading face, three scientific problems are summarized: the matching mechanism between coal and rock characteristics and cutting parameters of roadway boring machine, the spatial transfer mechanism of overburden load and the deformation mechanism of surrounding rock, the interaction relationship between anchor/cable roof and support mechanism. The technology system has been built, which is based on the real-time sensing of the geological environment in the excavation area, the intelligent cooperative operation of the multi-process of falling, loading and transporting coal, the aging control of surrounding rock of the drilling anchor support together with excavation, the anti-leakage and ventilation optimization of the large section roadway. ② The scientific problems of continuous and efficient backfilling are summarized from the two aspects of timely construction of large section roadway bearing system and its bearing performance regulation, including the co-bearing mechanism of background coal anchor/cable, the hydration consolidation mechanism of multi-component solid waste base backfill materials, and the space-time evolution law of physical and mechanical characteristics of backfill are clarified. A continuous and efficient backfill key technology system with the core of safe and efficient backfill space construction, backfill material performance control and backfill material flow-consolidation perception has been established. The breakthrough of relevant theories and technologies can provide a theoretical basis for raw material selection and ratio design of backfill materials, additive development/selection and working performance control, excavation rate and backfill step optimization design, consolidation monitoring of backfill body, etc. ③ Based on the key problems of roadway safety and surrounding rock easy to break, sheet and damage in the whole life cycle, the paper elaborates three scientific problems: the spatial and temporal distribution characteristics of stress field of roadway surrounding rock, the evolution mechanism of roadway deformation and damage, the engineering quality monitoring and stability regulation theory of roadway surrounding rock. The key technology system is formed with the intelligent stability warning of the rock surrounding the roadway and the deformation control of the rock surrounding the roadway as the core. It is of great significance to conduct the scientific research and technical demonstration of the “excavation-backfill-retention” construction method in coal mines, and to realize the synergy of large-scale solid waste disposal, efficient coal pillar section recovery and rapid roadway excavation, which can promote the green and low-carbon transformation and development of the coal industry.

Abstract Background The oxidative system plays an important role in the pathogenesis of schizophrenia. Inconsistent associations were found between hyperbilirubinemia and psychopathology as well as glycolipid metabolism in patients with schizophrenia at different episodes. This current study aimed to examine these associations in patients with acute-episode and drug-free (AEDF) schizophrenia. Methods This is a retrospective study using 5 years of data from May 2017 to May 2022 extracted from the electronic medical record system of Chaohu Hospital of Anhui Medical University. Healthy controls (HCs) from the local medical screening center during the same period were also included. Participants’ data of the bilirubin levels [total bilirubin (TB), conjugated bilirubin (CB), unconjugated bilirubin (UCB)], glycolipid metabolic parameters and the score of the Brief Psychiatric Rating Scale (BPRS) were collected. Results A total of 1468 case records were identified through the initial search. After screening, 89 AEDF patients and 100 HCs were included. Compared with HCs, patients had a higher CB level, and lower levels of glycolipid metabolic parameters excluding high density lipoprotein-cholesterol (HDL-C) (all P

Abstract Background Ginger is a common aromatic vegetable with a wide range of functional ingredients and considerable medicinal and nutritional properties. Numerous studies have shown that ginger and its active ingredients have suppressive effects on manifold tumours, including ovarian cancer (OC). However, the molecular mechanism by which ginger inhibits OC is not clear. The aim of this study was to investigate the function and mechanism of ginger in OC. Methods The estimation of n6-methyladenosine (m6A) levels was performed using the m6A RNA Methylation Quantification Kit, and RT-qPCR was used to determine the expression of m6A-related genes and proteins. The m6A methylationome was detected by MeRIP-seq, following analysis of the data. Differential methylation of genes was assessed utilizing RT-qPCR and Western Blotting. The effect of ginger on SKOV3 invasion in ovarian cancer cells was investigated using the wound healing assay and transwell assays. Results Ginger significantly reduced the m6A level of OC cells SKOV3. The 3’UTR region is the major site of modification for m6A methylation, and its key molecular activities include Cell Adhesion Molecules, according to meRIP-seq results. Moreover, it was observed that Ginger aids significantly in downregulating the CLDN7, CLDN11 mRNA, and protein expression. The results of wound healing assay and transwell assay showed that ginger significantly inhibited the invasion of OC cells SKOV3. Conclusions Ginger inhibits ovarian cancer cells’ SKOV3 invasion by regulating m6A methylation through CLDN7, CLDN11, and CD274.

Abstract Massive increases in the risks of depressive disorders and the ensuing suicide have become the overarching menace for children/adolescents. Despite global consensus to instigate psychological healthcare policy for these children/adolescents, their effects remain largely unclear neither from a small amount of official data nor from small-scale scientific studies. More importantly, in underprivileged children/adolescents in lower-middle-economic-status countries/areas, the data collection may not be as equally accessible as in developed countries/areas, thus resulting in underrepresented observations. To address these challenges, we released a large-scale and multi-center cohort dataset (n = 249,772) showing the effects of primary psychological healthcare on decreasing depression and suicidal ideation in these children/adolescents who were underrepresented in previous studies or current healthcare systems, including unattended children/adolescents, orphans, children/adolescents in especially difficult circumstances, and “left-behind” and “single-parenting” children/adolescents. We provided all individual data recording the depressive symptoms and suicide ideation that had been collected at baseline (Oct 2022) and half-year follow-up (May 2023) from practicing this psychological healthcare system.

Abstract Purpose Previous observational studies have revealed a potential link between non-alcoholic fatty liver disease (NAFLD) and gestational diabetes mellitus (GDM), but their causal relationship remains unclear. Thus, this study aimed to examine whether a causal link exists between genetically determined NAFLD and GDM. Methods Utilizing publicly accessible genome-wide association studies (GWAS), a two-sample bidirectional Mendelian randomization (MR) analysis was conducted. The GWASs data pertaining to NAFLD and GDM were obtained from the UK Biobank Consortium and FinnGen database in primary analysis, respectively. The random-effects inverse variance weighted (IVW) method was utilized as primary analysis method. Several sensitivity analyses were utilized to verify the robustness of the results. Additionally, we also analyzed the causal effect of potential shared influencing factors on these two conditions. Results The result of the IVW method showed that there was no significant causal relationship between genetically determined NAFLD and GDM (OR = 0.98, 95% CI: 0.90–1.07, P = 0.691). Similarly, our reverse MR analysis failed to detect a significant causal effect of GDM on NAFLD (OR = 1.14, 95% CI: 0.97–1.36, P = 0.118). Sensitivity analyses further confirmed the robustness of the results. Moreover, we found that genetically determined body mass index, waist-to-hip ratio, triglycerides, and television viewing time may be positively correlated with NAFLD and GDM, while high-density lipoprotein cholesterol and apolipoprotein A-I may both be negatively correlated with NAFLD and GDM. Conclusions The current bidirectional MR study failed to provide sufficient genetic evidence for the causal relationship between NAFLD and GDM.

Abstract DNA damage repair (DDR) genes are known to be closely associated with the progression of Hepatocellular carcinoma (HCC). Here we report a unique cluster of “deletion-up” genes in HCC, which are accordantly overexpressed in HCC patients and predict the unfavorable prognosis. Binding motif analysis and further validation with ChIP-qPCR unveil that the AP-2α directly modulate the transcription of critical DNA repair genes including TOP2A, NUDT1, POLD1, and PARP1, which facilitates the sanitation of oxidized DNA lesions. Structural analysis and the following validation identify LEI110 as a potent AP-2α inhibitor. Together, we demonstrate that LEI110 stabilizes AP-2α and sensitizes HCC cells toward DNA-damaging reagents. Altogether, we identify AP-2α as a crucial transcription modulator in HCC and propose small-molecule inhibitors targeting AP-2α are a promising novel class of anticancer agents. Our study provides insights into the concept of macroscopic inhibition of DNA damage repair-related genes in cancer treatment.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3′-untranslated region (3′ UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

Sepsis is a severe systemic infectious disease that often leads to multi-organ dysfunction. One of the common and serious complications of sepsis is renal injury. In this study, we aimed to investigate the potential mechanistic role of a novel compound called H-151 in septic kidney injury. We also examined its impact on renal function and mouse survival rates. Initially, we confirmed abnormal activation of the STING–TBK1 signaling pathway in the kidneys of septic mice. Subsequently, we treated the mice with H-151 and observed significant improvement in sepsis-induced renal dysfunction. This was evidenced by reductions in blood creatinine and urea nitrogen levels, as well as a marked decrease in inflammatory cytokine levels. Furthermore, H-151 substantially improved the seven-day survival rate of septic mice, indicating its therapeutic potential. Importantly, H-151 also exhibited an inhibitory effect on renal apoptosis levels, further highlighting its mechanism of protecting against septic kidney injury. These study findings not only offer new insights into the treatment of septic renal injury but also provide crucial clues for further investigations into the regulatory mechanisms of the STING–TBK1 signaling pathway and potential drug targets.

To expedite the achievement of the ''30–60 double carbon'' goal, it is imperative to create a novel, low-carbon, cost-effective, and sustainable backfill material for mining purposes. Against this background, this paper investigates the workability, carbonation performance and carbon sequestration capacity of coal gangue (CG), magnesium slag (MS) and fly ash (FA) as magnesium coal slag solid waste backfill material. The results of the study show that: (1) The rheological properties of the CFM fresh slurry conform to the Herschel-Balkley (H-B) model, and its flowability meets the requirements of mine backfill transport. With increasing MS content, the yield stress, apparent viscosity, thixotropy and shear thickening of CFM fresh slurry increase, and the micro-slump and diffusion diameter decrease. (2) Carbonation curing can effectively improve the early UCS of CFM. The highest UCS of CFM was 8.854 MPa after 7 days of carbonation curing, which was 27.84 times higher than that of standard curing. In addition, the UCS of CFM increased with the increase of curing age and MS content. (3) CFM produces a large number of carbonation products such as calcium carbonate after carbonation curing, which makes its microstructure denser. (4) CFM can absorb up to 14.55 % of CO2 after carbonation. (5) The volume stability of CFM is significantly improved after carbonation curing. In summary, CFM is not only a new type of low-cost, low-carbon and sustainable solid waste backfill material, but its practical application in the field of mine backfilling also has great potential for the realization of magnesium coal slag solid waste resource utilization and CO2 sequestration.

Abstract Background Particulate β‐glucans (WGP) are natural compounds with regulatory roles in various biological processes, including tumorigenesis and inflammatory diseases such as allergic asthma. However, their impact on mast cells (MCs), contributors to airway hyperresponsiveness (AHR) and inflammation in asthma mice, remains unknown. Methods C57BL/6 mice underwent repeated OVA sensitization without alum, followed by Ovalbumin (OVA) challenge. Mice received daily oral administration of WGP (OAW) at doses of 50 or 150 mg/kg before sensitization and challenge. We assessed airway function, lung histopathology, and pulmonary inflammatory cell composition in the airways, as well as proinflammatory cytokines and chemokines in the bronchoalveolar lavage fluid (BALF). Results The 150 mg/kg OAW treatment mitigated OVA‐induced AHR and airway inflammation, evidenced by reduced airway reactivity to aerosolized methacholine (Mch), diminished inflammatory cell infiltration, and goblet cell hyperplasia in lung tissues. Additionally, OAW hindered the recruitment of inflammatory cells, including MCs and eosinophils, in lung tissues and BALF. OAW treatment attenuated proinflammatory tumor necrosis factor (TNF)‐α and IL‐6 levels in BALF. Notably, OAW significantly downregulated the expression of chemokines CCL3, CCL5, CCL20, CCL22, CXCL9, and CXCL10 in BALF. Conclusion These results highlight OAW's robust anti‐inflammatory properties, suggesting potential benefits in treating MC‐dependent AHR and allergic inflammation by influencing inflammatory cell infiltration and regulating proinflammatory cytokines and chemokines in the airways.

Liquid biopsies including pleural fluid or plasma are commonly applied for patients with advanced non-small cell lung cancer (NSCLC) and pleural effusion (PE) to guide the treatment. ALK-TKIs are the first options for patients with ALK-positive mutations and combining ALK-TKIs with angiogenic agents may improve survival. We report here one case with ALK-positive lung adenocarcinoma in which the patient achieved a prolonged progression-free survival (PFS) of 97 months after undergoing precise pleural effusion NGS and receiving combined bevacizumab treatment following multiple-line ALK-TKI resistance.

This study aimed to explore the potential effects of 8-week parents-accompanied swimming on the physical capacity and intelligence of preschool children in China. Thirty-six boys (mean age 3.56 ± 0.27 years) were divided into three groups: the traditional physical exercise group (TP, n = 12), the accompanied swimming group (AS, n = 12) and the independent swimming group (IS, n = 12). Participants’ physical capacity was assessed before and after the intervention using the following indicators: height, weight, distance of tennis ball throw, standing long jump distance, time for the 10-meter shuttle run, time for a two-legged continuous jump, sit-and-reach distance, and time on the walking balance beam. Intelligence was assessed at three points: pre-test, mid-test after 4 weeks, and post-test. Data were analyzed using a two-way repeated measures ANOVA, Bonferroni test (p

Abstract Background Depressive symptoms associated with schizophrenia are closely related to stigma and quality of life(QOL). There is, however, no thorough research on the connection between the three. This study sought to investigate the possible factors influencing depressive symptoms in people with schizophrenia (PWS) in rural Chaohu, China, and to further explore the role of depression severity in stigma and lifestyle quality. Methods Eight hundred twenty-one schizophrenia patients accomplished the entire scale, including the 9-item Patient Health Questionnaire (PHQ-9), the Social Impact Scale (SIS), and the World Health Organization on Quality of Life Brief Scale(WHOQOL—BREF). A straightforward mediation model was employed to determine if the intensity of the depression could act as a mediator between stigma and QOL. Results Two hundred seventy-nine schizophrenia patients (34%) had depressive symptoms (PHQ ≥ 10), and 542 patients (66%) did not (PHQ

Abstract Background RC48-antibody-drug conjugates (ADC) link humanized anti-HER2 immunoglobulin with monomethyl auristatin E (MMAE). Clinical trials suggest promising antitumor activity in HER2-expressing solid tumors. This study probes RC48-ADC’s efficacy and safety in patients with HER2-expressing advanced or metastatic solid tumors. Method Data was collected from 23 advanced cancer patients treated with RC48-ADC at our oncology center between July 2021 and December 2022. These patients exhibited at least 1 + expression of HER2 immunohistochemistry, had previously experienced at least one failed systemic chemotherapy, and were treated with RC48-ADC until the occurrence of intolerable adverse reactions or disease progression. The primary endpoint was the disease control rate (DCR), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Results 23 of 25 screened patients received RC48 treatment. The ORR was 43.5% (95% CI, 23.2-63.7%) with a median PFS of 6.0 months (95% CI, 4.8–7.4). In the low-to-medium HER2 expression subgroup, ORR was 37.5%, median PFS 5.75 months. In the high HER2 expression subgroup, ORR was 57.1%, median PFS 7 months. For the cohort combining RC48 with PD-1 inhibitors, ORR was 53.8%, median PFS 8 months. In the concurrent local radiation therapy subgroup, ORR was 40.0%, median PFS 6.0 months. Treatment-related adverse events (TRAEs) were anemia (60.8%), leukopenia (56.2%), raised transaminases (52.17%), and neutropenia (43.5%). Five patients (21.7%) experienced Grade 3 symptoms, including anemia (21.7%) and neutropenia (14.0%). No Grade 4 adverse reactions or deaths were reported. Conclusion RC48-ADC shows promising efficacy and manageable safety in HER2-expressing advanced or metastatic solid tumor patients.

Abstract Although physiological measurements, subjective evaluation and other methods have been applied to visual attention research, architects still lack a systematic quantitative classification method when assessing the visual attention to built colonial heritage. This study aimed to investigate the relationship between people’s visual behaviour and subjective evaluation when observing built colonial heritage and to construct a prediction model based on eye-movement metrics and subjective evaluation indicators to distinguish the visual attention to built colonial heritage. This study recorded data from 54 participants while observing five scenes of built colonial heritage, and the results showed that participants had different visual behaviours and subjective evaluations when viewing built colonial heritage in different scenes. And visual attention to built colonial heritage was negatively correlated with the average saccades peak velocity and average saccades amplitude and positively correlated with the average pupil diameter; visual attention was correlated with 12 subjective evaluation indicators. The eye-movement metrics and subjective evaluation indicators with correlation to visual attention were used as input variables to construct a prediction model of visual attention to built colonial heritage based on the BP neural network. Different built colonial heritage’s low, middle and high visual attention were identified with high accuracy (74.46%). This quantitative method can help architects to measure the visual attention to built colonial heritage to develop conservation and renewal strategies.

BackgroundThe role of drug repositioning in the treatment of ovarian cancer has received increasing attention. Although promising results have been achieved, there are also major controversies.MethodsIn this study, we conducted a drug-target Mendelian randomisation (MR) analysis to systematically investigate the reported effects and relevance of traditional drugs in the treatment of ovarian cancer. The inverse-variance weighted (IVW) method was used in the main analysis to estimate the causal effect. Several MR methods were used simultaneously to test the robustness of the results.ResultsBy screening 31 drugs with 110 targets, FNTA, HSPA5, NEU1, CCND1, CASP1, CASP3 were negatively correlated with ovarian cancer, and HMGCR, PLA2G4A, ITGAL, PTGS1, FNTB were positively correlated with ovarian cancer.ConclusionStatins (HMGCR blockers), lonafarnib (farnesyltransferase inhibitors), the anti-inflammatory drug aspirin, and the anti-malarial drug adiponectin all have potential therapeutic roles in ovarian cancer treatment.

Abstract Photodynamic therapy (PDT) is a promising treatment against bacteria‐caused infections. By producing large amounts of reactive oxygen species (ROS), PDT can effectively eliminate pathogenic bacteria, without causing drug resistance. However, excessive ROS may also impose an oxidative stress on surrounding tissues, resulting in local inflammation. To avoid this major drawback and limit pro‐inflammation during PDT, this work prepared a supramolecular photosensitizer (TPP‐CN/CP5) based on host‐guest interactions between a cysteine‐responsive cyano‐tetraphenylporphyrin (TPP‐CN) and a water‐soluble carboxylatopillar[5]arene (CP5). TPP‐CN/CP5 not only possesses excellent photodynamic antibacterial properties, but also shows good anti‐inflammatory and cell protection capabilities. Under 660 nm light irradiation, TPP‐CN/CP5 could rapidly produce abundant ROS for sterilization. After the PDT process, the addition of cysteine (Cys) triggers the release of H2S from TPP‐CN. H2S then stops the induced inflammation by inhibiting the production of related inflammatory factors. Both in vitro and in vivo experiments show the excellent antibacterial effects and anti‐inflammatory abilities of TPP‐CN/CP5. These results will certainly promote the clinical application of PDT in the treatment of bacterial infectious diseases.

Aim: To survey the mental health symptoms, job satisfaction, and quality of life of psychiatric nurses working at psychiatric hospitals in China in the early stage of the pandemic, and to examine their associated factors. Methods: We conducted a national survey in 41 tertiary psychiatric hospitals. The Depression Anxiety Stress Scale-Chinese version (DASS-C21), the Minnesota Satisfaction Questionnaire (MSQ), and the World Health Organization Quality of Life-Chinese version (WHOQOL-BREF-CHN) were used to assess participants’ mental health, job satisfaction, and quality of life, respectively. The study was reported in accordance with STROBE guidelines. Results: In total, 9193 nurses completed the survey, the sample was predominantly female (79.2%). The overall prevalence of reported depressive, anxious, and stress symptoms was 27.5%, 30.8%, and 14.4%, respectively. The general job satisfaction level of all participants was about 76.8%. The quality of life and general health status were about 22.3% and 23.2%, respectively. Multiple linear regression analysis showed that the experience of frontline work and negative attitudes toward COVID-19 were positively associated with mental health symptoms and negatively associated with job satisfaction and quality of life (all P

The digital economy has emerged as an innovative economy that utilizes digital technologies and electronic communication to conduct economic and business activities across a wide range of sectors, including e-commerce, digital marketing, digital financial services, software development, computer games, and cloud services. The use of digital technologies and electronic communication has resulted in a significant shift towards online business interactions, leading to improved user experiences, faster processing, and easier access to services and products. The digital economy is recognized as a primary driver of economic growth and development in many advanced countries and is continually expanding due to its significant impact on economic and business activities. In this research, we aim to examine the digital economy and its impact on businesses and users, evaluating the opportunity for easy and quick access to products and services that lead to increased efficiency and productivity. The digital economy has significant impacts on various economic, social, and cultural fields, including changes in the way people work and interact with each other, promoting more flexible and remote work arrangements, and increasing global connectivity. Additionally, the digital economy has impacted education, healthcare, entertainment, and other sectors. Advances in technology and electronic communication have driven the global economy towards digitization, and the role of the digital economy in advancing global digitalization is critical. Its impact is expected to continue to increase in the coming years.

ObjectivesTo study the socio-demographic characteristics and the prevalence of depression, anxiety, and stress among clinical therapists in China during the early Coronavirus disease 2019 (COVID-19) pandemic and to identify associated factors.MethodThis cross-sectional study was part of a multicenter, nationally representative survey conducted through WeChat from January 2021 to March 2021. Data, including socio-demographics, health-related behaviors, and information on whether they participated in the frontline work of treating COVID-19, were collected anonymously. Respondents also completed the Depression Anxiety Stress Scales-21 (DASS-21).ResultsIn total, 396 clinical therapists in the selected hospitals completed the questionnaires, with a response rate of 89.0%. Respondents were predominantly female (77.3%). About 6.6% of the participants were current tobacco users, and 20.7% had participated in the frontline work of treating COVID-19. Overall, 22.0%, 17.9%, and 8.8% of participants were classified as having clinically meaningful depression, anxiety, and stress, respectively, based on DASS-21 scores. Multiple logistic regression in Model 1 and Model 2 showed that depression, anxiety, and stress were associated with regular physical activity and frequent insomnia (all, p < 0.05). In anxiety model 2, the associated factors for anxiety during the pandemic were identified as education (master’s degree or more, OR=0.520; 95% CI=0.283-0.955), marital status (single, OR=2.064; 95% CI=1.022-4.168), tobacco use (OR=4.265; 95% CI=1.352-13.454), regular physical activity (OR=0.357; 95% CI=0.192-0.663), frequent insomnia (OR=6.298; 95% CI =2.522-15.729), and participation in the frontline work of treating COVID-19 (OR=3.179; 95% CI=1.697-5.954). The COVID-19 epidemic did not significantly increase the depression and stress levels among clinical therapists, but it did significantly increase anxiety levels.ConclusionDuring the COVID-19 pandemic, depression, anxiety and stress were relatively common among clinical therapists in China. Regular physical activity and good sleep were important protective factors against emotional problems. Therefore, encouraging regular physical activity and actively addressing clinical therapists’ sleep problems is beneficial to improving the ability to cope with negative emotions. The COVID-19 epidemic significantly increased anxiety, and awareness and interventions should be recommended to reduce anxiety among clinical therapists during the COVID-19 pandemic.

Abstract Background Lung cancer is one of the most common malignant cancers worldwide. Previous studies have shown that Afzelin, a flavonoid, possesses anticancer activity. The aim of this study was to explore Afzelin’s effect on lung cancer cells and delineate potential anti-cancer mechanism. Methods The effect of Afzelin on cell viability, proliferation, and apoptosis of lung cancer cells i.e., A549 and H1299 cells, was studied. The targets for Afzelin in lung cancer were predicted using SwissTargetPrediction, Next, the GO analysis and pathway enrichment were analyzed using String. For in vitro studies, the overexpression plasmid of NQO2, the identified target of Afzelin, was transfected into Afzelin-treated cells to verify the regulatory role of Afzelin on its target and signaling pathway. Results In in vitro studies, Afzelin markedly inhibited cell viability, proliferation, and raised apoptotic rate of A549 and H1299 cells. In addition, Afzelin activated endoplasmic reticulum (ER) stress and increased ATP, HMGB1, and CRT levels in lung cancer cells, indicating that Afzelin induced immunogenic cell death (ICD). SwissTargetPrediction identified NQO2 as a target of Afzelin. Further, Afzelin markedly inhibited NQO2 protein expression and in turn, overexpression of NQO2 attenuated the effect of Afzelin on A549 and H1299 cells. Conclusion Afzelin inhibits lung cancer progression by targeting NQO2, in turn, activating ER stress and inducing ICD.

Abstract In this study, we examined the impact of demyelinating and neuroinflammation on trigeminal neuralgia (TN) by utilizing models of chronic constriction injury to the infraorbital nerve (CCI). The CCI rats were treated with either VX-765 (an inhibitor of caspase-1) or a control solution of PBS/DMSO to observe the effects on neurobehavioral and neuropathological outcomes. The histochemical changes, pyroptosis-related proteins were assessed using immunohistochemistry, Elisa, and western blotting. RSC96 cells were pretreated with belnacasan (VX-765, an inhibitor of caspase-1), Gasdermin D(GSDMD)-targeting siRNAs, cobalt protoporphyrin (CoPP) or zinc protoporphyrin (Znpp) before being exposed to H2O2. Following these treatments, the Reactive oxygen species (ROS) level, cell viability, percentage of pyroptosis, pyroptosis-related proteins, nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 level was measured. The scanning electron microscopy revealed increased ball-like bulge and membrane pore formation in the CCI group. In the CCI and CCI+ Vehicle groups, we found ROS level and expression of pyroptosis-related proteins increased. While, treatment with VX-765resulted in a decreased expression of GSDMD, IL-1, IL-18, and caspase-1 decreased. In the in-vitro study, RSC96 cells showed mild pyroptosis and overall mild edema after being exposed to H2O2. The ROS level, percentage of pyroptosis, pyroptosis-related proteins, Nrf2 and HO-1 level increased significantly in the H2O2 group. While, the percentage of pyroptosis and pyroptosis-related proteins decreased significantly in the H2O2 + VX-765 group, H2O2 + siRNA group, and H2O2 + VX-765 + siRNA group. After treatment with HO-1-inhibitor Znpp and HO-1-activator Copp, the percentage of pyroptosis and pyroptosis-related proteins increased and decreased significantly respectively. In conclusions, the pyroptosis of Schwann cell in the CCI model generated the demyelination of TN nerve. The ROS is an upstream event of NLRP3 inflammasome activation which induced eventual pyroptosis. The Nrf2/HO-1 signaling pathway could protect the H2O2-induced pyroptosis in RSC96 cells.

Abstract Genetic engineering of immune cells has opened new avenues for improving their functionality but it remains a challenge to pinpoint which genes or combination of genes are the most beneficial to target. Here, we conduct High Multiplicity of Perturbations and Cellular Indexing of Transcriptomes and Epitopes (HMPCITE-seq) to find combinations of genes whose joint targeting improves antigen-presenting cell activity and enhances their ability to activate T cells. Specifically, we perform two genome-wide CRISPR screens in bone marrow dendritic cells and identify negative regulators of CD86, that participate in the co-stimulation programs, including Chd4, Stat5b, Egr2, Med12, and positive regulators of PD-L1, that participate in the co-inhibitory programs, including Sptlc2, Nckap1l, and Pi4kb. To identify the genetic interactions between top-ranked genes and find superior combinations to target, we perform high-order Perturb-Seq experiments and we show that targeting both Cebpb and Med12 results in a better phenotype compared to the single perturbations or other combinations of perturbations.

A simple, mild and efficient method was proposed to construct fused tricyclic skeletons based on Mannich reaction. This work not only develops a new method to construct the tricyclic skeletons effectively, but also provides a new insight into the fused tricyclic skeletons containing flexible ring, which will greatly contribute to the research and development of the tricyclic energetic compounds. The relationship of structure-activity was studied by weak interactions calculation, single crystal structures analysis, electrostatic potentials calculation. The experimental and theoretical investigations suggest that the fused tricyclic skeleton containing flexible ring possesses better thermal stability and can be derivatized more easily compared with the similar aromatic fused tricyclic skeleton. Besides, the energetic derivates based on the fused tricyclic skeleton containing flexible ring possess good comprehensive properties: 2 (D ​= ​7726 ​m ​s−1, p ​= ​22.7 ​GPa) and 4 (D ​= ​8151 ​m ​s−1, p ​= ​26.3 ​GPa). All these results suggest that the fused tricyclic skeleton containing flexible ring is an ideal candidate to construct energetic compounds.

The sandwich plate (SP) with supported mass can model structural systems such as platform or floor with installed vibration-sensitive apparatus under random loading. The stochastic optimal control (in time domain) of periodic (in space) viscoelastomer (VE) SP with supported mass subjected to random excitation is an important research subject, which can fully use VE controllability, but it is a challenging problem on optimal bounded parametric control (OBPC). In this paper, a stochastic OBPC for periodic VESP with supported mass subjected to random base loading is proposed according to the stochastic dynamical programming (SDP) principle. Response-reduction capability using the proposed OBPC is studied to demonstrate further control effectiveness of periodic SP via SDP. Controllable VE core modulus of SP is distributed periodically in space. Differential equations for coupling vibration of periodic SP with supported mass are derived and transformed into multi-dimensional system equations with parameters as nonlinear functions of bounded control. The OBPC problem is established by the system equations and performance index with bound constraint. Then, an SDP equation is derived according to the SDP principle. The OBPC law is obtained from the SDP equation under bound constraint. Optimally controlled responses are calculated and compared with passively controlled responses to evaluate control effectiveness. Numerical results on responses and statistics of SP via the proposed OBPC show further remarkable control effectiveness.

Yellowing leaves are ideal materials for studying the metabolic pathways of photosynthetic pigment chloroplast development, and the mechanism of photosynthetic systems. Here, we obtained a triploid material HCC (2n = 3x = 26), which was derived from hybridization between the artificial tetraploid Cucumis × hytivus (2n = 4x = 38, HHCC) and the cultivated cucumber Cucumis sativus (2n = 2x = 14, CC), and this triploid HCC showed obvious leaf yellowing characteristics. Phenotypic observation results showed that chloroplast development was impaired, the chlorophyll content decreased, and photosynthesis decreased in yellowing HCC leaves. The transcriptome results indicated that HCC-GLK is significantly downregulated in HCC and participates in the regulation of leaf yellowing. GO enrichment analysis revealed that differential genes were enriched in the heme binding and tetrapyrrole binding pathways related to leaf color. KEGG enrichment analysis revealed that differential genes were predominantly enriched in photosynthesis-related pathways. The experimental results of VIGS and yeast hybridization showed that silencing the GLK gene can induce leaf yellowing in cucumber plants, and the GLK protein can affect plant chloroplast development by interacting with the CAB3C protein (light-harvesting chlorophyll a/b binding) in the plant chlorophyll synthesis pathway. The current findings have not only enhanced our understanding of the regulatory mechanism of the GLK transcription factor in cucumber but also introduced novel insights and directions for investigating the molecular mechanism underlying polyploid leaf yellowing.

Thorough and precise gene structure annotations are essential for maximizing the benefits of genomic data and unveiling valuable genetic insights. The cucumber genome was first released in 2009 and updated in 2019. To increase the accuracy of the predicted gene models, 64 published RNA-seq data and 9 new strand-specific RNA-seq data from multiple tissues were used for manual comparison with the gene models. The updated annotation file (V3.1) contains an increased number (24,145) of predicted genes compared to the previous version (24,317 genes), with a higher BUSCO value of 96.9%. A total of 6231 and 1490 transcripts were adjusted and newly added, respectively, accounting for 31.99% of the overall gene tally. These newly added and adjusted genes were renamed (CsaV3.1_XGXXXXX), while genes remaining unaltered preserved their original designations. A random selection of 21 modified/added genes were validated using RT-PCR analyses. Additionally, tissue-specific patterns of gene expression were examined using the newly obtained transcriptome data with the revised gene prediction model. This improved annotation of the cucumber genome will provide essential and accurate resources for studies in cucumber.

With the improvement of the energy density and sensing accuracy of wearable devices, there is increasing interest in applying wearable electronics in daily life. However, traditional rigid plate-structured wearable devices cannot meet the human body’s wearing habits and make users may feel uncomfortable after wearing them for a long time. Fabric-type wearable electronics can be conformably coated on human skin without discomfort from mismatches in mechanical properties between the human body and electronics. Although state-of-the-art textile-based wearable devices have shown unique advantages in the field of e-textiles, real-world scenarios often involve stretching, bending, and wetting. Further efforts should be made to achieve “comfortable wearing” due to the great challenge of achieving both promising electrical properties and comfort in a single device. This review presents a comprehensive overview of the advances in smart fabric-based wearable electronics toward comfortable wearing, emphasizing their stretchability, hydrophobicity, air permeability, stability, and color-change abilities. Through addressing the challenges that persist in fabric-type wearable electronics, we are optimistic that these will be soon ubiquitous in our daily lives, offering exceptionally comfortable wearing experiences for health monitoring, sports performance tracking, and even fashion, paving the way for a more comfortable and technologically advanced future.

To develop a cost-effective, high-viscosity asphalt for porous asphalt pavement, we utilized SBS, tackifier, and solubilizer as the main raw materials, identified the optimal composition through an orthogonal experiment of three factors and three levels, and prepared a low-cost high-viscosity asphalt. We compared its conventional and rheological properties against those of rubber asphalt, SBS modified asphalt, and matrix asphalt, employing fluorescence microscopy and Fourier transform infrared spectroscopy for microstructural analysis. The results indicate that the optimal formula composition for high-viscosity asphalt was 4–5% styrene-butadiene-styrene (SBS) + 1–2% tackifier +0–3% solubilizer +0.15% stabilizer. The components evenly dispersed and the performances were enhanced with chemical and physical modification. Compared with SBS modified asphalt, rubber asphalt, and matrix asphalt, the softening point, 5 °C ductility, and 60 °C dynamic viscosity of high-viscosity asphalt were significantly improved, while the 175 °C Brookfield viscosity was equivalent to SBS modified asphalt. In particular, the 60 °C dynamic viscosity reaches 383,180 Pa·s. Rheological tests indicate that the high- and low-temperature grade of high-viscosity asphalt reaches 88–18 °C, and that high-viscosity asphalt has the best high-temperature resistance to permanent deformation and low-temperature resistance to cracking. It can save about 30% cost compared to commercially available high-viscosity asphalt, which is conducive to the promotion and application of porous asphalt pavement.