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Abstract Background Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. Methods All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. Discussion With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. Systematic review registration PROSPERO CRD42021272686.

Abstract Rare earth element (REE)-rich phosphorite in the Guizhou region mainly exists in the Doushantuo Formation and Gezhongwu Formation in early Cambrian strata, which are some of the important strata containing phosphorite resources in China. The early Cambrian Zhijin phosphorite in Guizhou Province, China, has high rare earth element and yttrium (REY) contents of up to 2500 ppm, with heavy REY (HREY) contents accounting for ~ 30% of the total REY contents. However, the specific controlling source and environment of phosphorite (especially the REEs in Zhijin phosphorite) are still unsolved. Through field geological investigations; mineralogical, geochemical, Sr–Nd isotope analyses; and tectonic characteristics, the material source, sedimentary environment and seawater dynamics of REEs in phosphorite are studied. It is considered that the REEs enriched in the Zhijin phosphorite are mainly affected by precipitation from hydrothermal fluid. Moreover, from the late Ediacaran to the early Cambrian, the depositional environment from the bottom to the top of the water tended to be hypoxic, and the activity of hot water fluid tended to be strong. The change in redox conditions is closely related to the rise and fall of sea level. Combined with the tectonic background, these results show that the weakly oxidized environment may be an important factor controlling the enrichment of REEs. The enrichment of REEs may be closely related to volcanic hydrothermal activity, later diagenesis and seawater dynamics.

Abstract Background Immune checkpoint inhibitors (ICIs) can lead to life-threatening pneumonitis, and pre-existing interstitial lung abnormalities (ILAs) are a risk factor for checkpoint inhibitor pneumonitis (CIP). However, the subjective assessment of ILA and the lack of standardized methods restrict its clinical utility as a predictive factor. This study aims to identify non-small cell lung cancer (NSCLC) patients at high risk of CIP using quantitative imaging. Methods This cohort study involved 206 cases in the training set and 111 cases in the validation set. It included locally advanced or metastatic NSCLC patients who underwent ICI therapy. A deep learning algorithm labeled the interstitial lesions and computed their volume. Two predictive models were developed to predict the probability of grade ≥ 2 CIP or severe CIP (grade ≥ 3). Cox proportional hazard models were employed to analyze predictors of progression-free survival (PFS). Results In a training cohort of 206 patients, 21.4% experienced CIP. Two models were developed to predict the probability of CIP based on different predictors. Model 1 utilized age, histology, and preexisting ground glass opacity (GGO) percentage of the whole lung to predict grade ≥ 2 CIP, while Model 2 used histology and GGO percentage in the right lower lung to predict grade ≥ 3 CIP. These models were validated, and their accuracy was assessed. In another exploratory analysis, the presence of GGOs involving more than one lobe on pretreatment CT scans was identified as a risk factor for progression-free survival. Conclusions The assessment of GGO volume and distribution on pre-treatment CT scans could assist in monitoring and manage the risk of CIP in NSCLC patients receiving ICI therapy. Clinical relevance statement This study’s quantitative imaging and computational analysis can help identify NSCLC patients at high risk of CIP, allowing for better risk management and potentially improved outcomes in those receivingICI treatment.

Failure to obtain timely fire services will lead to thermal runaway phenomenon, which will seriously threaten the lives of people and property safety. In this study, a dynamic method was proposed to estimate fire service accessibility based on real-time traffic. To validate the method, a total of 110,055 POls extracted from online maps and existing 12 fire stations in Yiyang were used as fire service demand points and supply points. Travel times of fire trucks from supply points to demand points were calculated based on real-time traffic, and a total of 550,275 valid samples were obtained. The results showed that the ≥10 min fire service coverage rate in Yiyang is only 71.60 %. Based on the distribution area of demand points ≥10 min, the locations of three optimization solutions of new fire stations are proposed. By calculating the total average time (TAT) of the three optimization solutions of proposed new fire stations, it is concluded that TAT decreases by 743.99 s, 99.72 s, 92.59 s, respectively. From perspectives of safety and economy, the construction of the 10 fire stations of optimized solution I will effectively improve the regional fire service level.

Abstract Background Mitochondria, which serve as the fundamental organelle for cellular energy and metabolism, are closely linked to the growth and survival of cancer cells. This study aims to identify and assess Sideroflexin1 (SFXN1), an unprecedented mitochondrial gene, as a potential prognostic biomarker for lung adenocarcinoma (LUAD). Methods The mRNA and protein levels of SFXN1 were investigated based on the Cancer Genome Atlas (TCGA) LUAD dataset, and then validated by real-time quantitative PCR, Western Blotting and immunohistochemistry from our clinical samples. The clinical correlation and prognostic value were evaluated by the TCGA cohort and verified via our clinical dataset (n = 90). The somatic mutation, drug sensitivity data, immune cell infiltration and single-cell RNA sequencing data of SFXN1 were analyzed through public databases. Results SFXN1 was markedly upregulated at both mRNA and protein levels in LUAD, and high expression of SFXN1 were correlated with larger tumor size, positive lymph node metastasis, and advanced clinical stage. Furthermore, SFXN1 upregulation was significantly associated with poor clinical prognosis. SFXN1 co-expressed genes were also analyzed, which were mainly involved in the cell cycle, central carbon metabolism, DNA repair, and the HIF-1α signaling pathway. Additionally, SFXN1 expression correlated with the expression of multiple immunomodulators, which act to regulate the tumor immune microenvironment. Results also demonstrated an association between SFXN1 expression and increased immune cell infiltration, such as activated CD8 + T cells, natural killer cells (NKs), activated dendritic cells (DCs), and macrophages. LUAD patients with high SFXN1 expression exhibited heightened sensitivity to multiple chemotherapies and targeted drugs and predicted a poor response to immunotherapy. SFXN1 represented an independent prognostic marker for LUAD patients with an improved prognostic value for overall survival when combined with clinical stage information. Conclusions SFXN1 is frequently upregulated in LUAD and has a significant impact on the tumor immune environment. Our study uncovers the potential of SFXN1 as a prognostic biomarker and as a novel target for intervention in LUAD.

Extracellular polymeric substances (EPS) constitutes crucial elements within bacterial biofilms, facilitating accelerated antimicrobial resistance and conferring defense against the host's immune cells. Developing precise and effective antibiofilm approaches and strategies, tailored to the specific characteristics of EPS composition, can offer valuable insights for the creation of novel antimicrobial drugs. This, in turn, holds the potential to mitigate the alarming issue of bacterial drug resistance. Current analysis of EPS compositions relies heavily on colorimetric approaches with a significant bias, which is likely due to the selection of a standard compound and the cross-interference of various EPS compounds. Considering the pivotal role of EPS in biofilm functionality, it is imperative for EPS research to delve deeper into the analysis of intricate compositions, moving beyond the current focus on polymeric materials. This necessitates a shift from heavy reliance on colorimetric analytic methods to more comprehensive and nuanced analytical approaches. In this study, we have provided a comprehensive summary of existing analytical methods utilized in the characterization of EPS compositions. Additionally, novel strategies aimed at targeting EPS to enhance biofilm penetration were explored, with a specific focus on highlighting the limitations associated with colorimetric methods. Furthermore, we have outlined the challenges faced in identifying additional components of EPS and propose a prospective research plan to address these challenges. This review has the potential to guide future researchers in the search for novel compounds capable of suppressing EPS, thereby inhibiting biofilm formation. This insight opens up a new avenue for exploration within this research domain.

Abstract Background Circulation dysfunction is a major contributing factor to thrombosis in patients with atrial fibrillation (AF) for which effective interventions are lacking. Growing evidence indicates that regulating the paraventricular nucleus (PVN), an autonomic control center, could offer a novel strategy for treating cardiovascular and circulatory diseases. Concurrently, electroacupuncture (EA) at Xinshu (BL15), a form of peripheral nerve stimulation, has shown efficacy in treating several cardiovascular conditions, although its specific mechanism remains unclear. This study aimed to assess the impact of EA at BL15 on circulatory dysfunction in a rat AF model and investigate the pivotal role of PVN neuronal activity. Methods To mimic the onset of AF, male SD rats received tail intravenous injection of ACh-CaCl2 and were then subjected to EA at BL15, sham EA, or EA at Shenshu (BL23). Macro- and micro-circulation function were evaluated using in vivo ultrasound imaging and laser doppler testing, respectively. Vasomotricity was assessed by measuring dimension changes during vascular relaxation and contraction. Vascular endothelial function was measured using myograph, and the activation of the autonomic nerve system was evaluated through nerve activity signals. Additionally, chemogenetic manipulation was used to block PVN neuronal activation to further elucidate the role of PVN activation in the prevention of AF-induced blood circulation dysfunction through EA treatment. Results Our data demonstrate that EA at BL15, but not BL23 or sham EA, effectively prevented AF-induced macro- and micro-circulation dysfunction. Furthermore, EA at BL15 restored AF-induced vasomotricity impairment. Additionally, EA treatment prevented abnormal activation of the autonomic nerve system induced by AF, although it did not address vascular endothelial dysfunction. Importantly, excessive activation of PVN neurons negated the protective effects of EA treatment on AF-induced circulation dysfunction in rats. Conclusion These results indicate that EA treatment at BL15 modulates PVN neuronal activity and provides protection against AF-induced circulatory dysfunction.

Micro-alloying Mg alloys with rare earth elements is an economical and promising way to improve their corrosion resistance. It is of great importance to understand their corrosion behavior for designing corrosion-resistant Mg alloys. In this work, Mg-11Al-0.2Y alloy was prepared for exploring its corrosion behavior in 3.5 wt.% neutral NaCl solution. It exhibits a low corrosion current density of 2.3 µA/cm2 after immersion for 1 d due to the formation of a protective surface film containing Al2O3, MgO and Mg(OH)2. However, nano-scaled pores exhibit at the film/matrix interface, which undermines integrity and protectiveness of the surface film after long-term exposure to chloride solution.

Abstract Background Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation and concurrent mutations have a poor prognosis. This study aimed to examine anlotinib plus icotinib as a first-line treatment option for advanced NSCLC carrying EGFR mutation with or without concurrent mutations. Methods This phase 2, single-arm, multicenter trial (ClinicalTrials.gov NCT03736837) was performed at five hospitals in China from December 2018 to November 2020. Non-squamous NSCLC cases with EGFR-sensitizing mutations were treated with anlotinib and icotinib. The primary endpoint was progression-free survival (PFS). Secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Results Sixty participants were enrolled, including 31 (52%) and 29 (48%) with concurrent mutations and pathogenic concurrent mutations, respectively. The median follow-up was 26.9 (range, 15.0-38.9) months. ORR and DCR were 68.5% and 98.2%, respectively. Median PFS was 15.1 (95%CI: 12.6–17.6) months which met the primary endpoint, median DoR was 13.5 (95%CI: 10.0-17.1) months, and median OS was 30.0 (95%CI: 25.5–34.5) months. Median PFS and OS in patients with pathogenic concurrent mutations were 15.6 (95%CI: 12.5–18.7) months and not reached (95%CI: 17.46 months to not reached), respectively. All patients experienced TRAEs, including 26 (43%) and 1 (1.7%) who had grade ≥ 3 and serious treatment-related adverse events (TRAEs). Conclusions Anlotinib combined with icotinib was effective and well-tolerated as a first-line treatment option for EGFR mutation-positive advanced NSCLC with or without concurrent mutations. Trial registration ClinicalTrials.gov identifier: NCT03736837.

BackgroundDiabetic retinopathy (DR) is the most frequent complication of type 2 diabetes and remains the leading cause of preventable blindness. Current clinical decisions regarding the administration of antidiabetic drugs do not sufficiently incorporate the risk of DR due to the inconclusive evidence from preceding meta-analyses. This umbrella review aimed to systematically evaluate the effects of antidiabetic drugs on DR in people with type 2 diabetes.MethodsA systematic literature search was undertaken in Medline, Embase, and the Cochrane Library (from inception till 17th May 2022) without language restrictions to identify systematic reviews and meta-analyses of randomized controlled trials or longitudinal studies that examined the association between antidiabetic drugs and DR in people with type 2 diabetes. Two authors independently extracted data and assessed the quality of included studies using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist, and evidence assessment was performed using the GRADE (Grading of recommendations, Assessment, Development and Evaluation). Random-effects models were applied to calculate relative risk (RR) or odds ratios (OR) with 95% confidence intervals (CI). This study was registered with PROSPERO (CRD42022332052).ResultsWith trial evidence from 11 systematic reviews and meta-analyses, we found that the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or dipeptidyl peptidase-4 inhibitors (DPP-4i) was not statistically associated with the risk of DR, compared to either placebo (RR: GLP-1 RA, 0.98, 0.89-1.08; SGLT-2i, 1.00, 95% CI 0.79-1.27; DPP-4i, 1.17, 0.99-1.39) or other antidiabetic drugs. Compared to other antidiabetic drugs, meglitinides (0.34, 0.01-8.25), SGLT-2i (0.73, 0.10-5.16), thiazolidinediones (0.92, 0.67-1.26), metformin (1.15, 0.81-1.63), sulphonylureas (1.24, 0.93-1.65), and acarbose (4.21, 0.44-40.43) were not statistically associated with the risk of DR. With evidence from longitudinal studies only, insulin was found to have a higher risk of DR than other antidiabetic drugs (OR: 2.47, 95% CI: 2.04-2.99).ConclusionOur results indicate that antidiabetic drugs are generally safe to prescribe regarding the risk of DR among people with type 2 diabetes. Further robust and large-scale trials investigating the effects of insulin, meglitinides, and acarbose on DR are warranted.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=332052, identifier CRD42022332052.

Summary: Background: Abnormal liver function was frequently observed in nonalcoholic fatty liver disease (NAFLD) patients infected with SARS-CoV-2. Our aim was to explore the effect of SARS-CoV-2 inactivated vaccines on liver function abnormality among NAFLD patients with COVID-19. Methods: The multi-center retrospective cohort included 517 NAFLD patients with COVID-19 from 1 April to 30 June 2022. Participants who received 2 doses of the vaccine (n = 274) were propensity score matched (PSM) with 243 unvaccinated controls. The primary outcome was liver function abnormality and the secondary outcome was viral shedding duration. Logistic and Cox regression models were used to calculate the odds ratio (OR) and hazard ratio (HR) for the outcomes. Sensitivity analysis was conducted to assess robustness. Findings: PSM identified 171 pairs of vaccinated and unvaccinated patients. Liver function abnormality was less frequent in the vaccinated group (adjusted OR, 0.556 [95% CI (confidence interval), 0.356–0.869], p = 0.010). Additionally, the vaccinated group demonstrated a lower incidence of abnormal bilirubin levels (total bilirubin: adjusted OR, 0.223 [95% CI, 0.072–0.690], p = 0.009; direct bilirubin: adjusted OR, 0.175 [95% CI, 0.080–0.384], p

The strategy of rare-earth elements addition into Mg alloys has been successfully developed and applied to enhance the mechanical performance and corrosion resistance of Mg alloys. Although this strategy has also been applied to enhance their high-temperature oxidation resistance, the mechanistic understanding of the beneficial effects remains elusive. Here, the oxidation of Mg–4Nd and Mg-4Nd–1Y alloys in Ar–20%O2 at 500 °C was studied and compared. It was found that even though a continuous layer of Nd2O3 did not form, the Nd addition could still enhance the oxidation tolerance of Mg–4Nd alloy by facilitating the generation of a more continuous and intact oxide scale and working as oxygen sinks to delay the violent oxidation of Mg. The formation of a continuous Y2O3 layer on Mg-4Nd–1Y alloy suggests that Y was more capable of facilitating the external oxidation due to its much faster diffusion rate in Mg matrix than that of Nd. However, the Nd addition could decrease the critical content of Y necessary for the oxidation transition from internal to external because of the synergistic effect of the Nd and Y addition. The dissolution of the thermal unstable Mg12Nd precipitates resulted in a localized increase of Nd content, accelerating the oxidation by increasing the preferential oxidation of Nd. Hence, in the design of oxidation-resistant Mg alloys, the addition of RE elements with faster diffusion rate and the addition of multiple alloy elements are preferred. In addition, the number of thermal unstable precipitates needs to be strictly controlled.

Background Identifying existing care pathways is the first step for understanding how services can be improved to enable early diagnosis and effective follow-up care for non-communicable diseases (NCDs); however, evidence on how care pathways can and should be identified in low- and middle-income countries (LMICs) is lacking. Objective To describe generalisability and lessons learned from recruitment and data collection for the quantitative component of a mixed methods study designed to determine the care pathway for atrial fibrillation (AF) in Brazil, China and Sri Lanka. Methods Adults (≥18 years) that spoke the local language and with an AF diagnosis were eligible. We excluded anyone with a hearing or cognitive impairment or ineligible address. Eligible participants were identified using electronic records in Brazil and China; in Sri Lanka, researchers attended the outpatient clinics to identify eligible participants. Data were collected using two quantitative questionnaires administered at least 2-months apart. A minimum sample size of 238 was required for each country. Results The required sample size was met in Brazil (n = 267) and China (n = 298), but a large proportion of AF patients could not be contacted (47% and 27%, respectively) or refused to participate (36% and 38%, respectively). In Sri Lanka, recruitment was challenging, resulting in a reduced sample (n = 151). Mean age of participants from Brazil, China and Sri Lanka was 69 (SD = 11.3), 65 (SD = 12.8) and 58 (SD = 11.7), respectively. Females accounted for 49% of the Brazil sample, 62% in China and 70% in Sri Lanka. Conclusions Generalisability was an issue in Brazil and China, as was selection bias. Recruitment bias was highlighted in Sri Lanka. Additional or alternative recruitment methods may be required to ensure generalisability and reduce bias in future studies aimed at identifying NCD care pathways in LMICs.

An adequate thermodynamic model is required for describing the long-period stacking ordered (LPSO) phase because previously developed models cannot account for the accurate atomic occupancy of the LPSO structure. In this study, atomic structures of the equilibrated 18R and 10H phases in Mg–Y–Al alloys were systematically investigated via atomic-resolution high-angle annular dark-field scanning transmission electron microscopy (HAADF-TEM) and first-principles calculations. Three structures (α-type, β-type, and γ-type) with different numbers of Mg layers (one, two, and three, respectively) sandwiched between L12 structures were present in the 18R phase. Meanwhile, δ-type (without Mg layers), ε-type (with one Mg layer), and ζ-type (with two Mg layers) structures were detected in the 10H phase. The presence of the interstitial atoms in the L12 structure was confirmed by TEM and theoretical calculations. Based on the obtained results, a new thermodynamic model for the LPSO phase was constructed and successfully applied to establish the thermodynamic description of the Mg–Y–Al system. The CALPHAD-type calculation data obtained using the proposed thermodynamic description were in good agreement with the experimental results. The findings of this study can help elucidate the formation mechanism of LPSO phases and guide Mg–Y–Al alloy design.

This paper investigates $ \mathcal{L}_{2}-\mathcal{L}_{\infty} $ control for memristive neural networks (MNNs) with a non-necessarily differentiable time-varying delay. The objective is to design an output-feedback controller to ensure the $ \mathcal{L}_{2}-\mathcal{L}_{\infty} $ stability of the considered MNN. A criterion on the $ \mathcal{L}_{2}-\mathcal{L}_{\infty} $ stability is proposed using a Lyapunov functional, the Bessel-Legendre inequality, and the convex combination inequality. Then, a linear matrix inequalities-based design scheme for the required output-feedback controller is developed by decoupling nonlinear terms. Finally, two examples are presented to verify the proposed $ \mathcal{L}_{2}-\mathcal{L}_{\infty} $ stability criterion and design method.

Immunotherapy is a clinically effective method for treating tumors. Manganese can activate the cGAS-STING signaling pathway and induce an anti-tumor immune response. However, its efficacy is hindered by non-specific distribution and low uptake rates. In this study, we employed microfluidic technology to design and develop an innovative preparation process, resulting in the creation of a novel manganese lipid nanoparticle (LNM). The lipid manganese nanoparticle produced in this process boasts a high manganese payload, excellent stability, the capacity for large-scale production, and high batch repeatability. LNM has effectively demonstrated the ability to activate the cGAS-STING signaling pathway, induce the production of pro-inflammatory cytokines, and inhibit tumor development. Notably, LNM does not require combination chemotherapy drugs or other immune activators. Therefore, LNM presents a safe, straightforward, and efficient strategy for anti-tumor immune activation, with the potential for scalable production.

Thedistribution of products stands out as one of the pivotal activities for logistics companies in recent years, particularly in the aftermath of the COVID-19 pandemic and other geopolitical events. Intense competition compels companies to efficiently execute their logistical processes, with cross-docking emerging as a frequently applied solution. However, the location of cross-dock terminals in urban areas remains a problem insufficiently addressed in the literature, with a dearth of studies and models tackling this issue. This paper introduces a novel and innovative model for locating cross-dock terminals based on the CI-DEA–IDOCRIW–MABAC (Composite Indicators–Data Envelopment Analysis-Integrated Determination of Objective Criteria Weights–Multi-Attributive Border Approximation Area Comparison) methods. In the process of defining input indicators, the following three sources were utilized: relevant literature, practical insights from logistics experts, and the knowledge and experience of the authors. Eight inputs and three outputs were considered (the number of users in the observed channel; the area served by the channel; the average distance a vehicle travels in one delivery; the required number of vehicles; labor availability; competition; construction, and expansion possibilities; proximity to the main infrastructure and traffic facilities; the average number of deliveries; average delivered quantity; and service level). The model underwent testing in a case study analyzing nine distribution channels (areas within the observed urban zone). The results indicated that alternative A4 (in the southwest area) ranked the highest since it was the best-ranked in accordance with the most important criteria, suggesting that the terminal is best located in the southwest zone. The accuracy of the results was confirmed by company management. By developing a completely new model and addressing the identified gap in the literature, this paper provides unequivocal scientific contributions.

The molecular mechanisms underlying acquired chemoresistance to proteasome inhibitors (PIs) in multiple myeloma (MM) remain to be explored. Here, the authors highlight the role of heterochromatin protein 1 gamma as a potential target for overcoming resistance to PIs in MM.

In order to improve the utilization rate of cable while ensuring safety and reliability, accurate and rapid evaluation of transient temperature rise of directly buried power cables is useful to improve the management level of dynamic capacity increase and emergency load conditions. Since the existing thermal circuit model is relatively complex or not very accurate, an equivalent three-branch transient thermal circuit model is presented for the complex cable structure and heat dissipation environment based on the uniqueness of the temperature field. Considering the electric circuit similarity, the transient analysis method of the centralized parameter network in the circuit is used to establish the transient adjoint model of the thermal capacity branch, provide the node conduction matrix of the transient thermal circuit model, and write the node temperature rise equation as a function of the node heat flow. By comparing the solution of the thermal circuit model with the finite element results, and the genetic algorithm is used to optimize and obtain the equivalent thermal resistance and thermal capacity parameters of the transient thermal circuit model. The comparison of finite element calculation results proves that the proposed three-branch transient thermal circuit model is more accurate than the two-branch thermal circuit model. Compared to the traditional all-part thermal circuit model, the three-branch model can be rapidly solved and easily applied in engineering.

Background C-reactive protein (CRP) is a prototypical acute phase protein in humans with the function of regulating immune cells. Serum CRP levels are elevated in multiple myeloma (MM), associated with MM cell proliferation and bone destruction. However, its direct effects on T lymphocytes in MM have not been elucidated.Methods Public data sets were used to explore the correlation of CRP levels with immune cell infiltration and cytotoxicity score of CD8+ T cells in MM. In vitro, repeated freeze-thaw myeloma cell lines were taken as tumor antigens to load dendritic cells (DCs) derived from HLA-A*0201-positive healthy donors. MM-specific cytotoxic T cells (MM-CTL) were obtained from T lymphocytes of the corresponding donors pulsed with these DCs. B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T cells were manipulated by transfecting with lentivirus encoding an anti-BCMA single-chain variable fragment. Then T cells from healthy controls, MM-CTLs and BCMA CAR-T cells were exposed to CRP and analyzed for cell proliferation, cytotoxicity, immunophenotypes. CRP binding capacity to T cells before and after Fc gamma receptors IIb (FcγRIIb) blockage, p38 mitogen-activated protein kinase (MAPK) pathway and the downstream molecules were also detected. In vivo, both normal C57BL/6J mice and the Vk*MYC myeloma mouse models were applied to confirm the impact of CRP on T cells.Results CRP levels were negatively correlated with cell-infiltration and cytotoxicity score of CD8+ T cells in MM. In vitro experiments showed that CRP inhibited T-cell proliferation in a dose-dependent manner, impaired the cytotoxic activity and upregulated expression of senescent markers in CD8+ T cells. In vivo results validated the suppressive role of CRP in CD8+ T cells. CRP could bind to CD8+ T cells, mainly to the naïve T subset, while the binding was dramatically decreased by FcγRIIb blockage. Furthermore, CRP resulted in increased phosphorylation of p38 MAPK, elevated levels of reactive oxygen species and oxidized glutathione in CD8+ T cells.Conclusions We found that CRP impaired immune response of CD8+ T cells via FcγRIIb-p38MAPK-ROS signaling pathway. The study casted new insights into the role of CRP in anti-myeloma immunity, providing implications for future immunotherapy in MM.

Introduction Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk–benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.Methods and analysis Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure–outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.Ethics and dissemination Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.

Significant progress has been made in convolutional neural networks (CNN) based gas recognition. However, existing electronic nose (e-Nose) algorithms all use the closed-set assumption that the test and training samples are in the same label space and can only detect objects of known classes. However, in realistic scenarios, collecting data and training for every possible gas would waste much resource. Open-set identification aims to actively reject samples from unknown classes by reducing the intra-class spacing and, thus, not misclassifying them as known classes. In this study, we propose a data preprocessing method to enhance the performance of closed-set recognition by augmenting the eigenvalues of each gas. We then implement the open-set recognition task for gases using an open-set recognition model. These methods contribute to improved recognition accuracy for gases and provide an effective means of handling unknown class samples. Experimental results show that our approach can identify unknown samples well while maintaining accuracy for available classes.

Sepsis ranks among the most common health problems worldwide, characterized by organ dysfunction resulting from infection. Excessive inflammatory responses, cytokine storms, and immune-induced microthrombosis are pivotal factors influencing the progression of sepsis. Our objective was to identify novel immune-related hub genes for sepsis through bioinformatic analysis, subsequently validating their specificity and potential as diagnostic and prognostic biomarkers in an animal experiment involving a sepsis mice model. Gene expression profiles of healthy controls and patients with sepsis were obtained from the Gene Expression Omnibus (GEO) and analysis of differentially expressed genes (DEGs) was conducted. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to analyze genes within crucial modules. The functional annotated DEGs which related to the immune signal pathways were used for constructing protein–protein interaction (PPI) analysis. Following this, two hub genes, FERMT3 and CD3G, were identified through correlation analyses associated with sequential organ failure assessment (SOFA) scores. These two hub genes were associated with cell adhesion, migration, thrombosis, and T-cell activation. Furthermore, immune infiltration analysis was conducted to investigate the inflammation microenvironment influenced by the hub genes. The efficacy and specificity of the two hub genes were validated through a mice sepsis model study. Concurrently, we observed a significant negative correlation between the expression of CD3G and IL-1β and GRO/KC. These findings suggest that these two genes probably play important roles in the pathogenesis and progression of sepsis, presenting the potential to serve as more stable biomarkers for sepsis diagnosis and prognosis, deserving further study.

The number of tunnel fire accidents has increased with the scale of expressway tunnel construction and traffic flow. Due to the severity of tunnel fires, improving tunnel fire safety and reducing fire accident hazards has become a societal concern. It is essential to explore and evaluate tunnel fire safety literacy among the population. In this study, an online and on-site questionnaire survey was conducted in Hunan Province, China. A total of 1990 questionnaires were collected, of which 1573 were valid. Overall statistical analysis, descriptive statistics, and correlation analysis were performed on valid questionnaires. The results show that the overall level score rate of awareness of drivers and passengers regarding tunnel fire safety was only 0.43. In total, 58.42% of people were unaware of the pedestrian cross passages in expressway tunnels, and 68.40% were unable to recognize them. Similarly, 46.47% of people were unable to recognize evacuation signs in expressway tunnels. In addition, 39.29% of people chose the wrong evacuation behavior. The percentage of people who were aware of the correct usage of firefighting facilities in expressway tunnels was below 50.00%. Correlation analysis results show that tunnel users’ demographic characteristics significantly affected their cognition of expressway tunnel escape methods. This study shows that tunnel users’ emergency escape knowledge regarding tunnels is relatively low. Corresponding countermeasures were proposed to guide policy decisions for enhancing tunnel fire safety.

Meningioangiomatosis (MA) is a rare malformation or hamartomatous lesion in the central nervous system, characterized by a plaque-like mass within the leptomeninges and cerebral cortex. An even rarer condition is MA complicated with meningiomas. We herein report a case of meningioma associated with MA that might be erroneously interpreted as a higher-grade lesion or an invasion by preoperative radiologic and postoperative histological examinations.

High-strength Mg alloys are often sought-after for automotive and aerospace applications, but they have an inferior corrosion resistance. Here, the authors develop a Mg-11Y-1Al (wt. %) alloy that shows both significantly improved mechanical properties and corrosion resistance.

Resumo Fundamento A associação entre o status de saúde cardiovascular ideal ( ideal cardiovascular health ( ICVH) e diagnóstico de fibrilação ou flutter atrial (FFA) foi menos estudado em comparação a outras doenças cardiovasculares. Objetivos Analisar a associação entre o diagnóstico de FFA e métricas e escores de ICVH no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Métodos Este estudo analisou dados de 13141 participantes com dados completos. Os traçados eletrocardiográficos foram codificados de acordo com o Sistema de Minnesota, em um centro de leitura centralizado. As métricas do ICVH (dieta, atividade física, índice de massa corporal, tabagismo, glicemia de jeju, e colesterol total) e escores do ICVH foram calculados conforme proposto pela American Heart Association . Modelos de regressão logística bruta e ajustada foram construídos para analisar associações de métricas e escores do ICVH com diagnóstico de FFA. O nível de significância foi estabelecido em 0,05. Resultados A idade mediana da amostra foi de 55 anos, e 54,4% eram mulheres. Nos modelos ajustados, os escores de ICVH não apresentaram associação significativa com diagnóstico de FFA prevalente [odds ratio (OR):0,96; intervalo de confiança de 95% (IC95%):0,80-1,16; p=0,70). Perfis de pressão arterial ideal (OR:0,33; IC95%:0,1-0,74; p=0,007) e colesterol total ideal (OR:1,88; IC95%:1,19-2,98; p=0,007) foram significativamente associados com o diagnóstico de FFA. Conclusões Não foram identificadas associações significativas entre escores de ICVH global e diagnóstico de FFA após ajuste multivariado em nossas análises, devido, ao menos em parte, às associações antagônicas da FFA com métricas de pressão arterial e de colesterol total do ICVH. Nossos resultados sugerem que estimar a prevenção da FFA por meio de escore de ICVH global pode não ser adequado, e as métricas do ICVH devem ser consideradas separadamente.

Abstract Motivation The empowerment of design for cultural and creative products in the digital media era is further amplified by social media platforms,its emotional and subconscious impact on users is important and profound. The development of the network economy has promoted this trend. At the same time, this trend has further promoted the growth of cultural and creative products market. However, too obscure appearance design can hardly arouse the resonance of different cultural groups in a short time. As an effective method to bridge the cultural gap between consumers, emotional design has become an important driving force for the development of cultural and creative products. Purpose The purpose of this study is to understand the impact of emotional factors on the willingness and preferences of ordinary consumers to buy Chinese cultural and creative products, and to further explore whether there are cognitive differences between the emotional design standards defined and promoted by professionals and the excellent design recognized by consumers according to their life experience and personal subjective emotional preferences. Design/methodology/approach Through the construction of the emotional design model, this study selects four award-winning products in the cultural and creative product design competition and four commercial products with high sales volume in the online stores as research cases. Through 176 valid questionnaires conducted by non-professionals, this study makes an analysis by using the structural equation. Conclusions The study found that consumers' preference and purchase intention of Chinese cultural and creative products are affected by emotional design standards, but the impact results depend on the interaction of many factors. At the same time, there are also significant differences in cognitive paths between them.

Abstract Background Rumpel Leede sign (RLS) is a clinical presentation observed at the extremities due to pressure applied externally. The appearance ranges from scattered pin-point rashes to an entire arm covered with petechial hemorrhage depending upon the severity. This phenomenon is relatively uncommon in clinical practice. Case presentation A 64 year old female patient developed a rash in the normal skin area below the compression area on the second day of single catheter coronary angiography. The patient's rash resolved without treatment after 3 days. Conclusions We report a case of hypertension and hyperlipidemia with a petechial rash on the skin under the tourniquet compressed by the radial artery after coronary angiography, which is consistent with the Rumpel-Leede phenomenon. clinicians should be watchful of these symptoms.

The 3D visualization of the porosity in high-pressure die casting (HPDC) Mg alloys AZ91D and Mg4Ce2Al0.5Mn (EA42) was investigated by X-ray computed tomography. It was demonstrated that the volumetric porosity at the near-gate location for alloy EA42 was significantly higher than that far from the gate location. This difference resulted from the low valid time during intensified casting pressure conditions. Specimens of alloy EA42 exhibited a narrow pore distribution in the side view (∼0.5 mm) compared to the wide distribution (∼1.8 mm) of alloy AZ91D, which was mainly attributed to the formation mechanism of the defect band. The formation of microporosity in the defect band of alloy EA42 was inhibited because of the significant latent heat released by a large amount of the Al11Ce3 phase segregated in the defect band during solidification. Additionally, an effective estimator (Z-Propagation) was introduced, which is proposed to predict the projected area fraction of the porosity (f) involved during tensile failure with better effectiveness compared with traditional methods based on the actual fractured surface. By coupling the Z-Propagation method with the critical local strain model, the logarithmic fracture strain and true fracture stress of the specimens were predicted within 3.03% and 1.65% of the absolute value of the average relative error (AARE), respectively.

Background Immunotherapies targeting CD38 have demonstrated salient efficacy in relapsed/refractory multiple myeloma (MM). However, loss of CD38 antigen and outgrowth of CD38 negative plasma cells have emerged as a major obstacle in clinics. All-trans retinoic acid (ATRA) has been reported to upregulate CD38 expression, but the mechanism and adaptive genetic background remain unexplored.Methods The efficacy of ATRA in upregulating CD38 expression in MM cells is evaluated by flow cytometry. The interaction between NSD2 and the RARα is analyzed by immunoprecipitation, and the nuclear condensation of RARα is evaluated under laser confocal microscope. A graft model of MM is established in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice, and the tumor burden is assessed by in vivo fluorescence imaging.Results We report that ATRA upregulates MM cells CD38 in a non-linear manner, which is t(4;14) translocation dependent, and t(4;14) translocation-induced NSD2 shows positive correlation with ATRA-induced level of, but not with basal level of CD38 expression. Mechanistically, NSD2 interacts with the ATRA receptor, RARα, and protects it from degradation. Meanwhile, NSD2 enhances the nuclear condensation of RARα and modifies the histone H3 dimethylation at lysine 36 on CD38 promoter. Knockdown of NSD2 attenuates the sensitization of MM against ATRA induced CD38 upregulation. Translationally, ATRA is prone to augment the efficacy of anti-CD38 CAR T cells in NSD2high MM cells in vitro and in vivo.Conclusion This study elucidates a mechanism of ATRA in regulating CD38 expression and expands the clinical potential of ATRA in improving immunotherapies against CD38 in patients with MM.Cite Now

BackgroundCyclin-dependent kinases (CDKs) play a key role in cell proliferation in lung adenocarcinoma (LUAD). Comprehensive analysis of CDKs to elucidate their clinical significance and interactions with the tumor immune microenvironment is needed.MethodsRNA expression, somatic mutation, copy number variation, and single-cell RNA sequencing data were downloaded from public datasets. First, we comprehensively evaluated the expression profile and prognostic characteristics of 26 CDKs in LUAD, and CDK1 was selected as a candidate for further analysis. Then, a systematic analysis was performed to explore the relationships of CDK1 with clinical characteristics and tumor immune microenvironment factors in LUAD.ResultsCDK1 was markedly upregulated at both the mRNA and protein level in LUAD. Moreover, overexpression of CDK1 was related to poor clinical outcomes. CDK1 coexpressed genes were mainly involved in the cell cycle, the DNA repair process, and the p53 signaling pathway. In addition, CDK1 expression was found to be correlated with the expression of multiple immunomodulators and chemokines, which participate in activating and suppressing the immune microenvironment. CDK1 expression was also correlated with increased infiltration of numerous immune cells, including CD4+ T cells and M1 macrophages. Patients with high CDK1 expression tended to have a poor response to immunotherapy but were sensitive to multiple chemotherapies and targeted drugs. The MDK-NCL and SPP1-CD44 ligand−receptor pairs were markedly activated in the intercellular communication network. CDK1 was an independent prognostic factor for LUAD and improved the ability to predict overall survival when combined with tumor stage.ConclusionCDK1 plays an essential role in reshaping the tumor immune microenvironment and might be a prognostic and treatment biomarker in LUAD.

Introduction One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions).Methods and analysis Pregnant women aged 15–49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using modified Poisson and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using random-effects meta-analyses.Ethics and dissemination Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences.

Aiming at weak representation ability and severe loss of time series features in the traditional methods when facing large-scale and complex power load forecasting tasks, an LSTM-Autoencoder model that integrates long-term and short-term features of the samples is proposed for load forecasting. The encoder part simultaneously receives long time series and short time series as input to extract time series features of different levels and generate related latent vectors. The decoder tries to reconstruct the input sequence while outputting the prediction results to ensure that the latent vectors are meaningful. In addition, the model also uses a mixture of supervised and unsupervised training methods. Experiments based on a publicly available dataset from Alberta Electric System Operator showed that the method presented in this research is superior to many existing mainstream methods, with a mean absolute error of less than 52MW between the prediction results and the actual load values.

Objective To assess the independent association of maternal lipid levels with birth weight and cord blood insulin (CBI) level.Setting The Born in Guangzhou Cohort Study, Guangzhou, China.Participants Women who delivered between January 2015 and June 2016 and with umbilical cord blood retained were eligible for this study. Those with prepregnancy health conditions, without an available fasting blood sample in the second trimester, or without demographic and glycaemic information were excluded. After random selection, data from 1522 mother–child pairs were used in this study.Exposures and outcome measures Additive Bayesian network analysis was used to investigate the interdependency of lipid profiles with other metabolic risk factors (prepregnancy body mass index (BMI), fasting glucose and early gestational weight gain) in association with birth weight and CBI, along with multivariable linear regression models.Results In multivariable linear regressions, maternal triglyceride was associated with increased birth weight (adjusted β=67.46, 95% CI 41.85 to 93.06 g per mmol/L) and CBI (adjusted β=0.89, 95% CI 0.06 to 1.72 μU/mL per mmol/L increase), while high-density lipoprotein cholesterol was associated with decreased birth weight (adjusted β=−45.29, 95% CI −85.49 to −5.09 g per mmol/L). After considering the interdependency of maternal metabolic risk factors in the Network analysis, none of the maternal lipid profiles was independently associated with birth weight and CBI. Instead, prepregnancy BMI was the global strongest factor for birth weight and CBI directly and indirectly.Conclusions Gestational dyslipidaemia appears to be secondary to metabolic dysfunction with no clear association with metabolic adverse outcomes in neonates. Maternal prepregnancy overweight/obesity appears the most influential upstream metabolic risk factor for both maternal and neonatal metabolic health; these data imply weight management may need to be addressed from the preconception period and during early pregnancy.

Objective Achieving good oral health-related quality of life (OHRQOL) is of particular concern in children. The inter-relations among oral health knowledge, self-efficacy, behaviours and OHRQOL in children groups remain unclear. This study aimed to explore the inter-relations between these oral health behaviour-related factors and OHRQOL in primary school children.Methods In this cross-sectional study, 651 children in grades 2 and 3 were recruited in October 2020 from two primary schools in Minhang District, Shanghai, China. Data were collected through self-reported questionnaires, consisting of demographic characteristics, oral health knowledge, self-efficacy, oral health behaviours and OHRQOL. Pearson’s correlation analyses were used to analyse the relationship between study variables. Structural equation models were used to test the inter-relations between OHRQOL and oral health behaviour-related factors.Results Four hypothetical structural equation models were tested and one of them was selected as the most appropriate model, which explained 15.0% of the variance in OHRQOL. This selected model showed that oral health behaviours were directly related to OHRQOL. Oral health knowledge was indirectly associated with OHRQOL through both self-efficacy and oral health behaviours. Self-efficacy was directly associated with OHRQOL or was indirectly associated with OHRQOL through oral health behaviours.Conclusion This study revealed a pathway of association between children’s oral health knowledge and their OHRQOL, in which children’s oral health self-efficacy and behaviours had indirect effects. This provides a basis for understanding the mechanism of oral health promotion interventions to improve children’s OHRQOL and helps to identify direct or indirect intervention targets.

Introduction Atrial fibrillation (AF) is the most common arrhythmia globally. It is associated with a fivefold risk in stroke, but early diagnosis and effective treatment can reduce this risk. AF is often underdiagnosed, particularly in low-income and middle-income countries (LMICs) where screening for AF is not always feasible or considered common practice in primary care settings. Epidemiological data on AF in LMICs is often incomplete particularly in vulnerable populations. This LMIC research collaborative aims to identify the prevalence of AF in the Northern Sri Lankan community.Methods and analysis A cross-sectional household survey piloted and codesigned through a series of community engagement events will be administered in all five districts in Northern Province, Sri Lanka. A multistage cluster sampling approach will be used starting at district level, then the Divisional Secretariats followed by Grama Niladhari divisions. Twenty households will be selected from each cluster. The study aims to recruit 10 000 participants aged 50 years or older, 1 participant per household. Demographic and socioeconomic characteristics, well-being and lifestyle and anthropometric measurements will be collected using a digital data platform (REDCap, Research Electronic Data Capture) by trained data collectors. Participants will be screened for AF using a fingertip single-lead ECG via a smartphone application (AliveCor) with rhythm strips reviewed by a consultant cardiologist. Prevalence of AF and risk factors will be established at province and district-levels. Adjusted ORs and population attributable fractions for AF risk factors will be determined.Ethics and dissemination This study was approved by the Ethics Review Committee of Faculty of Medicine at University of Jaffna. Written informed consent will be obtained from all participants. Findings will be disseminated through publication in a peer-reviewed journal and presentations at conferences. The findings will enable early treatment for new AF diagnoses and inform interventions to improve community-based management of AF in LMICs.

Abstract Background The relation between cigarette smoking and metabolic syndrome (MetS) remains unclear, and previous studies focusing on MetS are limited in sample size. We investigated the association between life-course smoking and MetS with independent discovery and replication samples. Methods Preliminary analysis utilized data from an annual cross-sectional survey of 15,222 participants aged ≥ 60 years in Tianjin, China. Suggestive associations were followed-up in 8565 adults from the China Health and Nutrition Survey. MetS was identified according to the criteria of the Chinese Diabetes Society in 2013. Life-course smoking was assessed by a comprehensive smoking index (CSI), based on information on smoking intensity, duration, and time since cessation across life-course, collected through standard questionnaires. Participants were divided into four groups: non-smokers; and the tertiles of CSI in ever smokers. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between life-course smoking and MetS. Results In the discovery sample, ORs of MetS were 2.01 (95%CI: 1.64–2.47) and 1.76 (95%CI: 1.44–2.16) for smokers in the highest and second tertile of CSI compared with never smokers. Potential interaction was shown for age, with increased ORs for MetS associated with smoking limited to individuals who aged

Abstract Background The present study aimed to develop and test an extended theory of planned behavior (TPB), which includes attitudes, subjective norms and perceived behavioral control, oral health knowledge, and past oral health behavior on the intention to improve oral health behaviors among primary school students in Shanghai, China. Methods A school-based cross-sectional study was conducted with 414 students in the third-grade from 10 classes of Mingqiang Primary School located in Shanghai, China. Participants were recruited in October 2019. Data were collected through self-reported questionnaires, consisting of demographic characteristics, TPB variables, oral health knowledge and past oral health behaviors. Exploratory factor analysis was used to analyze TPB items. Pearson’s correlation and hierarchical regression analyses were conducted to identify the associated factors of intention to improve oral health behaviors. Results The study showed that among students in the third grade, attitudes, subjective norms, perceived behavioral control, and past oral health behaviors were associated with the intention to improve oral health behaviors. In the hierarchical regression analysis, age and sex were entered in Model 1 which significantly explained 3.00% of the variance (F = 6.26, p

Abstract Objectives This study aims to explore the prevalence of sexual satisfaction among Chinese cancer survivors, and explore the association of sexual satisfaction with comorbidity and lifestyle factors. Methods A cross‐sectional study was performed among 3996 Chinese cancer survivors recruited at Shanghai Cancer Rehabilitation Club from March to April 2017. Data were collected through self‐reported questionnaires. The questionnaire includes information about demographic, cancer characteristics, comorbidities, lifestyle factors, and sexual satisfaction. Sexual satisfaction was measured by a single‐item scale. The distribution of sexual satisfaction among different demographic and cancer characteristics was compared using the chi‐squared test. Logistic regression models were conducted to assess the effects of lifestyle factors, comorbidities on sexual satisfaction after adjustment for demographic and cancer characteristics. Results More than 40% of male and female cancer survivors reported no sexual satisfaction. Sexual satisfaction of cancer survivors is significantly associated with both the number and the type of comorbidities. Heart disease, musculoskeletal system disease, diabetes, and hyperlipidemia are the comorbidities significantly associated with sexual satisfaction of cancer survivors. Lifestyle factors other than smoking, including exercise or fitness, drinking alcohol, and eating fruits and vegetables are significantly correlated with sexual satisfaction. Besides, all of the above associations show gender differences. In addition, demographic characteristics include sex, age, marital status, living status, and average monthly income are also significantly associated with sexual satisfaction of cancer survivors. Conclusion Comorbidity and lifestyle factors are associated with sexual satisfaction of cancer survivors, and the associations show gender differences. Improving the lifestyles of cancer survivors, and controlling and reducing their comorbidities are important for improving their sexual satisfaction.

Newcastle disease (ND) is an acute and highly contagious disease caused by the Newcastle disease virus (NDV) infecting poultry, which has caused great harm to the poultry industry around the world. Rapid diagnosis of NDV is important to early treatment and early institution of control measures. In this review, we comprehensively summarize the most recent research into NDV, including historical overview, molecular structure, and infection mechanism. We then focus on detection strategies for NDV, including virus isolation, serological assays (such as hemagglutination and hemagglutination-inhibition tests, enzyme linked immunosorbent assay, reporter virus neutralization test, Immunofluorescence assay, and Immune colloidal gold technique), molecular assays (such as reverse transcription polymerase chain reaction, real-time quantitative PCR, and loop-mediated isothermal amplification) and other assays. The performance of the different serological and molecular biology assays currently available was also analyzed. To conclude, we examine the limitations of currently available strategies for the detection of NDV to lay the groundwork for new detection assays.

Abstract Dysregulation of circular RNA (circRNA) expression is involved in the progression of cancer. Here, we aimed to study the potential function of hsa_circ_0006401 in colorectal cancer (CRC). CircRNA hsa_circ_0006401 expression levels in CRC and adjacent nontumor tissues were analyzed by real-time quantitative PCR (qRT-PCR) and circRNA in situ hybridization (RNA-ISH). Then, CRC cell proliferation was assessed by cell counting. Wound-healing and transwell assays were utilized to detect the effect of hsa_circ_0006401 on CRC migration. A circRNA-ORF construct was created, and a specific antibody against the splice junction of hsa_circ_0006401 was prepared. Finally, the proteins directly binding to hsa_circ_0006401 peptides were identified by immunoprecipitation combined with mass spectrometry. In our study, we found hsa_circ_0006401 was closely related to CRC metastasis and exhibited upregulated expression in metastatic CRC tissue samples. Proliferation and migration were inhibited in vitro when hsa_circ_0006401 expression was silenced. Downregulation of hsa_circ_0006401 expression decreased CRC proliferation and liver metastasis in vivo. A 198-aa peptide was encoded by sequences of the splice junction absent from col6a3. Hsa_circ_0006401 promoted CRC proliferation and migration by encoding the hsa_circ_0006401 peptide. Hsa_circ_0006401 peptides decreased the mRNA and protein level of the host gene col6a3 by promoting col6a3 mRNA stabilation. In conclusion, our study revealed that circRNAs generated from col6a3 that contain an open-reading frame (ORF) encode a novel 198-aa functional peptide and hsa_circ_0006401 peptides promote stability of the host gene col6a3 mRNA to promote CRC proliferation and metastasis.

Abstract Background 20-hydroxyecdysone (20E) plays important roles in insect molting and metamorphosis. 20E-induced autophagy has been detected during the larval–pupal transition in different insects. In Bombyx mori, autophagy is induced by 20E in the larval fat body. Long non-coding RNAs (lncRNAs) function in various biological processes in many organisms, including insects. Many lncRNAs have been reported to be potential for autophagy occurrence in mammals, but it has not been investigated in insects. Results RNA libraries from the fat body of B. mori dissected at 2 and 6 h post-injection with 20E were constructed and sequenced, and comprehensive analysis of lncRNAs and mRNAs was performed. A total of 1035 lncRNAs were identified, including 905 lincRNAs and 130 antisense lncRNAs. Compared with mRNAs, lncRNAs had longer transcript length and fewer exons. 132 lncRNAs were found differentially expressed at 2 h post injection, compared with 64 lncRNAs at 6 h post injection. Thirty differentially expressed lncRNAs were common at 2 and 6 h post-injection, and were hypothesized to be associated with the 20E response. Target gene analysis predicted 6493 lncRNA-mRNA cis pairs and 42,797 lncRNA-mRNA trans pairs. The expression profiles of LNC_000560 were highly consistent with its potential target genes, Atg4B, and RNAi of LNC_000560 significantly decreased the expression of LNC_000560 and Atg4B. These results indicated that LNC_000560 was potentially involved in the 20E-induced autophagy of the fat body by regulating Atg4B. Conclusions This study provides the genome-wide identification and functional characterization of lncRNAs associated with 20E-induced autophagy in the fat body of B. mori. LNC_000560 and its potential target gene were identified to be related to 20-regulated autophagy in B. mori. These results will be helpful for further studying the regulatory mechanisms of lncRNAs in autophagy and other biological processes in this insect model.

AimWe aimed to compare the mortality of individuals at low, moderate, and high risk of diabetic foot disease (DFD) in the context of newly diagnosed type 2 diabetes, before developing active diabetic foot problem.MethodsThis was a population-based cohort study of adults with newly diagnosed type 2 diabetes utilizing IQVIA Medical Research Data. The outcome was all-cause mortality among individuals with low, moderate, and high risk of DFD, and also in those with no record of foot assessment and those who declined foot examination.ResultsOf 225,787 individuals with newly diagnosed type 2 diabetes, 34,061 (15.1%) died during the study period from January 1, 2000 to December 31, 2019. Moderate risk and high risk of DFD were associated with increased mortality risk compared to low risk of DFD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.42, 1.58; aHR 2.01, 95% CI 1.84, 2.20, respectively). Individuals who declined foot examination or who had no record also had increased mortality risk of 75% and 25% vs. those at low risk of DFD, respectively (aHR 1.75, 95% CI 1.51, 2.04; aHR 1.25, 95% CI 1.20, 1.30).ConclusionIndividuals with new-onset type 2 diabetes who had moderate to high risk of DFD were more likely to die compared to those at low risk of DFD. The associations between declined foot examination and absence of foot examinations, and increased risk of mortality further highlight the importance of assessing foot risk as it identifies not only patients at risk of diabetic foot ulceration but also mortality.

Background: Qingfei Paidu decoction (QFPDD) has been widely used in treating coronavirus disease 2019 (COVID-19) in China. However, studies on the treatment effect of COVID-19 patients and other respiratory diseases have not been well demonstrated. Our study aims to determine the treatment effect of QFPDD in combination with conventional treatment on COVID-19 patients and other respiratory diseases.Methods: This retrospective study recruited COVID-19 patients who were treated with QFPDD for at least two courses (6 days) from seven hospitals in five provinces from January 21 to March 18 2020. Demographic, epidemiological, clinical, laboratory, computed tomography characteristics, treatment, and outcome data were collected and analyzed. The improvements in clinical symptoms before and after QFPDD treatment were compared.Results: Eight COVID-19 patients were included in this study. Of them, six were males (75.0%). The median age of the patients was 66 (60–82) years. Four patients were classified as mild and moderate cases (50.0%); there were two severe cases (25.0%) and critical cases (25.0%). The most common symptom was cough (7 [87.5%]), followed by fever (6 [75.0%]), fatigue (4 [50.0%]), asthma (4 [50.0%]), and anorexia (3 [37.5%]). Abnormal findings included decrease in neutrophils (3 [37.5%]), lymphocytes (2 [25.0%]), alkaline phosphatase (3 [37.5%]), lactic dehydrogenase (4 [50.0%]), erythrocyte sedimentation rate (2 [25.0%]), and C-reactive protein (5 [83.3%]) at admission. After one course (3 days) of QFPDD, nasal obstruction and sore throat completely disappeared, and fever (5 [83.3%]), fatigue (2 [50.0%]), and cough (2 [28.6%]) were improved. After two courses (6 days), the fever disappeared completely in all patients, and the other symptoms showed a tendency to improve. In non-severe patients, 87.5% baseline symptoms completely disappeared. In severe patients, 61.1% of the baseline symptoms completely disappeared after patients were administered QFPDD for two courses. Of the abnormal indicators, 55.6% returned to normal levels. The median duration to complete fever recovery was 1.0 day. The median durations of viral shedding and hospitalization were 10.5 and 21.5 days, respectively. None of the patients worsened and died, and no serious adverse events occurred related to QFPDD during hospitalization.Conclusion: QFPDD combined with conventional treatment improved clinical symptoms in COVID-19 patients with other respiratory diseases, and no serious adverse reactions associated with QFPDD were observed. Larger sample studies confirm our findings in the future.

Abstract Standards‐based levee design aims to protect against events with specific probabilities, for example eliminating overtopping from a storm surge with a 1% annual exceedance probability (i.e., a “100‐year” event). This allows levee segments to be analyzed independently but ignores interior dynamics and overall risk. We present and implement a framework for calculating optimal risk‐informed design heights. Using this design paradigm and multi‐objective evolutionary algorithms, we identify levee and floodwall design heights that minimize the total system cost and expected flood losses over 50 years. With our model, decision makers may feasibly evaluate hundreds or thousands of alternative designs over a large ensemble of future states of the world. Comparing to the existing design elevations of the Larose to Golden Meadow Hurricane Protection Project in coastal Louisiana, over multiple climate change scenarios, we identify system configurations of similar cost that reduce the expected value of discounted residual risk of 26%–73% ($8–85 million). We also achieve the same residual risk at 90%–97% of the cost of the existing system (saving $19–73 million).

Depression is the most common type of neuropsychiatric illness and has increasingly become a major cause of disability. Unfortunately, the recent global pandemic of COVID-19 has dramatically increased the incidence of depression and has significantly increased the burden of mental health care worldwide. Since full remission of the clinical symptoms of depression has not been achieved with current treatments, there is a constant need to discover new compounds that meet the major clinical needs. Recently, the roles of sigma receptors, especially the sigma-1 receptor subtype, have attracted increasing attention as potential new targets and target-specific drugs due to their translocation property that produces a broad spectrum of biological functions. Even clinical first-line antidepressants with or without affinity for sigma-1 receptors have different pharmacological profiles. Thus, the regulatory role of sigma-1 receptors might be useful in treating these central nervous system (CNS) diseases. In addition, long-term mental stress disrupts the homeostasis in the CNS. In this review, we discuss the topical literature concerning sigma-1 receptor antidepressant mechanism of action in the regulation of intracellular proteostasis, calcium homeostasis and especially the dynamic Excitatory/Inhibitory (E/I) balance in the brain. Furthermore, based on these discoveries, we discuss sigma-1 receptor ligands with respect to their promise as targets for fast-onset action drugs in treating depression.

Deep-tissue optical imaging is a longstanding challenge limited by scattering. Both optical imaging and treatment can benefit from focusing light in deep tissue beyond one transport mean free path. Wavefront shaping based on time-reversed ultrasonically encoded (TRUE) optical focusing utilizes ultrasound focus, which is much less scattered than light in biological tissues as the 'guide star'. However, the traditional TRUE is limited by the ultrasound focusing area and pressure tagging efficiency, especially in acoustically heterogeneous medium. Even the improved version of iterative TRUE comes at a large time consumption, which limits the application of TRUE. To address this problem, we proposed a method called time-reversed photoacoustic wave guided time-reversed ultrasonically encoded (TRPA-TRUE) optical focusing by integrating accurate ultrasonic focusing through acoustically heterogeneous medium guided by time-reversing PA signals, and the ultrasound modulation of diffused coherent light with optical phase conjugation (OPC), achieving dynamic focusing of light into scattering medium. Simulation results show that the focusing accuracy of the proposed method has been significantly improved compared with conventional TRUE, which is more suitable for practical applications that suffers severe acoustic distortion, e.g. transcranial optical focusing.

In recent years, the number of malicious web pages has increased dramatically, posing a great challenge to network security. While current machine learning-based detection methods have emerged as a promising alternative to traditional detection techniques. However, these methods are commonly based on single-modal features or simple stacking of classifiers built on various features. As a result, these techniques are not capable of effectively fusing features from different modalities, ultimately limiting the detection effectiveness. To address this limitation, we propose a malicious web page detection method based on multi-modal learning and pre-trained models. First, in the input stage, the raw URL and HTML tag sequences of web pages are used as input features. To help the subsequent model learn the relationship between the two modalities and avoid information confusion, modal-type encoding, and positional encoding are introduced. Next, a single-stream neural network based on the ConvBERT pre-trained model is used as the backbone classifier, and it learns the representation of multi-modal features through fine-tuning. For the output part of the model, a linear layer based on large margin softmax is applied to the decision-making. This activation function effectively increases the classification boundary and improves the robustness. In addition, a coarse-grained modal matching loss is added to the model optimization objective to assist the models in learning the cross-modal association features. Experimental results on synthetic datasets show that our proposed method outperforms traditional single-modal detection methods in general, and has advantages over baseline models in terms of accuracy and reliability.

Zearalenone (ZEN) is an important secondary metabolite of Fusarium fungi, exposure to which can cause reproductive disorders through its effects on ovarian granulosa cells (GCs) in many mammals, especially in pigs. This study aimed to investigate the protective effects of Cyanidin-3-O-glucoside (C3G) on the ZEN-induced negative effects in porcine GCs (pGCs). The pGCs were treated with 30 µM ZEN and/or 20 µM C3G for 24 h; they were divided into a control (Ctrl) group, ZEN group, ZEN+C3G (Z+C) group, and a C3G group. Bioinformatics analysis was used to systematically screen differentially expressed genes (DEGs) in the rescue process. Results showed that C3G could effectively rescue ZEN-induced apoptosis in pGCs, and notably increase cell viability and proliferation. Furthermore, 116 DEGs were identified, and the phosphatidylinositide 3-kinases-protein kinase B (PI3K-AKT) signaling pathway was the center of attention, of which five genes and the PI3K-AKT signaling pathway were confirmed by real-time quantitative PCR (qPCR) and/or Western blot (WB). As analyzed, ZEN inhibited mRNA and protein levels of integrin subunit alpha-7 (ITGA7), and promoted the expression of cell cycle inhibition kinase cyclin-D3 (CCND3) and cyclin-dependent kinase inhibitor 1 (CDKN1A). After the knock-down of ITGA7 by siRNA, the PI3K-AKT signaling pathway was significantly inhibited. Meanwhile, proliferating cell nuclear antigen (PCNA) expression decreased, and apoptosis rates and pro-apoptotic proteins increased. In conclusion, our study demonstrated that C3G exhibited significant protective effects on the ZEN-induced inhibition of proliferation and apoptosis via the ITGA7-PI3K-AKT pathway.