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To understand the shale gas reservoirs in the first member of the Permian Maokou Formation (Mao 1 Member) in Nanchuan area of the Sichuan Basin, we used outcrops, cores, mineralogical and geochemical datas, thin-section analysis, and argon-ion-polishing scanning electron microscopy results with logging and seismic attribute prediction techniques to study the sedimentary facies, source rocks, reservoir properties and types. The geological characteristics and enrichment model of shale gas reservoirs of the Mao 1 Member were revealed and are summarized as follows: (1) the Maokou Formation can be divided into four members from bottom to top. The Mao 1 Member is located in the relatively deep-water gentle slope of a carbonate platform, comprising well-developed dark-gray/grayish-black carbonaceous mudstone, calcareous mudstone, argillaceous limestone, and bioclastic limestone. Carbonaceous and calcareous mudstones, with a relatively high total organic carbon content (TOC0.5–5.1%) and moderate thermal maturity (Ro: 2.0–2.3%), are potentially good hydrocarbon source rocks with possibly new type of atypical shale gas reservoir; (2) organic pores, dissolution pores, grain margin fractures, and shrinkage fractures are developed in the Mao 1 Member and may form a reservoir of a complex “pore–fracture–network,” which is beneficial to gas storage and migration; (3) the shale gas in the Mao 1 Member has the accumulation and enrichment model of “integrated source and reservoir, continuous distribution, and structure-fracture dual reservoir control” with a continuous distribution area exceeding 500 km2 and a geological resource volume exceeding 70 billion cubic meters; therefore, it has great exploration potential for shale gas. The research results are crucial in improving the understanding of new type of shale gas geology and guide shale gas exploration in southeastern Sichuan.

Nervonic acid plays an important role in nutrition and function of the human body. Malania oleifera, Acer truncatum and Xanthoceras sorbifolium are China’s unique woody plant rich in nervonic acid in seed oil. This study aims to investigate the lipid composition of these 3 special resources. Their fatty acids were detected by gas chromatography coupled with flame detector (GC-FID). Triglycerides (TAGs) and phospholipids (PLs) were detected by shotgun-mass spectrometry (shotgun-MS). Results showed that M. oleifera oil presented the highest level of nervonic acid (46.20 ​± ​0.22%) among the 3 oils. Seeds oil of A. truncatum and X. sorbifolium had 3.53 ​± ​0.20% and 1.83 ​± ​0.21% nervonic acid respectively. 53 species of TAGs and 15 species of PLs were identified in M. oleifera oil, with PLs content of 499.94 ​± ​22.34 ​μg/g. In A. truncatum oil, PL and TAG species were twice more than those in M. oleifera oil, and its’ content of PLs was 76.27 ​± ​3.21 ​μg/g. In X. sorbifolium oil, 75 TAGs and 34 ​PLs were detected, with the lowest PLs at 23.84 ​± ​0.17 ​μg/g. The results demonstrated that these 3 vegetable oils have great potential to become nervonic acid supplements for human health.

At present, researches on the pore evolution of shale reservoir and its evolution mechanism are still at such a groping stage that a consensus has not yet reached. Based on core analysis and thermal simulation experiments, the pore types, pore structures and pore-size change rules of shale gas reservoirs of Upper Ordovician Wufeng–Lower Silurian Longmaxi Fms in the southeastern (SE) Sichuan Basin and its basin-margin transition zone (hereinafter referred to as the basin-margin transition zone of SE Chongqing) were studied by means of argon ion polishing–scanning electron microscopy (SEM) and atomic force microscopy. Then, the evolution characteristics of organic pores were discussed, and the influence of associated minerals on pore evolution was analyzed. Finally, a pore evolution model for the shale gas reservoirs in this area was established. And the following research results were obtained. First, three types of reservoir spaces are mainly developed in the high-quality shale reservoirs of Wufeng–Longmaxi Fms in this area, including fracture, inorganic pore and organic pore. And the organic pores provide the primary reservoir space of shale gas, which can be divided into four categories, i.e., amorphous kerogen pores, structured kerogen pores, asphaltene pores and paleontology fossil pores. Second, organic contracted fractures are related to the contraction of organic matters, first appearing on one side of the organic matters and then becomes wider and wider with the increase of temperatures. Third, organic pores are mostly the “spongy” pores distributed densely inside the organic matters. When Ro is in the range of 1.56–3.50%, macropores and mesopores are dominant. And when Ro exceeds 3.50%, macropores decrease while mesopores and micropores increase. Fourth, the types of organic matters and the content of associated minerals (e.g. clay minerals, siliceous particles and pyrite) play an important role in the development of pores. In conclusion, the pore evolution law of Wufeng–Longmaxi shale in the basin-margin transition zone of SE Chongqing is that with the increase of burial depth, inorganic porosity decreases significantly, organic porosity increases first and then decreases, and the total porosity shows a change trend of decreasing first, then increasing and finally decreasing continuously. Keywords: SE sichuan basin, Basin-margin transition zone, Late Ordovician–Early silurian, Shale gas, Reservoir, Organic pore, Inorganic pore, Pore evolution model

The southeastern Sichuan Basin and its basin-margin transition zone (hereinafter referred to as “the basin-margin transition zone of SE Chongqing”) is the focus of normal-pressure shale gas exploration in China. In order to summarize the geological characteristics and enrichment laws of shale gas in the basin-margin transition zone of SE Chongqing, we analyzed the geological characteristics of shale gas reservoirs in the Nanchuan–Wulong area of this transition zone from the aspects of sedimentary formation, tectonic reworking and production characteristics by using geophysical, drilling, logging and testing data, and then we compared it with the overpressure shale gas reservoirs in the Jiaoshiba Block. Finally, we explored the main factors controlling the enrichment & high yields of normal-pressure shale gas in this transition zone and their hydrocarbon accumulation patterns. And the following research results were obtained. (1) Different from the over-pressure shale gas reservoirs in Jiaoshiba Block, the normal-pressure shale gas reservoirs in this transition zone are characterized by lower organic porosities, more developed micro-fractures, higher ratios of adsorbed gas, greater differences of stresses in two directions, lower geothermal gradients, lower formation pressure coefficients, higher initial fluid production rates and higher fluid flowback rates. (2) The enrichment & high yields of normal-pressure shale gas in this area is mainly controlled by three factors, i.e., carbon-rich, silicate-rich and graptolite-rich shale, organic pores, and tectonic stress field, among which, the first factor controlled by deepwater continental shelf facies is the basis of shale gas enrichment, the second is the main controlling factor of shale gas enrichment, and the third is the key factor of high-yield shale gas. (3) The hydrocarbon accumulation patterns of normal-pressure shale gas reservoirs in the transition zone can be divided into four types, including the anticline type, the syncline type, the slope type and the reverse fault type. And the enrichment & high-yield characteristics of shale gas in different hydrocarbon accumulation patterns are also clarified. In conclusion, the research results enrich the geological theory of enrichment & high-yield laws of normal-pressure shale gas and provide a support for the exploration and development of normal-pressure shale gas in complex structures. Keywords: SE Sichuan basin, Transition zone at the basin margin, Late ordovician–early silurian, Normal-pressure shale gas, Main factors controlling high yield, Tectonic stress field, Gas accumulation

Abstract Background Turnover intention (TI) indicates an employee’s intention to depart from their current role within a defined timeframe. In China, the Targeted Admission Medical Education (TAME) program, initiated in 2010, offers tuition-free education to cultivate rural doctors. Despite continuous professional development (CPD) being considered a viable retention strategy, TI of alumni doctors from the TAME program remains high in recent years. This study aims to describe the prevalence of “turnover intention” among alumni doctors of the TAME program doctors in rural placements, and associated factors that predict high turnover intention. Methods A snowball sampling method was adopted to collect survey responses from 1,369 alumni doctors of the TAME program in Jiangxi Province, China. Based on the survey data, a binary variable was constructed to measure the turnover intention, and multivariate binary logistic regression models were used to investigate the relationship between doctors’ turnover intention and demographic characteristics, work environment characteristics, and CPD activities. Results were presented using adjusted odds ratios with 95% confidence intervals. Results Among the 1,369 alumni doctors of the TAME program surveyed in this study, 392 (28.6%) expressed intentions to leave their current positions. Of the respondents, 620 (45.3%) were female, and 930 (67.9%) were married. Additionally, 1,232 respondents (90%) indicated that their fathers were engaged in farm work. Strong associations with turnover intention were notably found among individuals who had undergone training at a higher-level healthcare institution for more than three months (aOR = 6.810, 95% CI: 3.333 to 13.909, p-value

In this study, we investigated the oxidation of the Mg-11Y-1Al alloy at 500 °C in an Ar-20%O2 environment. Multiscale analysis showed the network-like long-period stacking ordered (LPSO) phase transformed into needle-like LPSO and polygonal Mg24Y5 phases, leading to the formation of a high-dense network of needle-like oxides at the oxidation front. These oxides grew laterally along the oxide/matrix interfaces, forming a thicker, continuous scale that effectively blocked elemental diffusion. Hence, the preferential oxidation along the needle-like LPSO is believed to accelerate the formation of a thicker and continuous oxide scale, further improving the oxidation resistance of the Mg-11Y-1Al alloy.

Abstract Background Obesity and metabolic syndrome (MetS) have become urgent worldwide health problems, predisposing patients to unfavorable myocardial status and thyroid dysfunction. Low-carbohydrate diet (LCD) and time-restricted eating (TRE) have been confirmed to be effective methods for weight management and improving MetS, but their effects on the myocardium and thyroid are unclear. Methods We conducted a secondary analysis in a randomized clinical diet-induced weight-loss trial. Participants (N = 169) diagnosed with MetS were randomized to the LCD group, the 8 h TRE group, or the combination of the LCD and TRE group for 3 months. Myocardial enzymes and thyroid function were tested before and after the intervention. Pearson’s or Spearman’s correlation was assessed between functions of the myocardium and thyroid and cardiometabolic parameters at baseline. Results A total of 162 participants who began the trial were included in the intention-to-treat (ITT) analysis, and 57 participants who adhered to their assigned protocol were involved in the per-protocol (PP) analysis. Relative to baseline, lactate dehydrogenase, creatine kinase MB, hydroxybutyrate dehydrogenase, and free triiodothyronine (FT3) declined, and free thyroxine (FT4) increased after all 3 interventions (both analyses). Creatine kinase (CK) decreased only in the TRE (− 18 [44] U/L, P

Abstract Background Pregnancy complications might lead to the development of autoimmune diseases in women. This review aims to summarise studies evaluating the association between pregnancy complications and the development of autoimmune diseases in women. Methods Medline, CINAHL, and Cochrane databases were searched up to January 2024. Nineteen pregnancy complications and 15 autoimmune conditions were included. Title, abstract, full-text screening, data extraction, and quality assessment were performed by two reviewers independently. Data were synthesised using narrative and quantitative methods. Results were presented using odds ratios (OR), relative risks (RR), incidence rate ratios (IRR), and 95% confidence intervals (CI). Results Thirty studies were included. One study reported composite exposure to pregnancy complications had a risk of any autoimmune disease RR 3.20 (2.90–3.51) compared to women without pregnancy complications. Women with hyperemesis gravidarum had a higher risk of developing coeliac disease (n = 1) IRR 1.98 (1.27–2.94), Crohn’s disease (n = 1) IRR 1.61 (1.25–2.04), psoriasis (n = 1) IRR 1.33 (1.01–1.71), and rheumatoid arthritis (n = 2) IRR 1.35 (1.09–1.64). Miscarriage associated with subsequent diagnosis of Sjogren syndrome (n = 2) IRR 1.33 (1.06–2.81) and rheumatoid arthritis (n = 4) OR 1.11 (1.04–1.20). Gestational hypertension/preeclampsia was linked with the development of systemic sclerosis (n = 2) IRR 2.60 (1.10–4.60) and T1DM (n = 2) IRR 2.37 (2.09–2.68). Stillbirth associated with composite autoimmune conditions (n = 2) RR 5.82 (95% CI 4.87–6.81) and aIRR 1.25 (1.12–1.40). Postpartum psychosis was associated with autoimmune thyroid disease (n = 1) aIRR2.26 (1.61–2.90). Conclusions Women with pregnancy complications subsequently had a higher risk of being diagnosed with autoimmune conditions. Whether this is due to pre-existing undiagnosed health conditions or being causally linked to pregnancy complications is not known.

Magnesium matrix composites have garnered significant attention in recent years owing to their exceptional lightweight properties and notable potential in various engineering applications. The interface generally acts as a “bridge” between the matrix and reinforcement, playing crucial roles in critical processes such as load transfer, failure behavior, and carrier transport. A deep understanding of the interfacial structures, properties, and effects holds paramount significance in the study of composites. This paper presents a comprehensive review of prior researches related to the interface of Mg matrix composites. Firstly, the different interfacial structures and interaction mechanisms encompassing mechanical, physical, and chemical bonding are introduced. Subsequently, the interfacial mechanical properties and their influence on the overall properties are discussed. Finally, the paper addresses diverse interface modification methods including matrix alloying and reinforcement surface treatment.

ObjectiveThis study aimed to explore the clinical characteristics of thyroid-associated ophthalmopathy (TAO) with hyperlipidemia and to identify the key lipid indicator.MethodsPatients with TAO were recruited to this study and divided into two groups based on the presence of hyperlipidemia. TAO patients with hyperlipidemia were further classified based on the type of hyperlipidemia. Basic and clinical information of the patients were collected, and comparisons between groups were carried out. Correlation analyses, regression analyses, and stratified analysis were performed to assess the correlations and relationship of the serum lipids with the ophthalmic indicators.ResultsA total of 273 patients with TAO were recruited, including 158 patients with hyperlipidemia and 115 patients without hyperlipidemia. Patients with hyperlipidemia, especially those with mixed hyperlipidemia, exhibited high intraocular pressure (IOP). Spearman’s correlation analysis and partial correlation analysis showed that apolipoprotein E (ApoE) was positively related to IOP levels after controlling for confounding factors, including age, gender, BMI, smoking history, triiodothyronine (T3), and thyrotropin (thyroid-stimulating hormone, TSH). Moreover, multiple linear regression obtained a regression equation including ApoE, gender, age, and BMI and showed that elevated ApoE levels were associated with elevated IOP [β = 0.072, 95% confidence interval (CI) = 0.037–0.155, p = 0.030]. Stratified analysis highlighted the impact of ApoE on IOP in younger patients (≤48 years), female patients, patients with normal BMI (

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.

The activated B-cell–like subtype of diffuse large B-cell lymphoma (ABC-DLBCL) displays a worse outcome than the germinal center B-cell–like subtype (GCB-DLBCL). Currently, targeting tumor microenvironment (TME) is the promising approach to cure DLBCL with profound molecular heterogeneity, however, the factors affecting the tumor-promoting TME of ABCDLBCL are elusive. Here, cytokine interleukin-16 (IL-16) is expressed in tumor cells of ABCDLBCL and secreted by the cleavage of active caspase-3. The serum IL-16 levels are not only a sensitive marker of treatment response but also positively correlated with unfavorable prognosis in DLBCL patients. While IL-16 shows few direct promotional effects on tumor cell growth in vitro, its bioactive form significantly promotes tumor progression in vivo. Mechanically, IL-16 increases the infiltration of macrophages by the chemotaxis of CD4+ monocytes in the TME enhancing angiogenesis, and the expression of cytokine IL-6 and IL-10, as well as decreasing T cell infiltration to accelerate tumor progression. This study demonstrates that IL-16 exerts a novel role in coordinating the bidirectional interactions between tumor progression and the TME. IMM0306, a fusion protein of CD20 mAb with the CD47 binding domain of SIRPα, reverses the tumorpromoting effects of IL-16,which provides new insight into treatment strategy in ABC-DLBCL.

Abstract Objective To improve our understanding of systemic lupus erythematosus (SLE)‐macrophage activation syndrome (MAS). Methods A systematic review was performed, to retrieve all those papers on patients with SLE‐MAS, in individual or aggregated form. The data in each of these medical records were extracted and analyzed to identify the characteristics of SLE‐MAS. Results A total of 86 SLE‐MAS patients were included (25 males and 61 females. The mean (±standard error of the mean) age was 31.21 ± 1.694 years. MAS occurred as the initial presentation of SLE in 47 people (54.65%) and during the course of SLE in 39 (45.35%). A coinfection was reported in 23 (26.74%) patients. The mean Lupus Erythematosus Disease Activity Index 2000 (SLEDAI‐2K) score was 16.54 ± 0.9462. Overall, 10 patients (11.63%) died. The SLEDAI‐2K score was higher in patients with MAS as an initial manifestation of SLE than in those where MAS occurred during the course of SLE. The proportion of patients receiving steroid pulse therapy was lower in patients with coinfections. The deceased group demonstrated lower platelet and ferritin levels. Multiple regression analysis revealed that age and thrombocytopenia were independent factors associated with poor prognosis. In receiver operating characteristic analysis, a platelet count cutoff value of ≤47 × 109/L was a predictor of poor outcome. Conclusions SLE‐MAS patients demonstrated high lupus activity, and lupus activity was especially higher in patients with MAS as an initial manifestation. Lupus activity was the predominant trigger of lupus MAS. Thrombocytopenia was an independent factor for poor prognosis.

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 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.

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.

In recent years, the number of underwater road tunnels in Chinese cities has increased. However, the current situation of personal fire safety literacy as it pertains to these tunnels remains unclear. To address this gap, a questionnaire survey was conducted to investigate people’s awareness of escape slides, evacuation signs, and the correct evacuation paths for fire escape. A total of 1049 respondents in Changsha, China, were surveyed, with 791 valid questionnaires collected and analyzed. The findings revealed that a significant proportion of respondents (81.80%) were unaware of the presence of escape slides in underwater road tunnels, while 87.86% could not recognize them and 93.05% could not use them. Only 42.04% of respondents could identify evacuation signs in underwater road tunnels. In the event of a fire, just half of the respondents could select the appropriate escape or evacuation path. Additionally, demographic differences among respondents also influenced their level of fire safety literacy. Based on these findings, it is recommended that the government and relevant organizations should enhance the dissemination of knowledge regarding escape slides and evacuation signs in underwater road tunnels.

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

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.

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.

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.

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.

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.

With the emergence of intelligent policing, the channels of mass to call police are widened, unstructured police records increase immensely, and the difficulty of police entity recognition is magnified.For this pain point, BERT model was introduced to generate the word vector, the self-attention mechanism was integrated to capture the long-distance dependence between words, and the BERT-BiGRU-SelfAtt-CRF police entity recognition model was constructed.In order to verify the performance and generalization ability of this model, experiments were carried out on public datasets.And to prove the feasibility and efficiency of this model in the police field, experiments were run on the annotated police dataset.Ultimately, the results showed that BERT-BiGRU-SelfAtt-CRF model outperformed other models on the police dataset, with the precision of 82.45%, recall rate of 79.03%, and F1 value of 80.72%.It is concluded that this model can meet the requirements of actual police work, and it is feasible and effective in the field of police entity recognition.

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.

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.

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.

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.

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.

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.

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

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.