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Abstract Soundscape quality is important for fostering social interactions in urban public spaces. This study focuses on how and to what extent the compositions of the soundscape affect the sociability of urban public spaces where human sound is focused. Four 360° experimental soundscape samples were designed as foreground/background/no human sound type and signal sound type, based on the raw data collected in Peace Gardens, Sheffield, United Kingdom. Following Affordance Theory, sociability was analyzed by the experimental survey through two aspects—suitability and stimulation level—through a questionnaire consisting of Soundscape Quality evaluation (SQE) and Level of Willingness for social interactions (LoW), respectively. 120 participants were recruited in the same site representing the compositions of space users. Results show that only foreground human sound type significantly enhanced both suitability and stimulation levels, other samples were evaluated with either high suitability/low stimulation or low suitability/high stimulation. Results indicate people prefer a human sound dominated soundscape with high complexity and this preference was varied among different companion types and age groups. To achieve high sociability, it is suggested to create a complex and eventful soundscape within the range of pleasantness accompanied by a centripetal spatial form, and concerns users' diverse demographic backgrounds.

Abstract Background Follicular cysts contribute significantly to reproductive loss in high-yield dairy cows. This results from the death of follicular granulosa cells (GCs) caused by oxidative stress. Quercetin is known to have significant antioxidant and anti-apoptotic effects. However, the effect of quercetin on follicular cysts has yet been elucidated. Therefore, this study aimed to explore the anti-oxidant and anti-apoptosis effects and potential molecular mechanisms of quercetin in H2O2-induced primary cow GCs and 3-nitropropionic acid (3-NPA)-induced mouse model of oxidative stress and thus treat ovarian cysts in dairy cows. Results In this study, compared with estrus cows, cows with follicular cysts showed heightened levels of oxidative stress and increased follicular cell apoptosis, while autophagy levels were reduced. A model of oxidative stress was induced in vitro by H2O2 and showed significant increases in apoptosis together with reduced autophagy. These effects were significantly ameliorated by quercetin. Effects similar to those of quercetin were observed after treatment of cells with the reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC). Further investigations using chloroquine (autophagy inhibitor), rapamycin (autophagy activator), selisistat (SIRT1 inhibitor), and compound C (AMPK inhibitor) showed that chloroquine counteracted the effects of quercetin on oxidative stress-induced apoptosis, while rapamycin had the same effect as quercetin. In addition, the SIRT1/AMPK pathway inhibitors antagonized quercetin-mediated mitigation of the effects of oxidative stress on increased apoptosis and reduced autophagy. Consistent with the results in vitro, in mouse ovarian oxidative stress model induced by 3-NPA, quercetin activated autophagy through the SIRT1/AMPK signaling pathway, while alleviating oxidative stress damage and inhibiting apoptosis in mouse ovaries. Conclusions These findings indicate that quercetin can inhibit apoptosis in GCs and restore ovarian function by activating autophagy through the SIRT1/ROS/AMPK signaling pathway, suggesting a new direction for the treatment of ovarian follicular cysts in high-yield dairy cows.

Micro-alloyed low carbon MnCrNiCuMo steels were proposed to produce heavy plates with a maximum thickness of 100 mm. An integrated industrial route including a thermo-mechanical control process (TMCP) based on a study on continuous cooling transformation was applied in industrial production. Comprehensive mechanical properties tests including the measurement on resistance against crack initiation using crack tip opening displacement (CTOD) approach were conducted. Large scale wide-plate temperature gradient double tension (DT) technique was employed to evaluate the crack arrest toughness Kca in the heavy plates under different conditions. Nil-ductility transition temperature (NDTT) was also tested across the entire thickness section of the plates. The results showed that heavy steel plates were qualified being brittle crack arrest (BCA) products at EH47 grade with yield strength high than 460 MPa. High crack initiation toughness was exhibited by both Charpy-V notch impact property and CTOD values. Crack arrest toughness at −10 °C greater than 253 MPa √m was achieved in a plate even with thickness of 100 mm. The mean value of crack arrest toughness at different temperature measured by the DT approach can be indexed by the highest NDTT in the interior section of the heavy plates leading to an empirical prediction model. Further, fracture mechanics based master curve approach was used to statistically predict crack arrest toughness distribution over a wide range of temperatures showing improved predictability over the empirical model and an existing model in the literature.

This study aimed to investigate the impact of specific landscape elements on pedestrians’ emotional experiences during walking. During the study, footages were recorded by participants while walking to obtain real-time visual element data, including greenery, building and road visibility. And electroencephalogram (EEG) indicators of β/α, (α+θ)/β, θ/β and θ/α ratio were collected to represent levels of arousal, fatigue, attention and relaxation. Our findings suggested strong correlations between θ/α ratio with both greenery and road visibility. Conversely, other indicators were primarily influenced by greenery and building visibility. Regarding the combined impact of elements, the most positive emotions were observed when green visibility exceeded 51%. However, the peak alertness was achieved with building visibility between 5.2% and 31%. The lowest fatigue and the highest attention level were recorded under building visibility less than 5.2%, and the highest level of relaxation occurred with road visibility less than 10%. In terms of the influence of time, the entire walking process could be delineated by the five and 8 min marks, classified into novelty, adaptation and sustained phase based on the patterns of emotional changes observed in the participants. Consequently, the visual elements and their combinations, and duration play regulatory roles in pedestrians' emotional experiences.

AbstractContext Traditional Chinese medicines (TCMs) have emerged as potential adjuvant therapies to treat non-small cell lung cancer. More direct comparative studies must be conducted among various oral TCMs.Objective This network meta-analysis evaluates the efficacy and safety of seven oral TCMs combined with chemotherapy in treating NSCLC.Methods The analysis included Zilongjin, Banmao, Hongdoushan, Huachansu, Kanglaite, Xihuang, and Pingxiao TCMs. Randomized-controlled trials (RCTs) were identified from the following databases: China National Infrastructure, Wanfang, PubMed, Embase, and the Cochrane Library up to April 2023. Two researchers independently extracted data.Results Sixty-eight RCTs (5,099 patients) were included. Compared to chemotherapy, Banmao capsules [odds ratio (OR) = 2.69, 95% confidence interval (CI) 1.96–3.69)] and Huachansu tablets [OR = 2.35, 95%CI (1.81, 3.05)] ranked in the top two in terms of increasing disease control rate. The two main TCMs to improve the objective response rate were Banmao capsules [OR = 3.49, 95%CI (2.17, 5.60)] and Zilongjin tablets [OR = 2.62, 95%CI (1.92, 3.57)]. Zilongjin tablets [OR = 3.47, 95%CI (2.14, 5.63)] and Huachansu tablets [OR = 3.30, 95%CI (1.65, 6.60)] were ranked as the top two in improving Karnofsky performance status. Hongdoushan capsules (SUCRA = 18.8%) and Banmao capsules (SUCRA = 19.8%) were the top two in reducing gastrointestinal toxicity. Zilongjin tablets (SUCRA = 18.9%) and Banmao capsules (SUCRA = 26.6%) were the top two to reduce liver and kidney toxicity. Hongdoushan capsules (SUCRA = 15.7%) and Huachansu tablets (SUCRA = 16.8%) ranked the top two in reducing thrombocytopenia. Banmao capsules (SUCRA = 14.3%) and Zilongjin tablets (SUCRA = 26.3%) were the top two decreasing leukopenia.Conclusions Combining oral TCMs with platinum-based chemotherapy has shown superior efficacy compared to platinum-based chemotherapy alone in treating NSCLC.

Abstract Pair density wave (PDW) is a distinct superconducting state characterized by a periodic modulation of its order parameter in real space. Its intricate interplay with the charge density wave (CDW) state is a continuing topic of interest in condensed matter physics. While PDW states have been discovered in cuprates and other unconventional superconductors, the understanding of diverse PDWs and their interactions with different types of CDWs remains limited. Here, utilizing scanning tunneling microscopy, we unveil the subtle correlations between PDW ground states and two distinct CDW phases — namely, anion-centered-CDW (AC-CDW) and hollow-centered-CDW (HC-CDW) — in 2H-NbSe2. In both CDW regions, we observe coexisting PDWs with a commensurate structure that aligns with the underlying CDW phase. The superconducting gap size, Δ(r), related to the pairing order parameter is in phase with the charge density in both CDW regions. Meanwhile, the coherence peak height, H(r), qualitatively reflecting the electron-pair density, exhibits a phase difference of approximately 2π/3 relative to the CDW. The three-fold rotational symmetry is preserved in the HC-CDW region but is spontaneously broken in the AC-CDW region due to the PDW state, leading to the emergence of nematic superconductivity.

Abstract Background Evidence suggests that coronavirus disease 2019 (COVID-19) is associated with the risk of cardiovascular diseases (CVDs). However, the results are inconsistent, and the causality remains to be established. We aimed to investigate the potential causal relationship between COVID-19 and CVDs by using two-sample Mendelian randomization (MR) analysis. Methods Summary‐level data for COVID-19 and CVDs including myocarditis, heart failure (HF), acute myocardial infarction (AMI), arrhythmia and venous thromboembolism (VTE) were obtained from the IEU OpenGWAS project, a public genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) were used as instrumental variables. Five complementary MR methods were performed, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode and simple mode methods. IVW method was considered as the primary approach. Besides, sensitivity analyses, including Cochran’s Q test, MR-Egger intercept test, and leave-one-out analysis, were performed to evaluate the robustness of the results. Results According to the IVW results, our MR study indicated that genetically predicted COVID-19 was not causally connected with the risk of CVDs [myocarditis: odds ratio (OR) = 1.407, 95% confidence interval (CI) = 0.761-2.602, p-value = 0.277; HF: OR = 1.180, 95% CI = 0.980-1.420, p-value = 0.080; AMI: OR = 1.002, 95% CI = 0.998-1.005, p-value = 0.241; arrhythmia: OR = 0.865, 95% CI = 0.717-1.044, p-value = 0.132; VTE: OR = 1.013, 95% CI = 0.997-1.028, p-value = 0.115]. The supplementary MR methods showed similar results. Sensitivity analyses suggested that the causal estimates were robust. Conclusion This two-sample MR analysis did not provide sufficient evidence for a causal relationship between COVID-19 and the risk of acute CVDs, which may provide new insights into the prevention of acute CVDs in COVID-19 patients.

Abstract Non-alcoholic steatohepatitis (NASH) is a hepatocyte inflammation based on hepatocellular steatosis, yet there is no effective drug treatment. Atherosclerosis (AS) is caused by lipid deposition in the endothelium, which can lead to various cardiovascular diseases. NASH and AS share common risk factors, and NASH can also elevate the risk of AS, causing a higher morbidity and mortality rate for atherosclerotic heart disease. Therefore, timely detection and diagnosis of NASH and AS are particularly important. In this study, differential gene expression analysis and weighted gene co-expression network analysis were performed on the AS (GSE100927) and NASH (GSE89632) datasets to obtain common crosstalk genes, respectively. Then, candidate Hub genes were screened using four topological algorithms and externally validated in the GSE43292 and GSE63067 datasets to obtain Hub genes. Furthermore, immune infiltration analysis and gene set variation analysis were performed on the Hub genes to explore the underlying mechanisms. The DGIbd database was used to screen candidate drugs for AS and NASH. Finally, a NASH model was constructed using free fatty acid-induced human L02 cells, an AS model was constructed using lipopolysaccharide-induced HUVECs, and a co-morbidity model was constructed using L02 cells and HUVECs to verify Hub gene expression. The result showed that a total of 113 genes common to both AS and NASH were identified as crosstalk genes, and enrichment analysis indicated that these genes were mainly involved in the regulation of immune and metabolism-related pathways. 28 candidate Hub genes were screened according to four topological algorithms, and CXCL9, IL2RB, and SPP1 were identified as Hub genes after in vitro experiments and external dataset validation. The ROC curves and SVM modeling demonstrated the good diagnostic efficacy of these three Hub genes. In addition, the Hub genes are strongly associated with immune cell infiltration, especially macrophages and γ–δ T cell infiltration. Finally, five potential therapeutic drugs were identified. has-miR-185 and hsa-miR-335 were closely related to AS and NASH. This study demonstrates that CXCL9, IL2RB, and SPP1 may serve as potential biomarkers for the diagnosis of the co-morbidity patterns of AS and NASH and as potential targets for drug therapy.

Achieving a high color rendering index (CRI) and luminous stability in single-structured Ce:Y3Al5O12 (Ce:YAG) phosphor ceramics (PCs) is crucial for high-power white light-emitting diodes or laser diodes (LEDs/LDs). However, cyan valleys and insufficient amounts of the red component in the Ce:YAG emission spectra significantly limit their real applications. In this work, a series of Ce,Mn:Y3(Al,Sc)2Al3O12 (Ce,Mn:YSAG) PCs were fabricated by vacuum sintering, and efficient spectral regulation was realized for full-color lighting. The cyan valley was filled by the blueshifted emission peak of Ce3+ via Sc3+ doping. The orange‒red emission at approximately 580 nm was effectively supplemented via Mn2+ doping. In particular, CRI of Ce,Mn:YSAG increased from 56.4 to 85.8, a 52% increase compared with that of Ce:YAG under high-power LED excitation, and the operating temperature was stable at approximately 50 °C for long working time. Moreover, CRI of 80.9 could still be obtained for PC-based white LDs. These results indicated that Ce,Mn:YSAG PC, which has excellent CRI and luminous stability, is an extremely promising color convertor for high-power white LEDs/LDs.

Kidney stones are a foremost clinical concern in urology with CaOx crystals accounting for roughly 80% of these renal formations. This research endeavor seeks to ascertain the protective effects of Metformin-encapsulated selenium nanoparticles (M@Se NPs), combined with a 55% hydroethanolic flower extract from Myrtus communis L. (MCL) in countering the formation of kidney stones in Male Sprague Dawley rats. The particle's diameter was measured to be 39 nm and 13.8 nm from DLS and HR-TEM analysis. Rat groups administered with the MCL-M@Se NPs (1:1.5:1) exhibited reduced renal stone formation in urine and serum analysis compared to the negative control group. Histological evaluations of kidney samples using H&E, and MTS staining indicated a subdued presence of ECM deposition in contrast to other rat groups. Conclusively, the protective mechanism of MCL-M@Se NPs against CaOx stone damage can be confidently attributed to the obstruction of the MAPK signaling pathway.

BackgroundAtherosclerosis is a leading cause of cardiovascular disease worldwide, while carotid atherosclerosis (CAS) is more likely to cause ischemic cerebrovascular events. Emerging evidence suggests that cuproptosis may be associated with an increased risk of atherosclerotic cardiovascular disease. This study aims to explore the potential mechanisms linking cuproptosis and CAS.MethodsThe GSE100927 and GSE43292 datasets were merged to screen for CAS differentially expressed genes (DEGs) and intersected with cuproptosis-related genes to obtain CAS cuproptosis-related genes (CASCRGs). Unsupervised cluster analysis was performed on CAS samples to identify cuproptosis molecular clusters. Weighted gene co-expression network analysis was performed on all samples and cuproptosis molecule clusters to identify common module genes. CAS-specific DEGs were identified in the GSE100927 dataset and intersected with common module genes to obtain candidate hub genes. Finally, 83 machine learning models were constructed to screen hub genes and construct a nomogram to predict the incidence of CAS.ResultsFour ASCRGs (NLRP3, SLC31A2, CDKN2A, and GLS) were identified as regulators of the immune infiltration microenvironment in CAS. CAS samples were identified with two cuproptosis-related molecular clusters with significant biological function differences based on ASCRGs. 220 common module hub genes and 1,518 CAS-specific DEGs were intersected to obtain 58 candidate hub genes, and the machine learning model showed that the Lasso + XGBoost model exhibited the best discriminative performance. Further external validation of single gene differential analysis and nomogram identified SGCE, PCDH7, RAB23, and RIMKLB as hub genes; SGCE and PCDH7 were also used as biomarkers to characterize CAS plaque stability. Finally, a nomogram was developed to assess the incidence of CAS and exhibited satisfactory predictive performance.ConclusionsCuproptosis alters the CAS immune infiltration microenvironment and may regulate actin cytoskeleton formation.

Validating the satellite soil moisture products is always an active research topic for the application of the products and improvement of the retrieval algorithms, attracting extensive attention. Nevertheless, seldom existing validation activities focus on the validation of high-resolution soil moisture products at the fine scale. To this end, an experiment was conducted in the middle stream of the Heihe River Basin in northwestern China in August to October of 2021, aiming to validate high-resolution satellite remote sensing products of soil moisture. The paper introduces the design, composite, and preliminary results of the experiment. A soil moisture observation network was established with two kinds of sensors (CS616 and Stevens Hydra Probe) validated against soil core measurements. Several synchronized campaigns were performed, and data were collected to validate the SMAP/Sentinel-1 L2 Radiometer/Radar 30-Second Scene 3 and 1 km EASE-Grid Soil Moisture (SPL2SMAP_S) products. Besides, an optical trapezoid model (OPTRAM) and collected Sentinel-2 data were applied to estimate soil moisture and to map irrigated area. Preliminary analyses show that: 1) Steven probes perform best, with an RMSE = 0.040 m3m−3 and ubRMSE=0.034 m3m−3; 2) Both the SPL2SMAP_S products at 3 km and 1 km show large RMSE (0.128 m3m−3 for 3 km and 0.158 m3m−3 for 1 km) and ubRMSE (0.115 m3m−3 for 3 km and 0.158 m3m−3 for 1 km); 3) The OPTRAM retrievals over bare surface present relatively smaller RMSE (0.06 m3m−3) and ubRMSE (0.057 m3m−3), while retrievals over vegetated croplands present a relatively large RMSE/ubRMSE (0.083/0.083 m3m−3), and the retrievals can identify the irrigated area at field scale. Overall, the experiment provides fruitful methodologies and datasets for the validation of high-resolution remote sensing products, benefiting the development and improvement of soil moisture retrieval algorithms and products to support irrigation scheduling and management at a precision agricultural scale in the future.

STK11 (serine-threonine kinase 11), also known as LKB1 (liver kinase B1) is a highly conserved master kinase that regulates cellular metabolism and polarity through a complex signaling network involving AMPK and 12 other AMPK-related kinases. Germline mutations in LKB1 have been causatively linked to Peutz-Jeghers Syndrome (PJS), an autosomal dominant hereditary disease with high cancer susceptibility. The identification of inactivating somatic mutations in LKB1 in different types of cancer further supports its tumor suppressive role. Deleterious mutations in LKB1 are frequently observed in patients with epithelial ovarian cancer. However, its inconsistent effects on tumorigenesis and cancer progression suggest that its functional impact is genetic context-dependent, requiring cooperation with other oncogenic lesions. In this review, we summarize the pleiotropic functions of LKB1 and how its altered activity in cancer cells is linked to oncogenic proliferation and growth, metastasis, metabolic reprogramming, genomic instability, and immune modulation. We also review the current mechanistic understandings of this master kinase as well as therapeutic implications with particular focus on the effects of LKB1 deficiency in ovarian cancer pathogenesis. Lastly, we discuss whether LKB1 deficiency can be exploited as an Achilles heel in ovarian cancer.

Abstract Background It remains unclear whether conservative oxygen therapy (COT) or liberal oxygen therapy (LOT) is more beneficial to the clinical outcomes of intensive care unit (ICU) patients. We systematically reviewed the efficacy and safety of conservative versus liberal oxygen therapy for ICU patients. Methods We systematically searched PubMed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, MedRxiv, and BioRxiv for reports on randomized controlled trials (RCTs) that compared the effects of COT versus LOT on the clinical outcomes of ICU patients published in English before April 2024. The primary outcome was the mortality rate, secondary outcomes included ICU and hospital length of stay, days free from mechanical ventilation support (MVF), vasopressor-free time (VFT), and adverse events. Results In all, 13 RCTs involving 10,632 patients were included in analyses. Meta-analysis showed COT did not reduce mortality at 30-day (risk ratio [RR] = 1.01, 95% confidence interval [CI] 0.94 to 1.09, I2 = 42%, P = 0.78), 90-day (RR = 1.01, 95% CI 0.95 to 1.08, I2 = 9%, P = 0.69), or longest follow-up (RR = 1.00, 95% CI 0.95 to 1.06, I2 = 22%, P = 0.95) compared to LOT in ICU patients. In subgroup analyses, no significant difference was observed between the two groups in terms of the different ICU, baseline P/F, and actual PaO2. In addition, COT did not affect ICU length of stay, hospital length of stay, or VFT, it only affected MVF days. Conclusions COT did not reduce all-cause mortality in ICU patients. Further RCTs are urgently needed to confirm the impact of COT strategy on specific populations.

Abstract Atherosclerosis (AS) is the pathologic basis of various cardiovascular and cerebrovascular events, with a high degree of heterogeneity among different arterial beds. However, mechanistic differences between arterial beds remain unexplored. The aim of this study was to explore key genes and potential mechanistic differences between AS in different arterial beds through bioinformatics analysis. Carotid atherosclerosis (CAS), femoral atherosclerosis (FAS), infrapopliteal atherosclerosis (IPAS), abdominal aortic atherosclerosis (AAS), and AS-specific differentially expressed genes (DEGs) were screened from the GSE100927 and GSE57691 datasets. Immune infiltration analysis was used to identify AS immune cell infiltration differences. Unsupervised cluster analysis of AS samples from different regions based on macrophage polarization gene expression profiles. Weighted gene co-expression network analysis (WGCNA) was performed to identify the most relevant module genes with AS. Hub genes were then screened by LASSO regression, SVM-REF, and single-gene differential analysis, and a nomogram was constructed to predict the risk of AS development. The results showed that differential expression analysis identified 5, 4, 121, and 62 CAS, FAS, IPAS, AAS-specific DEGs, and 42 AS-common DEGs, respectively. Immune infiltration analysis demonstrated that the degree of macrophage and mast cell enrichment differed significantly in different regions of AS. The CAS, FAS, IPAS, and AAS could be distinguished into two different biologically functional and stable molecular clusters based on macrophage polarization gene expression profiles, especially for cardiomyopathy and glycolipid metabolic processes. Hub genes for 6 AS (ADAP2, CSF3R, FABP5, ITGAX, MYOC, and SPP1), 4 IPAS (CLECL1, DIO2, F2RL2, and GUCY1A2), and 3 AAS (RPL21, RPL26, and RPL10A) were obtained based on module gene, gender stratification, machine learning algorithms, and single-gene difference analysis, respectively, and these genes were effective in differentiating between different regions of AS. This study demonstrates that there are similarities and heterogeneities in the pathogenesis of AS between different arterial beds.

The utilization of high-strength and tough petroleum casing steel has become the focus of various research groups worldwide, particularly in the past decade. However, defining its forming behavior presents several challenges, stemming from the complexity of enhancing strength and toughness on the steel's characteristics. To address this issue, this study employed a low-carbon microalloyed steel and introduced V and Nb elements sequentially, resulting in three groups of steels under investigation. Subsequently, mechanical properties and microstructure characteristics were examined. Interestingly, the addition of V and Nb elements resulted in both tensile and yield strengths above 1200 MPa and 1173 MPa, respectively, satisfying the criteria for the V170 oil casing. Furthermore, after adding V, V(C,N) precipitates uniformly in the steel. Still, the Nb element is not completely precipitated as there is a significant amount of Nb in solid solution. The effective grain size of the investigated steel increases from 0.92 μm to 0.98 μm after adding V and Nb elements, accompanied by a reduction in the fraction of HAGB from 47.4 % to 42.4 %. Therefore, V element plays a vital and positive role in improving the mechanical properties of the experimental steel, while Nb element has only a minor effect.

The diversity and delicate balance of the oral microbiome contribute to oral health, with its disruption leading to oral and systemic diseases. Toothpaste includes elements like traditional additives such as sodium lauryl sulfate (SLS) as well as novel postbiotics derived from probiotics, which are commonly employed for maintaining oral hygiene and a healthy oral cavity. However, the response of the oral microbiota to these treatments remains poorly understood. In this study, we systematically investigated the impact of SLS, and toothpaste containing postbiotics (hereafter, postbiotic toothpaste) across three systems: biofilms, animal models, and clinical populations. SLS was found to kill bacteria in both preformed biofilms (mature biofilms) and developing biofilms (immature biofilms), and disturbed the microbial community structure by increasing the number of pathogenic bacteria. SLS also destroyed periodontal tissue, promoted alveolar bone resorption, and enhanced the extent of inflammatory response level. The postbiotic toothpaste favored bacterial homeostasis and the normal development of the two types of biofilms in vitro, and attenuated periodontitis and gingivitis in vivo via modulation of oral microecology. Importantly, the postbiotic toothpaste mitigated the adverse effects of SLS when used in combination, both in vitro and in vivo. Overall, the findings of this study describe the impact of toothpaste components on oral microflora and stress the necessity for obtaining a comprehensive understanding of oral microbial ecology by considering multiple aspects.

Colorectal cancer is the third most common cancer and the second most lethal cancer in the world. The main cause of the disease is due to dietary and behavioral factors. The treatment of this complex disease is mainly based on traditional treatments, including surgery, radiotherapy, and chemotherapy. Due to its high prevalence and high morbidity, more effective treatments with fewer side effects are urgently needed. In recent years, immunotherapy has become a potential therapeutic alternative and one of the fastest-developing treatments. Immunotherapy inhibits tumor growth by activating or enhancing the immune system to recognize and attack cancer cells. This review presents the latest immunotherapies for immune checkpoint inhibitors, cell therapy, tumor-infiltrating lymphocytes, and oncolytic viruses. Some of these have shown promising results in clinical trials and are used in clinical treatment.

Abstract By modulating subwavelength structures and integrating functional materials, 2D artificial microstructures (2D AMs), including heterostructures, superlattices, metasurfaces and microcavities, offer a powerful platform for significant manipulation of light fields and functions. These structures hold great promise in high‐performance and highly integrated optoelectronic devices. However, a comprehensive summary of 2D AMs remains elusive for photonics and optoelectronics. This review focuses on the latest breakthroughs in 2D AM devices, categorized into electronic devices, photonic devices, and optoelectronic devices. The control of electronic and optical properties through tuning twisted angles is discussed. Some typical strategies that enhance light‐matter interactions are introduced, covering the integration of 2D materials with external photonic structures and intrinsic polaritonic resonances. Additionally, the influences of external stimuli, such as vertical electric fields, enhanced optical fields and plasmonic confinements, on optoelectronic properties is analysed. The integrations of these devices are also thoroughly addressed. Challenges and future perspectives are summarized to stimulate research and development of 2D AMs for future photonics and optoelectronics.

BackgroundWhile previous research has established an association between inflammatory bowel disease (IBD) and osteoporosis (OP), the nature of this association in different populations remains unclear.ObjectiveOur study used linkage disequilibrium scores(LDSC) regression analysis and Mendelian randomization(MR) to assess the genetic correlation and causal relationship between IBD and OP in European and East Asian populations.MethodsWe performed separate genetic correlation and causal analyses for IBD and OP in European and East Asian populations, used the product of coefficients method to estimate the mediating effect of nutritional status on the causal relationship, and used multi-trait analysis to explore the biological mechanisms underlying the IBD-nutrition-OP causal pathway.ResultsOur analysis revealed a significant genetic correlation and causal relationship between IBD and OP in the European population. Conversely, no such correlation or causal relationship was observed in the East Asian population. Mediation analysis revealed a significant mediating effect of nutritional status on the causal pathway between IBD and OP in the European population. Multi-trait analysis of the IBD-nutrition-OP causal pathway identified MFAP2, ATP13A2, SERPINA1, FTO and VCAN as deleterious variants.ConclusionOur findings establish a genetic correlation and causal relationship between IBD and OP in the European population, with nutritional status playing a crucial mediating role.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.

Objective To provide an initial understanding of problems and potential solution strategies for part-time clinical pharmacist work in China, and provide references for the training of part-time clinical pharmacists.Methods The study was conducted in a tertiary teaching hospital in China, and the project lasted 6 months. Phenomenological methods were used to guide the research design. Research data were obtained by conducting one-to-one semistructured interviews with part-time clinical pharmacists, and interview data were coded and analysed through thematic analysis.Results A total of 21 pharmacists were interviewed in a semistructured manner, and the results showed that following problems exist in the work of part-time clinical pharmacists: the existing professional knowledge is not adequate to meet the demands of clinical service; the career orientation of part-time clinical pharmacists is not clear; lack of professional self-confidence in clinical pharmacy practice; there is no suitable entry point to carry out pharmacy service work; it is difficult to communicate effectively, and for in addition, 17 potential solution strategies are proposed for the current problems, which can provide reference for the development of part-time clinical pharmacists’ work.Conclusions The work performed by part-time clinical pharmacists is currently immature and the strategies derived from this study may serve as potential solutions to resolve the part-time clinical pharmacy practice challenges.

Composite ceramic phosphor (CCP) is a candidate light-conversion material to obtain the high-quality laser lighting source. Phosphors based on the transmissive configuration model could not simultaneously meet the requirements of angular color uniformity and high thermal stability. In this study, a novel composite structure ceramic was designed, including Al2O3–YAG:Ce/YAG layered ceramic with a size of 1 mm × 1 mm for lighting, and Al2O3 ceramic (φ = 16.0 mm) was used as the wrapping material due to its outstanding thermal stability. The prepared ceramics exhibited excellent thermal performance and no yellow ring phenomenon. Through this design, we achieved the match of the intensity distribution of the blue and yellow lights, resulting in a high angular color uniformity of 0.9 with a view angle of ±80°. All ceramics showed no luminous saturation phenomenon, even the laser power density was increased up to 47.51 W/mm2. A high-brightness white-light source with a luminous flux of 618 lm, a luminous efficiency of 126 lm/W, a CCT of 6615 K, and a CRI of 69.9 was obtained in the transmissive configuration. In particular, the surface temperature of the ceramic was as low as 74.1 ℃ under a high laser radiation (47.51 W/mm2). These results indicate that Al2O3/Al2O3–YAG:Ce/YAG composite structure ceramic is a promising luminescent material in the high-power laser lighting applications.

Abstract Objective This study aimed to investigate the risk factors for peripheral arteriosclerosis (PAS) and peripheral artery disease (PAD) in chronic obstructive pulmonary disease (COPD) patients and potential ultrasound indicators that could be used to improve detection. Method Outpatients seeking care between January 1, 2017, and December 31, 2020, in The First Affiliated Hospital of China Medical University were prospectively recruited. Subjects were divided into COPD and non-COPD (control) groups, and the COPD group was further divided into PAD and non-PAD subgroup, at the same time, PAS and non-PAS subgroup. Indicators of PAD -ankle-brachial index (ABI), indicators of PAS- pulse wave velocity (PWV), and ultrasound indices -peak systolic blood flow velocity (PSV) and blood flow acceleration velocity (AccV) were compared. Result Sixty-nine (61.6%) of 112 enrolled subjects had COPD. COPD patients had higher age, and blood pressure (BP)lower than controls. Seventeen (24.6%) COPD patients had PAD, the prevalence of PAD increases with the decrease of lung function, and seven (16.3%) non-COPD patients had PAD, however, there was no significant statistical difference between COPD and non-COPD groups. Fifty (72.5%) COPD patients had PAS, and thirty-four (79.1%) non-COPD patients had PAS, however, there was also no significant difference. The PAS subgroup had higher age, body mass index(BMI), body fat percentage(BFP), lower FEV1 and FEV1/FVC, as well as higher levels of right brachial artery and left dorsalis pedis artery AccV. Factors that correlated with ABI were 6MWD, post-bronchodilator FEV1, FEV1/ FVC, and maximal middle expiratory flow between 75% and 25% of FVC. Age, BP, and 6MWD, but not pulmonary function, were associated with brachial-ankle PWV (baPWV). There was a positive correlation between baPWV and radial artery AccV bilaterally. Conclusion Radial artery AccV correlated well with baPWV, which suggests that ultrasound could be used to assess both morphological and functional changes in vessels, may serving as a better method to identify PAS in high-risk COPD patients.

Most state-of-the-art synthetic aperture radar (SAR) ship detection methods based on deep learning require large amounts of labeled data for network training. However, the annotation process requires significant manpower and resources especially for SAR images, since relevant background knowledge should be necessary for the annotators. Considering the available optical imagery datasets with labels, we propose an unsupervised oriented SAR ship detection method based on cross-modality distribution alignment, termed as CroMoDa. It consists of four components: 1) image-level feature alignment; 2) low-level feature despeckling; 3) cross-modality pseudo-label self-training; and 4) cross-modality object alignment. By aligning the multilevel feature distributions, modality-invariant features across the two imagery modalities can be learned. Considering speckle noise and other interferences in SAR images, the proposed loss term conducted on low-level features can enhance the object information to improve the detection accuracy. Moreover, the proposed pseudo-label self-training can better generate oriented SAR ship annotations than the other methods, which facilitates learning more discriminative features for SAR ship instances. With two optical–SAR dataset configurations, the proposed method is effectively evaluated by comparing to the other state of the arts, which demonstrates the great potential for SAR ship detection in real applications.

Abstract As urban density increases, it becomes increasingly common for multiple functions to coexist within the same space, intensifying the complexity of human activity dynamics. However, traditional urban zoning, which relies on the spatial distribution of urban functions and human activities, focuses on the spatial heterogeneity of urban space and fails to capture the temporal dynamics of urban space usage. This paper aims to investigate the daily rhythm of urban space usage and illustrate how the distribution and combination of urban functions affect the daily usage rhythm. Taking Beijing in China as a case, we first identified the daily rhythm of urban space usage with the k-means algorithm and zoned urban space accordingly. Subsequently, multinomial logistic (MNL) models were employed to elucidate how the distribution and combination of urban functions influenced these daily usage patterns. Furthermore, a validation study in typical zones was conducted. The results revealed the existence of a distinct daily rhythm in urban space usage, resulting in the classification of urban space into seven distinct zones: high equilibrium, low equilibrium, diurnal, nocturnal, morning, evening, and noon-type zones. Also, we found that this daily usage rhythm is closely intertwined with the distribution and coexistence of urban functions. Our findings could provide valuable insights for the enhancement of various intricate aspects within urban decision-making processes, including urban planning, transportation management, and more, at a fine-grained scale.

Abstract Objective The role of the Hospital Pharmacy Preceptor (HPP) is pivotal in upholding the excellence of experiential training and fostering the professional growth of pharmacy interns. However, there is a lack of studies that provide an overview of pharmacy internships from the perspective of HPP. This study explores the experience and expectations of HPPs regarding existing problems and possible coping strategies in intern teaching. Methods This is a qualitative study that was conducted through individual interviews and focus group discussions. HPPs were invited as participants from large-scale tertiary hospitals in representative provinces of mainland China. Interview and focus group discussion data were analyzed using thematic analysis to see emerging themes from the data. Nvivo 12 was utilized for data management and processing. Results Eight individual interviews and two focus group discussions were conducted, involving 14 HPPs as participants. Upon the examination of the interviews and focus group data, four themes were summarized regarding HPPs’ perceptions: 1) current presenting problems; 2) possible coping strategies; 3) something HPPs should do; 4) something interns should do. Conclusion This study found that from the HPPs’ perspective, the hospital-based pharmacy internship still has some problems from policy to practice, which need to be addressed by the joint efforts of the state, schools, internship bases, pharmacy preceptors, and students.

Medium Mn steels are the primary candidates in the fields of automobile, construction machinery et al. due to the advantages of high strength-ductility combination, and low costs. By now, the balance of good performance and high preparation efficiency is still a critical issue to be unsolved, which restricts their further applications. This work designs a novel Al-contained medium Mn low-density steel and explores the effect of a short intercritical-annealing process. The microstructure evolution of multi-scales, especially the austenite characteristics and Mn partitioning behaviors is analyzed, and the relationship between austenite and tensile properties is discussed. The results indicate Al can broaden the annealing processing window and improve the annealing temperature. When annealed at 780 °C, the austenite reverted transformation happens quickly and after annealing for 3 min, the austenite volume fraction maintains stable in the range of 52.4–56.7 vol%, but the morphology and Mn concentration are very different. A large amount of blocky austenite with a coarse size of more than 1 μm and a low Mn concentration of 8–9 wt% forms at the longer annealing time of 20 min, while the austenite almost presents a lath-like shape with a high Mn concentration exceeding 10 wt% at annealing time of 4 min. The tensile properties are closely related to the volume fraction and mechanical stability of austenite, and the sample annealed for 4 min exhibited the best performance with tensile strength of 1192 MPa and total elongation of 33 %, due to its slow TRIP effect.

The development of a tuberculosis (TB) vaccine is imperative. Employing multi-stage Mycobacterium tuberculosis (Mtb) antigens as targeted antigens represents a critical strategy in establishing an effective novel TB vaccine. In this investigation, we evaluated the immunogenicity and protective efficacy of a recombinant adenovirus vaccine expressing two fusion proteins, Ag85B-ESAT6 (AE) and Rv2031c-Rv2626c (R2), derived from multi-stage antigens of Mtb via intranasal administration in mice. Intranasal delivery of Ad-AE-R2 induced both long-lasting mucosal and systemic immunities, with a preferential elicitation of CD8+ T cell immunity demonstrated by the accumulation and retention of CD8+ T cells in BALF, lung, and spleen, as well as the generation of CD8+ TRM cells in BALF and lung tissues. Compared to subcutaneous immunization with Bacillus Calmette-Guerin (BCG), Ad-AE-R2 provided superior protection against high-dose intratracheal BCG challenge, specifically within the lungs of mice. Our findings support the notion that empowering T cells within the respiratory mucosa is crucial for TB vaccine development while highlighting targeting CD8+ T cell immunity as an effective strategy for optimizing TB vaccines and emphasizing that eliciting systemic memory immunity is also vital for the successful development of a TB mucosal vaccine. Furthermore, our results demonstrate that the BCG challenge serves as a convenient and efficient method to evaluate candidate vaccine efficacy.

Improving crop water productivity (WP) in the face of drought conditions and optimizing water allocation for irrigated crops are critical steps toward mitigating the challenges associated with agricultural water use. To investigate the effects of regulated deficit irrigation (RDI) at different growth stages on maize yield and WP, a 4-year field experiment was conducted on spring maize under film drip irrigation from 2016 to 2019 in an arid region of northwest China. RDI significantly reduced plant height, leaf area index (LAI) and dry matter accumulation (DM). Notably, the moderate RDI treatment, denoted as 65/80ET (before and after ''/'' represent the irrigation volume relative to fully irrigation in the late vegetative and reproductive growth stages, respectively), reduced crop water consumption. This reduction was accompanied by the maintenance of relatively high grain yield and a significant increase in the harvest index, thereby resulting in a marked improvement in WP. In summary, the results of this study indicate that the 65/80ET treatment can effectively stabilize yield while improving efficiency. As such, it can be considered a viable RDI strategy for achieving water-saving, yield stability and enhanced efficiency in maize production.

Diffuse large B-cell lymphoma (DLBCL) stands as the most prevalent subtype of non-Hodgkin's lymphoma and exhibits significant heterogeneity. Various forms of programmed cell death (PCD) have been established to have close associations with tumor onset and progression. To this end, this study has compiled 16 PCD-related genes. The investigation delved into genes linked with prognosis, constructing risk models through consecutive application of univariate Cox regression analysis and Lasso-Cox regression analysis. Furthermore, we employed RT-qPCR to validate the mRNA expression levels of certain diagnosis-related genes. Subsequently, the models underwent validation through KM survival curves and ROC curves, respectively. Additionally, nomogram models were formulated employing prognosis-related genes and risk scores. Lastly, disparities in immune cell infiltration abundance and the expression of immune checkpoint-associated genes between high- and low-risk groups, as classified by risk models, were explored. These findings contribute to a more comprehensive understanding of the role played by the 16 PCD-associated genes in DLBCL, shedding light on potential novel therapeutic strategies for the condition.

ABSTRACTPreeclampsia (PE), a pregnancy-specific syndrome, has been associated with the gut bacteriome. Here, to investigate the impact of the gut virome on the development of PE, we identified over 8,000 nonredundant viruses from the fecal metagenomes of 40 early-onset PE and 37 healthy pregnant women and profiled their abundances. Comparison and correlation analysis showed that PE-enriched viruses frequently connected to Blautia species enriched in PE. By contrast, bacteria linked to PE-depleted viruses were often the Bacteroidaceae members such as Bacteroides spp., Phocaeicola spp., Parabacteroides spp., and Alistipes shahii. In terms of viral function, PE-depleted viruses had auxiliary metabolic genes that participated in the metabolism of simple and complex polysaccharides, sulfur metabolism, lipopolysaccharide biosynthesis, and peptidoglycan biosynthesis, while PE-enriched viruses had a gene encoding cyclic pyranopterin monophosphate synthase, which seemed to be special, that participates in the biosynthesis of the molybdenum cofactor. Furthermore, the classification model based on gut viral signatures was developed to discriminate PE patients from healthy controls and showed an area under the receiver operating characteristic curve of 0.922 that was better than that of the bacterium-based model. This study opens up new avenues for further research, providing valuable insights into the PE gut virome and offering potential directions for future mechanistic and therapeutic investigations, with the ultimate goal of improving the diagnosis and management of PE.IMPORTANCEThe importance of this study lies in its exploration of the previously overlooked but potentially critical role of the gut virome in preeclampsia (PE). While the association between PE and the gut bacteriome has been recognized, this research takes a pioneering step into understanding how the gut virome, represented by over 8,000 nonredundant viruses, contributes to this condition. The findings reveal intriguing connections between PE-enriched viruses and specific gut bacteria, such as the prevalence of Blautia species in individuals with PE, contrasting with bacteria linked to PE-depleted viruses, including members of the Bacteroidaceae family. These viral interactions and associations provide a deeper understanding of the complex dynamics at play in PE.

Summary: Background: The prevalence, epidemiological and clinical heterogeneities, and impact profiles of individuals with preserved ratio impaired spirometry (PRISm), pre-COPD, young COPD, and mild COPD in general Chinese population were not known yet. Methods: Data were obtained from the China Pulmonary Health study (2012–2015), a nationally representative cross-sectional survey that recruited 50,991 adults aged 20 years or older. Definitions of the four early disease status were consistent with the latest publications and the Global Initiative for Chronic Obstructive Lung Disease criteria. Findings: The age-standardised prevalences of PRISm, pre-COPD, young COPD, and mild COPD were 5.5% (95% confidence interval, 4.3–6.9), 7.2% (5.9–8.8), 1.1% (0.7–1.8), and 3.1% (2.5–3.8), respectively. In summary, mild COPD was under more direct or established impact factor exposures, such as older age, male gender, lower education level, lower family income, biomass use, air pollution, and more accumulative cigarette exposures; young COPD and pre-COPD experienced more personal and parents’ events in earlier lives, such as history of bronchitis or pneumonia in childhood, frequent chronic cough in childhood, parental history of respiratory diseases, passive smoke exposure in childhood, and mother exposed to passive smoke while pregnant; pre-COPD coexisted with heavier symptoms and comorbidities burdens; young COPD exhibited worse airway obstruction; and most of the four early disease status harbored small airway dysfunction. Overall, older age, male gender, lower education level, living in the urban area, occupational exposure, frequent chronic cough in childhood, more accumulated cigarette exposure, comorbid with cardiovascular disease and gastroesophageal reflux disease were all associated with increased presence of the four early COPD status; different impact profiles were additionally observed with distinct entities. Over the four categories, less than 10% had ever taken pulmonary function test; less than 1% reported a previously diagnosed COPD; and no more than 13% had received pharmaceutical treatment. Interpretation: Significant heterogeneities in prevalence, epidemiological and clinical features, and impact profiles were noted under varied defining criteria of early COPD; a unified and validated definition for an early disease stage is warranted. Closer attention, better management, and further research need to be administrated to these population. Funding: Chinese Academy of Medical Sciences Institute of Respiratory Medicine Grant for Young Scholars (No. 2023-ZF-9); China International Medical Foundation (No. Z-2017-24-2301); Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (No. 2021-I2M-1-049); National High Level Hospital Clinical Research Funding (No. 2022-NHLHCRF-LX-01); Major Program of National Natural Science Foundation of China (No. 82090011).

BackgroundDopamine, a frequently used therapeutic agent for critically ill patients, has been shown to be implicated in clinical infections recently, however, the precise mechanisms underlying this association remain elusive. Klebsiella quasivariicola, a novel strain belonging to the Klebsiella species, exhibits potential pathogenic attributes. The impact of dopamine on K. quasivariicola infection has aroused our interest.ObjectiveConsidering the contribution of host immune factors during infection, this study aimed to investigate the intricate interactions between K. quasivariicola, dopamine, and macrophages were explored.MethodsRAW264.7 cells and C57/BL6 mice were infected with K. quasivariicola, and the bacterial growth within macrophage, the production of inflammatory cytokines and the pathological changes in mice lungs were detected, in the absence or presence of dopamine. ResultsDopamine inhibited the growth of K. quasivariicola in the medium, but promoted bacterial growth when co-cultured with macrophages. The expression of proinflammatory cytokines increased in RAW 264.7 cells infected with K. quasivariicola, and a significant rise was observed upon the addition of dopamine. The infection of K. quasivariicola in mice induced an inflammatory response and lung injury, which were exacerbated by the administration of dopamine. ConclusionsOur findings suggest that dopamine may be one of the potential risk factors associated with K. quasivariicola infection. This empirical insight provides solid references for clinical precision medicine. Furthermore, an in vitro model of microbes-drugs-host immune cells for inhibitor screening was proposed to more accurately replicate the complex in vivo environment. This fundamental work had contributed to the present understanding of the crosstalk between pathogen, dopamine and host immune cells.

Abstract Background Migraine is a primary headache, which has been producing heavy disease burden globally. There is no data on the incidence of migraine among women of childbearing age worldwide, including China. This study aimed to investigate the time trend in incidence rate of migraine among women of childbearing age in China from 1999 to 2019, and to make a prediction for 2030. Methods Data on migraine incidence and population among women of childbearing age in China were derived from the Global Burden of Diseases Study 2019. Crude and age-standardized incidence rates of migraine (CIR, ASIR) were presented. The trend in migraine during 1990–2019 was examined using annual percent change and average annual percent change based on Joinpoint regression models. Age-period-cohort model was introduced to estimate the independent effect of age, period and cohort on migraine incidence rate among participants over the three decades. Bayesian age-period-cohort analysis was conducted to predict migraine incidence rate for 2030 among women of childbearing age in China. Results For women of childbearing age in China, the case number, CIR and ASIR of migraine kept rising, with a cumulative percentage increase of 10.87%, 2.01% and 5.65%, respectively, from 1990 to 2019. An annual percent increase of 0.18% in the ASIR was observed over the three decades. As for the age, period and cohort effects, the adjusted cohort-specific relative risks constantly increased from 0.91 (95% CI: 0.90, 0.93) in the 1940–1949 cohort to 1.04 (95% CI: 1.03, 1.05) in the 1995–2004 cohort, while the period-specific relative risks initially declined from 1.00 (95% CI: 0.99, 1.00) in 1990–1994 cohort to 0.99 (95% CI: 0.98, 0.99) in 1995–1999 cohort, and then increased to 1.04 (95% CI: 1.03, 1.04) in 2015–2019 cohort. Moreover, the age-specific relative risks of migraine followed a bimodal pattern with peaks at the age-group of 25–29 years (CIR = 1718.27/100000) and 35–39 years (CIR = 1635.18/100000). Projection modeling showed that the CIR and ASIR of migraine will continue to significantly increase from 2020 to 2030. Conclusion Migraine incidence remained an increasing trend from 1990 to 2019 and is projected to continually increase till 2030 among women of childbearing age in China. This study has important public health implication for population-level migraine prevention in China. Precision intervention strategies and approaches shall be considered in campaigns initiated for migraine prevention among Chinese women of childbearing age.

Abstract Background Bacterial infection, complex wound microenvironment and persistent inflammation cause delayed wound healing and scar formation, thereby disrupting the normal function and appearance of skin tissue, which is one of the most problematic clinical issues. Although Ag NPs have a strong antibacterial effect, they tend to oxidize and form aggregates in aqueous solution, which reduces their antibacterial efficacy and increases their toxicity to tissues and organs. Current research on scar treatment is limited and mainly relies on growth factors and drugs to reduce inflammation and scar tissue formation. Therefore, there is a need to develop methods that effectively combine drug delivery, antimicrobial and anti-inflammatory agents to modulate the wound microenvironment, promote wound healing, and prevent skin scarring. Results Herein, we developed an innovative Ag nanocomposite hydrogel (Ag NCH) by incorporating Ag nanoparticles (Ag NPs) into a matrix formed by linking catechol-modified hyaluronic acid (HA-CA) with 4-arm PEG-SH. The Ag NPs serve dual functions: they act as reservoirs for releasing Ag/Ag+ at the wound site to combat bacterial infections, and they also function as cross-linkers to ensure the sustained release of basic fibroblast growth factor (bFGF). The potent antibacterial effect of the Ag NPs embedded in the hydrogel against S.aureus was validated through comprehensive in vitro and in vivo analyses. The microstructural analysis of the hydrogels and the in vitro release studies confirmed that the Ag NCH possesses smaller pore sizes and facilitates a slower, more sustained release of bFGF. When applied to acute and infected wound sites, the Ag NCH demonstrated remarkable capabilities in reshaping the immune and regenerative microenvironment. It induced a shift from M1 to M2 macrophage polarization, down-regulated the expression of pro-inflammatory factors such as IL-6 and TNF-α, and up-regulated the expression of anti-inflammatory IL-10. Furthermore, the Ag NCH played a crucial role in regulating collagen deposition and alignment, promoting the formation of mature blood vessels, and significantly enhancing tissue reconstruction and scarless wound healing processes. Conclusions We think the designed Ag NCH can provide a promising therapeutic strategy for clinical applications in scarless wound healing and antibacterial therapy. Graphical Abstract

Abstract 153-Residue copper-zinc superoxide dismutase 1 (hSOD1) is the first gene whose mutation was linked to FALS. To date, > 180 ALS-causing mutations have been identified within hSOD1, yet the underlying mechanism still remains mysterious. Mature hSOD1 is exceptionally stable constrained by a disulfide bridge to adopt a Greek-key β-barrel fold that accommodates copper/zinc cofactors. Conversely, nascent hSOD1 is unfolded and susceptible to aggregation and amyloid formation, requiring Zn2+ to initiate folding to a coexistence of folded and unfolded states. Recent studies demonstrate mutations that disrupt Zn2+-binding correlate with their ability to form toxic aggregates. Therefore, to decode the role of cations in hSOD1 folding provides not only mechanistic insights, but may bear therapeutic implications for hSOD1-linked ALS. Here by NMR, we visualized the effect of 12 cations: 8 essential for humans (Na+, K+, Ca2+, Zn2+, Mg2+, Mn2+, Cu2+, Fe2+), 3 mimicking zinc (Ni2+, Cd2+, Co2+), and environmentally abundant Al3+. Surprisingly, most cations, including Zn2+-mimics, showed negligible binding or induction for folding of nascent hSOD1. Cu2+ exhibited extensive binding to the unfolded state but led to severe aggregation. Unexpectedly, for the first time Fe2+ was deciphered to have Zn2+-like folding-inducing capacity. Zn2+ was unable to induce folding of H80S/D83S-hSOD1, while Fe2+ could. In contrast, Zn2+ could trigger folding of G93A-hSOD1, but Fe2+ failed. Notably, pre-existing Fe2+ disrupted the Zn2+-induced folding of G93A-hSOD1. Comparing with the ATP-induced folded state, our findings delineate that hSOD1 maturation requires: (1) intrinsic folding capacity encoded by the sequence; (2) specific Zn2+-coordination; (3) disulfide formation and Cu-load catalyzed by hCCS. This study unveils a previously-unknown interplay of cations in governing the initial folding of hSOD1, emphasizing the pivotal role of Zn2+ in hSOD1-related ALS and implying new hSOD1-dependent mechanisms for Cu2+/Fe2+-induced cytotoxicity, likely relevant to aging and other diseases.

With the substantial improvement of Synthetic Aperture Radar (SAR) regarding swath width and spatial and temporal resolutions, a time series obtained by registering SAR images acquired at different times can provide more accurate information on the dynamic changes in the observed areas. However, inherent speckle noise and outliers along the temporal dimension in the time series pose serious challenges for subsequent interpretation tasks. Although existing state-of-the-art methods can effectively suppress the speckle noise in a SAR time series, outliers along the temporal dimension will interfere with the denoising results. To better solve this problem, this paper proposes an additive signal decomposition method in the logarithm domain that can suppress the speckle noise and separate stable data and outliers along the temporal dimension in a time series, thus eliminating the impact of outliers on the denoising results. When the simulated data are disturbed by outliers, the proposed method can achieve an approximately 3 dB improvement in the Peak Signal-to-Noise Ratio (PSNR) compared to the other state-of-the-art methods. On Sentinel-1 data, the proposed method robustly suppresses the speckle noise in a time series, and the obtained outliers along the temporal dimension provide reference data for subsequent interpretation tasks.

Abstract In this study, we comprehensively investigate the structure and operational principles of the Rotary Direct Drive Electro-Hydraulic Pressure Servo Valve (RDDPV). Our objective is to establish the dynamics equations governing the motor, slide valve, and bias mechanism of the valve. Additionally, we construct a mathematical model for the servo valve controller, while ensuring the linearization of the controller model. Furthermore, we conduct an in-depth analysis of the static characteristics of the valve, including linearity, dead zone, hysteresis loop, and zero drift. Regarding the dynamic characteristics, we establish a dynamic mathematical model for the RDDPV valve. Subsequently, we subject the servo valve to analysis with a focus on frequency response and dynamic response, using the control current as the input and the pressure as the output. To perform these analyses, we employ the software package SIMULINK of MATLAB, facilitating dynamic simulations. Remarkably, the simulation results exhibit the valve's conformity to design requirements, underscoring its suitability for subsequent research and development endeavors. Through our rigorous investigation, we offer essential technical support for the forthcoming stages of the valve's research and development, thereby laying a robust foundation for its further advancement.

Abstract ALS-causing C71G-hPFN1 coexists in both folded and unfolded states, while nascent hSOD1 is unfolded. So far, the mechanisms underlying their ALS-triggering potential remain enigmatic. Here we show by NMR that ATP completely converts C71G-hPFN1 into the folded state at a 1:2 ratio, while inducing nascent hSOD1 into two co-existing states at a 1:8 ratio. Surprisingly, the inducing capacity of ATP comes from its triphosphate, but free triphosphate triggers aggregation. The inducing capacity ranks as: ATP = ATPP = PPP > ADP = AMP−PNP = AMP−PCP = PP, while AMP, adenosine, P, and NaCl show no conversion. Mechanistically, ATP and triphosphate appear to enhance the intrinsic folding capacity encoded in the sequences, as unveiled by comparing conformations and dynamics of ATP- and Zn2+-induced hSOD1 folded states. Our study provides a mechanism for the finding that some single-cell organisms employ polyphosphates as primordial chaperones, and sheds light on the enigma of age-related onset of familial ALS and risk increase of neurodegenerative diseases.

Surface scattering greatly impacts and improves the acoustic quality of an auditorium, affecting properties such as the reverberation time, early decay time, definition, and sound strength. However, this aspect has not been sufficiently investigated to date. In this study, six completed auditoriums are taken as research samples and computer simulations are performed to analyze the variation patterns in the acoustic-quality parameters as functions of increments in the surface scattering coefficients. The results show that the reverberation time and early decay time change marginally (

The structural relaxation analysis has been carried out on LixNi0.8Co0.1Mn0.1O2 (NCM-811) and LixNi0.55Co0.20Mn0.25O2 (NCM-552025) after the lithium extraction at 0.1 C-rate to the high-voltage region (x ≤ 0.12). For NCM-811, the H3 phase appeared as the major phase with a small amount of the H2 phase after the lithium extraction. At the relaxation period, no significant phase change was observed and the structural variation including Li- and Ni-interlayer distances was small. On the other hand, NCM-552025 exhibited the single phase of the H2 even at deep lithium extraction up to x = 0.06. In the H2 phase, a slight increase in c-length was observed during the relaxation, which is the result of an increase in the Li-interlayer distance with a decrease in the Ni-interlayer. The relaxation behavior of interlayer distances can be explained by the localization of a small number of mobile lithium-ions.

Abstract Background In all international medical student (IMS) programs in China, language barriers between IMSs and Chinese patients greatly reduced the learning in clinical practice and brought great challenges to IMSs in their transition from preclinical to clinical practice. This study aimed to investigate the role of bilingual simulated patients (B-SPs) in IMSs learning of medical history collection in China. Methods 48 IMSs of grade 4 between October 2020 to Jan 2021 were enrolled in this study. During the training of medical history collection, students were randomly arranged into two groups trained with either B-SPs (B-SP group) or English-speaking SP (E-SP group). All SPs in Objective Structured Clinical Exam station (OSCE) were trained in the Affiliated Hospital of Wuhan University. Clinical skills in medical history collection were assessed by instructors during pre-clinical, post-clinical OSCE and clinical rotations. Results The scores of IMSs in each group were analyzed in terms of medical history collection including the ability to effectively consult for information and key communication skills related to patient care. Our results indicated that IMS in B-SP group obtained similar scores in preclinical training for history collection (67.3 ± 8.46 vs 67.69 ± 8.86, P

BackgroundMaternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. ObjectiveThis study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). MethodsThis case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was

BackgroundNovel coronaviruses have emerged and caused major epidemics and pandemics in the past 2 decades, including SARS-CoV-1, MERS-CoV, and SARS-CoV-2, which led to the current COVID-19 pandemic. These coronaviruses are marked by their potential to produce disproportionally large transmission clusters from superspreading events (SSEs). As prompt action is crucial to contain and mitigate SSEs, real-time epidemic size estimation could characterize the transmission heterogeneity and inform timely implementation of control measures. ObjectiveThis study aimed to estimate the epidemic size of SSEs to inform effective surveillance and rapid mitigation responses. MethodsWe developed a statistical framework based on back-calculation to estimate the epidemic size of ongoing coronavirus SSEs. We first validated the framework in simulated scenarios with the epidemiological characteristics of SARS, MERS, and COVID-19 SSEs. As case studies, we retrospectively applied the framework to the Amoy Gardens SARS outbreak in Hong Kong in 2003, a series of nosocomial MERS outbreaks in South Korea in 2015, and 2 COVID-19 outbreaks originating from restaurants in Hong Kong in 2020. ResultsThe accuracy and precision of the estimation of epidemic size of SSEs improved with longer observation time; larger SSE size; and more accurate prior information about the epidemiological characteristics, such as the distribution of the incubation period and the distribution of the onset-to-confirmation delay. By retrospectively applying the framework, we found that the 95% credible interval of the estimates contained the true epidemic size after 37% of cases were reported in the Amoy Garden SARS SSE in Hong Kong, 41% to 62% of cases were observed in the 3 nosocomial MERS SSEs in South Korea, and 76% to 86% of cases were confirmed in the 2 COVID-19 SSEs in Hong Kong. ConclusionsOur framework can be readily integrated into coronavirus surveillance systems to enhance situation awareness of ongoing SSEs.

IntroductionThe utilization of large-scale claims databases has greatly improved the management, accessibility, and integration of extensive medical data. However, its potential for systematically identifying comorbidities in the context of skin diseases remains unexplored.MethodsThis study aims to assess the capability of a comprehensive claims database in identifying comorbidities linked to 14 specific skin and skin-related conditions and examining temporal changes in their association patterns. This study employed a retrospective case-control cohort design utilizing 13 million skin/skin-related patients and 2 million randomly sampled controls from Optum’s de-identified Clinformatics® Data Mart Database spanning the period from 2001 to 2018. A broad spectrum of comorbidities encompassing cancer, diabetes, respiratory, mental, immunity, gastrointestinal, and cardiovascular conditions were examined for each of the 14 skin and skin-related disorders in the study.ResultsUsing the established type-2 diabetes (T2D) and psoriasis comorbidity as example, we demonstrated the association is significant (P-values

BackgroundThe impact of lipid metabolism on bone metabolism remains controversial, and the extent to which human traits mediate the effects of lipid metabolism on bone metabolism remains unclear.ObjectiveThis study utilized mendelian randomization to investigate the effects of blood lipids on bone mineral density (BMD) at various skeletal sites and examined the mediating role of human traits in this process.MethodsWe leveraged genetic data from large-scale genome-wide association studies on blood lipids (n=1,320,016), forearm bone mineral density (FA-BMD) (n=10,805), lumbar spine bone mineral density (LS-BMD) (n=44,731), and femoral neck bone mineral density (FN-BMD) (n=49,988) to infer causal relationships between lipid and bone metabolism. The coefficient product method was employed to calculate the indirect effects of human traits and the proportion of mediating effects.ResultsThe results showed that a 1 standard deviation(SD) increase in HDL-C, LDL-C and TC was associated with a decrease in LS-BMD of 0.039 g/cm2, 0.045 g/cm2 and 0.054 g/cm2, respectively. The proportion of mediating effects of systolic blood pressure (SBP) on HDL-C to LS-BMD was 3.17%, but suppression effects occurred in the causal relationship of LDL-C and TC to LS-BMD. Additionally, the proportion of mediating effects of hand grip strength (HGS) on the TC to LS-BMD pathway were 6.90% and 4.60% for the left and right hands, respectively.ConclusionIn conclusion, a negative causal relationship was established between lipid metabolism and bone metabolism. Our results indicated that SBP and HGS served as mediators for the effects of lipid metabolism on bone metabolism.

Background Acute respiratory distress syndrome (ARDS) is a common complication in patients with acute pancreatitis (AP), especially when patients complicated with acute kidney injury (AKI), resulting in increased duration of hospitalization and mortality. It is of potential clinical significance to develop a predictive model to identify the the high-risk patients.Method AP patients complicated with AKI from January 2019 to March 2022 were enrolled in this study and randomly divided into training cohort and validation cohort at a ratio of 2:1. The Least absolute shrinkage and selection operator(LASSO) regression and machine learning algorithms were applied to select features. A nomogram was developed based on the multivariate logistic regression. The performance of the nomogram was evaluated by AUC, calibration curves, and decision curve analysis.Results A total of 292 patients were enrolled in the study, with 206 in the training cohort and 86 in the validation cohort. Multivariate logistic analysis showed that IAP (Odds Ratio (OR)=4.60, 95%CI:1.23-18.24, p = 0.02), shock (OR = 12.99, 95%CI:3.47-64.04, p