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Construction sites are not generally flat but heterogeneous. It would be of significance to explore the patterns of ground response where soil and rock strata laterally distribute near the ground surface. Shaking table test of scaled free-field model was conducted to investigate the local site effect caused by the influence of soil-rock strata. In this test, model ground with artificial soil and rock was designed to reproduce the dynamic characteristics of the prototype. Recorded earthquake waves and site-specific artificial waves were selected as the bedrock motions inputted from the shaking table, in both transverse (SH wave) and longitudinal (SV wave) directions. Four sites of the ground were classified according to the combination of the soil deposit and the rock. The stranded spectral ratio (SSR) was introduced to identify the fundamental frequency and the amplification amplitude of the four sites. Correspondingly, one-dimension (1D) theoretical analysis was used to clarify the amplification effects affecting by the local constitution at each local site of the ground by comparing the response spectral ratios with the 1D analysis results (Aggravation factor). Site-specific parameters, such as the peak ground acceleration, arias intensity, and acceleration response spectra, were documented with discussions. It was found that the amplifications of locations vary with thickness of soil deposit, nonlinearity of soil property under increasing seismic intensity, and scattering of high-frequency components of input motion.

Feminist Translation is an important research topic of our times. Meanwhile, this trend is gaining increasing attention in China. However, the research on male images in female literature remains insufficient, since those male characters pale easily in comparison with those gorgeous ladies in feminist translation studies. Therefore, the authors choose as the research subject male images in translations of Pride and Prejudice as it seeks to analyze the influence of feminism on male and female translators. To achieve this, the authors carry out a contrast analysis of the language of two Chinese versions of Pride and Prejudice, done respectively by Mr. Wang Keyi and Ms. Lei Limei. The main logic behind our research method is that nuances in translation can give insight into translators' opinions. As a result, readers can detect the influence of feminism on translators, by comparing the expressions used to interpret male figures of a shared original text. In the third part, the authors conclude that gender plays a certain role in translations: male images created by women tend to be more in line with that of the original text, while gentlemen interpreted by men correspond mostly with that of social cognition. Given this, the authors analyze, at the end of this paper, translators’ personal experiences and historical background as a way to seek reasons for these differences.

Background: Several clinical trials have demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) reduce the incidence of non-fatal myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unclear. In this study, we applied a network pharmacology method to investigate the mechanisms by which GLP-1RAs reduce MI occurrence in patients with T2DM.Methods: Targets of three GLP-1RAs (liraglutide, semaglutide, and albiglutide), T2DM, and MI were retrieved from online databases. The intersection process and associated targets retrieval were employed to obtain the related targets of GLP-1RAs against T2DM and MI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) enrichment analyses were performed. The STRING database was used to obtain the protein-protein interaction (PPI) network, and Cytoscape was used to identify core targets, transcription factors, and modules.Results: A total of 198 targets were retrieved for the three drugs and 511 targets for T2DM with MI. Finally, 51 related targets, including 31 intersection targets and 20 associated targets, were predicted to interfere with the progression of T2DM and MI on using GLP-1RAs. The STRING database was used to establish a PPI network comprising 46 nodes and 175 edges. The PPI network was analyzed using Cytoscape, and seven core targets were screened: AGT, TGFB1, STAT3, TIMP1, MMP9, MMP1, and MMP2. The transcription factor MAFB regulates all seven core targets. The cluster analysis generated three modules. The GO analysis for 51 targets indicated that the terms were mainly enriched in the extracellular matrix, angiotensin, platelets, and endopeptidase. The results of KEGG analysis revealed that the 51 targets primarily participated in the renin-angiotensin system, complement and coagulation cascades, hypertrophic cardiomyopathy, and AGE-RAGE signaling pathway in diabetic complications.Conclusion: GLP-1RAs exert multi-dimensional effects on reducing the occurrence of MI in T2DM patients by interfering with targets, biological processes, and cellular signaling pathways related to atheromatous plaque, myocardial remodeling, and thrombosis.

Background Peptic ulcer disease is one of the most common diseases in gastroenterology clinics. However, reported data about the global burden of peptic ulcer disease are still scarce. Methods This was a secondary data analysis on the prevalence, mortality and disability-adjusted life years (DALYs) due to peptic ulcer disease by sex, age group and socio-demographic index (SDI) at the global level in 21 regions and 204 countries and territories between 1990 and 2019 using the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Results Globally, the prevalence cases of peptic ulcer disease increased from 6 434 103 (95% uncertainty interval 5 405 963 to 7 627 971) in 1990 to 8 090 476 (6 794 576 to 9 584 000) in 2019. However, the age-standardized prevalence rate decreased from 143.4 (120.5 to 170.2) per 100 000 population in 1990 to 99.4 (83.9 to 117.5) per 100 000 population in 2019. Moreover, the age-standardized mortality rate decreased by 59.4% (55.3 to 63.1) and the DALYs rate fell by 60.6% (56.8 to 63.9) from 1990 to 2019. Across SDI quintiles, low-middle and low SDI quintiles had the highest age-standardized prevalence, mortality and DALYs rates from 1990 to 2019. Conclusion The age-standardized prevalence, mortality and DALYs estimates of peptic ulcer disease decreased from 1990 to 2019 globally, but more efforts are needed for the prevention, early diagnosis and treatment of peptic ulcer disease in low SDI and low-middle SDI groups of countries.

High-contrast mechanochromic (MC) materials are prominent candidates for sensor, security, and memory applications; however, the development of materials with a large luminescence change (Δλem > 10...

In this letter, high-performance AlGaN/GaN Schottky barrier diodes (SBDs) with a great balance between forward and reverse characteristics are demonstrated. Benefiting from a plasma-free, low-damaged wet etching technique of an AlGaN layer at the anode region and low work-function tungsten (W) as the anode, lateral GaN SBDs with a low turn-on voltage ( $\text{V}_{{\mathrm {T}}}$ ) of 0.43 V and a low reverse current ( $\text{I}_{{\mathrm {R}}}$ ) of 90 nA/mm are obtained. Meanwhile, owing to the flattened self-terminated etching surface and the assistance of SiN passivation grown by low-pressure chemical vapor deposition, a high breakdown voltage of 1.83 kV and a power figure-of-merit (FOM) of 1.20 GW/cm 2 are achieved for the fabricated GaN SBD with a spatial distance ( $\text{L}_{{\mathrm {AC}}}$ ) of $15 ~\mu \text{m}$ from cathode to anode. The lateral GaN SBD fabricated with the optimized wet etching technique shows great potential for next-generation power electronics.

This study aimed to investigate the optimal activation of plastic aligner for the canine distal movement by combining the stress and strain of periodontal ligament. Computer-aided design models of the upper canine, periodontal ligament, alveolar bone, and plastic aligner were constructed. The stresses and strains of periodontal ligament were acquired by fitting plastic aligner on the canine, which will cause the canine distal-direction movement. The activation of plastic aligner was set into 12 groups, including 0.050, 0.100, 0.125, 0.150, 0.175, 0.200, 0.225, 0.250, 0.275, 0.300, 0.350, and 0.400 mm. Assuming the volume-averaged hydrostatic stress (VAHS) ranging from 4.7 to 16 kPa to be the optimal stress, and an average strain no less than 0.3 to be the optimal strain. The optimal activation of plastic aligner was acquired based on the optimal stress and average strain. As the activation increased, the stress and strain of periodontal ligament increased visibly. The degree of activation of plastic aligner was nonlinearly and positively related to VAHS and average strain. According to the fitted curves, the activation corresponding to the optimal stress was 0.07–0.24 mm and the activation was not less than 0.21 mm based on the optimal strain. The optimal activation of plastic aligner for the canine distal movement was 0.21–0.24 mm in this study. The degree of activation affects the force system of orthodontic tooth movement, and it should be taken into consideration to obtain healthy and efficient tooth movement. The activation with 0.21–0.24 mm seems optimal for orthodontic tooth movement in the plastic aligner system in this study.

The Epstein-Barr virus (EBV) is involved in the carcinogenesis of gastric cancer (GC) upon infection of normal cell and induces a highly variable composition of the tumour microenvironment (TME). However, systematic bioinformatics analysis of key genes associated with EBV regulation of immune infiltration is still lacking. In the present study, the TCGA and GEO databases were recruited to analyse the association between EBV infection and the profile of immune infiltration in GC. The weighted gene co-expression analysis (WGCNA) was applied to shed light on the key gene modules associated with EBV-associated immune infiltration in GC. 204 GC tissues were used to analysed the expression of key hub genes by using the immunohistochemical method. Real-time PCR was used to evaluate the association between the expression of EBV latent/lytic genes and key immune infiltration genes. Our results suggested that EBV infection changed the TME of GC mainly regulates the TIICs. The top three hub genes of blue (GBP1, IRF1, and LAP3) and brown (BIN2, ITGAL, and LILRB1) modules as representative genes were associated with EBV infection and GC immune infiltration. Furthermore, EBV-encoded LMP1 expression is account for the overexpression of GBP1 and IRF1. EBV infection significantly changes the TME of GC, and the activation of key immune genes was more dependent on the invasiveness of the whole EBV virion instead of single EBV latent/lytic gene expression.

Squamous cell carcinoma is the most common malignant tumor of the oral cavity and its adjacent sites, which endangers the physical and mental health of patients and has a complex etiology. Chronic infection is considered to be a risk factor in cancer development. Evidence suggests that periodontal pathogens, such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, are associated with oral squamous cell carcinoma (OSCC). They can stimulate tumorigenesis by promoting epithelial cells proliferation while inhibiting apoptosis and regulating the inflammatory microenvironment. Candida albicans promotes OSCC progression and metastasis through multiple mechanisms. Moreover, oral human papillomavirus (HPV) can induce oropharyngeal squamous cell carcinoma (OPSCC). There is evidence that HPV16 can integrate with host cells' DNA and activate oncogenes. Additionally, oral dysbiosis and synergistic effects in the oral microbial communities can promote cancer development. In this review, we will discuss the biological characteristics of oral microbiome associated with OSCC and OPSCC and then highlight the mechanisms by which oral microbiome is involved in oral oncogenesis, tumor progression, and metastasis. These findings may have positive implications for early diagnosis and treatment of oral cancer.

Long-distance (LD) travel accounts for over 30% of person-trip miles, with important energy and emissions impact. LD business travel can often be replaced by remote participation, so targeting such trips for cost, time, and emissions savings may be a wise strategy for protection of the climate, budgets, and human health. To appreciate Americans’ LD travel choices better, a 73-question online survey was conducted in 2019 that captured 2,327 LD (over 100 mi each way) trips made by 929 respondents during the previous 12 months, of which 490 round trips were for business purposes. Predictive models for LD trips per adult per year, overnights, LD travel times, and willingness to participate remotely and/or purchase carbon offsets for those trips were developed using respondents in Austin only. As expected, those educated to degree level tend to travel more often, for both business and nonbusiness purposes; everything else is constant. People who undertake LD travel more frequently are more likely to spend less time in transit/en route. Single people or those from large households educated to degree level are more likely to be willing to pay for the carbon emissions produced by their flights. Out of the 298 LD business trips made by Austinites, remote participation is possible for approximately a quarter, and the respondents involved are willing to participate remotely in 44% of those trips. In other words, Austinites appeared willing to participate remotely in slightly over 10% of their business trips overall, at least before the COVID-19 pandemic. This is definitely not enough to address climate change concerns as a result of carbon emissions from LD travel.

Surface downward shortwave radiation (DSR) and photosynthetically active radiation (PAR) play critical roles in the Earth’s surface processes. As the main inputs of various ecological, hydrological, carbon, and solar photovoltaic models, increasing requirements for high spatiotemporal resolution DSR and PAR estimation with high accuracy have been observed in recent years. However, few existing products satisfy all of these requirements. This study employed a well-established physical-based look-up table (LUT) approach to the GeoNEX gridded top-of-atmosphere bidirectional reflectance factor data acquired by the Advanced Himawari Imager (AHI) and Advanced Baseline Imager (ABI) sensors. It produced a data product of DSR and PAR over both AHI and ABI coverage at an hourly temporal step with a 1 km spatial resolution. GeoNEX DSR data were validated over 63 stations, and GeoNEX PAR data were validated over 27 stations. The validation showed that the new GeoNEX DSR and PAR products have accuracy higher than other existing products, with root mean square error (RMSE) of hourly GeoNEX DSR achieving 74.3 W / m2 (18.0 %), daily DSR estimation achieving 18.0 W / m2 (9.2 %), hourly GeoNEX PAR achieving 34.9 W / m2 (19.6 %), and daily PAR achieving 9.5 W / m2 (10.5 %). The study also demonstrated the application of the high spatiotemporal resolution GeoNEX DSR product in investigating the spatial heterogeneity and temporal variability of surface solar radiation. The data product can be accessed through NASA Advanced Supercomputing Division GeoNEX data portal https://data.nas.nasa.gov/geonex/geonexdata/GOES16/GEONEX-L2/DSR-PAR/ and https://data.nas.nasa.gov/geonex/geonexdata/HIMAWARI8/GEONEX-L2/DSR-PAR/ (https://doi.org/10.5281/zenodo.7023863, Wang & Li, 2022).

Recently, it has become popular to study the use of extracellular vesicles (EVs) secreted by stem cells to repair damaged tissues or lost cells. Various cell types and physiological fluids release EVs, and they play an important role in cell-to-cell communication. Moreover, EVs have been implicated in important processes, such as immune responses, homeostasis maintenance, coagulation, inflammation, cancer progression, angiogenesis, and antigen presentation. Thus, EVs participate in both physiological and pathological progression. The main classes of EVs include exosomes, microvesicles (MVs), and apoptotic bodies (ApoBDs). Exosomes, which carry a mass of signal molecules such as RNA, DNA, proteins, and lipids, are the most important of these EVs subsets. Currently, exosomes are generating substantial interest in the scientific community. Exosomes loaded hydrogels or under different cultural environments exhibit different properties and functions. Therefore, the exosomes obtained from different sources and conditions are worth reviewing. More importantly, no review article has compared the different EVs, such as exosomes, MVs, ApoBDs, and mesenchymal stem cell (MSC) lysates, which are special soluble substances. The differentiation between EVs and MSC lysates is a logical approach. Accordingly, this review provides an update on the latest progress in studying the roles of culture-condition stimulated exosomes or their loaded hydrogels and the differentiation between exosomes, MVs, ApoBDs, and MSC lysates. Published studies were retrieved from the PubMed® database for review.

Parkinson’s disease (PD) has a characteristically unilateral pattern of symptoms at onset and in the early stages; this lateralization is considered a diagnostically important diagnosis feature. We aimed to compare the graph-theoretical properties of whole-brain networks generated by using resting-state functional MRI (rs-fMRI), diffusion tensor imaging (DTI), and the resting-state-informed structural connectome (rsSC) in patients with left-onset PD (LPD), right-onset PD (RPD), and healthy controls (HCs). We recruited 26 patients with PD (13 with LPD and 13 with RPD) as well as 13 age- and sex-matched HCs. Rs-fMRI and DTI were performed in all subjects. Graph-theoretical analysis was used to calculate the local and global efficiency of a whole-brain network generated by rs-fMRI, DTI, and rsSC. Two-sample t-tests and Pearson correlation analysis were conducted. Significantly decreased global and local efficiency were revealed specifically in LPD patients compared with HCs when the rsSC network was used; no significant intergroup difference was found by using rs-fMRI or DTI alone. For rsSC network analysis, multiple network metrics were found to be abnormal in LPD. The degree centrality of the left precuneus was significantly correlated with the Unified Parkinson’s Disease Rating Scale (UPDRS) score and disease duration (p = 0.030, r = 0.599; p = 0.037, r = 0.582). The topological properties of motor-related brain networks can differentiate LPD and RPD. Nodal metrics may serve as important structural features for PD diagnosis and monitoring of disease progression. Collectively, these findings may provide neurobiological insights into the lateralization of PD onset.

Background: To assess the association between serum lactate dehydrogenase (LDH) levels and mortality in intensive care unit patients. Materials & methods: A total of 1981 patients in the eICU Collaborative Research Database were divided into four groups according to quartiles of LDH levels. Logistic regressions were performed. Results: Elevated LDH levels were significantly associated with higher mortality (intensive care unit mortality: Q2 vs Q1: 1.046 [0.622–1.758]; Q3 vs Q1: 1.667 [1.029–2.699]; and Q4 vs Q1: 1.760 [1.092–2.839]). Similar results persisted in patients with different acute physiology and chronic health evaluation IV scores, and with or without sepsis. Conclusion: The serum LDH level may aid in the early identification of mortality risk in critically ill patients.

In this letter, we demonstrate a high-performance lateral AlGaN/GaN Schottky barrier diode (SBD) using an 80-nm thick GaN cap layer as the passivation layer and a low work-function tungsten (W) layer as the anode. A low turn-on voltage ( ${V}_{ON}$ ) of 0.38 V and a high breakdown voltage of 2.08 kV are obtained at the same time. Additionally, the normalized dynamic on-resistance ( ${R}_{ON,dyn}$ ) becomes only a factor of 1.13 higher than the static on-resistance ( ${R}_{ON}$ ) after a 10-s-long bias test at 900 V. Also owing to the impressively stability of ${R}_{ON,dyn}$ and ${V}_{ON}$ under long-duration stress, these lateral GaN SBDs with a thick GaN cap layer show a great potential for the next-generation of power electronic devices.

BackgroundDecreased serum albumin level (SAL) is associated with adverse clinical outcomes. We designed the present study to further assess the prognostic value of SAL in critically ill patients based on data from large intensive care unit (ICU) databases.MethodsThis retrospective cohort study recruited 18,353 patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Restricted cubic splines (RCS) were performed to visualize the association of SAL at admission with ICU and hospital mortalities. The prognostic value of SAL was analyzed using logistic regression models and receiver operating characteristic (ROC) curves in overall patients and subgroups.ResultsRestricted cubic splines revealed rapid increasing risks in ICU and hospital mortalities when SAL declined to below 30 g/l. Patients with SAL p < 0.001) and hospital (23.9% vs. 10.7%, p < 0.001) mortalities than those with SAL ≥30 g/l. Multivariable logistic regression model revealed that SAL ConclusionsDecreased SAL is associated with increased risk of mortality. However, it possesses low sensitivity and specificity for outcome prediction in critically ill patients, especially in those with cirrhosis.

Background. There were controversies over the relationship between Anion gap (AG) and mortality in critically ill patients. Therefore, a large multicenter cohort study was conducted to evaluate the association of AG and mortality in large-scale intensive care units (ICUs) patients. Methods. This retrospective cohort study included adult ICU patients enrolled from eICU Collaborative Research Database. According to initial serum AG upon ICU admission, patients were divided into three groups: AG < 8 mmol / L , 8 ≤ AG ≤ 16 mmol / L , and AG > 16 mmol / L . Logistic regression models were built to investigate the association between serum AG and ICU and hospital mortalities. Serum AG was added into Acute Physiology and Chronic Health Evaluation (APACHE) IV score and the model discrimination was assessed by the area under the curve (AUC) of receiver operating characteristic curves. The relationship between serum AG and mortalities in patients with different acid-base status and serum lactate were also evaluated. An external validation was performed with the Critical care database comprising patients with infection at Zigong Fourth People’s Hospital. Results. A total of 8520 patients entered the final cohort. There are 42 patients with serum AG < 8 mmol / L , 3238 patients with 8 ≤ AG ≤ 16 mmol / L , and 5240 patients with AG > 16 mmol / L . Serum AG > 16 mmol / L is related with increased ICU mortality (odds ratio [OR], 1.530; 95% confidence interval [CI], 1.305–1.794) and hospital mortality (OR, 1.618; 95% CI, 1.415–1.849), compared with 8 ≤ AG ≤ 16 mmol / L . Adding Serum AG to APACHE IV score could statistically improve the prediction of ICU (0.770 [0.761–0.779] to 0.774 [0.765–0.783], P = 0.001 ) and hospital mortalities (0.756 [0.747–0.765] to 0.761 [0.751–0.770], P = 0.012 ). The associations between serum AG and mortalities remain robust in patients with different acid-base statuses and serum lactate. The findings are validated in the external cohort. Conclusions. Initial serum AG > 16 mmol / L after ICU admission is associated with increased mortality in critically ill patients.

Background Recent studies have shown that chronic kidney disease (CKD) prevalence is significantly higher in patients with hepatic steatosis (HS); however, it remains unclear whether HS is associated with serum creatinine (SCr). We aimed to explore the association between SCr levels and HS in a Chinese population. Methods We performed a cross-sectional study among 56,569 Chinese individuals. SCr level, other clinical and laboratory parameters, abdominal ultrasound and noninvasive fibrosis scores were extracted, and the fibrosis 4 score (FIB-4) was calculated. Results A total of 27.1% of the subjects had HS. After 1:1 propensity score matching (PSM) according to sex and age, we included 13,301 subjects with HS and 13,301 subjects without HS. SCr levels were significantly higher in the HS group than in the non-HS group [73.19 ± 15.14(μmoI/L) vs. 71.75 ± 17.49(μmoI/L), p Conclusions Our results showed an independent association between SCr level and HS risk in a Chinese population.

Platelets play important roles in thrombosis, hemostasis, inflammation, and infection. We aimed to evaluate the association between platelet count and its variation trend and prognosis of patient with infectious diseases in intensive care units (ICUs). This retrospective cohort study extracted 4,251 critically ill adult patients with infectious diseases from the eICU Collaborative Research Database, whose platelet counts were measured daily during the first 7 days after admission. In the survivors, platelet counts decreased in the first days after admission, reached a nadir on day 3, and then returned and continued to rise above the admission value. In non-survivors, the platelet counts decreased after admission, without a subsequent upturn. We defined three subgroups according to the nadir platelet counts within 7 days: ≤50, 50-130, and ≥130 × 10

The objective of this study is to evaluate the field variability of jointed concrete pavement (JCP) faulting and its effects on pavement performance. The standard deviation of faulting along both the longitudinal and transverse directions are calculated. Based on these, the overall variability is determined, and the required sample sizes needed for a given precision at a certain confidence level are calculated and presented. This calculation is very important as state departments of transportation are required to report faulting every 0.1 mi to the Federal Highway Administration as required by the 2015 FAST Act. On average, twice the number of measurements are needed on jointed reinforced concrete pavements (JRCP) to achieve the same confidence and precision as on jointed plain concrete pavements (JPCP). For example, a sample size of 13 is needed to achieve a 95% confidence interval with a precision of 1.0 mm for average faulting of JPCP, while 26 measurements are required for JRCP ones. Average faulting was found to correlate with several climatic, structural, and traffic variables, while no significant difference was found between edge and outer wheelpath measurements. The application of Portland cement concrete overlay and the use of dowel bars (rather than aggregate interlock) are found to significantly reduce faulting. Older sections located on higher functional classes, and in regions of high precipitation or where the daily temperature change is larger, tend to have higher faulting, and might require larger samples sizes as compared with the rest when faulting surveys are to be conducted.

Myofibrillar protein accounting for about 60% of total muscle proteins is expected to be a promising source of bioactive peptides. The purpose of the present study was to purify antioxidant peptides from myofibrillar protein hydrolysate of chicken breast by ultrafiltration and gel filtration chromatography, and evaluate their chemical antioxidant activities and protective effects in H2O2-stressed NIH-3T3 cells. Four major peptides were identified using nano-LC-ESI-MS/MS as ITTNPYDY, IGWSPLGSL, ITTNPYDYHY, and LRVAPEEHPTL. The sequenced peptides were synthesized and exhibited remarkable radical-scavenging ability, ORAC (108.2–133.5 μM TE per mg peptide), and FRAP (75.4–92.5 mM Fe2+ per mg peptide). Structure–activity relationship indicated that the antioxidant capacity of the peptides was more related to the presence of hydrophobic and antioxidant amino acids (including Trp, Val, Ile, Leu, Ala, Pro, Gly, Asp, His, and Tyr) in the sequences as well as their molecular structures. Moreover, they protected NIH-3T3 cells against oxidative damage through inhibiting ROS generation and lipid peroxidation. Especially, the antioxidant peptides ITTNPYDY and IGWSPLGSL significantly (p < 0.05) elevated intracellular glutathione level and antioxidant enzyme activities, and suppressed apoptosis by blocking caspase-3 activation. This work highlights that the selected peptides may serve as functional food ingredients with antioxidant and cytoprotective characteristics.

Ovarian hyperandrogenism is one of the characteristics of polycystic ovary syndrome (PCOS) and androgen receptor (AR) in ovarian granulosa cells (GCs) functions as an important element to the accumulation of androgens. This study verified the existence of alternative splicing variant of AR (AR-SVs) in the GCs of PCOS patients and found that the function of AR decreased significantly in the presence of AR-SVs. And compared to the normal individuals, the expression of Serine/arginine-rich splicing factor 2(SRSF2) was higher and the expression of SRSF3 was lower in the GCs of patients with AR-SVs. More importantly, we found that the expression of SRSF2 was inhibited and that the expression of AR was decreased after the successful upregulation of miRNA-183, and testostrone (T) concentrations in the culture medium were increased. The results also showed that the expression of SRSF3 decreased when miRNA-124 was successfully upregulated, while the expression of AR significantly increased; however, the function of AR was also inhibited when T concentration in the culture medium was increased. This study has proved that SRSFs are regulated by corresponding miRNAs, and the altered expression of SRSFs interferenced the alternative splicing process of AR and ultimately decreased the function of AR, leading to the accumulation of androgens in the ovary.

Previous studies have emphasized the association between baseline body mass index (BMI) and mortality in patients during a stay in the intensive care unit (ICU). However, to our knowledge, few studies have focused on BMI change during an ICU stay. The aim of this study was to explore the prognostic value of BMI change during ICU hospitalization.This was a multicenter, retrospective cohort study with data extracted from the eICU Collaborative Research Database. Logistic regression models were used to explore the relationship between BMI change and mortality in ICU patients. BMI change was calculated as follows: {[discharge ICU weight (kg) - admission ICU weight (kg)] / height (m)Compared with those with weight loss (n = 17 134), patients with weight gain during ICU hospitalization (n = 17 436) were associated with higher hospital mortality (odds ratio [OR], 1.251; 95% confidence interval [CI], 1.155-1.356; P0.001) and ICU mortality (OR, 1.360; 95% CI, 1.227-1.506; P0.001) after multivariable adjustment. The associations remained robust in patients with different baseline BMI levels and were especially remarkable among those with higher APACHE IV score and the longer ICU stay.The present study exposed the potential hazard of increasing BMI for hospital and ICU mortalities during ICU hospitalization and indicating that patients in the ICU may benefit from a more balanced nutritional strategy.

Heat-treated cancer cells have thermo-resistance due to the up-regulated levels of heat shock proteins (HSP) resulting in low therapeutic efficiency and ineffective ablation of tumors. In this work, we report pH-responsive Ag2S nanodots (Ag2S NDs) loaded with HSP70 inhibitor (QE-PEG-Ag2S) for enhanced photothermal cancer therapy. QE-PEG-Ag2S was easily prepared via self-assembly of hydrophobic Ag2S NDs, amphiphilic pH-responsive PEG5k-PAE10k polymer, and an HSP70 inhibitor quercetin (QE). QE-PEG-Ag2S has ideal water-solubility and biocompatibility, can rapidly enter cells, and preferentially accumulate in cell lysosomes. The slightly acidic environment of tumor cells and the acidity of lysosomes as well as the high temperature generated by photothermal therapy under irradiation of NIR light (808 nm) promote the release of the inhibitor molecules to reduce the heat resistance of cancer cells and improve the in vivo photothermal therapy efficiency. Moreover, QE-PEG-Ag2S has good photoacoustic imaging (PAI) ability; this QE-PEG-Ag2S concentration dependent signal can precisely follow the accumulation of the nanomaterials in tumors and dictate the correct time for light therapy. As a result, QE-PEG-Ag2S achieved complete tumor ablation effect with no recurrence when only irradiated with NIR light for 10 min. This approach offers a new approach for the theranostic applications of Ag2S NDs. STATEMENT OF SIGNIFICANCE: In this work, pH-responsive Ag2S nanodots loaded with the heat shock protein inhibitor for enhanced photothermal cancer therapy have been simply prepared via self-assembly process. This nanoagent possesses ideal water-solubility and biocompatibility, can rapidly enter cells, and preferentially accumulate in cell lysosomes. The acidic environment of tumor cells and the acidity of lysosomes, as well as the high temperature generated by photothermal therapy under irradiation of NIR light promote the release of the inhibitor molecules from the nanoagent to improve the in vivo photothermal therapy efficiency. Moreover, the photoacoustic imaging (PAI) of the nanoagent can precisely follow the accumulation of the nanomaterials in tumors and dictate the light therapy time to guarantee the complete tumor ablation effect with no recurrence.

Although previous studies have indicated that older people with diabetes mellitus (DM) had an approximately two times larger white matter hyperintensity (WMH) load than those without DM, the influence of WMHs on cognition is uncertain and inconsistent in the literature. It is unclear whether the short-range fibers in the juxtacortical region, traditionally considered to be spared from WMH pathology, are enhanced as an adaptive response to deep WM degeneration in older diabetic people with normal cognition. Moreover, the specific effect of vitamin B12 deficiency, commonly accompanied by DM, remains to be investigated. This study implemented a specialized analysis of the superficial cortical short-range fiber connectivity density (SFiCD) based on a data-driven framework in 70 older individuals with DM and low serum vitamin B12. Moreover, the effects of time and vitamin B12 supplementation were assessed based on a randomized placebo-controlled trial in 59 individuals. The results demonstrated a higher SFiCD in diabetic individuals with a higher deep WMH load. Additionally, a significant interaction between DWMH load and homocysteine on SFiCD was found. During the 27-month follow-up period, a longitudinal increase in the SFiCD was observed in the bilateral frontal cortices. However, the observed longitudinal SFiCD change was not dependent on vitamin B12 supplementation; thus, the specific reason for the longitudinal cortical short fiber densification may need further study. Overall, these findings may help us better understand the neurobiology of brain plasticity in older patients with DM, as well as the interplay among DM, WMH, and vitamin B12 deficiency.

Gallbladder and biliary diseases (GBDs) are one of the most prevalent medical issues in the digestive system. This study was designed to describe the characteristics of prevalence, death, and disability-adjusted life years (DALYs) of GBDs during 1990-2019 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019.Prevalence, death, and DALYs for GBDs in different locations, years, sex, and age groups were estimated using DisMod-MR 2.1 and a generic Cause of Death Ensemble Modeling approach. Countries and territories were categorized according to socio-demographic index (SDI) quintiles.The prevalence cases (127 345 732 to 193 493 378), death cases (82 430 to 124 941), and DALYs (4 604 821 to 6 352 738) of GBDs increased from 1990 to 2019. However, the age-standardized rates of indicators decreased over the 30-year period (prevalence, 2851.84 to 2350.78 per 100 000 population; death, 2.40 to 1.65 per 100 000 population; DALYs, 106.76 to 78.25 per 100 000 population). In 2019, the high and middle-high SDI regions had higher age-standardized prevalence rates, the low SDI region had the highest age-standardized death rate, and the middle SDI region had the highest DALYs and age-standardized DALYs rate of GBDs. Being female, older age, and high body mass index were important risk factors for the burden of GBDs.Globally, there were improvements in overall health with regard to GBDs over the 30 years. However, the prevention of GBDs should be promoted in middle, middle-high, and high SDI regions, while more medical resources should be provided to improve treatment levels in low SDI region.

A general and facile visible-light mediated protocol for the synthesis of 2-arylamino-5-aryl-1,3,4- thiadiazoles via one-pot condensation and intramolecular C–S coupling cascade reaction has been developed. This protocol is mild, practical, metal-free and exogenous oxidant-free, and only involves Eosin Y as photocatalyst using oxygen as the sole terminal oxidant. This protocol exhibits synthetic simplicity, broad scope of substrates, and excellent functional group compatibility. Gram-scale synthesis can be also facilitated with a satisfactory yield, which opens up the possibility of practical applications.

Many long non-coding RNAs (lncRNA) are highly dysregulated in cancer and are emerging as therapeutic targets. One example is NEAT1, which consists of two overlapping lncRNA isoforms, NEAT1_1 (3.7 kb) and NEAT1_2 (23 kb), that are functionally distinct. The longer NEAT1_2 is responsible for scaffolding gene-regulatory nuclear bodies termed paraspeckles, whereas NEAT1_1 is involved in paraspeckle-independent function. The NEAT1 isoform ratio is dependent on the efficient cleavage and polyadenylation of NEAT1_1 at the expense of NEAT1_2. Here, we developed a targeted antisense oligonucleotide (ASO) approach to sterically block NEAT1_1 polyadenylation processing, achieving upregulation of NEAT1_2 and abundant paraspeckles. We have applied these ASOs to cells of the heterogeneous infant cancer, neuroblastoma, as we found higher NEAT1_1:NEAT1_2 ratio and lack of paraspeckles in high-risk neuroblastoma cells. These ASOs decrease NEAT1_1 levels, increase NEAT1_2/paraspeckles and concomitantly reduce cell viability in high-risk neuroblastoma specifically. In contrast, overexpression of NEAT1_1 has the opposite effect, increasing cell proliferation. Transcriptomic analyses of high-risk neuroblastoma cells with altered NEAT1 ratios and increased paraspeckle abundance after ASO treatment showed an upregulation of differentiation pathways, as opposed to the usual aggressive neuroblastic phenotype. Thus, we have developed potential anti-cancer ASO drugs that can transiently increase growth-inhibiting NEAT1_2 RNA at the expense of growth-promoting NEAT1_1 RNA. These ASOs, unlike others that degrade lncRNAs, provide insights into the importance of altering lncRNA polyadenylation events to suppress tumorigenesis as a strategy to combat cancer.

Levels of reactive oxygen species (ROS) in cancer cells or in the tumor microenvironment differ noticeably from those in normal cells and cellular microenvironments because ROS play important roles in all aspects of tumor physiology. However, due to the lack of adequate tools, it is difficult to study the relationship between ROS, especially certain types of ROS (e.g., HOCl), and cancer. We report herein an HOCl-specific fluorescent probe, FDOCl-20, containing a thiocarbamide group as a receptor, for the visualization of HOCl in solid tumors in vivo. This probe displays high selectivity and sensitivity to HOCl, and is appropriate for use in acidic conditions, including the tumor microenvironment. Using FDOCl-20 as a tool, we can visualize HOCl in solid tumors in vivo. Importantly, the fluorescent intensity of FDOCl-20 is proportional to tumor volume. Thus, FDOCl-20 is a useful tool to investigate the relationship between HOCl and the physiological processes of tumors.

Detection of Aβ protofibrils at the early stage of Alzheimer's disease was realized by a novel near-infrared probe (DCM-AN) based on dicyanomethylene-4H-pyran. This probe exhibits high affinity towards Aβ protofibrils in vitro and in brain sections of transgenic mouse models for Alzheimer's disease.

Antibiotic residues in foods have aroused wide public concern because of their potential side-effects. It is imperative to develop a simple, accurate and reliable method for the detection of antibiotic residues in foods. In this paper, we report a novel, facile and sensitive method for the detection of ampicillin in milk using a commercial personal glucose meter (PGM). Magnetic beads (MBs) were employed as the platform, an ampicillin aptamer was used as the recognition element and streptavidin was utilized as the bridge to link invertase and the aptamer. After the hydrolysis of sucrose to glucose, the concentration of glucose was quantitatively measured using the PGM. The difference of PGM signals with and without addition of ampicillin exhibits a good linear correlation with the logarithm of ampicillin concentrations in the range of 2.5 × 10-10 mol L-1 to 1.0 × 10-7 mol L-1 with a detection limit of 2.5 × 10-10 mol L-1 (S/N = 3). Finally, the proposed method was successfully applied for the detection of ampicillin residue in milk.

Background Ovarian cancer is characterized by high metastatic potential and high mortality. More than 80% of primary ovarian malignancies are epithelial ovarian cancers. There is increasing evidence that Speckle-type POZ protein (SPOP) is highly correlated with the development of various types of cancer. However, the effects of SPOP on epithelial ovarian cancer and the associated molecular mechanisms remain unclear. Materials and methods We compared SPOP expression between epithelial ovarian cancer tissues and normal ovarian tissues by using immunohistochemical staining. To determine the role of SPOP in epithelial ovarian cancer cells, we overexpressed or knocked down SPOP in the epithelial ovarian cancer cell line OVCAR-3 using lentiviral vectors. Results Our results from the present study indicated that SPOP expression was significantly downregulated in human epithelial ovarian cancer and was associated with the FIGO stage and the histopathologic grading of the tumor. The overexpression and knockdown experiments revealed that SPOP inhibited proliferation while promoting apoptosis in ovarian cancer cells. Inhibition of SPOP mis-activated the Hedgehog (Hh) signaling pathway, thereby inhibiting apoptosis in ovarian cancer cells. Conclusion SPOP suppresses proliferation and promotes apoptosis in human ovarian cancer cells by inhibiting the Hh signaling pathway, offering the possibility of new approaches for the treatment of ovarian cancer.

Copy number variation (CNV) of 16p11.2 is a common genetic factor contributing to the etiology of abnormal weight status, while the underlying mechanism is not fully elucidated yet.The 16p11.2 CNV mouse model with microduplication of the 7Slx1b-Sept1 region (dp/+) is evaluated under normal chow conditions. Compared to the wild type littermates (WT), the dp/+ mice exhibit obvious obese phenotype characterized by significant increase in body mass index, fat pad mass, and fat ratio, with visceral-dominant fat deposits at 12-week age. White adipose tissue (WAT), liver tissue, and plasma are sampled to assess the comorbid metabolic syndrome. In dp/+ mice, histopathologic analyses reveal hypertrophic adipocytes and hepatic steatosis; serological examinations show hyperlipemia and hyperinsulinemia. Further, by comparing lipidomic and transcriptomic profiling of epididymal WAT between dp/+ and WT mice, the study finds the triglyceride (TG) accumulation in dp/+ mice in association with the dysfunction of lipid droplets. Validation of TG-metabolism-associated genes in WAT and in primary cultured adipocytes show enhanced TG synthesis and declined TG hydrolysis in the dp/+ model.This study elucidates that the imbalanced TG synthesis/hydrolysis in adipocytic lipid droplets may contribute to the hypertrophic obesity and metabolic disorders in mice with 16p11.2 microduplication.

Manipulating droplets by light in microscale allows precise control of microfluidics, liquid delivery, micromachines, and so on. Among these applications, microfluidic technology is of particular interest for miniaturization of the portable analysis systems, which require the integration of various liquid operations in one device. Here, a photodeformable microfluidic platform is constructed by combining Laplace pressure and capillary condensation to integrate the transportation, fusion, separation, and mixing of liquid slugs in one chip. The Laplace pressure, attributed to the photodeformation of the liquid crystal polymers, is generated to propel the slug. The capillary condensation is introduced by the delicate design of the fluid channels, allowing the fusion and separation of slugs without any connected microvalves. Catalytic oxidation reaction and protein detection processes are realized in the platform, which are amenable to a variety of miniaturized bio-medical applications, such as portable analysis and point of care testing.

Herein, a waste cotton fabrics-based nanosystem was fabricated to simultaneously remove copper (Cu(II)) and lead ions (Pb(II)) from water and soil. Therein, carboxyl-functionalized zinc oxide microsphere (ZnO-COOH) with peanut shape was carried by cotton fabric (CF) to get CF/ZnO-COOH nanosystem. CF/ZnO-COOH with a good foldable property possessed a high removal capacity for Cu(II) and Pb(II) via electrostatic attraction and chelation. The result indicated that their removal efficiencies of CF/ZnO-COOH could reach over 95% after 2 h. The adsorption process was consistent with Langmuir (R

Although previous studies have indicated that older people with diabetes mellitus (DM) had an approximately two times larger white matter hyperintensity (WMH) load than those without DM, the influence of WMHs on cognition is uncertain and inconsistent in the literature. It is unclear whether the short-range fibers in the juxtacortical region, traditionally considered to be spared from WMH pathology, are enhanced as an adaptive response to deep WM degeneration in older diabetic people with normal cognition. Moreover, the specific effect of vitamin B

Cancer cell survival, function and fate strongly depend on endoplasmic reticulum (ER) proteostasis. Although previous studies have implicated the ER stress signaling network in all stages of cancer development, its role in cancer metastasis remains to be elucidated. In this study, we investigated the role of Gremlin-1 (GREM1), a secreted protein, in the invasion and metastasis of colorectal cancer (CRC) cells in vitro and in vivo. Firstly, public datasets showed a positive correlation between high expression of GREM1 and a poor prognosis for CRC. Secondly, GREM1 enhanced motility and invasion of CRC cells by epithelial–mesenchymal transition (EMT). Thirdly, GREM1 upregulated expression of activating transcription factor 6 (ATF6) and downregulated that of ATF4, and modulation of the two key players of the unfolded protein response (UPR) was possibly through activation of PI3K/AKT/mTOR and antagonization of BMP2 signaling pathways, respectively. Taken together, our results demonstrate that GREM1 is an invasion-promoting factor via regulation of ATF6 and ATF4 expression in CRC cells, suggesting GREM1 may be a potential pharmacological target for colorectal cancer treatment.

Myofibrillar protein accounting for about 60% of total muscle proteins is expected to be a promising source of bioactive peptides. The purpose of the present study was to purify antioxidant peptides from myofibrillar protein hydrolysate of chicken breast by ultrafiltration and gel filtration chromatography, and evaluate their chemical antioxidant activities and protective effects in H2O2-stressed NIH-3T3 cells. Four major peptides were identified using nano-LC-ESI-MS/MS as ITTNPYDY, IGWSPLGSL, ITTNPYDYHY, and LRVAPEEHPTL. The sequenced peptides were synthesized and exhibited remarkable radical-scavenging ability, ORAC (108.2-133.5 μM TE per mg peptide), and FRAP (75.4-92.5 mM Fe2+ per mg peptide). Structure-activity relationship indicated that the antioxidant capacity of the peptides was more related to the presence of hydrophobic and antioxidant amino acids (including Trp, Val, Ile, Leu, Ala, Pro, Gly, Asp, His, and Tyr) in the sequences as well as their molecular structures. Moreover, they protected NIH-3T3 cells against oxidative damage through inhibiting ROS generation and lipid peroxidation. Especially, the antioxidant peptides ITTNPYDY and IGWSPLGSL significantly (p0.05) elevated intracellular glutathione level and antioxidant enzyme activities, and suppressed apoptosis by blocking caspase-3 activation. This work highlights that the selected peptides may serve as functional food ingredients with antioxidant and cytoprotective characteristics.

This study aimed to investigate the optimal activation of plastic aligner for the canine distal movement by combining the stress and strain of periodontal ligament. Computer-aided design models of the upper canine, periodontal ligament, alveolar bone, and plastic aligner were constructed. The stresses and strains of periodontal ligament were acquired by fitting plastic aligner on the canine, which will cause the canine distal-direction movement. The activation of plastic aligner was set into 12 groups, including 0.050, 0.100, 0.125, 0.150, 0.175, 0.200, 0.225, 0.250, 0.275, 0.300, 0.350, and 0.400 mm. Assuming the volume-averaged hydrostatic stress (VAHS) ranging from 4.7 to 16 kPa to be the optimal stress, and an average strain no less than 0.3 to be the optimal strain. The optimal activation of plastic aligner was acquired based on the optimal stress and average strain. As the activation increased, the stress and strain of periodontal ligament increased visibly. The degree of activation of plastic aligner was nonlinearly and positively related to VAHS and average strain. According to the fitted curves, the activation corresponding to the optimal stress was 0.07-0.24 mm and the activation was not less than 0.21 mm based on the optimal strain. The optimal activation of plastic aligner for the canine distal movement was 0.21-0.24 mm in this study. The degree of activation affects the force system of orthodontic tooth movement, and it should be taken into consideration to obtain healthy and efficient tooth movement. The activation with 0.21-0.24 mm seems optimal for orthodontic tooth movement in the plastic aligner system in this study.

Electric vehicles have taken a larger market share in the world market throughout the previous years. China plays an important role in the electric vehicle markets in the world. Therefore, we are more than willing to find out the potential customers within the country. Using information extracted from a self-made survey, which contains questions about customers’ backgrounds and personal preferences between March 2021 and April 2021, we are able to recognize the characteristics of the target customers. After we collected all of our respondents, we used K-Means clustering to predict the potential customers’ group. The results contain the characteristics of the customers who have the higher possibility to purchase an electric vehicle. Our findings can show us what exact group of people are interested in electric vehicles base on big data.

Self-assembled nanostructures of amphiphilic peptides have a wide range of applications in bioimaging and delivery systems. In this study, we design and synthesize a biocompatible amphiphilic peptide (C-3) consisting of an RVRRFFF sequence and a nitrobenzoxadiazole fluorophore that can self-assemble into stable micelles for specifically detecting furin, a kind of proprotein convertase with promoting tumor progression. The self-assembly of C-3 with a β-sheet nanostructure is capable of a rapid and specific response to furin in only 5 min in aqueous solution because of the existence of the RVRR motif in the C-3 molecule. The C-3 nanostructures thus can selectively distinguish high furin-expressing cancer cells, like MDA-MB-231 cells, a kind of human breast cancer cells, from normal cells. Furthermore, the C-3 self-assembly can stay in living cells for a long time and are capable of durable detection of intracellular furin, being good for tracer analysis. To our knowledge, this is the first example of self-assembly of a soluble amphiphilic peptide that can selectively detect furin in high furin-expressing live cells.

The overproduction of HOCl is highly correlated with diseases such as atherosclerosis, rheumatoid arthritis, and cancer. Whilst acting as a marker of these diseases, HOCl might also be used as an activator of prodrugs or drug delivery systems for the treatment of the corresponding disease. In this work, a new platform of HOCl probes has been developed that integrates detection, imaging, and therapeutic functions. The probes can detect HOCl, using both NIR emission and the naked eye in vitro, with high sensitivity and selectivity at ultralow concentrations (the detection limit is at the nanomolar level). Basal levels of HOCl can be imaged in HL-60 cells without special stimulation. Moreover, the probes provided by this platform can rapidly release either amino- or carboxy-containing compounds from prodrugs, during HOCl detection and imaging, to realize a therapeutic effect.

We have developed a new cell-penetrating peptide (CPP) using a repeated protease (furin) substrate. This CPP can not only deliver cargo into cells but can also be cleaved by furin in cells and release the cargo. Cell-impermeable antitumor pro-apoptotic peptide KLAKLAKKLAKLAK (KLA) and chemotherapy drug chlorambucil were chosen to be delivered by the CPP into live cancer cells and their cytotoxicity was greatly enhanced for in vivo cancer treatment.