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Abstract Background Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for non-small cell lung cancer (NSCLC). The variability in patient responses necessitates a blood-based, multi-cohort gene signature to predict ICI response in NSCLC. Methods We performed transcriptomic profiling of peripheral blood mononuclear cell (PBMC) and buffy coat (BC) samples from three independent cohorts of NSCLC patients treated with ICIs: a retrospective cohort (PMBCR, n = 59), a retrospective validation cohort (BC, n = 44), and a prospective validation cohort (PBMCP, n = 42). We identified a 5-gene signature (UQCRB, NDUFA3, CDKN2D, FMNL1-DT, and APOL3) predictive of ICI response and validated its clinical utility in the prospective PBMCP cohort. Response was evaluated using RECIST criteria, and patients were followed up for progression-free survival (PFS) and overall survival (OS). Results In the prospective PBMCP cohort, the 5-gene signature demonstrated high accuracy in stratifying patients into responders and non-responders (AUC = 0.89, 95% CI: 0.80–0.99). Predicted responders exhibited significantly longer PFS compared to predicted non-responders (median: 13.8 months vs. 4.2 months, HR = 0.21, 95% CI: 0.07–0.58, p = 0.005). Conclusion Our study confirms a 5-gene signature as a key biomarker for ICI response in NSCLC, enhancing treatment precision.

Abstract The pig is an important model for studying human diseases and is also a significant livestock species, yet its testicular development remains underexplored. Here, we employ single-cell RNA sequencing to characterize the transcriptomic landscapes across multiple developmental stages of Bama pig testes from fetal stage through infancy, puberty to adulthood, and made comparisons with those of humans and mice. We reveal an exceptionally early onset of porcine meiosis shortly after birth, and identify a distinct subtype of porcine spermatogonia resembling transcriptome state 0 spermatogonial stem cells identified in humans, which were previously thought to be primate specific. We also discover the persistent presence of proliferating progenitors for myoid cells in postnatal testes. The regulatory roles of Leydig cell steroidogenesis and estrogen synthesis in supporting cell lineages are also explored, including the potential impact of estrogen on Sertoli cell maturation and spermatogenesis. Overall, this study offers valuable insights into porcine testicular development, paving the way for future research in reproductive biology, advancements in agricultural breeding, and potential applications in translational medicine.

To reduce the manufacturing cost of D-allulose, a recyclable and reusable inorganic catalyst was developed for D-allulose production, and process using this catalyst to produce D-allulose also was optimized in this article. Zeolitic imidazolate framework-67 (ZIF-67) was synthesized using Co2+ and 2-methylimidazole in aqueous phase. Then the structure of ZIF-67 was characterized. The single factor test was carried out to select suitable value of pH (A), catalytic temperature (B) and reaction time (C). Based on the results of single factor experiments, the catalytic process was optimized using response surface methodology. The results showed that ZIF-67 had a rhombic dodecahedral structure and exhibited excellent catalytic performance. The Design Expert 13 software predicted the optimal reaction condition was pH11.1, 80.0 ℃ and 11.2 min. Under these conditions, the catalytic activity of ZIF-67 was 1003.5 µmol·min−1·g−1. A D-allulose inorganic catalyst was developed and the optimal reaction condition was carried out using response surface methodology in this paper. It also opens up a new path for the industrial production of D-allulose.

Phenological changes are of great significance to the study of climate response and ecological environment.Based on the MODIS V6 snow product and reflectivity product in the past 20 years， the snow and lake ice phenology in the Qinghai Lake Basin were obtained， and the spatial distribution characteristics of the two were analyzed.On this basis， Theil-Sen Median method and linear regression method were used to analyze the variation trend of snow phenology and lake ice phenology， as well as the correlation between them in low altitude areas.The results show that： （1） Freeze-up start， Break-up start and Exist Duration of lake ice in Qinghai Lake are in the range of 321~389 d， 425~464 d and 0~174 d， respectively.On the whole， Freeze-up start and Break-up start of lake ice were delayed， and the delay rates were 0.3 d·a-1 and 0.2 d·a-1， respectively.Exist Duration of lake ice showed a shortening trend， with a shortening rate of 0.6 d·a-1.There is a significant correlation between lake ice phenology and longitude.From east to west， Freeze-up start is postponed， Break-up start is advanced， and Exist Duration of lake ice is shortened.（2） Start of snow cover days， End of snow cover days and Snow cover days in Qinghai Lake Basin are distributed in the range of 275~404 d， 353~484 d and 3~209 d， respectively.Among them， start of snow cover days and End of snow cover days showed an early trend and a delayed trend respectively， and the change rates were 0.8 d·a-1 and 0.11 d·a-1 respectively.Snow cover days showed an increasing trend， with a growth rate of 0.6 d·a-1.Snow phenology is closely related to altitude.With the increase of altitude， start of snow cover days is advanced， End of snow cover days is delayed， and Snow cover days increases.（3） Air temperature and negative accumulated temperature in winter are important factors affecting lake ice phenology.With the increase of temperature and negative accumulated temperature in winter， Freeze-up start will be delayed， Break-up start will be advanced， and Exist Duration of lake ice will be shortened.For snow phenology， there is a significant negative correlation between Snow cover days and the temperature.The temperature decreases and Snow cover days increases.（4） There is a potential relationship between some snow cover and lake ice phenology parameters in low-altitude watersheds.There is a significant negative correlation between the beginning date of snow cover and the beginning date of lake ice freezing， and the correlation coefficient is -0.404.As the lake surface insulation layer， the increase of snow cover days will also greatly slow down the speed of lake ice melting， resulting in the delay of lake ice melting date.Therefore， there is a positive correlation between the two， and the correlation coefficient is 0.349.The change law of ecosystem in the basin revealed by this study is of positive significance to the local ecosystem， and can provide theoretical basis and technical support for the environmental monitoring of Qinghai Lake Basin.

Abstract R-loops are three-stranded nucleic acid structures composed of an RNA–DNA hybrid and a displaced DNA strand. They are widespread and play crucial roles in regulating gene expression, DNA replication, and DNA and histone modifications. However, their regulatory mechanisms remain unclear. As R-loop detection technology advances, changes in R-loop levels have been observed in cancer models, often associated with transcription-replication conflicts and genomic instability. N6-methyladenosine (m6A) is an RNA epigenetic modification that regulates gene expression by affecting RNA localization, splicing, translation, and degradation. Upon reviewing the literature, we found that R-loops with m6A modifications are implicated in tumor development and progression. This article summarizes the molecular mechanisms and detection methods of R-loops and m6A modifications in gene regulation, and reviews recent research on m6A-modified R-loops in oncology. Our goal is to provide new insights into the origins of genomic instability in cancer and potential strategies for targeted therapy.

Abstract Background Several recent studies reported the potential adverse effects of titanium exposure on glucose homeostasis among the non-pregnant population, but the association of titanium exposure with gestational diabetes mellitus (GDM) is scarce. Methods The present study of 1,449 pregnant women was conducted within the Jiangsu Birth Cohort (JBC) study in China. Urine samples were collected in the early pregnancy, and urinary titanium concentration and non-targeted metabolomics were measured. Poisson regression estimated the association of titanium exposure in the early pregnancy with subsequent risk of GDM. Multiple linear regression screened for titanium-related urine metabolites. Mediation analyses assessed the mediating effects of candidate metabolites and pathways. Results As parameterized in tertiles, titanium showed positive dose–response relationship with GDM risk (P for trend = 0.008), with women at the highest tertile of titanium exposure having 30% increased risk of GDM [relative risk (RR) = 1.30 (95% CI: 1.06, 1.61)] when compared to those exposure at the first tertile level. Meanwhile, we identified the titanium-related metabolites involved in four amino acid metabolic pathways. Notably, the perturbation of the aminoacyl-tRNA biosynthesis and alanine, aspartate and glutamate metabolism mediated 27.1% and 31.0%, respectively, of the relative effect of titanium exposure on GDM. Specifically, three titanium-related metabolites, choline, creatine and L-alanine, demonstrated predominant mediation effects on the association between titanium exposure and GDM risk. Conclusions In this prospective study, we uniquely identified a correlation between early pregnancy titanium exposure and increased GDM risk. We unveiled novel insights into how perturbations in amino acid metabolism may mediate the link between titanium exposure and GDM. Notably, choline, creatine, and L-alanine emerged as key mediators influencing this association. Our findings imply that elevated titanium exposure in early pregnancy can lead to amino acid dysmetabolism, thereby elevating GDM risk. Graphical Abstract

Abstract Background Currently, most elderly chronic heart failure (CHF) patients go home for rehabilitation after certain treatment in hospitals. However, the results of their rehabilitation at home are not satisfactory. According to studies, dyadic treatments can increase the efficiency of home rehabilitation, enhance both partners' quality of life, lessen the caregiver's load of care, and alleviate the strain of medical resources. Thus, the aim of our research is to design a study protocol that included elderly CHF patients and their informal caregivers as an intervention unit and to explore the impact of the protocol on their health and physical outcomes. Methods This is a prospective randomized controlled trial conducted in a triple-A hospital. In total, 80 elderly CHF patients and informal caregivers (80 dyads) will be recruited with informed consent. Based on the randomized numbers, they are divided into a control group (40 dyads) and an intervention group (40 dyads), subjects in the control group will receive usual care, and subjects in the intervention group will receive a home-based disease management program based on the Theory of Dyadic Illness Management on the basis of the control group. The duration of the intervention is 3 months, and the follow-up is 6 months. Data is collected at enrolment, 3 months after the intervention, and 3 months after the end of the intervention. The primary outcome is patients’ quality of life and readmission. Secondary outcomes include patients’ self-management behaviors, anxiety, and depression and caregivers’ quality of life and care burden. Discussion This study focuses on whether this home-based disease management program can improve the quality of life of elderly patients with CHF, reduce the readmission rate, enhance their self-management capacity, reduce negative emotions, and reduce the burden of informal caregivers. It can provide a new perspective on home management and cardiac rehabilitation of heart failure disease in the elderly, as well as alleviate problems such as the burden of healthcare resources. Trial registration Chinese Clinical Trials Registry ChiCRT2300068026. Registered on 3 February 2023, manuscript Version: 1.0, https://www.chictr.org.cn/ .

Abstract Background Therapeutic approaches that combine conventional photodynamic therapy (PDT) with gas therapy (GT) to sensitize PDT are an attractive strategy, but the molecular structure design of the complex lacks effective guiding strategies. Results Herein, we have developed a nanoplatforms Cy-NMNO@SiO2 based on mesoporous silica materials loaded NIR-activatable small-molecule fluorescent probe Cy-NMNO for the synergistic treatment of photodynamic therapy/gas therapy (PDT/GT) in antibacterial and skin cancer. The theoretical calculation results showed that the low dissociation of N-NO in Cy-NMNO enabled it to dissociate effectively under NIR light irradiation, which is conducive to produce Cy and NO. Cy showed better 1O2 generation performance than Cy-NMNO. The cytotoxicity of Cy-NMNO obtained via the synergistic effect of GT and PDT synergistically enhances the effect of photodynamic therapy, thus achieving more effective tumor treatment and sterilization than conventional PDT. Moreover, the nanoplatforms Cy-NMNO@SiO2 realized efficient drug loading and drug delivery. Conclusions This work not only offers a promising approach for PDT-GT synergistic drug delivery system, but also provides a valuable reference for the design of its drug molecules. Graphical Abstract

Abstract In heavy oil reservoirs, favorable reservoir properties have a positive impact on the production performance during CO2 huff-n-puff. It is significant to study the screening method of applicable conditions for CO2 huff-n-puff in actual reservoirs. To solve these problems, this paper introduced the orthogonal design method to analyze the main factors based on numerical simulation. The technical analysis and the economic evaluation were both employed to obtain the applicable conditions of selecting oil layers or injection wells during CO2 huff-n-puff. And a new algorithms of machine learning, the random forest algorithm, was introduce to find the weighted factors and the scoring standards that were suitable for CO2 huff-n-puff. Finally, a set of method for screening suitable reservoir conditions was established. Based on the introduction of orthogonal analysis method and random forest algorithm, a software was established to achieve the purpose of analyzing the feasibility of CO2 huff-n-puff considering different reservoir geological parameters. This method increased the accuracy and efficiency in screening reservoir conditions that was suitable for CO2 huff-n-puff.

Abstract Background Ambient particulate matter (PM) exposure is recognized as a risk factor for cardiovascular disease (CVD). However, the extent to which PM exposure is associated with CVD via triglyceride glucose (TyG)-related indicators remains unknown. This study examines the relationship between long-term PM exposure and CVD events, further assessing whether TyG-related indicators mediate this association. Methods This cohort study involved 7,532 individuals aged at least 45 years who were not diagnosed with CVD in 2011 from the China Longitudinal Study of Health and Retirement (CHARLS) and were followed up for the occurrence of CVD until 2020. The annual PM concentration data at the city level, with aerodynamic diameters ≤ 1 μm (PM1), ≤ 2.5 μm (PM2.5), and ≤ 10 μm (PM10), were obtained from the ChinaHighAirPollutants (CHAP). The average concentration of PM in the 3 years before the baseline survey in 2011 was defined as the long-term exposure level of the individual. The relationship between PM exposure and CVD incidence was examined via Cox proportional hazards models, with a focus on probing the role of TyG-related indicators through mediation analysis. Results A total of 1,865 individuals with CVD were diagnosed over the span of a 7.4-year follow-up period. The 3-year average concentrations before baseline were 31.29 µg/m³ for PM1, 56.03 µg/m³ for PM2.5, and 95.73 µg/m³ for PM10. In fully adjusted model, the Cox proportional hazards models revealed that an increase of 10 µg/m³ in the PM1, PM2.5, and PM10 exposure concentrations corresponded to elevated CVD risk, with HRs (95% CI) of 1.135 (1.078–1.195), 1.092 (1.062–1.123), and 1.075 (1.059–1.090), respectively. Mediation analyses further suggested that the correlation between PM exposure and CVD could be partly mediated via TyG-BMI, TyG-WC, and TyG-WHtR, with mediation proportions varying from 5.54 to 15.30%. Conclusion A significant correlation was observed between long-term PM exposure and increased CVD risk, with TyG-related indicators, such as TyG-BMI, TyG-WC, and TyG-WHtR, partially mediating this relationship.

Super 13Cr, as an economy stainless steel (SS) for oil country tubular goods, needs stable corrosion resistance in high-pressure and high-temperature (HPHT) downhole medium. Severe plastic deformation (SPD) are the surface modification technology to improve mechanical properties, fatigue behavior and corrosion resistance of metals, and shot peening (SP) has been the most widely used SPD process. However, there are quite limited studies about the microsutructure evolution, residual stress, and high-temperature corrosion behavior of SP-treated martensitic SS. In this study, super 13Cr martensitic SS was treated by SP with various air pressures and nozzle speeds. The surface characteristics and high-temperature corrosion behaviour in 3.17 mol/L K2HPO4 solution were investigated through finite element model analysis, characterization of residual stress and microstructure, as well as electrochemical and stress corrosion cracking (SCC) tests at 160 °C and 10 MPa. The results showed that SP-treated super 13Cr could generate high-level compressive residual stress and SPD microstucture, including nano-sized equiaxed grains, gradient lamellar structure and fragmented carbides. Increasing air pressure contributed to achieve uniform nanocrystalline, but tended to generate high dislocation density and surface defects. The improving effect of SP treatment at low air pressure of 0.15 MPa on passivation ability was limited, and high air pressure adversely impacted corrosion resistance. SP-treated specimens showed high SCC susceptibility, due to the introduction of more surface defects, high angle grain boundaries, and dislocations.

Abstract Background Plants that contain brewing microorganisms are used in traditional fermentation starters, which are an essential part of local diet, nutrition, life, and health. Regionally, the plant species used and the microorganisms included in traditional fermentation starters are diverse, endowing local fermented drinks with different flavors and health benefits. However, related traditional knowledge has been scarcely documented or revealed. Methods An ethnobotanical survey was conducted in five towns of Nayong County in northwestern Guizhou, China. Snowball sampling, semi-structured interviews, free lists, and participatory observation were used to collect information on Jiuqu Plants (JPs) and jiuqu-making techniques. The PacBio platform was used to study the microbial community structure and diversity in the Chuanqing people’s jiuqu. Results In total, 225 informants were interviewed, including 116 who provided plants and technological processes for making Chinese baijiu jiuqu (CBJ) and 139 who provided information about making fermented glutinous rice jiuqu (FGRJ). This study found that older people have more abundant knowledge about CBJ plants. Poaceae was found to be the dominant family used in making CBJ and FGRJ (7 species each). Compared to individual plant parts, the whole plant is most commonly used in two kinds of jiuqu (19.5% in CBJ and 22.6% in FGRJ). The Chuanqing people’s jiuqu is used to treat dietary stagnation and indigestion. The highest relative frequency of citation of the CBJ plant was Ficus tikoua Bureau, and the counterpart of the FGRJ plant was Buddleja macrostachya Benth. The dominant bacterial species in jiuqu were Gluconobacter japonicus (YQ1, YQ4) and Pediococcus pentosaceus (YQ2, YQ3), and the dominant fungal species was Rhizopus oryzae. Conclusion For the first time, this study documents the unique traditional jiuqu knowledge and reveals the microbial mystery behind the FGRJ of the Chuanqing people. Therefore, this study encourages the use of online social media platforms in order to spread Jiuqu culture, the use of the new media wave in order to create multimedia databases, and also suggests that local communities should develop preservation intervention programs, in addition to nurturing the inheritors in order to prevent the disappearance of traditional Jiuqu knowledge. This research contributes to the conservation and demystification of the traditional jiuqu knowledge of the Chuanqing people and lays the foundation for further research on its microbiology, nutrition, and metabolomics.

Parameter identification involves the estimation of undisclosed parameters within a system based on observed data and mathematical models. In this investigation, we employ DAISY to meticulously examine the structural identifiability of parameters of a within-host SARS-CoV-2 epidemic model, taking into account an array of observable datasets. Furthermore, Monte Carlo simulations are performed to offer a comprehensive practical analysis of model parameters. Lastly, sensitivity analysis is employed to ascertain that decreasing the replication rate of the SARS-CoV-2 virus and curbing the infectious period are the most efficacious measures in alleviating the dissemination of COVID-19 amongst hosts.

Abstract Increasing research efforts are focused on studying the synthesis and mechanisms of nanomedicine in urologic cancer. We performed a bibliometric study of the literature on nanomedicine in urologic cancer over the last 23 years, focusing on aspects such as researchers, institutions, nations, and keywords. We searched for papers in the Web of Science Core Collection from January 1, 2001, to December 29, 2023. Only reviews and original articles written in English were considered. A total of 2386 papers satisfied the given criteria for inclusion. The publications included in the study originated from 90 nations. The United States had the largest number of published papers, accounting for more than 31.01% of the total. The leading institution in this field is the Chinese Academy of Sciences, with a publishing output of 2.35%. Farokhzad, Omid C., is the most prolific author, with 21 articles, and has garnered the most citations, totaling 6271. The latest phrase to enter the top ten most common lists was "gold nanoparticles." We searched for papers in the Web of Science Core Collection from January 1, 2000, to November 28, 2023. Only reviews and original articles written in English were considered. This is the first bibliometric study of nanomedicine in urologic cancer. This article provides a comprehensive analysis of the current state of research on nanomedicine in urologic cancer over the last 23 years. On the basis of this study, future researchers can identify noteworthy publications, journals, and potential collaborators and explore cutting-edge research directions.

Abstract Background Iron deficiency anemia (IDA) is a common health problem worldwide. The objective of this study was to noninvasively and quantitatively evaluate early changes in left ventricular systolic function in patients with IDA using the left ventricular press–strain loop (LV-PSL). Methods Sixty-two patients with IDA were selected and divided into two groups based on hemoglobin (Hb) concentration: Group B with Hb > 9 g/dL and group C with 6 g/dL

Objective To investigate the genotypes of human papillomavirus (HPV) infection in male patients with condyloma acuminatum (CA) and to develop a model for predicting recurrence risk. Methods Wart samples were collected from 724 CA patients at Jiaozhou Branch of Shanghai East Hospital, Tongji University from January 2021 to June 2023. Human papillomavirus DNA was extracted and genomic DNA was genotyped. Multivariate logistic regression analysis was used to analyze the risk factors for recurrence within 6 months after being cured with physiotherapy, and a prediction model for recurrence risk was developed. Receiver operating characteristic (ROC) curves was used to verify the prediction value of the prediction model. Results Among 724 CA patients, the main genotypes were HPV 6, 11, 16, and 42. Multivariate logistic regression analysis showed that a disease course of ≥ 6 months, high-risk HPV infection, multiple HPV infections, and the number of warts ≥ 5 were independent risk factors for recurrence (P13.00, the sensitivity and specificity were 71.39% and 83.01%, respectively, and the area under the curve (AUC) was 0.863. Conclusions The main genotypes of HPV infection are HPV 6, 11, 16, and 42 in male CA patients. The prediction model for recurrence risk factors has high predictive value for predicting recurrence of CA.

Abstract Alternative polyadenylation (APA) is a crucial mechanism for regulating gene expression during pre-mRNA 3′ processing. Pre-mRNA 3′ end processing factors is the main factor involved in this process. However, pre-mRNA 3′ end processing factors in different cancer expression profiles and the relationship between pre-mRNA 3′ end processing factors and tumor microenvironment and the prognosis of the same patient is still unclear. In this study, we conducted a comprehensive exploration of the core pre-mRNA 3′ end processing factors across various cancer types by utilizing common cancer database, and revealing a robust correlation between the expression of these core factors and tumor characteristics. Leveraging advanced bioinformatics databases, we evaluated the expression levels and prognostic relevance of pre-mRNA 3′ end processing factors across pan-cancer tissues. Our extensive pan-cancer analysis revealed unique expression patterns of pre-mRNA 3′ end processing factors in both tumor and adjacent non-tumorous tissues. Notably, we found a significant correlation between the expression levels of pre-mRNA 3′ end processing factors and patient prognosis. Furthermore, we identified strong associations between pre-mRNA 3′ end processing factors expression and various factors, such as stromal, immune, RNA stemness, and DNA stemness scores across pan-cancer tissues. Our data also highlighted a link between the expression of pre-mRNA 3′ end processing factors and sensitivity to specific drugs, including pyrazoloacndine, amonaflide, and chelerythrinede, among others. We found four key pre-mRNA 3′ end processing factors that play a crucial role in mRNA preprocessing. Our study illuminates the potential promotion and inhibition role of pre-mRNA 3′ end processing regulators in the progression of cancer, CPSF2, CPSF3, CSTF2, SYMPK offering valuable insights for future research investigations on these regulators as diagnostic markers and therapeutic targets across pan-cancer.

Abstract To understand the ecology of species and promote biotechnology through beneficial strain selection for improving starch yield in maize wet-milling steeping, bacterial diversity and community structure during the counter-current steeping process in a commercial steeping system were characterized and investigated. The microbial diversity in the steeping liquor, which consisted of 16 phyla, 131 families, and 290 genera, was more abundant compared to those present on the surface of unsteeped maize. As the counter-current steeping progressed, exposing newer maize to the older steepwater, Lactobacillus dominated, replacing Rahnella, Pseudomonas, Pantoea, and Serratia. The thermophilic and acidophilic microbial consortia were enriched through adaptive evolution engineering and employed to improve starch yield. Several steeping strategies were evaluated, including water alone, SO2 alone, mono-culture of B. coagulans, microbial consortia, and a combination of consortium and SO2. Combining the microbial consortium with SO2 significantly increased the starch yield to, about 66.4 ± 0.5%, a 22% and 46% increase over SO2 alone and the consortium alone, respectively. Scanning electron microscope (SEM) of steeped maize structure indicated that the combination of consortium and SO2 disrupted the protein matrix and widened gaps between starch granules in maize endosperm. This released proteins into the steepwater and left starch granules in the aleurone layer. The steeping strategy of using thermophilic and acidophilic microbial consortium as additives shows potential application as an environmentally friendly alternative to conventional maize steeping procedures.

Abstract Background The coronavirus disease (COVID-19) pandemic has accentuated the need for effective clinical skills training in infectious diseases. This study aimed to explore the influencing factors of infectious disease clinical skills training based on scenario simulation teaching for medical staff in China. Methods This hospital-based, cross-sectional study was conducted at the Third People’s Hospital of Shenzhen between March and December 2022. Scenario simulation teaching was applied, and factors such as gender, educational level, professional background, and previous experience were examined to determine their impact on qualification outcomes. Results The study included participants primarily between the ages of 20–40 years, with a higher proportion of women holding university degrees. Nurses and physicians were more likely to qualify, indicating the significance of professional backgrounds. Women showed a higher likelihood of qualifying than men and higher educational attainment correlated with better qualification rates. Prior experience with protective clothing in isolation wards was a significant determinant of successful qualification. Multivariate analysis underscored the influence of sex, education, and previous experience on training effectiveness. Conclusion Scenario simulation is an effective strategy for training clinical skills in treating infectious diseases. This study highlights the importance of considering sex, education, professional background, and prior experience when designing training programs to enhance the efficacy and relevance of infectious disease training.

Advanced metastatic colon cancer is difficult to treat with existing chemotherapy medicines, and hypoxic microenvironment is closely related to angiogenesis and distant metastasis of colon cancer. Quercetin, a natural flavonoid, has been shown anti-tumor effects. The aim of this study is to investigate the effect of quercetin alone or combined with 5-FU on the invasion and metastasis of advanced metastatic or primary colorectal cancer in hypoxic environment. The cytotoxicity of quercetin or/and 5-FU on colon cancer cells using CCK8 assay, Hoechst 33342, flow cytometry and AO staining. The effects of quercetin or/and 5-FU on the migration and invasion were determined by transwell, cell scratching method and murine xenograft models. The potential mechanism was explored by Western blot and immunofluorescent assay. The results revealed quercetin effectively inhibited the invasion and migration of high metastatic advanced colon cancer LOVO cells under hypoxia through the inhibition of ROS and the expression of HIF-1α and PI3K/AKT pathway. Combination of quercetin and 5-FU could promote the inhibition of 5-FU on the invasion and migration of LOVO cells. Moreover, quercetin also significantly inhibited the proliferation of either LOVO cells or HT-29 ​cells under hypoxia by inducing apoptosis and autophagy, particularly, showing stronger inhibition on HT-29 ​cells than LOVO cells. In conclusion, quercetin inhibited the invasion and migration of advanced metastatic colon cancer LOVO cells under hypoxia through inhibition of ROS and HIF-1α expression and the downregulation of PI3K/AKT pathway. Moreover, quercetin alone or in combination with 5-FU can effectively inhibit the invasion and migration of high metastatic advanced colon cancer. Quercetin has the potential to be used as an effective anti-colon cancer drug alone or in combination for the clinical treatment of advanced colon cancer.

In the MODIS snow product collection 6.1 (C6.1), some snowy pixels are misclassified as cloud pixels due to an excessive cloud mask algorithm. This increases cloud contamination in normalized difference snow index (NDSI) and affects snow mapping accuracy. Northeast China is used as an example to develop excessive cloud mask removal and gap-filling algorithms, and generate a daily cloud-free NDSI dataset for each snow season from 2001 to 2020. To identify pseudo-cloud pixels, the green band and NDSI were used to distinguish forested snow and clouds, thin snow in plains and clouds, respectively. This decreased cloud from nearly 60% to below 30%. We developed a spatiotemporal cube cloud removal algorithm based on NDSI similarity (STNSI) for the remaining clouds in which the central cloudy pixel was filled with neighborhood pixels in the spatiotemporal cube. Meanwhile, bias correction was performed, and the average cloud decreased to below 1% after the first iteration. The produced STNSI NDSI has high precision under different underlying surfaces, with OA and FS values greater than 0.9. Compared with the existing STAR NDSI, STNSI NDSI snow mapping accuracy improved, especially in forested areas where OA improved by 37%. Moreover, removing many pseudo-cloud pixels greatly enhances gap-filling efficiency.

Many systemic diseases, including Alzheimer disease (AD), diabetes mellitus (DM) and cardiovascular disease, are associated with microbiota dysbiosis. The oral and intestinal microbiota are directly connected anatomically, and communicate with each other through the oral-gut microbiome axis to establish and maintain host microbial homeostasis. In addition to directly, periodontal bacteria may also be indirectly involved in the regulation of systemic health and disease through the disturbed gut. This paper provides evidence for the role of periodontal bacteria in systemic diseases via the oral-gut axis and the far-reaching implications of maintaining periodontal health in reducing the risk of many intestinal and parenteral diseases. This may provide insight into the underlying pathogenesis of many systemic diseases and the search for new preventive and therapeutic strategies.

Summary: Background: Large language models (LLMs) have shown promising performance in various healthcare domains, but their effectiveness in identifying specific clinical conditions in real medical records is less explored. This study evaluates LLMs for detecting signs of cognitive decline in real electronic health record (EHR) clinical notes, comparing their error profiles with traditional models. The insights gained will inform strategies for performance enhancement. Methods: This study, conducted at Mass General Brigham in Boston, MA, analysed clinical notes from the four years prior to a 2019 diagnosis of mild cognitive impairment in patients aged 50 and older. We developed prompts for two LLMs, Llama 2 and GPT-4, on Health Insurance Portability and Accountability Act (HIPAA)-compliant cloud-computing platforms using multiple approaches (e.g., hard prompting, retrieval augmented generation, and error analysis-based instructions) to select the optimal LLM-based method. Baseline models included a hierarchical attention-based neural network and XGBoost. Subsequently, we constructed an ensemble of the three models using a majority vote approach. Confusion-matrix-based scores were used for model evaluation. Findings: We used a randomly annotated sample of 4949 note sections from 1969 patients (women: 1046 [53.1%]; age: mean, 76.0 [SD, 13.3] years), filtered with keywords related to cognitive functions, for model development. For testing, a random annotated sample of 1996 note sections from 1161 patients (women: 619 [53.3%]; age: mean, 76.5 [SD, 10.2] years) without keyword filtering was utilised. GPT-4 demonstrated superior accuracy and efficiency compared to Llama 2, but did not outperform traditional models. The ensemble model outperformed the individual models in terms of all evaluation metrics with statistical significance (p

The application of low-condensation diesel in cold regions with extremely low ambient temperatures (−14 to −29 °C) has enabled the operation of diesel vehicles. Still, it may contribute to heavy haze pollution in cold regions during winter. Here we examine pollutant emissions from low-condensation diesel in China. We measure the emissions of elemental carbon (EC), organic carbon (OC), and elements, including heavy metals such as arsenic (As). Our results show that low-condensation diesel increased EC and OC emissions by 2.5 and 2.6 times compared to normal diesel fuel, respectively. Indicators of vehicular sources, including EC, As, lead (Pb), cadmium (Cd), chromium (Cr), nickel (Ni), and manganese (Mn), increased by approximately 20.2–162.5% when using low-condensation diesel. Seasonal variation of vehicular source indicators, observed at road site ambient environments revealed the enhancement of PM2.5 pollution by the application of low-condensation diesel in winter. These findings suggest that −35# diesel, a low-cetane index diesel, may enhance air pollution in winter, according to a dynamometer test conducted in laboratory. It raises questions about whether higher emissions are released if −35# diesel is applied to running vehicles in real-world cold ambient environments.

IntroductionHepatoid adenocarcinoma of the lung (HAL) is a special type of adenocarcinoma originating from the lung with adenoid- and hepatocyte-like differentiation. HAL is rare in clinical practice. Here, we present the case of a patient with HAL.Case presentationA 59-year-old man was admitted to the hospital 4 days because of lung mas observed. Chest computed tomography (CT) revealed a lobulated mass shadow in the right lower lobe, approximately 3.5 × 3.3 cm in size. CT-guided percutaneous biopsy of the right lower lung was performed. The pathological results indicated a moderately to poorly differentiated adenocarcinoma. The patient underwent thoracoscopic right middle and lower lobectomy and systematic lymph node dissection. The postoperative pathology was primary HAL, with the staging of T2bN2M0 (stage III A). Recurrence-free survival and overall survival were 6 and 19 months, respectively Preoperatively, the level of alpha-fetoprotein was negative; however, after recurrence, it increased to 87.8.ConclusionPulmonary hepatoid adenocarcinoma is a rare subtype of malignant lung tumor, combined silicosis is more rare. Early surgical intervention can benefit patients in the early stages of the disease, whereas chemotherapy remains the main systemic treatment modality for postoperative and advanced stages. With the increasing popularity of genetic testing, it is important to focus on improving genetic examination.

Abstract Climate change and large‐scale ecological restoration programs have profoundly influenced vegetation greening and gross primary productivity (GPP) in China's drylands. However, the specific pathways through which climatic factors and vegetation greening influence GPP remain poorly understood. This study examines the spatiotemporal changes in GPP across China's drylands from 2001 to 2020 and investigates the direct and indirect effects of climatic factors and leaf area index (LAI) on GPP. The results reveal that the overall improvement in vegetation cover has positively increased GPP in these regions. Although the direct effects of climatic factors on GPP are minimal, they exert a substantial indirect effect by regulating vegetation growth, highlighting that LAI is a key intermediary in mediating the effects of climatic factors on GPP. Furthermore, these complex interactions vary significantly along the aridity gradient. This study emphasizes the necessity of comprehensively considering the intricate interactions among multiple climate and vegetation factors.

The addition of non-templated nucleotides at the 3’ terminus of RNA is a pervasive and evolutionarily conserved posttranscriptional modification in eukaryotes. Apart from canonical poly(A) polymerases (PAPs), which are responsible for catalyzing polyadenylation of messenger RNAs in the nucleus, a distinct group of non-canonical PAPs (ncPAPs), also known as nucleotidyl transferase proteins (NTPs), mediate the addition of uridine and adenosine or of more intricate combinations of nucleotides. Among these, HEN1 SUPPRESSOR 1 (HESO1) and UTP: RNA URIDYLYLTRANSFERASE (URT1) are the two most extensively studied NTPs responsible for the addition of uridine to the 3’ ends of RNAs (RNA uridylation). Recent discoveries have improved our understanding of the functions and mechanisms of uridylation mediated by HESO1 and URT1 in RNA metabolism. Furthermore, more NTPs have been identified to function in the 3’ tailing of RNA and not solely through uridylation. Accumulating evidence indicates that RNA tailing plays important roles in plant growth and development, stress responses, and disease resistance. In this review, we examined the latest developments in RNA tailing by NTPs, with a focus on RNA uridylation and metabolism in plants. We also discussed the essential aspects for future research in this field.

Metastasis is the main cause of death in cancer patients, the lung is one of the most common metastatic organs of malignant solid tumors. Before tumor cells metastasize to the lungs, they interact with immunosuppressive cells, alveolar epithelial cells, and lung fibroblasts to form a pre-metastatic niche. The pre-metastatic niche is a key factor leading to tumor cell metastasis to the lungs. Research has found that traditional Chinese medicine and its components can inhibit the formation of pre-metastatic niche. Therefore, this article reviewed the research progress on the formation of lung pre-metastatic niche and the intervention of traditional Chinese medicine in pulmonary PMN, in order to provide new Chinese medicine prescriptions and research ideas for further clinical prevention and treatment of tumor metastasis to the lung.

Objective: The prognostic implication of phosphorus level in patients with coronary artery disease (CAD) remains controversial. We aimed to conduct a meta-analysis to evaluate the prognostic role of blood phosphorus level in CAD patients. Methods: We searched the PubMed, Web of Science, Scopus, and Embase databases until December 28, 2023, to identify prospective or retrospective longitudinal observational studies that examined the prognostic value of blood phosphorus level in CAD patients. Outcome measures included all-cause or cardiovascular mortality, heart failure, stroke, and major adverse cardiac events (MACEs). The prognostic value of blood phosphorus level was expressed by pooling the fully adjusted hazard ratios (HR) with 95 % confidence intervals (CI) for the hypophosphatemia or hyperphosphatemia compared to the reference normal phosphorus level. Results: Six studies involving 19,553 CAD patients were included. Meta-analysis showed that the hyperphosphatemia was significantly associated with higher risk of all-cause mortality (HR 1.39; 95 % CI 1.20–1.61), cardiovascular mortality (HR 1.37; 95 % CI 1.22–1.53), heart failure (HR 1.64; 95 % CI 1.44–1.87), and MACEs (HR 1.39; 95 % CI 1.03–1.88) but not stroke (HR 1.23; 95 % CI 0.79–1.92). However, non-significant association was found between hypophosphatemia and all-cause mortality (HR 1.21; 95 % CI 0.98–1.51), cardiovascular mortality (HR 1.07; 95 % CI 0.78–1.45), heart failure (HR 0.87; 95 % CI 0.72–1.05), stroke (HR 1.12; 95 % CI 0.76–1.67), and MACEs (HR 1.16; 95 % CI 0.99–1.36). Conclusions: Hyperphosphatemia, but not hypophosphatemia independently predicts all-cause mortality, cardiovascular mortality, heart failure, and MACEs in CAD patients.

Background: Few studies have compared the performances of those reported miRNAs as biomarkers for heart failure with reduced EF (HFrEF) in a population at high risk. The purpose of this study is to investigate comprehensively the performance of those miRNAs as biomarkers for HFrEF. Methods: By using bioinformatics methods, we also examined these miRNAs' target genes and possible signal transduction pathways. We collected serum samples from patients with HFrEF at Zhongshan Hospital. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of those miRNAs as biomarkers for HFrEF. miRWALK2.0, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to predict the target genes and pathways of selected miRNAs. Results: The study included 48 participants, of whom 30 had HFrEF and 18 had hypertension with normal left ventricular ejection fraction (LVEF). MiR-378, miR-195-5p were significantly decreased meanwhile ten miRNAs were remarkably elevated (miR-21-3p, miR-21-5p, miR-106-5p, miR-23a-3p, miR-208a-3p, miR-1-3p, miR-126-5p, miR-133a-3p, miR-133b, miR-223-3p) in the serum of the HFrEF group. Conclusion: The combination of miR 133a-3p, miR 378, miR 1-3p, miR 106b-5p, and miR 133b has excellent diagnostic performance for HFrEF, and there is a throng of mechanisms and pathways by which regulation of these miRNAs may affect the risk of HFrEF.

A feeding trial was conducted to evaluate growth, body composition, serum biochemistry, digestion and metabolism, and oxidation resistence of S. schlegelii fed 9 diets in a 3×3 factorial design (protein levels: 44 %, 48 %, 52 %; lipid levels: 6 %, 10 %, 14 %), to optimize protein and lipid levels for practical feed formula. Rockfish (114.25 g) were stocked into 27 cages in an offshore system and fed test diets to satiation twice daily for 8 weeks. Growth increased but feed conversion rate decreased with dietary protein increasing. Increasing dietary protein to >48 % led to reduced feeding intake but increased protein efficiency ratio. Lipid efficiency ratio increased with dietary protein increasing but decreased with dietary lipid increasing. Hepatosomatic index decreased coupling with the increases in condition factor and liver lipid content as dietary lipid increased to 14 %. Intraperitoneal fat ratio increased with dietary lipid increasing. Increasing dietary protein to > 48 % significantly elevated serum total protein and glucose concentrations, hepatic glycogen synthase activity. High-protein (52 %) diets elevated serum albumin and urea nitrogen concentrations, hepatic pyruvate kinase and alanine aminotransferase (ALT) activities but downregulated hepatic growth-hormone (GH) receptor. Activities of trypsin, lipase, serum superoxide dismutase and total antioxidant capacity decreased with the dietary lipid increasing. Increasing dietary lipid to > 10 % reduced serum GH concentration, and high-lipid (14 %) diets significantly enhanced serum triglyceride concentration and hepatic transaminases activities, and resulted in a visual increase of adipocytes in liver. Serum cholesterol and low-density lipoprotein decreased as dietary protein increased to 48–52 % or dietary lipid >10 %. Hepatic succinate dehydrogenase activity and serum IGF-1 significantly increased while hepatic fatty acid synthetase decreased as dietary protein increased to >48 % or dietary lipid >10 %. High-protein (52 %) diet or high-lipid (14 %) diet elevated serum malonaldehyde concentration. These findings suggested 48 % protein and 10 % lipid were the optimal in diet for subadult S. schlegelii.

Background: Cardiovascular disease originates in early life. We aimed to investigate the association between breastfeeding in infancy and cardiovascular disease in adult life. Methods: We followed 364,240 participants from UK Biobank aged 40–73 years from 2006 – 2010 to 2021. Information on breastfeeding in infancy was self-reported by questionnaire. Cox proportional hazard regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association between breastfeeding and cardiovascular disease in middle-aged and older adulthood. The multivariable Cox models were used by adjusting for the age (used as the time scale), sex, ethnicity, assessment centre, birth weight, multiple birth status, maternal smoking during pregnancy, Townsend deprivation index, smoking status, alcohol drinker status, physical activity, and menopausal status for women. Binary and multinomial multivariable logistic regression models were used to explore the associations of breastfeeding in infancy with cardiovascular disease risk factors including obesity, body composition, metabolic and inflammatory disorders. Results: During a median of 12.6 years of follow-up, we documented 29,796 new cases of cardiovascular disease, including 24,797 coronary heart disease and 6229 stroke. The multivariable adjusted HRs for breastfed versus non-breastfed were 0.94 (95% CI: 0.91, 0.96) for cardiovascular disease, 0.94 (95% CI: 0.91, 0.96) for coronary heart disease, and 0.95 (95% CI: 0.89, 1.01) for stroke. Furthermore, the strength of observed association between breastfeeding and cardiovascular disease seems to decrease with age (P for interaction

This study aims to evaluate the laboratory safety perception, awareness and attitude of undergraduates toward the chemistry teaching laboratory by means of a self-administered questionnaire. The survey contains a sample size of 959 undergraduates in Tianjin University of Technology involving four schools. Instrument reliability and validity are also tested. The results show that most of the students have a more positive laboratory environmental perception and safety awareness. However, the laboratory safety attitude needs improvement. In addition, there is a significant difference for both gender and school. This result could lead to the improvement of the subsequent safety education.

Understanding the precise mechanism of BMSC (bone marrow mesenchymal stem cell) osteogenesis is critical for metabolic bone diseases and bone reconstruction. The histone-lysine N-methyltransferase 2D (KMT2D) acts as an important methyltransferase related with congenital skeletal disorders, yet the function of KMT2D in osteogenesis was unclear. Here we found that KMT2D expression was decreased in BMSCs collected from ovariectomized mice. Moreover, during human BMSC differentiation under mineralization induction, the mRNA level of KMT2D was gradually elevated. After KMT2D knockdown, the in vitro osteogenic differentiation of BMSCs was inhibited, while the in vivo bone formation potential of BMSCs was attenuated. Further, in BMSCs, KMT2D knockdown reduced the level of phosphorylated protein kinase B (p-AKT). SC-79, a common activator of AKT signaling, reversed the suppressing influence of KMT2D knockdown on BMSCs differentiation towards osteoblast. These results indicate that the KMT2D-AKT pathway plays an essential role in the osteogenesis process of human BMSCs (hBMSCs), which might provide new avenues for the molecular medicine of bone diseases and regeneration.

Abstract The overall health condition of patients significantly affects the diagnosis, treatment, and prognosis of endodontic diseases. A systemic consideration of the patient’s overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy, as well as selecting appropriate therapeutic approaches. This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence, aiming to provide general guidance on clinical procedures, improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Abstract Focusing on the anthropogenic aerosols effects on the East Asian Summer Monsoon (EASM) progression, we found that aerosols delay the northward progression of EASM by one pentad in the south of the middle-lower reaches of the Yangtze River (PD1: pentads 25-35) and the North-Northeast China (PD3: pentads 38-42). However, aerosols have minimal impact on the seasonal march of EASM over the Yangtze-Huai River basin (PD2: pentads 36-37). In PD1 and PD3, aerosols reduce sea-land temperature differences. Also, a southward shift in the westerly jet causing lower-level north winds, which weakens the EASM in PD3. The delayed EASM progress shows its weakness in PD1 and PD3. While in PD2, EASM intensity weakens without affecting its northward progression. Aerosols, though affecting the position and intensity of Western Pacific Subtropical High, minimally influence its northward movement speed, hence no effect on the seasonal march of EASM in PD2.

The complete intestinal structure is important to ensure the rapid and h ealthy growth of fish. However, the feed composition, aquaculture water environment, intestinal microbial population, and other factors may affect the intestinal health of fish. Intestinal health problems caused by feed ingredients are mainly due to the antinutrient factors contained in raw materials. Antinutritional factors contained in high-level soybean meal can cause oxidative damage to the intestine, thus, inducing soybean meal-induced enteritis (SBMIE), which leads to a decreased appetite and the slow growth of fish. Alleviating the damage of soybean meal to the fish intestinal tract and improving intestinal health through nutrition are essential methods for ensuring the sustainable development of the feed industry, which has significant ecological and economic significance.As a functional amino acid, arginine is a precursor to the synthesis of bioactive substances, such as urea, glutamic acid, creatine, proline, polyamine, and nitric oxide. Arginine modulates metabolic regulation, including growth, immunity, intestinal barrier, and endocrine regulation. It plays a vital role in the immune regulation, maintenance, and protection of the intestinal mucosal structure and function. It has been reported that arginine is beneficial for repairing intestinal mucosal injury in poultry and aquatic animals. In this study, the carnivorous marine economic fish Sebastes schlegelii (54.97±0.12) g were used to investigate the repair effect and mechanism of arginine on SBMIE. This study aimed to provide a scientific basis for the application of arginine for maintaining the intestinal health of fish and provide a reference for the application of plant protein to the compound feed of the carnivorous economic fish S. schlegelii.The purpose of this study was to investigate the repairing effects of arginine on the growth performance, arginine metabolism, intestinal structure, antioxidant performance, relative expression levels of intestinal tight junction protein genes (occludin, clnd15, and zo-1), and inflammatory factor-related genes (il-1β, il-8, il-15, and tlr8) and anti-inflammatory factor-related gene (il-12b) of S. schlegelii with SBMIE. S. schlegelii were fed high-level soybean meal (40%) for 28 days to induce SBMIE. SBMIE-S. schlegelii weighing (54.97±0.12) g were used as the study animals. Four isonitrogen and isoenergetic experimental feeds were formulated. The basic formula was supplemented with 30% soybean meal, arginine 0 supplementation as the control group (D0), and 1%, 2%, and 3% arginine supplementation as the treatment groups, named D1, D2, and D3, respectively. Each diet group had three replicates, and each replicate consisted of 40 fish. The fish were randomly placed in 12 homemade cages (60 cm × 60 cm × 90 cm). The experiment lasted for 6 weeks. The experimental fish were fed twice a day (08:00 and 17:00), with the initial feeding amount being 1% of the body weight, and the feeding amount being adjusted according to the feeding situation. During the experiment, the bottom of the cages was cleaned, and the water was changed every day to maintain the water temperature at 18~22 ℃, the dissolved oxygen at > 6 mg/L, the pH at 7.6~8.2, the ammonia nitrogen content at < 0.05 mg/L, and the nitrite nitrogen content at < 0.05 mg/L. The light cycle was the natural cycle. The results showed that the weight gain rate of the fish in the D2 and D3 groups was significantly higher than that in D0 group (P < 0.05). The hepatosomatic and viscerosomatic indexes of the fish in the arginine treatment groups were significantly lower than those in the D0 group, and the condition factor was significantly higher than that in the D0 group (P < 0.05). There was no significant effect on the survival rate (P > 0.05). Diamine oxidase (DAO) activity, NO content, and iNOS activity values in the serum of the treatment groups were significantly lower than those in the D0 group (P < 0.05). The serum T-NOS activity in the D2 and D3 groups was significantly lower than that in the D0 group (P < 0.05). The duplicature height in the treatment groups was significantly higher than that in the D0 group, while no significant difference was found in the duplicature number and muscle thickness (P > 0.05). In group D0, the intestinal mucosa lamina propria widened, and the number of goblet cells increased, while in groups supplemented with arginine, the intestinal mucosa was intact, and the problems mentioned above improved significantly. Intestinal total antioxidant capacity (T-AOC) in arginine supplementation groups was significantly increased, and the highest value was found in group D2 (P < 0.05). The malondialdehyde content in groups D2 and D3 was decreased significantly compared to that in the D0 group (P < 0.05). The relative expression of occludin mRNA in each treatment group was significantly upregulated compared to that in the D0 group (P < 0.05). The relative expression level of clnd15 mRNA in the D2 group was significantly higher than that in the D0 and D1 groups (P < 0.05). The relative expression level of zo-1 mRNA in group D1 was significantly higher than that in the other groups (P < 0.05). The relative expression levels of IL-1β, IL-15, and TLR8 mRNA were downregulated in all treatment groups, while the relative expression of IL-12b mRNA was upregulated (P < 0.05). No significant differences were found in IL-8 mRNA relative expression (P > 0.05). In conclusion, under the conditions of this experiment, the growth and antioxidant performances of S. schlegelii with SBMIE were significantly increased, arginine metabolism and the intestinal structure were improved significantly, and the relative expression of intestinal tight junction protein and anti-inflammatory factor-related genes was upregulated, while that of inflammatory factor-related genes was downregulated, with arginine supplementation in a high-level soybean meal diet. Arginine (2% best) was effective in repairing SBMIE of S. schlegelii. The results of this study provide a theoretical basis for the mechanism of repairing SBMIE with arginine.

Abstract This study investigates the longitudinal dynamic changes in immune cells in COVID-19 patients over an extended period after recovery, as well as the interplay between immune cells and antibodies. Leveraging single-cell mass spectrometry, we selected six COVID-19 patients and four healthy controls, dissecting the evolving landscape within six months post-viral RNA clearance, alongside the levels of anti-spike protein antibodies. The T cell immunophenotype ascertained via single-cell mass spectrometry underwent validation through flow cytometry in 37 samples. Our findings illuminate that CD8 + T cells, gamma-delta (gd) T cells, and NK cells witnessed an increase, in contrast to the reduction observed in monocytes, B cells, and double-negative T (DNT) cells over time. The proportion of monocytes remained significantly elevated in COVID-19 patients compared to controls even after six-month. Subpopulation-wise, an upsurge manifested within various T effector memory subsets, CD45RA + T effector memory, gdT, and NK cells, whereas declines marked the populations of DNT, naive and memory B cells, and classical as well as non-classical monocytes. Noteworthy associations surfaced between DNT, gdT, CD4 + T, NK cells, and the anti-S antibody titer. This study reveals the changes in peripheral blood mononuclear cells of COVID-19 patients within 6 months after viral RNA clearance and sheds light on the interactions between immune cells and antibodies. The findings from this research contribute to a better understanding of immune transformations during the recovery from COVID-19 and offer guidance for protective measures against reinfection in the context of viral variants.

Abstract LHPP has been shown to be a new tumor suppressor, and has a tendency to be under-expressed in a variety of cancers. Oncolytic virotheray is a promising therapeutics for lung cancer in recent decade years. Here we successfully constructed a new recombinant oncolytic adenovirus GD55-LHPP and investigated the effect of GD55-LHPP on the growth of lung cancer cells in vitro and in vivo. The results showed that LHPP had lower expression in either lung cancer cells or clinical lung cancer tissues compared with normal cells or tissues, and GD55-LHPP effectively mediated LHPP expression in lung cancer cells. GD55-LHPP could effectively inhibit the proliferation of lung cancer cell lines and rarely affected normal cell growth. Mechanically, the oncolytic adenovirus GD55-LHPP was able to induce stronger apoptosis of lung cancer cells compared with GD55 through the activation of caspase signal pathway. Notably, GD55-LHPP also activated autophagy-related signal pathway. Further, GD55-LHPP efficiently inhibited tumor growth in lung cancer xenograft in mice and prolonged animal survival rate compared with the control GD55 or PBS. In conclusion, the novel construct GD55-LHPP provides a valuable strategy for lung cancer-targeted therapy and develop the role of tumor suppress gene LHPP in lung cancer gene therapy.

In this study, a passion fruit seed oil Pickering emulsion stabilized by β-lactoglobulin nanoparticles loaded with a ternary mixture of ferulic acid, quercetin and vanillic acid (β-LGCNPs) was prepared by an ultrasonic method. The particle size, stability, and microstructure, and antioxidant, digestibility, rheological properties and lipid oxidation products of Pickering emulsions prepared under varying conditions of nanoparticle concentration and oil phase ratio were investigated. The results showed that the Pickering emulsion was a stable oil-in-water (O/W) emulsion with β-LGCNPs adsorbed at the oil-water interface. The particle size of the emulsion was directly proportional to the particle concentration and inversely proportional to the oil phase ratio. The average particle size of the Pickering emulsion prepared at β-LGCNP concentration of 1.5% and 30% oil phase was (5.78 ± 0.10) μm. The emulsion had good stability under different ionic strength and pH conditions, showing stronger antioxidant properties than passion fruit seed oil. The free radical scavenging capacity was dependent on β-LGCNP concentration. After intestinal digestion for 2 h, the release rate of free fatty acids from the Pickering emulsion was (65.17 ± 1.52)%, which was 26.65% higher than that from passion fruit seed oil. The rheological results showed a shear-thinning phenomenon, indicating that the emulsion is a non-Newtonian fluid, and the elastic and viscous moduli increased with the increase in shear frequency. During 15 days of storage, the amount of lipid oxidation products including hydroperoxide and malondialdehyde (MDA), and the rate of lipid oxidation in the Pickering emulsion decreased. In summary, the Pickering emulsion stabilized with β-LGCNPs improved the stability, antioxidant activity, digestibility and lipid oxidation of passion fruit seed oil, which is conducive to expanding the application of passion fruit seed oil in the food field.

According to the abnormal fracture phenomenon of 87MnSi steel wire rod for bridge cable， the evolution of microstructure and mechanical properties during production processing were systematically analyzed. The results show that the microstructure of the rod is composed of pearlite and a small amount of proeutectoid ferrite， and the cementite lamellae are randomly distributed. After cold drawing， the cementite lamellae are rotated or fibrotic， and some cementite are broken and dissolved， the dissolution amount is 1.40wt.%（9.69%）. After ho-dip galvanizing， the dissolved cementite is spheroidized. In the process of cold drawing， hot-dip galvanizing and stabilization treatment， the microhardness of wire rod （329.8HV） increases （450.2HV） firstly， then decreases （447.9HV） and increases （474.8HV） finally. The cementite dissolved in the cold drawing process increases the hardness of the steel wire to 468.3HV， while the spheroidized cementite in the hot galvanizing process decreases the hardness to 439.8HV， and deteriorates tensile property. When the degree of spheroidization of cementite on the edge is obvious， the microstructure and mechanical properties of the steel wire inside and outside are greatly different， and the fracture is eventually caused by uneven force during stabilizing treatment.

In this paper, the active parts of sea cucumber (Apostichopus japonicus) with high antihypertensive activity were screened and the preparation process of active peptides was optimized. Different parts (body wall, intestine, and ovum) of A. japonicus were hydrolyzed by enzymolysis, and the ACE inhibition rate was used as an indicator to screen the optimal protease. The optimal active site for inhibition was selected by comparative screening of the half maximal inhibitory concentration (IC50) determination of ACE inhibitory rate of each lysate. Single factor and response surface tests were used to determine the optimum enzymatic hydrolysis conditions of the active peptides. The relative molecular weight of the protease hydrolysates was determined to determine its distribution range. The ACE inhibition activity of different components was analyzed after separation by ultrafiltration membrane. Search results, alkaline protease was selected as the optimal hydrolytic enzyme, and the IC50 values of ACE inhibition of each protease lysate from body wall, intestine and ovum were 1.11, 4.02, 0.65 mg/mL, respectively, so that A. japonicus ovum had a better ACE inhibition effect and were the optimal active site for inhibition. Its optimal preparation process parameters for enzymatic hydrolysis were as follows: 5 h enzymatic hydrolysis time, 3.5 U/mg enzyme added, 65.26 °C enzymatic hydrolysis temperature, 3.51% substrate concentration, pH9.02 enzymatic hydrolysis, and ACE inhibition rate of A. japonicusr ovum was 80.65%±0.52% under these conditions, which was close to the predicted value. The molecular weight of proteolytic products was concentrated under 3000 Da, accounting for 98.37% of the total content, of which 1000~3000 Da accounted for 9.50%, and less than 1000 Da accounted for 88.87%. The ACE inhibitory activity of oligopeptide components (IC50=0.30 mg/mL) isolated by ultrafiltration membrane was significantly higher than that of hydrolysates and trapped liquid components after process optimization. The results of this study would provide a theoretical basis for high-quality utilization of the by-products of A. japonicus, which could be used as high-quality resources for the isolation and purification of antihypertensive peptides.

Human milk oligosaccharides (HMOs) are key components of breast milk, playing a vital role in fostering the healthy development of infants and young children. Among the main HMOs components, 2′-fucosyllactose (2′-FL) and 3-fucosyllactose (3-FL) exhibit considerable benefits in terms of inhibiting pathogenic infections, regulating gut microbiota, and enhancing immunity. In recent years, the synthesis of 2′-FL and 3-FL has emerged as a prominent area of research in the field. Despite the potential advantages of chemical or enzymatic synthesis of 2′-FL and 3-FL, these methods are hindered by their inherent limitations, including intricate reaction procedures, high costs, and poor yield, which are not conducive to meeting the demand of the market. Therefore, more efficient microbial methods have been developed and applied in the commercial production of 2′-FL and 3-FL. This article systematically outlines the methods for preparing both 2′-FL and 3-FL, thoroughly expounds upon the engineering strategies for microbial synthesis of 2′-FL and 3-FL, and provides a compelling framework for further microbial production exploration of 2′-FL and 3-FL.

Abstract Background Osteocytes are critical mechanosensory cells in bone, and mechanically stimulated osteocytes produce exosomes that can induce osteogenesis. MicroRNAs (miRNAs) are important constituents of exosomes, and some miRNAs in osteocytes regulate osteogenic differentiation; previous studies have indicated that some differentially expressed miRNAs in mechanically strained osteocytes likely influence osteoblastic differentiation. Therefore, screening and selection of miRNAs that regulate osteogenic differentiation in exosomes of mechanically stimulated osteocytes are important. Results A mechanical tensile strain of 2500 με at 0.5 Hz 1 h per day for 3 days, elevated prostaglandin E2 (PGE2) and insulin-like growth factor-1 (IGF-1) levels and nitric oxide synthase (NOS) activity of MLO-Y4 osteocytes, and promoted osteogenic differentiation of MC3T3-E1 osteoblasts. Fourteen miRNAs differentially expressed only in MLO-Y4 osteocytes which were stimulated with mechanical tensile strain, were screened, and the miRNAs related to osteogenesis were identified. Four differentially expressed miRNAs (miR-1930-3p, miR-3110-5p, miR-3090-3p, and miR-3058-3p) were found only in mechanically strained osteocytes, and the four miRNAs, eight targeted mRNAs which were differentially expressed only in mechanically strained osteoblasts, were also identified. In addition, the mechanically strained osteocyte-derived exosomes promoted the osteoblastic differentiation of MC3T3-E1 cells in vitro, the exosomes were internalized by osteoblasts, and the up-regulated miR-3110-5p and miR-3058-3p in mechanically strained osteocytes, were both increased in the exosomes, which was verified via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Conclusions In osteocytes, a mechanical tensile strain of 2500 με at 0.5 Hz induced the fourteen differentially expressed miRNAs which probably were in exosomes of osteocytes and involved in osteogenesis. The mechanically strained osteocyte-derived exosomes which contained increased miR-3110-5p and miR-3058-3p (two of the 14 miRNAs), promoted osteoblastic differentiation.

We report a case of the meyerson phenomenon around cavernous hemangioma. A 23-year-old male presented with a dark purplish red nodule on the back for over 20 years, and pruritic annular erythema and papules with clear boundaries around the nodule for 1 day. Dermatological examination revealed a dark purplish red nodule about 0.7 cm in diameter on the back, encircled by a 1 cm diameter erythema with papules. Dermoscopic examination showed that several small purplish red cavities with clear boundaries and irregularly distributed dotted blood vessels on the skin lesion under the red background. The histopathology showed that the lesion was covered with squamous epithelium. Large irregular lumens, and sinusoids of different sizes contained red blood cells and fibrin in the superficial and deep dermis. The sinusoids were lined with a single layer of endothelial cells. The patient was diagnosed with the meyerson phenomenon around cavernous hemangioma. After surgical resection, the eczema-like dermatitis subsided. But hemangioma reoccurred without discomfort after more than 1 month. The patient is in follow-up.