SCPLPA: An miRNA-disease association prediction model based on spatial consistency projection and label propagation algorithm.

Identifying the association between miRNA and diseases is helpful for disease prevention, diagnosis and treatment. It is of great significance to use computational methods to predict potential human miRNA disease associations. Considering the shortcomings of existing computational methods, such as low prediction accuracy and weak generalization, we propose a new method called SCPLPA to predict miRNA-disease associations. First, a heterogeneous disease similarity network was constructed using the disease semantic similarity network and the disease Gaussian interaction spectrum kernel similarity network, while a heterogeneous miRNA similarity network was constructed using the miRNA functional similarity network and the miRNA Gaussian interaction spectrum kernel similarity network. Then, the estimated miRNA-disease association scores were evaluated by integrating the outcomes obtained by implementing label propagation algorithms in the heterogeneous disease similarity network and the heterogeneous miRNA similarity network. Finally, the spatial consistency projection algorithm of the network was used to extract miRNA disease association features to predict unverified associations between miRNA and diseases. SCPLPA was compared with four classical methods (MDHGI, NSEMDA, RFMDA and SNMFMDA), and the results of multiple evaluation metrics showed that SCPLPA exhibited the most outstanding predictive performance. Case studies have shown that SCPLPA can effectively identify miRNAs associated with colon neoplasms and kidney neoplasms. In summary, our proposed SCPLPA algorithm is easy to implement and can effectively predict miRNA disease associations, making it a reliable auxiliary tool for biomedical research.

Light-controlled soft bio-microrobot.

Micro/nanorobots hold exciting prospects for biomedical and even clinical applications due to their small size and high controllability. However, it is still a big challenge to maneuver micro/nanorobots into narrow spaces with high deformability and adaptability to perform complicated biomedical tasks. Here, we report a light-controlled soft bio-microrobots (called "Ebot") based on Euglena gracilis that are capable of performing multiple tasks in narrow microenvironments including intestinal mucosa with high controllability, deformability and adaptability. The motion of the Ebot can be precisely navigated via light-controlled polygonal flagellum beating. Moreover, the Ebot shows highly controlled deformability with different light illumination duration, which allows it to pass through narrow and curved microchannels with high adaptability. With these features, Ebots are able to execute multiple tasks, such as targeted drug delivery, selective removal of diseased cells in intestinal mucosa, as well as photodynamic therapy. This light-controlled Ebot provides a new bio-microrobotic tool, with many new possibilities for biomedical task execution in narrow and complicated spaces where conventional tools are difficult to access due to the lack of deformability and bio-adaptability.

Profiling DNA Cargos in Single Extracellular Vesicles via Hydrogel-Based Droplet Digital Multiple Displacement Amplification.

Due to the substantial heterogeneity among extracellular vesicle (EV) subpopulations, single-EV analysis has the potential to elucidate the mechanisms behind EV biogenesis and shed light on the myriad functions, leading to the development of novel diagnostics and therapeutics. While many studies have been devoted to reveal between-EV variations in surface proteins and RNAs, DNA cargos (EV-DNA) have received little attention. Here, we report a hydrogel-based droplet digital multiple displacement amplification approach for the comprehensive analysis of EV-DNA at the single-EV level. Single EVs are dispersed in thousands of hydrogel droplets and lysed for DNA amplification and identification. The droplet microfluidics strategy empowers the assay with single-molecule sensitivity and capability for absolute quantification of DNA-containing EVs. In particular, our findings indicate that 5-40% EVs are associated with DNA, depending on the cell of origin. Large EVs exhibit a higher proportion of DNA-containing EVs and a more substantial presence of intraluminal DNA, compared to small EVs. These DNA-containing EVs carry multiple DNA fragments on average. Furthermore, both double-stranded DNA and single-stranded DNA were able to be detected at the single-EV level. Utilizing this method, the abundance, distribution, and biophysical properties of EV-DNA in various EV populations are evaluated. The DNA level within EVs provides insight into the status of the originating cells and offers valuable information on the outcomes of anticancer treatments. The utilization of single-EV analysis for EV-DNA holds significant promise for early cancer detection and treatment response monitoring.

Glycobiology in osteoclast differentiation and function.

Glycans, either alone or in complex with glycan-binding proteins, are essential structures that can regulate cell biology by mediating protein stability or receptor dimerization under physiological and pathological conditions. Certain glycans are ligands for lectins, which are carbohydrate-specific receptors. Bone is a complex tissue that provides mechanical support for muscles and joints, and the regulation of bone mass in mammals is governed by complex interplay between bone-forming cells, called osteoblasts, and bone-resorbing cells, called osteoclasts. Bone erosion occurs when bone resorption notably exceeds bone formation. Osteoclasts may be activated during cancer, leading to a range of symptoms, including bone pain, fracture, and spinal cord compression. Our understanding of the role of protein glycosylation in cells and tissues involved in osteoclastogenesis suggests that glycosylation-based treatments can be used in the management of diseases. The aims of this review are to clarify the process of bone resorption and investigate the signaling pathways mediated by glycosylation and their roles in osteoclast biology. Moreover, we aim to outline how the lessons learned about these approaches are paving the way for future glycobiology-focused therapeutics.

Can Moving More and Sitting Less Improve the Academic Engagement of Adolescents?- A Study Based on Junior High School Students in Shanghai, China.

Purpose: The purpose of this study was to examine the relationships between academic engagement and moderate-to-vigorous physical activity (MVPA), muscle-strengthening exercise (MSE) and sedentary behavior (SB) among adolescents, so as to provide evidence from the perspective of exercising for students to learn efficiently, teachers to improve classroom teaching, and schools to improve educational quality. Methods: A questionnaire survey was conducted in 12 junior high schools in Shanghai, China, which were selected by a multi-stage stratified cluster sampling method. Then, with the valid data of 2078 students collected from the survey. A data analysis was performed using SPSS Statistics 26.0. Multiple linear regression models were adopted to analyze the factors affecting adolescent academic engagement and to determine whether MVPA, MSE, and SB play roles in it. Results: (1) The differences in academic engagement depended on the exercise adherence to the recommended amount of MVPA, MSE, and screen-based SB. (2) In terms of the three independent variables of total time, MSE (ß = 0.206) and MVPA (ß = 0.175) showed a significant positive correlation with academic engagement, while SB (ß = -0.155) was negatively correlated with academic engagement. (3) From the linear regression model of eight combination groups divided by the exercise adherence to the recommended amount of MVPA, MSE and SB, the group that met none of the recommendations (ß = -0.235) showed a significant negative effect on academic engagement, while the groups that met any two or all three of the recommendations demonstrated strong positive correlations with academic engagement (P < 0.001). Conclusion: Increasing adolescents' muscle-strengthening exercise and moderate-to-vigorous physical activity and reducing sedentary behavior can effectively promote academic engagement. Therefore, adolescents are suggested to reach the recommended amounts of physical activity, muscle-strengthening exercise, and sedentary behavior so as to improve academic engagement more effectively.

Socioeconomic status may affect association of vegetable intake with risk of ischemic cardio-cerebral vascular disease: a Mendelian randomization study.

Background: Previous studies found that increasing vegetable intake benefits are reduced after adjustment for socioeconomic factors. Using genetic variation as an instrumental variable for vegetable intake and socioeconomic status, we investigated the relationship between vegetable intake and ischemic cardio-cerebral vascular diseases and focused on whether socioeconomic status was a possible confounder. Methods: From three independent genome-wide association studies, we extracted instrumental variables reflecting raw and cooked vegetable intake, which were used to perform Mendelian randomization analysis. To evaluate the effects of socioeconomic factors on vegetable intake, univariate and multivariate Mendelian randomization analyses were performed using single nucleotide polymorphisms representing education attainment and household income reported in the literature. We also performed outlier assessment and a series of sensitivity analyses to confirm the results. Results: Genetically predicted raw and cooked vegetable intake were not associated with any ischemic cardio-cerebral vascular diseases and lipid components after Bonferroni correction. Univariate Mendelian randomized analysis revealed that raw vegetable intake was positively correlated with education attainment (ß = 0.04, p = 0.029) and household income (ß = 0.07, p < 0.001). Multivariate Mendelian randomized model showed a positive correlation between household income and raw vegetable intake (ß = 0.06, p = 0.004). Socioeconomic status was closely associated with eating habits and lifestyle related to the risk of cardiovascular diseases. Conclusion: Genetically determined raw and cooked vegetable intake was not associated with significant benefits in terms of ischemic cardio-cerebral vascular diseases while genetically determined socioeconomic status may have an impact on vegetable intake. Socioeconomic status, which was closely associated with other eating habits and lifestyle, may affect the association between vegetable intake and ischemic cardio-cerebral vascular diseases.

Butyrate Improves Porcine Endometrial Epithelial Cell Receptivity via Enhancing Acetylation of Histone H3K9.

SCOPE: Uterine receptivity is a major restriction of embryo implantation and survival, and the endometrial luminal epithelium serves as the transient gateway for uterine receptivity and embryo implantation. Butyrate is reported to promote the success of embryo implantation, but the effects and mechanism of butyrate on uterine receptivity are still unknown. METHODS AND RESULTS: Porcine endometrial epithelial cells (PEECs) are used as a model, and the cellular receptivity changes, metabolism, and gene expression profiles influenced by butyrate are analyzed. The study finds that butyrate improves receptive changes in PEECs, including inhibiting proliferation, exhibiting more pinocytosis on the cell surface, and increasing adhesiveness to porcine trophoblast cells. In addition, butyrate increases prostaglandin synthesis and markedly impacts purine metabolism, pyrimidine metabolism, and the FoxO signaling pathway. siRNA to inhibit the expression of FoxO1 and chromatin immunoprecipitation-sequencing (ChIP-seq) of H3K9ac are used to demonstrate that the H3K9ac/FoxO1/PCNA pathway can contribute to the effects of cell proliferation inhibition and uterine receptivity improvement induced by butyrate. CONCLUSION: The findings reveal that butyrate improves endometrial epithelial cell receptivity by enhancing the acetylation of histone H3K9, which shows nutritional regulation and therapeutic potential for poor uterine receptivity and difficulty in embryo implantation.

KATZNCP: a miRNA-disease association prediction model integrating KATZ algorithm and network consistency projection.

BACKGROUND: Clinical studies have shown that miRNAs are closely related to human health. The study of potential associations between miRNAs and diseases will contribute to a profound understanding of the mechanism of disease development, as well as human disease prevention and treatment. MiRNA-disease associations predicted by computational methods are the best complement to biological experiments. RESULTS: In this research, a federated computational model KATZNCP was proposed on the basis of the KATZ algorithm and network consistency projection to infer the potential miRNA-disease associations. In KATZNCP, a heterogeneous network was initially constructed by integrating the known miRNA-disease association, integrated miRNA similarities, and integrated disease similarities; then, the KATZ algorithm was implemented in the heterogeneous network to obtain the estimated miRNA-disease prediction scores. Finally, the precise scores were obtained by the network consistency projection method as the final prediction results. KATZNCP achieved the reliable predictive performance in leave-one-out cross-validation (LOOCV) with an AUC value of 0.9325, which was better than the state-of-the-art comparable algorithms. Furthermore, case studies of lung neoplasms and esophageal neoplasms demonstrated the excellent predictive performance of KATZNCP. CONCLUSION: A new computational model KATZNCP was proposed for predicting potential miRNA-drug associations based on KATZ and network consistency projections, which can effectively predict the potential miRNA-disease interactions. Therefore, KATZNCP can be used to provide guidance for future experiments.

Acoustic Atomization-Induced Pumping Based on a Vibrating Sharp-Tip Capillary.

Pumping is an essential component in many microfluidic applications. Developing simple, small-footprint, and flexible pumping methods is of great importance to achieve truly lab-on-a-chip systems. Here, we report a novel acoustic pump based on the atomization effect induced by a vibrating sharp-tip capillary. As the liquid is atomized by the vibrating capillary, negative pressure is generated to drive the movement of fluid without the need to fabricate special microstructures or use special channel materials. We studied the influence of the frequency, input power, internal diameter (ID) of the capillary tip, and liquid viscosity on the pumping flow rate. By adjusting the ID of the capillary from 30 µm to 80 µm and the power input from 1 Vpp to 5 Vpp, a flow rate range of 3 to 520 µL/min can be achieved. We also demonstrated the simultaneous operation of two pumps to generate parallel flow with a tunable flow rate ratio. Finally, the capability of performing complex pumping sequences was demonstrated by performing a bead-based ELISA in a 3D-printed microdevice.

Corrigendum to "Point-of-care testing for lysine concentration in swine serum via blue-emissive carbon dots entrapped microfluidic chip" [Animal Nutrition 12 (2023) 236-244].

[This corrects the article DOI: 10.1016/j.aninu.2022.08.017.].

LRP1B mutation is associated with tumor immune microenvironment and progression-free survival in lung adenocarcinoma treated with immune checkpoint inhibitors.

Background: Only a fraction of lung adenocarcinoma (LUAD) patients are eligible for immunotherapy. The identification of biomarkers for immunotherapy is crucial to improve patient outcomes. This study aims to systemically analyze LRP1B mutation and its association with the tumor immune microenvironment (TIME) and immunotherapy. Methods: A cohort of immune checkpoint inhibitors (ICIs)-treated LUAD patients was analyzed to assess the association of LRP1B mutation with immunotherapy prognosis. Another cohort of LUAD patients with genetic and transcriptomic data was also obtained from The Cancer Genome Atlas (TCGA). By investigating the ICIs and the TCGA-LUAD cohorts, we compared the differences in mutation profiles, immunogenicity, TIME, and DNA damage repair (DDR) mutations between the LRP1B-mutated and LRP1B wild-type groups. Additionally, we performed multiplex immunohistochemistry (mIHC) to validate the differences in the tumor microenvironment. Results: Our results revealed that LRP1B mutation is associated with multiple immune-related pathways. Analysis of TIME indicated that LUAD patients with LRP1B mutation expressed significant levels of genes involved in antigen presentation, cytotoxicity, chemokines, and pro-inflammatory mediators, whereas a few immune checkpoint genes were highly expressed in the LRP1B-mutated group as well. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) analysis indicated that LRP1B-mutated LUAD patients had higher infiltration of active immune cells. Multiplex IHC analysis showed that LRP1B-mutated LUAD patients had elevated programmed death ligand-1 (PD-L1) expression and immune cell infiltration. Patients with LRP1B mutation had higher tumor mutation burden, neoantigens, as well as more mutated genes in the DDR-related pathways. Finally, LRP1B-mutated LUAD patients showed a significant prolongation of progression-free survival (PFS) in the ICIs cohort and could be effectively predicted by our constructed nomogram. Conclusions: Our study suggests that LRP1B mutation is associated with higher immune cell infiltration and elevated immune gene expression in TIME and potentially serves as a prognostic biomarker for LUAD patients treated with ICIs.

Three tyrosine kinase inhibitors cause cardiotoxicity by inducing endoplasmic reticulum stress and inflammation in cardiomyocytes.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are anti-cancer therapeutics often prescribed for long-term treatment. Many of these treatments cause cardiotoxicity with limited cure. We aim to clarify molecular mechanisms of TKI-induced cardiotoxicity so as to find potential targets for treating the adverse cardiac complications. METHODS: Eight TKIs with different levels of cardiotoxicity reported are selected. Phenotypic and transcriptomic responses of human cardiomyocytes to TKIs at varying doses and times are profiled and analyzed. Stress responses and signaling pathways that modulate cardiotoxicity induced by three TKIs are validated in cardiomyocytes and rat hearts. RESULTS: Toxicity rank of the eight TKIs determined by measuring their effects on cell viability, contractility, and respiration is largely consistent with that derived from database or literature, indicating that human cardiomyocytes are a good cellular model for studying cardiotoxicity. When transcriptomes are measured for selected TKI treatments with different levels of toxicity in human cardiomyocytes, the data are classified into 7 clusters with mainly single-drug clusters. Drug-specific effects on the transcriptome dominate over dose-, time- or toxicity-dependent effects. Two clusters with three TKIs (afatinib, ponatinib, and sorafenib) have the top enriched pathway as the endoplasmic reticulum stress (ERS). All three TKIs induce ERS in rat primary cardiomyocytes and ponatinib activates the IRE1α-XBP1s axis downstream of ERS in the hearts of rats underwent a 7-day course of drug treatment. To look for potential triggers of ERS, we find that the three TKIs induce transient reactive oxygen species followed by lipid peroxidation. Inhibiting either PERK or IRE1α downstream of ERS blocks TKI-induced cardiac damages, represented by the induction of cardiac fetal and pro-inflammatory genes without causing more cell death. CONCLUSIONS: Our data contain rich information about phenotypic and transcriptional responses of human cardiomyocytes to eight TKIs, uncovering potential molecular mechanisms in modulating cardiotoxicity. ER stress is activated by multiple TKIs and leads to cardiotoxicity through promoting expression of pro-inflammatory factors and cardiac fetal genes. ER stress-induced inflammation is a promising therapeutic target to mitigate ponatinib- and sorafenib-induced cardiotoxicity.

Relationship between the Depth of Acetabuloplasty and Outcomes of Hip Arthroscopy in Patients with Global Pincer Femoroacetabular Impingement: Study with a Minimum Follow-Up Period of 2 Years.

OBJECTIVE: There has been no definite consensus on the ideal depth of acetabuloplasty, especially in cases of global pincer femoroacetabular impingement (FAI). This study aims to determine whether the depth of acetabuloplasty influences postoperative outcomes in cases of global pincer FAI. METHODS: Data were retrospectively collected from patients with global pincer FAI who underwent hip arthroscopy with a minimum follow-up period of 2 years from May 2014 to December 2018. Patients with global pincer FAI were subdivided into low or high resection depth groups based on whether the intraoperative acetabular rim was resected by more than 3 mm. Radiographic measurements; arthroscopic procedures; preoperative and postoperative PROs were recorded. Achievement of MCID and PASS was compared for the VAS, mHHS, HOS-ADL, and iHOT-12. A paired Student t-test was used to evaluate the significance of preoperative and postoperative PROs and two-tailed unpaired Student t-test was used to compare demographic data and PROs between different groups. MCID and PASS were evaluated using the chi-square test or the Fisher's exact test. RESULTS: A total of 41 hips with global pincer FAI (15 and 26 patients in low or high resection depth groups, respectively) were included in this study. Both groups showed significant postoperative improvements in the scores of all PROs (p < 0.001). Compared to the low resection depth group, the high resection depth group had a lower degree of improvement through hip arthroscopy, which manifested as lower postoperative mHHS scores (94.29 vs. 85.08, p = 0.006), higher VAS scores (0.93 vs. 2.54, p = 0.002), and lower improvements in VAS (-5.00 vs. -3.35, p = 0.028), HOS-ADL (34.99 vs. 23.90, p = 0.017) and iHOT-12 (39.89 vs. 29.27, p = 0.036). Patients in high resection depth group were less likely to achieve the MCID for the VAS score compared to low resection depth group in significant (73.3 vs. 26.9%, p = 0.004). CONCLUSIONS: For patients with global pincer, the outcomes in high resection depth group were slightly worse than the the low resection depth group. It is indicated that excessive resection of the acetabular rim during the procedure should be avoided.

Wake-Riding Effect-Inspired Opto-Hydrodynamic Diatombot for Non-Invasive Trapping and Removal of Nano-Biothreats.

Contamination of nano-biothreats, such as viruses, mycoplasmas, and pathogenic bacteria, is widespread in cell cultures and greatly threatens many cell-based bio-analysis and biomanufacturing. However, non-invasive trapping and removal of such biothreats during cell culturing, particularly many precious cells, is of great challenge. Here, inspired by the wake-riding effect, a biocompatible opto-hydrodynamic diatombot (OHD) based on optical trapping navigated rotational diatom (Phaeodactylum tricornutum Bohlin) for non-invasive trapping and removal of nano-biothreats is reported. Combining the opto-hydrodynamic effect and optical trapping, this rotational OHD enables the trapping of bio-targets down to sub-100 nm. Different nano-biothreats, such as adenoviruses, pathogenic bacteria, and mycoplasmas, are first demonstrated to be effectively trapped and removed by the OHD, without affecting culturing cells including precious cells such as hippocampal neurons. The removal efficiency is greatly enhanced via reconfigurable OHD array construction. Importantly, these OHDs show remarkable antibacterial capability, and further facilitate targeted gene delivery. This OHD serves as a smart micro-robotic platform for effective trapping and active removal of nano-biothreats in bio-microenvironments, and especially for cell culturing of many precious cells, with great promises for benefiting cell-based bio-analysis and biomanufacturing.

Associations between maternal exposure to ambient air pollution and very low birth weight: A birth cohort study in Chongqing, China.

Introduction: There have been many researches done on the association between maternal exposure to ambient air pollution and adverse pregnancy outcomes, but few studies related to very low birth weight (VLBW). This study thus explores the association between maternal exposure to ambient air pollutants and the risk of VLBW, and estimates the sensitive exposure time window. Methods: A retrospective cohort study analyzed in Chongqing, China, during 2015-2020. The Generalized Additive Model were applied to estimate exposures for each participant during each trimester and the entire pregnancy period. Results: For each 10 µg/m3 increase in PM2.5 during pregnancy, the relative risk of VLBW increased on the first trimester, with RR = 1.100 (95% CI: 1.012, 1.195) in the single-pollutant model. Similarly, for each 10 µg/m3 increase in PM10, there was a 12.9% (RR = 1.129, 95% CI: 1.055, 1.209) increase for VLBW on the first trimester in the single-pollutant model, and an 11.5% (RR = 1.115, 95% CI: 1.024, 1.213) increase in the multi-pollutant model, respectively. The first and second trimester exposures of NO2 were found to have statistically significant RR values for VLBW. The RR values on the first trimester were 1.131 (95% CI: 1.037, 1.233) and 1.112 (95% CI: 1.015, 1.218) in the single-pollutant model and multi-pollutant model, respectively; The RR values on the second trimester were 1.129 (95% CI: 1.027, 1.241) and 1.146 (95% CI: 1.038, 1.265) in the single-pollutant model and multi-pollutant model, respectively. The RR of O3 exposure for VLBW on the entire trimester was 1.076 (95% CI: 1.010-1.146), and on the second trimester was 1.078 (95% CI: 1:016, 1.144) in the single-pollutant model. Conclusion: This study indicates that maternal exposure to high levels of PM2.5, PM10, NO2, and O3 during pregnancy may increase the risk of very low birth weight, especially for exposure on the first and second trimester. Reducing the risk of early maternal exposure to ambient air pollution is thus necessary for pregnant women.

A pharmacokinetic model based on the SSA-1DCNN-Attention method.

To solve the problem of the lack of representativeness of the training set and the poor prediction accuracy due to the limited number of training samples when the machine learning method is used for the classification and prediction of pharmacokinetic indicators, this paper proposes a 1DCNN-Attention concentration prediction model optimized by the sparrow search algorithm (SSA). First, the SMOTE method is used to expand the small sample experimental data to make the data diverse and representative. Then a one-dimensional convolutional neural network (1DCNN) model is established, and the attention mechanism is introduced to calculate the weight of each variable for dividing the importance of each pharmacokinetic indicator by the output drug concentration. The SSA algorithm was used to optimize the parameters in the model to improve the prediction accuracy after data expansion. Taking the pharmacokinetic model of phenobarbital (PHB) combined with Cynanchum otophyllum saponins to treat epilepsy as an example, the concentration changes of PHB were predicted and the effectiveness of the method was verified. The results show that the proposed model has a better prediction effect than other methods.

Significance of CD80 as a Prognostic and Immunotherapeutic Biomarker in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is the primary cause of death among pulmonary cancer patients. Upregulation of CD80 may interact with cytotoxic T lymphocyte antigen 4 (CTLA4) to promote tumor progression and provide a potential target for biological antitumor therapy. However, the role of CD80 in LUAD is still unclear. To investigate the function of CD80 in LUAD, we collected transcriptomic data from 594 lung samples from The Cancer Genome Atlas of America (TCGA) database, along with the corresponding clinical information. We systematically explored the role of CD80 in LUAD using bioinformatics methods, including GO enrichment analysis, KEGG pathway analysis, Gene Set Enrichment Analysis (GSEA), co-expression analysis, and the CIBERSORT algorithm. Finally, we investigated the differences between the two subgroups of CD80 expression in terms of some drug sensitivity, using the pRRophetic package to screen small molecular drugs for therapeutic use. A predictive model based on CD80 for LUAD patients was successfully constructed. In addition, we discovered that the CD80-based prediction model was an independent prognostic factor. Co-expression analysis revealed 10 CD80-related genes, including oncogenes and immune-related genes. Functional analysis showed that the differentially expressed genes in patients with high CD80 expression were mainly located in immune-related signaling pathways. CD80 expression was also associated with immune cell infiltration and immune checkpoints. Highly expressing patients were more sensitive to several drugs, such as rapamycin, paclitaxel, crizotinib, and bortezomib. Finally, we found evidence that 15 different small molecular drugs may benefit the treatment of LUAD patients. This study found that elevated CD80 pairs could improve the prognosis of LUAD patients. CD80 is likely to be a potential as a prognostic and therapeutic target. The future use of small molecular drugs in combination with immune checkpoint blockade to enhance antitumor therapy and improve prognosis for LUAD patients is promising.

The short-term effects of air pollution exposure on preterm births in Chongqing, China: 2015-2020.

Accumulating evidence suggested that the risk of preterm births (PTBs) following prenatal exposure to air pollution was inconclusive. The aim of this study is to investigate the relationship between air pollution exposure in the days before delivery and PTB and assess the threshold effect of short-term prenatal exposure to air pollution on PTB. This study collected data including meteorological factors, air pollutants, and information in Birth Certificate System from 9 districts during 2015-2020 in Chongqing, China. Generalized additive models (GAMs) with the distributed lag non-linear models were conducted to assess the acute impact of air pollutants on the daily counts of PTB, after controlling for potential confounding factors. We observed that PM2.5 was related to increased occurrence of PTB on lag 0-3 and lag 10-21 days, with the strongest on the first day (RR = 1.017, 95%CI: 1.000-1.034) and then decreasing. The thresholds of PM2.5 for lag 1-7 and 1-30 days were 100 µg/m3 and 50 µg/m3, respectively. The lag effect of PM10 on PTB was very similar to that of PM2.5. In addition, the lagged and cumulative exposure of SO2 and NO2 was also associated with the increased risk of PTB. The lag relative risk and cumulative relative risk of CO exposure were the strongest, with a maximum RR at lag 0 (RR = 1.044, 95%CI: 1.018, 1.069). Importantly, the exposure-response curve of CO showed that RR increased rapidly when the concentration exceeded 1000 µg/m3. This study indicated significant associations between air pollution and PTB. The relative risk decreases with day lag, while the cumulative effect increases. Thus, pregnant women should understand the risk of air pollution and try to avoid high concentration exposure.

Point-of-care testing for lysine concentration in swine serum via blue-emissive carbon dot-entrapped microfluidic chip.

Lysine is one of the essential amino acids and plays a vital role in the growth, development and health of pigs. Blood lysine concentration is a direct indication of lysine status; however, current methods can not satisfy the demands for rapid and on-site lysine concentration measurement of swine serum. Here, we developed blue-emissive nitrogen-doped carbon dots as a fluorescence probe for the determination of lysine with high fluorescence quantum yield, stability, sensitivity and specificity. The carbon dots were entrapped within hydrogel microstructures to fabricate microfluidic chips for rapid assay for lysine quantification. We further developed an imaging attachment to integrate the microfluidic chip and a smartphone into a portable point-of-care testing platform. This platform requires only 3 µL sample and has a linear detection range of 25 to 300 µmol/L with a limit of detection less than 16 µmol/L, which covers the normal range of lysine concentration in swine serum. We tested lysine concentration in swine serum using this platform with high accuracy, low sample consumption, and within 3 min. Together, these results may provide a rapid and portable platform for dynamic monitoring of swine lysine status and contribute to precise feed formula modulation with low-protein diet strategy.

The Cartilage Protective Effect of Labrum Reconstruction Using Meniscus Allograft Compared with Labrum Resection in a Porcine Model.

PURPOSE: This study aimed to verify the femoral head cartilage protective effect of labral reconstruction in a porcine model. METHODS: Twelve pigs (24 hips) were divided into 3 groups: labrum defect group, lateral meniscus (LM) allograft group, and LM allograft wrapped with acellular peritoneum matrix (LM-APM) group before undergoing bilateral hip surgery. The pigs were sacrificed at 12 and 24 weeks postoperatively, while the femoral head cartilage was retrieved and then subjected to imaging measurement, macroscopic observations, and biomechanical and histological assessment. RESULTS: Imaging measurement and macroscopic observations revealed that the defect area of the labrum was filled in LM and LM-APM allograft groups after 24 weeks, whereas the labrum defect remained at 24 weeks in the control group. The femoral head cartilage corresponding to the area of labral resection in the labral defect group had worse macroscopic Osteoarthritis Research Society International (OARSI) scores, uneven and discontinuous cartilage on hematoxylin and eosin (H&E) staining and Safranin O staining, decreased histopathology OARSI Osteoarthritis Cartilage Histopathology Assessment System (OOCHAS) scores, and decreased elastic modulus and hardness at 12 and 24 weeks after surgery compared with the meniscus allograft groups. CONCLUSION: This study demonstrated that the LM allograft with or without APM for labral reconstruction had a chondroprotective effect on the femoral head in a porcine model.