Effects of yeast inoculation methods on caproic acid production and microbial community during anaerobic fermentation of Chinese cabbage waste.

To provide a sufficient supply of electron donors for the synthesis of caproic acid, yeast fermentation was employed to increase ethanol production in the anaerobic fermentation of Chinese cabbage waste (CCW). The results showed that the caproic acid yield of CCW with ethanol pre-fermentation was 7750.3 mg COD/L, accounting for 50.2% of the total volatile fatty acids (TVFAs), which was 32.5% higher than that of the CCW without yeast inoculation. The synchronous fermentation of yeast and seed sludge significantly promoted the growth of butyric acid consuming bacterium Bacteroides, resulting in low yields of butyric acid and caproic acid. With yeast inoculation, substrate competition for the efficient ethanol conversion in the early stage of acidogenic fermentation inhibited the hydrolysis and acidfication. Without yeast inoculation, the rapid accumulation of TVFAs severely inhibited the growth of Bacteroidetes. In the reactor with ethanol pre-fermentation, the key microorganism for caproic acid production, Clostridium_sensu_stricto_12, was selectively enriched.

Novel annual nitrogen management strategy improves crop yield and reduces greenhouse gas emissions in wheat-maize rotation systems under limited irrigation.

Excessive irrigation and nitrogen application have long seriously undermined agricultural sustainability in the North China Plain (NCP), leading to declining groundwater tables and intensified greenhouse gas (GHG) emissions. Developing low-input management practices that meet the growing food demand while reducing environmental costs is urgently needed. Here, we developed a novel nitrogen management strategy for a typical winter wheat-summer maize rotation system in the NCP under limited irrigation (wheat sowing irrigation only (W0) or sowing and jointing irrigation (W1)) and low nitrogen input (360 kg N ha-1, about 70 % of traditional annual nitrogen input). Novel nitrogen management strategy promoted efficient nitrogen fertilizer uptake and utilization by both crops via optimization of nitrogen fertilizer allocation between the two crops, i.e., increasing nitrogen inputs to wheat (from 180 to 240 kg N ha-1) while reducing nitrogen inputs to maize (from 180 to 120 kg N ha-1). Three-year field study demonstrated that integrated management practices combining novel nitrogen management strategy with limited irrigation increased annual yields and PFPN by 1.9-5.7 %, and reduced TGE by 55-68 kg CO2-eq ha-1 and GHGI by 2.2-10.3 %, without any additional cost. Our results provide agricultural operators and policymakers with practical and easy-to-scalable integrated management strategy, and offer key initiative to promote grain production in the NCP towards agriculture sustainable intensification with high productivity and efficiency, water conservation and emission reduction.

Pharmacokinetics of 4-Hydroxybenzaldehyde in Normal and Cerebral Ischemia-Reperfusion Injury Rats Based on Microdialysis Technique.

AIM: 4-Hydroxybenzaldehyde (4-HBd) is used for the treatment of headaches, dizziness, and convulsions. The objective of this study was to characterize the pharmacokinetics of 4-HBd in cerebral ischemia-reperfusion injury (CIRI) rats by microdialysis technology with high-performance liquid chromatography with diode-array detection (HPLC-DAD) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). METHODS: Microdialysis was used to collect blood, feces, and urine of normal and CIRI model rats. Pharmacokinetic parameters were determined using HPLC-DAD and 4-HBd metabolites were determined using UPLC-MS. RESULTS: After gavage of 4-HBd in normal and middle cerebral artery occlusion/reperfusion (MCAO/R) rats, it was widely distributed to all tissues (heart, liver, spleen, lung, kidney, and brain) in both the equilibrium and elimination phases, and the distribution pattern was basically the same; the highest concentration was found in the brain. The absolute bioavailability of 4-HBd was 5.33%; however, after intragastric administration in normal and MCAO/R rats, fecal and urinary excretion of 4-HBd accounted for 0.02% and 0.01% and for 0.01% and 0.03% of the dosage, respectively. Furthermore, 4-HBd was rapidly metabolized into 4-hydroxybenzoic acid (4-HBA) after administration in both the control and MCAO/R groups. Compared with the control, the peak time of 4-HBd plasma concentration in the MCAO/R rats decreased from 10.67 min to 8.83 min, the area under the concentration-time curve decreased significantly, and the half-life increased from 31.81 min to 78.85 min. CONCLUSIONS: The rapid absorption and low absolute bioavailability of 4-HBd by gavage in rats are followed by rapid and wide distribution to various tissues and organs, including the brain. The prototype drug is excreted in the feces and urine in low amounts, and it is metabolized to 4-HBA in large amounts in vivo; the pathological state of the MCAO/R model mainly affects its absorption degree and metabolism rate.

Risk Factors for Short-Term and Long-Term Low Back Pain After Transforaminal Endoscopic Lumbar Discectomy.

Introduction: Low back pain following transforaminal endoscopic lumbar discectomy (TELD) is prevalent (15-25% incidence). Modifying TELD techniques to avoid excessive disc removal has been suggested to reduce such pain. Facet injury, re-herniation, and disc space collapse might contribute. This retrospective study aimed to explore factors linked to post-TELD low back pain. Methods: A total of 351 patients with L3/4, L4/5, and L5/S1 intervertebral lumbar disc herniations, who underwent TELD at two spine centers, were included. Patients were followed for one year. Low back and leg pain visual analogue scale (VAS) scores, Oswestry Disability Index (ODI), Pfirrmann grade, and disc height were measured at 3 months and 1 year. Correlation analyses examined links between postoperative low back pain VAS scores, age, sex, disc/vertebrae height ratio (D/V H ratio), Pfirrmann grade, cannula position grade, re-herniation grade, high-intensity zone (HIZ), disc calcification, surgical grade, and other factors. Significant variables were identified using partial least square tests, with variable importance in projection (VIP) values quantifying their impact on low back pain. Results: Univariate analysis indicated that surgical grade correlated with long-term postoperative low back pain (P = 0.023), while re-herniation (P = 0.008, P = 0.000), disc height (P = 0.001, P = 0.034), and sex (P = 0.025, P = 0.003) correlated with both short- and long-term postoperative low back pain. Trephine/cannula position is correlated with short-term low back pain (P = 0.036). Worsening low back pain was associated with female sex, improper trephine/cannula position, re-herniation, and post-surgical disc space collapse. Intradiscal irrigation was linked to decreased low back pain. Discussion: This study highlights factors influencing low back pain after TELD. Loss of disc height, extent of re-herniation, quality of trephine/cannula position, and sex were associated with low back pain at both 3 months and 1-year post-TELD. Proper techniques, like minimizing disc height loss and re-herniation, may help mitigate postoperative low back pain.

Sodium Butyrate Induces Mitophagy and Apoptosis of Bovine Skeletal Muscle Satellite Cells through the Mammalian Target of Rapamycin Signaling Pathway.

Sodium butyrate (NaB) is one of the short-chain fatty acids and is notably produced in large amounts from dietary fiber in the gut. Recent evidence suggests that NaB induces cell proliferation and apoptosis. Skeletal muscle is rich in plenty of mitochondrial. However, it is unclear how NaB acts on host muscle cells and whether it is involved in mitochondria-related functions in myocytes. The present study aimed to investigate the role of NaB treatment on the proliferation, apoptosis, and mitophagy of bovine skeletal muscle satellite cells (BSCs). The results showed that NaB inhibited proliferation, promoted apoptosis of BSCs, and promoted mitophagy in a time- and dose-dependent manner in BSCs. In addition, 1 mM NaB increased the mitochondrial ROS level, decreased the mitochondrial membrane potential (MMP), increased the number of autophagic vesicles in mitochondria, and increased the mitochondrial DNA (mtDNA) and ATP level. The effects of the mTOR pathway on BSCs were investigated. The results showed that 1 mM NaB inhibited the mRNA and protein expression of mTOR and genes AKT1, FOXO1, and EIF4EBP1 in the mTOR signaling pathway. In contrast, the addition of PP242, an inhibitor of the mTOR signaling pathway also inhibited mRNA and protein expression levels of mTOR, AKT1, FOXO1, and EIF4EBP1 and promoted mitophagy and apoptosis, which were consistent with the effect of NaB treatment. NaB might promote mitophagy and apoptosis in BSCs by inhibiting the mTOR signaling pathway. Our results would expand the knowledge of sodium butyrate on bovine skeletal muscle cell state and mitochondrial function.

Association between host nitrogen absorption and root-associated microbial community in field-grown wheat.

Plant roots and rhizosphere soils assemble diverse microbial communities, and these root-associated microbiomes profoundly influence host development. Modern wheat has given rise to numerous cultivars for its wide range of ecological adaptations and commercial uses. Variations in nitrogen uptake by different wheat cultivars are widely observed in production practices. However, little is known about the composition and structure of the root-associated microbiota in different wheat cultivars, and it is not sure whether root-associated microbial communities are relevant in host nitrogen absorption. Therefore, there is an urgent need for systematic assessment of root-associated microbial communities and their association with host nitrogen absorption in field-grown wheat. Here, we investigated the root-associated microbial community composition, structure, and keystone taxa in wheat cultivars with different nitrogen absorption characteristics at different stages and their relationships with edaphic variables and host nitrogen uptake. Our results indicated that cultivar nitrogen absorption characteristics strongly interacted with bacterial and archaeal communities in the roots and edaphic physicochemical factors. The impact of host cultivar identity, developmental stage, and spatial niche on bacterial and archaeal community structure and network complexity increased progressively from rhizosphere soils to roots. The root microbial community had a significant direct effect on plant nitrogen absorption, while plant nitrogen absorption and soil temperature also significantly influenced root microbial community structure. The cultivar with higher nitrogen absorption at the jointing stage tended to cooperate with root microbial community to facilitate their own nitrogen absorption. Our work provides important information for further wheat microbiome manipulation to influence host nitrogen absorption. KEY POINTS: • Wheat cultivar and developmental stage affected microbiome structure and network. • The root microbial community strongly interacted with plant nitrogen absorption. • High nitrogen absorption cultivar tended to cooperate with root microbiome.

Classification of cervical disc herniation myelopathy or radiculopathy: a magnetic resonance imaging-based analysis.

Background: Preoperative magnetic resonance imaging (MRI) can clearly show the location and level of disc herniation. When the symptoms are consistent with the Prominent segments, surgical treatment can be indicated. However, the varied extents of the protruding masses in cervical disc herniation (CDH) have been rarely reported. This study aimed to characterize the severity of CDH and to develop a reproducible grading and zoning system for cervical disc degeneration. Methods: A total of 200 patients who presented with single CDH and underwent MRI/computed tomography (CT) scans were enrolled in this prospective study between 2018 and 2021. A total of 170 cervical discs were graded according to MRI by 3 spine surgeons in a blinded fashion. CDHs were graded 1-3, with regions A-C. All patients with grade 1 and mild C symptoms were excluded. The foramen facet spinal (FFS) classification based on MRI Japanese Orthopedic Association (JOA) scores and the incidence of complications were evaluated and analyzed, and follow-up outcomes were assessed. Results: Areas 2-A, 2-B, and 1-C had high motor function scores, areas 2-A, 3-A, and 2-AB had high sensory scores, but areas 3-AB and 3-A had low bladder function scores. Areas 3-AB had the most severe symptoms and the lowest scores. Area 1-C showed neurogenic abnormal sensation and higher visual analog scale (VAS) scores. A good/excellent outcome as indicated by the JOA score was 94.70% at 3 months and 92.35% at 1 year in 170 patients. The complication rate was 9.41%. The diagnostic coefficient of the FFS classification was 0.888, P<0.001. Conclusions: The FFS classification is an objective scoring system that can be applied similarly by multiple examiners and is correlated with clinical symptoms.

Magnetic Resonance Imaging-CCCFLS Scoring System: Toward Predicting Clinical Symptoms and C5 Paralysis.

STUDY DESIGN: A retrospective study. OBJECTIVE: To develop a new MRI scoring system to assess patients' clinical characteristics, outcomes and complications. METHODS: A retrospective 1-year follow-up study of 366 patients with cervical spondylosis from 2017 to 2021. The CCCFLS scores (cervical curvature and balance (CC), spinal cord curvature (SC), spinal cord compression ratio (CR), cerebrospinal fluid space (CFS). Spinal cord and lesion location (SL). Increased Signal Intensity (ISI) were divided into Mild group (0-6), Moderate group (6-12), and Severe group (12-18) for comparison, and the Japanese Orthopaedic Association (JOA) scores, visual analog scale (VAS), numerical rating scale (NRS), Neck Disability Index (NDI) and Nurick scores were evaluated. Correlation and regression analyses were performed between each variable and the total model in relation to clinical symptoms and C5 palsy. RESULTS: The CCCFLS scoring system was linearly correlated with JOA, NRS, Nurick and NDI scores, with significant differences in JOA scores among patients with different CC, CR, CFS, ISI scores, with a predictive model (R2 = 69.3%), and significant differences in preoperative and final follow-up clinical scores among the 3 groups, with a higher rate of improvement in JOA in the severe group (P < .05), while patients with and without C5 paralysis had significant differences in preoperative SC and SL (P < .05). CONCLUSIONS: CCCFLS scoring system can be divided into mild (0-6). moderate (6-12), severe (12-18) groups. It can effectively reflect the severity of clinical symptoms, and the improvement rate of JOA is better in the severe group, while the preoperative SC and SL scores are closely related to C5 palsy. LEVEL OF EVIDENCE: III.

SNHG 12 and hsa-miR-140-5P may play an important role in the ceRNA network related to hypertrophic cardiomyopathy.

Background: Competing endogenous RNA (ceRNA) networks play important roles in the mechanism and development of a variety of diseases. This study aimed to construct a ceRNA network of hypertrophic cardiomyopathy (HCM). Methods: We searched the Gene Expression Omnibus (GEO) database and then analyzed the RNAs of 353 samples to explore differentially expressed lncRNAs (DELs), microRNAs (miRNAs; DEMs), and messenger RNAs (DEmRNAs) during the progression of HCM. Weighted gene co-expression network analysis (WGCNA), Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and transcription factor (TF) prediction of miRNAs were also performed, and the GO terms, KEGG pathway terms, protein-protein interaction (PPI) network, and Pearson correlation network of the DEGs were visualized with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and through Pearson analysis. In addition, a ceRNA network related to HCM was constructed on the basis of the DELs, DEMs, and DEs. Finally, the function of the ceRNA network was explored via GO and KEGG enrichment analyses. Results: Through our analysis, 93 DELs (77 upregulated and 16 downregulated), 163 DEMs (91 upregulated and 72 downregulated), and 432 DEGs (238 upregulated and 194 downregulated) were screened. The functional enrichment analysis results for miRNAs showed that the miRNAs were mainly related to the VEGFR signaling network and the INFr pathway and were mainly regulated by TFs such as SOX1, TEAD1, and POU2F1. Gene set enrichment analysis (GSEA), GO analysis, and KEGG enrichment analysis showed that the DEGs were enriched in the Hedgehog signaling pathway, IL-17 signaling pathway, and TNF signaling pathway. In addition, a ceRNA network including 8 lncRNAs (e.g., LINC00324, SNHG12, and ALMS1-IT1), 7 miRNAs (e.g., hsa-miR-217, hsa-miR-184, and hsa-miR-140-5p), and 52 mRNAs (e.g., IGFBP5, TMED5, and MAGT1) was constructed. The results revealed that SNHG12, hsa-miR-140-5p, hsa-miR-217, TFRC, HDAC4, TJP1, IGFBP5, and CREB5 may form an important network involved in the pathology of HCM. Conclusions: The novel ceRNA network that we have demonstrated will provide new research points about molecular mechanisms of HCM.

Burden, Trends, and Inequalities of Heart Failure Globally, 1990 to 2019: A Secondary Analysis Based on the Global Burden of Disease 2019 Study.

Background Heart failure is a public health issue worldwide. However, no comprehensive study on the global burden of heart failure and its contributing causes has been reported. The present study aimed to quantify the burden, trends, and inequalities of heart failure globally. Methods and Results Heart failure data were extracted from the Global Burden of Diseases 2019 study. The number of cases, age-standardized prevalence, and years lived with disability in different locations from 1990 to 2019 were presented and compared. Joinpoint regression analysis was performed to assess trends in heart failure from 1990 to 2019. In 2019, the global age-standardized prevalence and years lived with disability rates for heart failure were 711.90 (95% uncertainty interval [UI], 591.15-858.29) and 63.92 (95% UI, 41.49-91.95) per 100 000 population, respectively. In general, the age-standardized rate decreased globally at an average annual percentage change of 0.3% (95% UI, 0.2-0.3). However, the rate increased at an average annual percentage change of 0.6% (95% UI, 0.4-0.8) from 2017 to 2019. Several nations and territories demonstrated an increased trend from 1990 to 2019, especially in less-developed countries. Ischemic heart disease and hypertensive heart disease accounted for the highest proportion of heart failure in 2019. Conclusions Heart failure remains a major health problem, with increased trends possible in the future. Efforts for prevention and control of heart failure should focus more on less-developed regions. It is essential to prevent and treat primary diseases such as ischemic heart disease and hypertensive heart disease for the control of heart failure.

A hiPSC-derived lineage-specific vascular smooth muscle cell-on-a-chip identifies aortic heterogeneity across segments.

Aortic aneurysm (AA), a potentially lethal condition with the characteristic of aortic dilatation, can only be treated by surgical or endovascular procedures. The underlying mechanisms of AA are unclear and early preventive treatment is still insufficient due to segmental aortic heterogeneity and the limitations of current disease models. Here, we firstly established a comprehensive lineage-specific vascular smooth muscle cell (SMC)-on-a-chip model using human induced pluripotent stem cells to yield cell lineages representing different segments of the aorta and tested the constructed organ-on-a-chip model under various tensile stress conditions. Bulk RNA sequencing, RT-qPCR, immunofluorescence, western blot and FACS analyses were performed to discover the segmental aortic heterogeneity of response for tensile stress and drug testing. The appropriate stretching frequency for all lineages of SMCs was 1.0 Hz, paraxial mesoderm (PM) SMCs were more sensitive to tensile stress than lateral mesoderm (LM) SMCs and neural crest (NC) SMCs. These differences may be related to the different transcriptional profiles of the tension-stressed distinct lineage-specific vascular SMCs, specifically in relation to the PI3K-Akt signaling pathway. Also, the organ-on-a-chip displayed contractile physiology, perfect fluid coordination, and was conducive to drug testing, displaying heterogeneous segmental aortic responses. Compared with LM-SMCs and NC-SMCs, PM-SMCs were more sensitive to ciprofloxacin. The model is evaluated as a novel and suitable supplement to AA animal models for determining differential physiology and drug response in different parts of the aorta. Furthermore, this system could pave the way for disease modeling, drug testing, and the personalized treatment of patients with AA in the future.

Rumen and Fecal Microbiota Characteristics of Qinchuan Cattle with Divergent Residual Feed Intake.

Residual feed intake (RFI) is one of the indicators of feed efficiency. To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). The results of taxonomic annotation revealed that Bacteroidetes and Firmicutes were the most dominant phyla in rumen and feces. Prevotella was identified as a potential biomarker in the rumen of the LRFI group by the LEfSe method, while Turicibacter and Prevotella might be potential biomarkers of the HRFI and LRFI group in feces, respectively. Functional annotation revealed that the microbiota in the rumen of the HRFI group had a greater ability to utilize dietary polysaccharides and dietary protein. Association analysis of rumen microbes (genus level) with host genes revealed that microbiota including Prevotella, Paraprevotella, Treponema, Oscillibacter, and Muribaculum, were significantly associated with differentially expressed genes regulating RFI. This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations.

Blood transcriptome reveals immune and metabolic-related genes involved in growth of pasteurized colostrum-fed calves.

The quality of colostrum is a key factor contributing to healthy calf growth, and pasteurization of colostrum can effectively reduce the counts of pathogenic microorganisms present in the colostrum. Physiological changes in calves fed with pasteurized colostrum have been well characterized, but little is known about the underlying molecular mechanisms. In this study, key genes and functional pathways through which pasteurized colostrum affects calf growth were identified through whole blood RNA sequencing. Our results showed that calves in the pasteurized group (n = 16) had higher body height and daily weight gain than those in the unpasteurized group (n = 16) in all months tested. Importantly, significant differences in body height were observed at 3 and 4 months of age (p < 0.05), and in daily weight gain at 2, 3, and 6 months of age (p < 0.05) between the two groups. Based on whole blood transcriptome data from 6-months old calves, 630 differentially expressed genes (DEGs), of which 235 were upregulated and 395 downregulated, were identified in the pasteurized compared to the unpasteurized colostrum groups. Most of the DEGs have functions in the immune response (e.g., CCL3, CXCL3, and IL1A) and metabolism (e.g., PTX3 and EXTL1). Protein-protein interaction analyses of DEGs revealed three key subnetworks and fifteen core genes, including UBA52 and RPS28, that have roles in protein synthesis, oxidative phosphorylation, and inflammatory responses. Twelve co-expression modules were identified through weighted gene co-expression network analysis. Among them, 17 genes in the two modules that significantly associated with pasteurization were mainly involved in the tricarboxylic acid cycle, NF-kappa B signaling, and NOD-like receptor signaling pathways. Finally, DEGs that underwent alternative splicing in calves fed pasteurized colostrum have roles in the immune response (SLCO4A1, AKR1C4, and MED13L), indicative of potential roles in immune regulation. Results from multiple analytical methods used suggest that differences in calf growth between the pasteurized and unpasteurized groups may be due to differential immune activity. Our data provide new insights into the impact of pasteurization on calf immune and metabolic-related pathways through its effects on gene expression.

Immobilization of lipase in chitosan-mesoporous silica material and pore size adjustment.

Mesoporous silica MCM-41 was modified by carboxyl groups and assembled with chitosan to produce a novel nanocarrier for the immobilization of lipase. The prepared composite was grafted with silane coupling agent KH560 to decrease the pore size of the mesoporous material and prevent the loss of shed lipase molecules. According to the characterization of the material before and after modification and determination of related parameters, the residual activity of the lipase fixed in the CTS-MCM-41 carrier was 85 % after seven repeated use cycles. The grafting rate of MCM-41 and shrinkage effect were maximized when the concentration of KH560 was 5.0 %, and the modification was performed at 4 h at 70 °C. Using glutaraldehyde as the crosslinking agent, the optimal conditions for enzyme immobilization involved a mass ratio of the carrier to enzyme of 4:1, glutaraldehyde solution volume of 3 %, reaction time of 3 h, and reaction temperature of 45 °C. Overall, the proposed innovative carrier for the fixation of lipase is stable and can physically control the free enzyme in the pore. Moreover, the efficient miniature lipase reactor can promote large-scale industrial production.

Effects of different deodorization methods on the oxidation of sterol components in rice bran oil.

Rice bran oil contains a significant quantity of phytosterols that have various active functions and are natural active substances beneficial to humans. It is well known that deodorization during refining affects the quality of rice bran oil. However, changes in phytosterols fraction caused by stripping with nitrogen compared to water vapor remain unexplored. We measured phytosterols in rice bran oil after deodorization with nitrogen and water vapor. The variations in sitosterol fraction, which accounts for the highest percentage of phytosterols in rice bran oil, were analyzed by Gas chromatography (GC), Fourier transform infrared spectrometer (FTIR), and Nuclear magnetic resonance (NMR). Results showed that using nitrogen as the stripping gas was more suitable for deodorization. It promoted the formation of phytosterol esters, reduced the production of phytosterol oxidation products and improved the oil quality. This study provides a theoretical basis for improving the industrial production quality of rice bran oil.

PM2.5 exposure exacerbates mice thoracic aortic aneurysm and dissection by inducing smooth muscle cell apoptosis via the MAPK pathway.

Air pollution is a major public health concern worldwide. Exposure to fine particulate matter (PM2.5) is closely associated with cardiovascular diseases. However, the effect of PM2.5 exposure on thoracic aortic aneurysm and dissection (TAAD) has not been fully elucidated. Diesel exhaust particulate (DEP) is an important component of PM2.5, which causes health effects and is closely related to the incidence of cardiovascular disease. In the current study, we found that DEP exposure increased the incidence of aortic dissection (AD) in ß-aminopropionitrile (BAPN)-induced thoracic aortic aneurysm (TAA). In addition, exposure to PM2.5 increased the diameter of the thoracic aorta in mice models. The number of apoptotic cells increased in the aortic wall of PM2.5-treated mice, as did the protein expression level of BAX/Bcl2 and cleaved caspase3/caspase3. Using a rhythmically stretching aortic mechanical simulation model, fluorescent staining indicated that PM2.5 administration could induce mitochondrial dysfunction and increase reactive oxygen species (ROS) levels in human aortic smooth muscle cells (HASMCs). Furthermore, ERK1/2 mitogen-activated protein kinase (MAPK) signaling pathways participated in the apoptosis of HASMCs after PM2.5 exposure. Therefore, we concluded that PM2.5 exposure could exacerbate the progression of TAAD, which could be induced by the increased apoptosis in HASMCs through the ERK1/2 MAPK signaling pathway.

Ciprofloxacin exacerbates dysfunction of smooth muscle cells in a microphysiological model of thoracic aortic aneurysm.

Ciprofloxacin use may be associated with adverse aortic events. However, the mechanism underlying the effect of ciprofloxacin on the progression of thoracic aortic aneurysm (TAA) is not well understood. Using an in vitro microphysiological model, we treated human aortic smooth muscle cells (HASMCs) derived from patients with bicuspid aortic valve- or tricuspid aortic valve-associated (BAV- or TAV-associated) TAAs with ciprofloxacin. TAA C57BL/6 mouse models were utilized to verify the effects of ciprofloxacin exposure. In the microphysiological model, real-time PCR, Western blotting, and RNA sequencing showed that ciprofloxacin exposure was associated with a downregulated contractile phenotype, an upregulated inflammatory reaction, and extracellular matrix (ECM) degradation in the normal HASMCs derived from the nondiseased aorta. Ciprofloxacin induced mitochondrial dysfunction in the HASMCs and further increased apoptosis by activating the ERK1/2 and P38 mitogen-activated protein kinase pathways. These adverse effects appeared to be more severe in the HASMCs derived from BAV- and TAV-associated TAAs than in the normal HASMCs when the ciprofloxacin concentration exceeded 100 µg/mL. In the aortic walls of the TAA-induced mice, ECM degradation and apoptosis were aggravated after ciprofloxacin exposure. Therefore, ciprofloxacin should be used with caution in patients with BAV- or TAV-associated TAAs.

Prediction of suicidal ideation among Chinese college students based on radial basis function neural network.

Background: Suicide is one of the leading causes of death for college students. The predictors of suicidal ideation among college students are inconsistent and few studies have systematically investigated psychological symptoms of college students to predict suicide. Therefore, this study aims to develop a suicidal ideation prediction model and explore important predictors of suicidal ideation among college students in China. Methods: We recruited 1,500 college students of Sichuan University and followed up for 4 years. Demographic information, behavioral and psychological information of the participants were collected using computer-based questionnaires. The Radial Basis Function Neural Network (RBFNN) method was used to develop three suicidal ideation risk prediction models and to identify important predictive factors for suicidal ideation among college students. Results: The incidence of suicidal ideation among college students in the last 12 months ranged from 3.00 to 4.07%. The prediction accuracies of all the three models were over 91.7%. The area under curve scores were up to 0.96. Previous suicidal ideation and poor subjective sleep quality were the most robust predictors. Poor self-rated mental health has also been identified to be an important predictor. Paranoid symptom, internet addiction, poor self-rated physical health, poor self-rated overall health, emotional abuse, low average annual household income per person and heavy study pressure were potential predictors for suicidal ideation. Conclusions: The study suggested that the RBFNN method was accurate in predicting suicidal ideation. And students who have ever had previous suicidal ideation and poor sleep quality should be paid consistent attention to.

Application of magnetic immobilized enzyme of nano dialdehyde starch in deacidification of rice bran oil.

Glutaraldehyde is usually used as a cross-linking agent in the immobilization of enzymes, but this will have a negative effect on the enzyme. Dialdehyde starch can effectively replace glutaraldehyde as a cross-linking agent, but the large particle size of dialdehyde starch affects the performance of immobilized enzyme. In this study, dialdehyde starch nanoparticles (DSNP) were combined with modified Fe3O4 to obtain magnetic carrier (MDSNP), and Candida Antarctica lipase B (CALB) was crosslinked to the carrier to obtain magnetic immobilized enzyme (MDSNPCALB). The characterization results show that the functional groups of each material have obvious characteristic absorption peaks, strong diffraction peaks and typical crystal structures, high magnetism, no coercivity, relatively good dispersion and nano particle size. MDSNPCALB was added to degummed rice bran oil (RBO) and ethanolamine was used as an acyl receptor for acylation and deacidification. After repeated use for 10 times, MDSNPCALB remained highly active, indicating that MDSNPCALB can be effectively used for the deacidification of RBO.

Orthotopic and Heterotopic Murine Models of Pancreatic Cancer Exhibit Different Immunological Microenvironments and Different Responses to Immunotherapy.

For decades, tumor-bearing murine models established using tumor cell lines have been the most commonly used models to study human cancers. Even though there are several studies reported that implant sites caused disparities in tumor behaviors, few of them illuminated the positional effect on immunotherapy. Herein, we describe surgical techniques for a novel orthotopic implantation of syngeneic pancreatic ductal adenocarcinoma (PDAC) tissue slices. This method has a high success modeling rate and stable growth kinetics, which makes it useful for testing novel therapeutics. Pathological examination indicated that the orthotopic tumor displayed poor vascularization, desmoplastic stromal reaction, and a highly immunosuppressive tumor microenvironment. This unique microenvironment resulted in limited response to PD1/CTLA4 blockade therapy and anti-MUC1 (αMUC1) CAR-T transfer treatment. To reverse the suppressive tumor microenvironment, we developed gene modified T-cells bearing a chimeric receptor in which activating receptor NKG2D fused to intracellular domains of 4-1BB and CD3ζ (NKG2D CAR). The NKG2D CAR-T cells target myeloid-derived suppressor cells (MDSCs), which overexpress Rae1 (NKG2D ligands) within the TME. Results indicated that NKG2D CAR-T cells eliminated MDSCs and improved antitumor activity of subsequently infused CAR-T cells. Moreover, we generated a bicistronic CAR-T, including αMUC1 CAR and NKG2D CAR separated by a P2A element. Treatment with the dual targeted bicistronic CAR-T cells also resulted in prolonged survival of orthotopic model mice. In summary, this study describes construction of a novel orthotopic PDAC model through implantation of tissue slices and discusses resistance to immunotherapy from the perspective of a PDAC microenvironment. Based on the obtained results, it is evident that elimination MDSCs by NKG2D CAR could rescue the impaired CAR-T cell activity.