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Lignocellulosic biomass is an abundant and renewable resource for biofuels and bio-based chemicals. Vanillin is one of the major phenolic inhibitors in biomass production using lignocellulose. To assess the response of Corynebacterium glutamicum to vanillin stress, we performed a global transcriptional response analysis. The transcriptional data showed that the vanillin stress not only affected the genes involved in degradation of vanillin, but also differentially regulated several genes related to the stress response, ribosome/translation, protein secretion, and the cell envelope. Moreover, deletion of the sigH or msrA gene in C. glutamicum resulted in a decrease in cell viability under vanillin stress. These insights will promote further engineering of model industrial strains, with enhanced tolerance or degradation ability to vanillin to enable suitable production of biofuels and bio-based chemicals from lignocellulosic biomass.

Epstein-Barr virus-induced gene 3 (EBI3) is a member of the interleukin-12 (IL-12) family structural subunit and can form a heterodimer with IL-27p28 and IL-12p35 subunit to build IL-27 and IL-35, respectively. However, IL-27 stimulates whereas IL-35 inhibits antitumor T cell responses. To date, little is known about the role of EBI3 in tumor microenvironment. In this study, firstly we assessed EBI3, IL-27p28, IL-12p35, gp130, and p-STAT3 expression with clinicopathological parameters of colorectal cancer (CRC) tissues; then we evaluated the antitumor T cell responses and tumor growth with a EBI3 blocking peptide. We found that elevated EBI3 may be associated with IL-12p35, gp130, and p-STAT3 to promote CRC progression. EBI3 blocking peptide promoted antitumor cytotoxic T lymphocyte (CTL) response by inducing Granzyme B, IFN-γ production, and p-STAT3 expression and inhibited CRC cell proliferation and tumor growth to associate with suppressing gp130 and p-STAT3 expression. Taken together, these results suggest that EBI3 may mediate a bidirectional reciprocal-regulation STAT3 signaling pathway to assist the tumor escape immune surveillance in CRC.

Gamma delta (γδ) T cells and cytokine-induced killer (CIK) cells, which are a heterogeneous population of T lymphocytes and natural killer T (NKT) cells, have been separately expanded ex vivo and shown to be capable of targeting and mediating cytotoxicity against various tumor cells in a major histocompatibility complex-unrestricted manner. However, the co-expansion and co-administration of these immune cells have not been explored. In this study we describe an efficient method to expand simultaneously both CIK and Vγ9Vδ2 T cells, termed as CIKZ cells, from human peripheral blood mononuclear cells (PBMCs) using Zometa, interferon-gamma (IFN-γ), interleukin 2 (IL-2), anti-CD3 antibody and engineered K562 feeder cells expressing CD64, CD137L and CD86. A 21-day culture of PBMCs with this method yielded nearly 20,000-fold expansion of CIKZ cells with γδ T cells making up over 20% of the expanded population. The expanded CIKZ cells exhibited antitumor cytotoxicity and could be modified to express anti-CD19 chimeric antigen receptor (CAR), anti-CEA CAR, and anti-HER2 CAR to enhance their specificity and cytotoxicity against CD19-, CEA-, or HER2-positive tumor cells. The tumor inhibitory activity of anti-CD19 CAR-modified CIKZ cells was further demonstrated in vivo in a Raji tumor mouse model. The findings herein substantiate the feasibility of co-expanding CIK and γδ cells for adoptive cellular immunotherapy applications such as CAR T-cell therapy against cancer.

This study was designed to evaluate the effects of low-intensity pulsed ultrasound on bone regeneration during the bone-tendon junction healing process and to explore the application of synchrotron radiation micro computed tomography in three dimensional visualization of the bone-tendon junction to evaluate the microarchitecture of new trabecular bone. Twenty four mature New Zealand rabbits underwent partial patellectomy to establish a bone-tendon junction injury model at the patella-patellar tendon complex. Animals were then divided into low-intensity pulsed ultrasound treatment (20 min/day, 7 times/week) and placebo control groups, and were euthanized at week 8 and 16 postoperatively (n = 6 for each group and time point). The patella-patellar tendon specimens were harvested for radiographic, histological and synchrotron radiation micro computed tomography detection. The area of the newly formed bone in the ultrasound group was significantly greater than that of control group at postoperative week 8 and 16. The high resolution three dimensional visualization images of the bone-tendon junction were acquired by synchrotron radiation micro computed tomography. Low-intensity pulsed ultrasound treatment promoted dense and irregular woven bone formation at week 8 with greater bone volume fraction, number and thickness of new trabecular bone but with lower separation. At week 16, ultrasound group specimens contained mature lamellar bone with higher bone volume fraction and thicker trabeculae than that of control group; however, there was no significant difference in separation and number of the new trabecular bone. This study confirms that low-intensity pulsed ultrasound treatment is able to promote bone formation and remodeling of new trabecular bone during the bone-tendon junction healing process in a rabbit model, and the synchrotron radiation micro computed tomography could be applied for three dimensional visualization to quantitatively evaluate the microarchitecture of new bone in bone-tendon junction.

SIRT1 exerts protective effects against endothelial cells dysfunction, inflammation and atherosclerosis, indicating an important role on myocardial infarction (MI) pathogenesis. Nonetheless, the effects of SIRT1 variants on MI risk remain poorly understood. Here we aimed to investigate the influence of SIRT1 polymorphisms on individual susceptibility to MI. Genotyping of three tagSNPs (rs7069102, rs3818292 and rs4746720) in SIRT1 gene was performed in a Chinese Han population, consisting of 287 MI cases and 654 control subjects. In a logistic regression analysis, we found that G allele of rs7069102 had increased MI risk with odds ratio (OR) of 1.57 [95% confidence interval (CI) = 1.15-2.16, Bonferroni corrected P (Pc) = 0.015] after adjustment for conventional risk factors compared to C allele. Similarly, the combined CG/GG genotypes was associated with the increased MI risk (OR = 1.64, 95% CI = 1.14-2.35, Pc = 0.021) compared to the CC genotype. Further stratified analysis revealed a more significant association with MI risk among younger subjects (≤ 55 years old). Consistent with these results, the haplotype rs7069102G-rs3818292A-rs4746720T containing the rs7069102 G allele was also associated with the increased MI risk (OR = 1.41, 95% CI = 1.09-1.84, Pc = 0.040). However, we did not detect any association of rs3818292 and rs4746720 with MI risk. Our study provides the first evidence that the tagSNP rs7069102 and haplotype rs7069102G-rs3818292A-rs4746720T in SIRT1 gene confer susceptibility to MI in the Chinese Han population.

Abstract: In this paper, the endothermic methanol decomposition reaction is used to obtain syngas by transforming middle and low temperature solar energy into chemical energy. A two-dimensional multiphysics coupling model of a middle and low temperature of 150~300 °C solar receiver/reactor was developed, which couples momentum equation in porous catalyst bed, the governing mass conservation with chemical reaction, and energy conservation incorporating conduction/convection/radiation heat transfer. The complex thermochemical conversion process of the middle and low temperature solar receiver/reactor (MLTSRR) system was analyzed. The numerical finite element method (FEM) model was validated by comparing it with the experimental data and a good agreement was obtained, revealing that the numerical FEM model is reliable. The characteristics of chemical reaction, coupled heat transfer, the components of reaction products, and the temperature fields in the receiver/reactor were also revealed and discussed. The effects of the annulus vacuum space and the glass tube on the performance of the solar receiver/reactor were further studied. It was revealed that when the direct normal irradiation increases from 200 W/m2 to 800 W/m2, the theoretical efficiency of solar energy transformed into chemical energy can reach 0.14–0.75. When the methanol feeding rate is 13 kg/h, the solar flux increases from 500 W/m2 to 1000 W/m2, methanol conversion can fall by 6.8–8.9% with air in the annulus, and methanol conversion can decrease by 21.8–28.9% when the glass is removed from the receiver/reactor.

Microvesicles (MVs) derived from mesenchymal stem cells (MSCs) have been shown to promote angiogenesis. This study was aimed to shed a light on the mechanisms by analyzing the angiogenesis-promoting compositions of MSC-MVs. Also we try to figure out the impact of hypoxia on angiogenesis.MVs were isolated from the culture supernatants of MSCs under hypoxia/normoxia and serum-deprivation condition. The morphological features of MVs were revealed by an electron microscope and the origin of the MVs was identified by a bead-bound assay. An antibody array was used to analyze the expression of angiogenic cytokines from MVs and the parent MSCs as well. The major candidate factors were screened and the results were validated by immune blotting.MSC-MVs were around 80 nm in diameter. They expressed CD29, CD44, and CD73, but not CD31 and CD45. Antibody array showed that both MSCs and MVs expressed many angiogenesis-promoting biomolecules, including interleukin-6 (IL-6), basic fibroblast growth factors (bFGF), and recptor of urokinase-type plasminogen activator (UPAR). MSC-MVs contained angiogenin, vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) and the receptor-2 for vascular endothelial growth factor at higher levels than the parent MSCs. Under hypoxic condition most cytokines were expressed in greater quantity than normoxic in MSCs while in MVs there was no significant difference between hypoxic and normoxic conditions except UPAR, Angiogenin, VEGF, IGF, Tie-2/TEK, and IL-6 which were higher in MVs under hypoxic conditions than those in normoxic condition.Upon serum-deprivation condition, MSCs could secrete MVs that contain a variety of factors contributing to their angiogenesis-promoting function. And among them, Angiogenin, VEGF, MCP-1, VEGF R2 might be of greater importance than the other cytokines. Also UPAR, Angiogenin, VEGF, IGF, Tie-2/TEK, IL-6 might be responsible for hypoxia-augmented proangiogenic effects of MVs.

This paper presents a useful and practical procurement approach using the joint replenishment and channel coordination (JR-CC) policy in a two-echelon supply chain considering the coordination cost. The objective is to determine a basic replenishment cycle time and the replenishment interval to minimize the total cost of the supply chain. To solve this NP-hard problem, a simple and improved differential evolution algorithm (IDE) is developed. The performance of the IDE is verified by benchmark functions. Moreover, results of comparative numerical example show the effectiveness of the proposed IDE. IDE can be used as a good candidate for the JR-CC model. Results of numerical examples also indicate that the JR-CC policy can result in considerable cost saving, and enhance the efficiency of a supply chain. But not all members in the supply chain can benefit a lot using this policy. Moreover, results of sensitivity analysis show that retailers have more willingness to adopt the JR-CC policy than the manufacturers because of the different cost savings.

Virus-derived gene transfer vectors have been successfully employed to express the transcription activator-like effector nucleases (TALENs) in mammalian cells. Since the DNA-binding domains of TALENs consist of the variable di-residue (RVD)-containing tandem repeat modules and virus genome with repeated sequences is susceptible to genetic recombination, we investigated several factors that might affect TALEN cleavage efficiency of baculoviral vectors. Using a TALEN system designed to target the AAVS1 locus, we observed increased sequence instability of the TALE repeat arrays when a higher multiplicity of infection (MOI) of recombinant viruses was used to produce the baculoviral vectors. We also detected more deleterious mutations in the TALE DNA-binding domains when both left and right TALEN arms were placed into a single expression cassette as compared to the viruses containing one arm only. The DNA sequence changes in the domains included deletion, addition, substitution, and DNA strand exchange between the left and right TALEN arms. Based on these observations, we have developed a protocol using a low MOI to produce baculoviral vectors expressing TALEN left and right arms separately. Cotransduction of the viruses produced by this optimal protocol provided an improved TALEN cleavage efficiency and enabled effective site-specific transgene integration in human cells.

A mathematical model is proposed to consider the effects of saturated diagnosis and vaccination on HIV/AIDS infection. By employing center manifold theory, we prove that there exists a backward bifurcation which suggests that the disease cannot be eradicated even if the basic reproduction number is less than unity. Global stability of the disease-free equilibrium is investigated for appropriate conditions. When the basic reproduction number is greater than unity, the system is uniformly persistent. The proposed model is applied to describe HIV infection among injecting drug users (IDUs) in Yunnan province, China. Numerical studies indicate that new cases and prevalence are sensitive to transmission rate, vaccination rate, and vaccine efficacy. The findings suggest that increasing vaccination rate and vaccine efficacy and enhancing interventions like reducing share injectors can greatly reduce the transmission of HIV among IDUs in Yunnan province, China.

We introduce stochasticity into the SIS model with saturated incidence. The existence and uniqueness of the positive solution are proved by employing the Lyapunov analysis method. Then, we carry out a detailed analysis on both its almost sure exponential stability and its pth moment exponential stability, which indicates that the pth moment exponential stability implies the almost sure exponential stability. Additionally, the results show that the conditions for the disease to become extinct are much weaker than those in the corresponding deterministic model. The conditions for the persistence in the mean and the existence of a stationary distribution are also established. Finally, we derive the expressions for the mean and variance of the stationary distribution. Compared with the corresponding deterministic model, the threshold value for the disease to die out is affected by the half saturation constant. That is, increasing the saturation effect can reduce the disease transmission. Computer simulations are presented to illustrate our theoretical results.

The triblock 18β-glycyrrhetinic acid-poly(ethylene glycol)-18β-glycyrrhetinic acid conjugates (GA-PEG-GA) based self-assembled micelles were synthesized and characterized by FTIR, NMR, transmission electron microscopy, and particle size analysis. The GA-PEG-GA conjugates having the critical micelle concentration of M were used to form nanosized micelles, with mean diameters of 159.21 ± 2.2 nm, and then paclitaxel (PTX) was incorporated into GA-PEG-GA micelles by self-assembly method. The physicochemical properties of the PTX loaded GA-PEG-GA micelles were evaluated including in vitro cellular uptake, cytotoxicity, drug release profile, and in vivo tissue distribution. The results demonstrate that the GA-PEG-GA micelles had low cytotoxicity and good ability of selectively delivering drug to hepatic cells in vitro and in vivo by the targeting moiety glycyrrhetinic acid. In conclusion, the GA-PEG-GA conjugates have potential medical applications for targeted delivery of poor soluble drug delivery.

Straw retention has been shown to reduce carbon dioxide (CO2) emission from agricultural soils. But it remains a big challenge for models to effectively predict CO2 emission fluxes under different straw retention methods. We used maize season data in the Griffith region, Australia, to test whether the denitrification-decomposition (DNDC) model could simulate annual CO2 emission. We also identified driving factors of CO2 emission by correlation analysis and path analysis. We show that the DNDC model was able to simulate CO2 emission under alternative straw retention scenarios. The correlation coefficients between simulated and observed daily values for treatments of straw burn and straw incorporation were 0.74 and 0.82, respectively, in the straw retention period and 0.72 and 0.83, respectively, in the crop growth period. The results also show that simulated values of annual CO2 emission for straw burn and straw incorporation were 3.45 t C ha−1 y−1 and 2.13 t C ha−1 y−1, respectively. In addition the DNDC model was found to be more suitable in simulating CO2 mission fluxes under straw incorporation. Finally the standard multiple regression describing the relationship between CO2 emissions and factors found that soil mean temperature (SMT), daily mean temperature (Tmean), and water-filled pore space (WFPS) were significant.

Background: Few studies have explored the associated factors of attitudes of nonpsychiatric nurses towards mental disorders. Therefore, this study is aimed to evaluate the attitudes of nonpsychiatric nurses towards mental disorders and especially explore the association between psychiatric clinical practice and these attitudes. Methods: A total of 1324 nonpsychiatric nurses and students majoring in nursing were recruited through an online questionnaire from December 2021 to March 2022 in Sichuan Province, China. Demographic information, personal care experience, psychiatric nursing education and the Community Attitudes towards the Mentally Ill (CAMI) were collected. A higher score indicates a stigmatizing attitude in the authoritarianism and social restrictiveness (SR) subscales and a positive attitude in the benevolence and community mental health ideology (CMHI) subscales. Multivariate linear regression was employed to analyze associated factors of attitudes towards mental disorders, and hierarchical linear regression was used to analyze the association between psychiatric clinical practice and the attitudes towards mental disorders. Results: Under the control of confounders, high education level, long residence in urban and personal care experience were positively correlated with score of authoritarianism and SR (p < 0.05), and negatively correlated with score of benevolence (p < 0.05). Long residence in urban and personal care experience were negatively correlated with score of CMHI (p < 0.05). Hierarchical linear regression analysis showed that after adjusting for demographic information, psychiatric clinical practice was associated with lower score of benevolence (B = -0.09, 95%CI = -0.17 ~ -0.003, p = 0.043) and CMHI (B = -0.09, 95%CI = -0.17 ~ -0.01, p = 0.027), but the initial associations between psychiatric clinical practice and authoritarianism, SR disappeared. Conclusions: High education level, long residence in urban, personal care experience and the psychiatric clinical practice were associated with the discrimination of nonpsychiatric nurses towards mental disorders. Further exploring practical strategies to optimize the psychiatric clinical practice experience of nonpsychiatric nurses could help improve their attitudes towards mental disorders. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence and associated factors of suicidal ideation and suicide attempts among adolescent and young adults in China from December 14, 2022 to February 28, 2023, when COVID-19 restrictions were lifted. Methods: Students in middle and high schools and colleges and universities in the province of Sichuan, China were asked to complete on-line cross-sectional surveys. Information was collected about sociodemographics, experiences related to the COVID-19 pandemic, suicidal ideation and suicide attempts. Participants also filled out the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 and the Social Support Rate Scale surveys. Factors associated with suicidal ideation or suicide attempts were explored using logistic regression. Results: Of the 82,873 respondents (aged 12 to 24 years), 21,292 (25.7%) reported having thought of suicide at least once in their lifetime, 10,382 (12.5%) reported having thought about suicide within the previous 12 months, and 1,123 (1.4%) reported having attempted it within the previous 12 months. Risk of lifetime suicidal ideation was higher among middle school students than among older students. Risk of suicidal ideation and risk of suicide attempts correlated directly with severity of symptoms of depression and anxiety, and inversely with level of social support. Greater risk of suicidal ideation and suicidal attempts was associated with: being female, living in an urban environment, attending a boarding school, currently being in love, having parents who divorced or remarried, having parents who exhibit non-authoritative parenting behavior, having higher family income, having been COVID-19 infected, having been quarantined for a long time, and being dissatisfied with one's education. Conclusions: Suicidal ideation and suicide attempts remain prevalent among young people in China. The potential associated factors identified in our study may be useful for targeting appropriate psychosocial interventions and developing mental health policies. [ABSTRACT FROM AUTHOR]

Hypergraphs and tensors extend classic graph and matrix theories to account for multiway relationships, which are ubiquitous in engineering, biological, and social systems. While the Kronecker product is a potent tool for analyzing the coupling of systems in a graph or matrix context, its utility in studying multiway interactions, such as those represented by tensors and hypergraphs, remains elusive. In this article, we present a comprehensive exploration of algebraic, structural, and spectral properties of the tensor Kronecker product. We express Tucker and tensor train decompositions and various tensor eigenvalues in terms of the tensor Kronecker product. Additionally, we utilize the tensor Kronecker product to form Kronecker hypergraphs, which are tensor-based hypergraph products, and investigate the structure and stability of polynomial dynamics on Kronecker hypergraphs. Finally, we provide numerical examples to demonstrate the utility of the tensor Kronecker product in computing Z-eigenvalues, performing various tensor decompositions, and determining the stability of polynomial systems. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the influence of aging on the effectiveness and tolerance of sacubitril/valsartan (sac/val) among hypertensive patients complicated with heart failure in a real-world setting. Methods: This multicenter, retrospective study included patients (=18 years old) admitted with a diagnosis of hypertension and heart failure, starting sac/val therapy between January 2020 and December 2021 from 3 medical centers. Patients were grouped by the cutoff age of 65 years. Outcomes were collected 31-365 days after the initiation of sac/val and were compared in a matched cohort after 1: 1 propensity score matching (PSM). Results: A total of 794 patients were finally analyzed. Blood pressure and cardiac functions improved significantly compared with values at baseline. There were 269 patients in each cohort (<65 years and ≥65 years) after PSM. After PSM, the incidence of hyperuricemia and hypotension in the elderly patients (≥65 years) was significantly higher than in those <65 years of age. Kaplan-Meier estimate suggested that the cumulative incidence of new or recurrent cardiovascular events increased significantly at the age of ≥65 years after the point of 3 months (log-rank P = .00087). Conclusion: Sac/val benefited patients in both cohorts by improving blood pressure and cardiac function. Elderly patients (=65 years) were susceptible to hypotension, low diastolic blood pressure, hyperuricemia, and underwent cardiac-related readmissions more frequently. [ABSTRACT FROM AUTHOR]