Search

The TMEM196 protein, which comprises four membrane-spanning domains, belongs to the TMEM protein family. TMEM196 was identified as a candidate tumor suppressor gene in lung cancer. However, its role and mechanism in lung cancer metastasis remain unclear. Here, we study the role of TMEM196 in tumor metastasis to further verify the function in lung cancer.In this study, we used qRT-PCR, western blot analysis and immunohistochemistry to examine the expression levels of TMEM196 and related proteins in lung cancer tissues and tumor cells. We utilized Transwell assays, xenograft nude mouse models, and TMEM196We found that TMEM196 mRNA and protein expression levels were significantly decreased in lung cancer tissues and cells. Low expression of TMEM196 in clinical patients was associated with poor prognosis. TMEM196 strongly inhibited tumor metastasis and progression in vitro and in vivo. The primary lung tumors induced by tail vein-inoculated B16 cells in TMEM196Our results revealed that TMEM196 acts as a novel lung cancer metastasis suppressor via the Wnt/β-catenin signaling pathway.

We aimed to elucidate the applicability of tumor organoids for inherent drug resistance of primary liver cancer (PLC) and mechanisms of acquired drug resistance.PLC tissues were used to establish organoids, organoid-derived xenograft (ODX) and patient-derived xenograft (PDX) models. Acquired drug resistance was induced in hepatocellular carcinoma (HCC) organoids. Gene expression profiling was performed by RNA-sequencing.Fifty-two organoids were established from 153 PLC patients. Compared with establishing PDX models, establishing organoids of HCC showed a trend toward a higher success rate (29.0% vs. 23.7%) and took less time (13.0 ± 4.7 vs. 25.1 ± 5.4 days, p = 2.28 × 10HCC organoids perform better than PDX for drug screening. Acquired sorafenib resistance in organoids promotes HCC aggressiveness via facilitating stemness, retro-differentiation and EMT. Phosphorylated S6 kinase may be predictive for drug resistance in HCC.

Background Although primary health care (PHC) has been proven to be effective in preventing and treating chronic diseases, the visits rate of PHC institutions is still not ideal. Some patients initially express a willingness to visit PHC institutions but end up seeking health services at non-PHC institutions, and the reasons for this behavior remain unclear. Therefore, the objective of this study is to analyze the factors that contribute to behavioral deviations among chronic disease patients who originally intended to visit PHC institutions. Methods Data were collected from a cross-sectional survey among chronic disease patients with original intention to visit PHC institutions in Fuqing City, China. The analysis framework was guided by Andersen’s behavioral model. Logistic regression models were employed to analyze the factors affecting the behavioral deviations among chronic disease patients with a willingness to visit PHC institutions. Results A total of 1,048 individuals were finally included and about 40% of the participants with the original willingness to seek care from PHC institutions finally chose non-PHC institutions in their subsequent visits. The results of logistic regression analyses indicated that at the predisposition factor level, older participants (aOR60-69 = 0.602, P 70-75 = 0.475, P P P P P P Conclusions The deviations between the original willingness of PHC institution visits and subsequent behavior among chronic disease patients were associated with a number of predisposing, enabling, and need factors. Developing the health insurance system, strengthening the technical capacity of PHC institutions, and steadily developing a new concept of orderly healthcare-seeking behavior among chronic disease patients, will help promote their access to PHC institutions as well as improve the effectiveness of the tiered medical system for chronic disease care.

Background Hepatic ischemia/reperfusion (I/R) injury is one of the major pathological processes associated with various liver surgeries. However, there is still a lack of strategies to protect against hepatic I/R injury because of the unknown underlying mechanism. The present study aimed to identify a potential strategy and provide a fundamental experimental basis for treating hepatic I/R injury. Method A classic 70% ischemia/reperfusion injury was established. Immunoprecipitation was used to identify direct interactions between proteins. The expression of proteins from different subcellular localizations was detected by Western blotting. Cell translocation was directly observed by immunofluorescence. HE, TUNEL and ELISA were performed for function tests. Result We report that tripartite motif containing 37 (TRIM37) aggravates hepatic I/R injury through the reinforcement of IKK-induced inflammation following dual patterns. Mechanistically, TRIM37 directly interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6), inducing K63 ubiquitination and eventually leading to the phosphorylation of IKKβ. TRIM37 enhances the translocation of IKKγ, a regulatory subunit of the IKK complex, from the nucleus to the cytoplasm, thereby stabilizing the cytoplasmic IKK complex and prolonging the duration of inflammation. Inhibition of IKK rescued the function of TRIM37 in vivo and in vitro. Conclusion Collectively, the present study discloses some potential function of TRIM37 in hepatic I/R injury. Targeting TRIM37 might be potential for treatment against hepatic I/R injury.Targeting TRIM37 might be a potential treatment strategy against hepatic I/R injury. Graphical Abstract

Synchronization (insertions–deletions) errors are still a major challenge for reliable information retrieval in DNA storage. Unlike traditional error correction codes (ECC) that add redundancy in the stored information, multiple sequence alignment (MSA) solves this problem by searching the conserved subsequences. In this paper, we conduct a comprehensive simulation study on the error correction capability of a typical MSA algorithm, MAFFT. Our results reveal that its capability exhibits a phase transition when there are around 20% errors. Below this critical value, increasing sequencing depth can eventually allow it to approach complete recovery. Otherwise, its performance plateaus at some poor levels. Given a reasonable sequencing depth (≤ 70), MSA could achieve complete recovery in the low error regime, and effectively correct 90% of the errors in the medium error regime. In addition, MSA is robust to imperfect clustering. It could also be combined with other means such as ECC, repeated markers, or any other code constraints. Furthermore, by selecting an appropriate sequencing depth, this strategy could achieve an optimal trade-off between cost and reading speed. MSA could be a competitive alternative for future DNA storage.

Background There is limited longitudinal evidence supporting the association between the hypertriglyceridemic-waist (HTGW) phenotype and hyperuricemia. This study aimed to examine the longitudinal relationship between hyperuricemia and the HTGW phenotype among males and females. Methods A total of 5562 hyperuricemia-free participants aged 45 or over from the China Health and Retirement Longitudinal Study (mean age: 59.0) were followed for 4 years. The HTGW phenotype was defined as having elevated triglyceride levels and enlarged waist circumference (cutoffs for males: 2.0 mmol/L and 90 cm; females: 1.5 mmol/L and 85 cm). Hyperuricemia was determined by uric acid cutoffs (males: 7 mg/dl; females: 6 mg/dl. Multivariate logistic regression models were used to assess the association between the HTGW phenotype and hyperuricemia. The joint effect of the HTGW phenotype and sex on hyperuricemia was quantified, and the multiplicative interaction was assessed. Results During the four-year follow-up, 549 (9.9%) incident hyperuricemia cases were ascertained. Compared with those with normal levels of triglycerides and waist circumference, participants with the HTGW phenotype had the highest risk of hyperuricemia (OR: 2.67; 95% CI: 1.95 to 3.66), followed by an OR of 1.96 (95% CI: 1.40 to 2.74) for only higher triglyceride levels and 1.39 (95% CI: 1.03 to 1.86) for only greater waist circumference. The association between HTGW and hyperuricemia was more prominent among females (OR = 2.36; 95% CI: 1.77 to 3.15) than males (OR = 1.29; 95% CI: 0.82 to 2.04), with evidence of a multiplicative interaction (P = 0.006). Conclusions Middle-aged and older females with the HTGW phenotype may at the highest risk of hyperuricemia. Future hyperuricemia prevention interventions should be primarily targeted for females with the HTGW phenotype.

A real-time assay for multiple enzyme activities in cascade reactions is required for research on metabolism and bioengineering. Tyrosinase has the bifunctional activity of monophenolase and diphenolase. A combined strategy of three-way calibration with excitation-emission matrix (EEM) fluorescence was developed for real-time and simultaneous determination of monophenolase and diphenolase activity with tyrosine as a substrate. Mathematical separation and second-order advantage were utilized to solve spectral overlapping and uncalibrated interferents during complex dynamic enzymatic processes. Kinetic evolution profiles of EEM were monitored to stack a fusion three-way data array together with static samples. Using a parallel factor analysis (PARAFAC) algorithm, pseudo-univariate calibration curves with limits of detection (LODs) of 3.00 μM and 0.85 μM were established to simultaneously and real-time measure tyrosine and DOPA. Progress curves for tyrosine consumption by monophenolase and DOPA consumption by diphenolase were obtained using the law of mass conservation to calculate the initial velocity. The LODs for monophenolase and diphenolase were 0.0232 U⋅mL

Overexpression of survivin is frequently observed in human malignancies and is associated with poor prognosis. The present study found that survivin is highly expressed in nasopharyngeal carcinoma (NPC) tumor tissues. Depleting survivin with shRNA inhibited cell viability, colony formation, and in vivo tumorigenesis of NPC cells. With a natural product screening, we identified Butein as a potential anti-tumor compound for NPC by reducing survivin protein level. Butein shortened the half-life of survivin and enhanced ubiquitination-mediated degradation. The mechanism study showed that Butein promoted the interaction between survivin and E3 ligase Fbxl7, and the knockdown of Fbxl7 compromised Butein-induced survivin ubiquitination. Butein suppressed the Akt-Wee1-CDK1 signaling and decreased survivin Thr34 phosphorylation, facilitating E3 ligase Fbxl7-mediated survivin ubiquitination and degradation. Moreover, Butein exhibited a strong in vivo anti-tumor activity, as the tumor volume of Butein-treated xenografts was reduced significantly. Butein alone or combined with cisplatin (CDDP) overcame chemoresistance in NPC xenograft tumors. Overall, our data indicate that Butein is a promising anti-tumor agent for NPC treatment.

Background To confront the serious challenge of antimicrobial resistance, using clinical practice guidelines (CPGs) standardizing the prescription behavior is vital. However, the overall mechanisms remains largely unknown as to how guidelines' use behavior can be improved. This study aimed to identify the determinants and investigate their relationship to bridge the knowledge gap of overall influencing mechanism of the use behavior of CPGs on antimicrobials. Methods By integrating theory of reasoned action (TRA) and organizational readiness for change (ORC), a structured questionnaire was developed to cover potential determinants that affect physicians’ use behaviors of CPGs on antimicrobials at the individual-level (attitude, subjective norm, and behavioral intention) and organizational-level (top management support and organizational resource allocation). A multi-stage random sampling was implemented to collect data from physicians in secondary and tertiary hospitals from eastern, central and western China. Structural equation model (SEM) was used to test the proposed hypotheses, and to analyze the relationship and mechanism among the factors. Result In total, 815 physicians were included. Most physicians demonstrated a positive tendency toward the use of CPGs on antimicrobials, with a mean score of 3.95 (SD = 0.70). The reliability and validity analysis showed the questionnaire constructed from the integrated theoretical model of TRA and ORC was acceptable. The SEM validation results also showed that the top management support (β = 0.688, P β = 0.129, P β = 0.164, P β = 0.322, P β = 0.424, P Conclusions This study revealed the influence mechanism of the use of CPGs on antimicrobials from the individual and organizational perspectives. These findings will not only help formulate future strategies to promote the use of CPGs on antimicrobials, but also provide clues for more effective prescription interventions.

Visualizing latent evidence at a crime scene has gained popularity in the field of forensic science during the past few years. Thus, this study designs and develops a one-click device for the rapid visualization and extraction of latent evidence through multimodal light source integration and light-guiding technology. Our device exhibits multispectral and angle timing functions for storing the captured evidence images. Furthermore, the geometric registration, feature extraction, feature optimization, and feature integration of the evidence images are processed by a backend system, and the images are then presented. Overall, this study enhances the standard and the technical content of evidence extraction and simplifies the evidence extraction process. In addition to the rapid handling of the scenes captured at a crime scene, the one-click device has other notable advantages, such as fast imaging, portability, being independent of the environmental conditions and the operator’s technical capabilities, and zero pollution to ensure the repeatability of material evidence extraction. Compared with the original optical forensics equipment, the spectrum and angle of our system are more extensive.

DNA storage has been a thriving interdisciplinary research area because of its high density, low maintenance cost, and long durability for information storage. However, the complexity of errors in DNA sequences including substitutions, insertions and deletions hinders its application for massive data storage. Motivated by the divide-and-conquer algorithm, we propose a hierarchical error correction strategy for text DNA storage. The basic idea is to design robust codes for common characters which have one-base error correction ability including insertion and/or deletion. The errors are gradually corrected by the codes in DNA reads, multiple alignment of character lines, and finally word spelling. On one hand, the proposed encoding method provides a systematic way to design storage friendly codes, such as 50% GC content, no more than 2-base homopolymers, and robustness against secondary structures. On the other hand, the proposed error correction method not only corrects single insertion or deletion, but also deals with multiple insertions or deletions. Simulation results demonstrate that the proposed method can correct more than 98% errors when error rate is less than or equal to 0.05. Thus, it is more powerful and adaptable to the complicated DNA storage applications.

The climate change model of Daniel et al. (Proc Natl Acad Sci USA 116(42):20886-20891, 2019. https://doi.org/10.1073/pnas.1817444116) is an important contribution to the carbon pricing literature. However, the computational methodology proposed in this paper is costly, thus limiting the flexibility and scalability of this basic approach. In this paper we introduce several modern computational techniques, often used in optimization applications, such as vectorization and automatic differentiation for gradient computation, to dramatically improve computational performance: this allows for increased scalability and sensitivity analysis (including the analysis of suboptimal policies). Such studies are reported in this paper yielding a number of new experimental insights. For example, our new code illustrates the cost of postponing climate change mitigation is significant. Specifically, postponing climate change mitigation until 2030 is equivalent to giving up $5.4 trillion (in 2015 US dollars).

To explore the relationship between Mycoplasma hyorhinis infection and tyrosine kinase inhibitor (TKI) resistance in lung adenocarcinoma patients. Mycoplasma hyorhinis infection can be verified with the monoclonal antibody PD4, which specifically recognizes a distinct protein of M. hyorhinis. Immunohistochemistry (IHC), using PD4 to detect M. hyorhinis, was performed on paraffin-embedded lung adenocarcinoma tissues of patients who had epidermal growth factor (EGFR) mutations and had received oral TKI. The number of patients enrolled in our study was 101. Assessments following TKI treatment were performed until objective disease progression or stable disease at the cutoff date was reached. In all of the patients, the primary endpoint was investigator-assessed progression-free survival (PFS). Immunohistochemistry revealed that 61 of 101 cases (60.4%) of lung adenocarcinoma were positive for M. hyorhinis, which comprised of 31 low-positive cases and 30 high-positive cases; the remaining 40 cases (39.6%) were negative. The median PFS was significantly longer in the negative group [18 months (95% CI 14.15–21.85)] than in the low-positive group [10 months (95% CI 7.70–12.30); hazard ratio (HR) 4.095, 95% CI 2.254–7.438; p

The h index has been comprehensively developed and diffusely applied following its initial proposal in 2005 by Jorge Hirsch. However, while the numbers of papers and authors measured continue to grow, it is not known whether such increases in quantity mean that the research itself is advancing. Accordingly, the present study sets out to establish an analysis method, based on the concept of entropy, with which to elucidate the evolution of the h index. The results suggest that there are four stages, as follows: the emerging stage, the preliminary growth stage, the real growth stage, and the maturity stage. Meanwhile, the research of the h index is found to be in flux, and it is concluded that further development of the metric will require profound theoretical achievements as well as embedded innovation, or else the evolution of the h index will decline following a shortened maturity stage.

Deoxynivalenol (DON) is a widely distributed mycotoxin that frequently occurs in various foodstuffs, and poses a health risk to human and animals. Biodegradation of DON to less- or non-toxic substances using naturally existing microorganisms is considered the best approach for DON detoxification. Although various microorganisms capable of detoxifying DON have been reported; however, such studies on probiotic strains are scarce. In this study, a bacterial strain (ASAG 216) showed to possess the capability of detoxifying 100 μg/mL DON by 81.1% within 8 h was isolated from the intestine of a donkey. After morphological observation and 16S rDNA sequence analysis, the strain was identified as Bacillus subtilis. The DON-degradation potential of B. subtilis ASAG 216 was predominantly attributed to the culture supernatant, which turned to be sensitive to heat, sodium dodecyl sulfate, and proteinase K treatment, indicating the possible presence of extracellular proteins or enzymes in the supernatant which were responsible for DON degradation. Moreover, B. subtilis ASAG 216 has a broad temperature (35–50 °C) and pH (6.5–9.0) tolerance on DON degradation, apart from its ability to withstand conditions which generally prevail during the intestinal transit. In addition, the tested strain showed antimicrobial activity against Escherichia coli, Staphylococcus aureus and Salmonella typhimurium. These results provide satisfactory grounds for the potential use of B. subtilis ASAG 216 as a new feed additive to address DON contamination.

Herein, a new activated porous carbon (APC) was proposed by carbonizing waste biomass of pinecone which could be obtained in large quantities and subsequently activation of zinc chloride. Then small Co3O4 nanoparticles were loaded on the surface and holes of APC to prepare the final Co3O4/APC nanocomposites. The as-prepared APC had a lotus root-like and layered porous structure with a large number of mesopores and micropores. The APC reduced the agglomeration of small Co3O4 particles which were uniformly anchored on the surface of APC. When applied for the anode of lithium-ion batteries, the Co3O4/APC nanocomposites had a reversible capacity of 625 mAh g−1 after 200 cycles at the current density of 500 mA g−1. The Co3O4/APC nanocomposites also had a good rate performance. Above all, this work could transform waste biomass into sustainable resource, and the raw materials were easy to obtain in large quantities.

Lamellar Ni3Si was electrochemically prepared. Its structure and microhardness were controlled by the directional solidification growth rate and selective corrosion time. It exhibits strong corrosion resistance to acid and alkali. The mass of Ni3Si stationed in 50 wt pct H2SO4 and 25 wt pct NaOH after 200 hours remained 94.4 and 98.8 pct, respectively. The prepared Ni(OH)2/Ni3Si electrode using lamellar Ni3Si compound as a matrix delivered a higher areal capacity and cycle stability than the Ni(OH)2 electrode.

Background Overexpression of Skp2 plays a critical role in tumorigenesis and correlates with poor prognosis in human malignancies. Thus, Skp2 has been proposed as an attractive target for anti-tumor interventions. Methods The expression of Skp2 in human colorectal cancer (CRC) and the role of Skp2 in tumorigenic properties and irradiation sensitivities of CRC cells were examined by anchorage-dependent and -independent growth assays, immunoblot, flow cytometry, immunohistochemical staining, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiments. Results Skp2 is highly expressed in CRC patient tissues. Blocking Skp2 expression reduces the tumorigenic properties of CRC cells in vitro and in vivo. Depletion of Skp2 confers sensitivity to irradiation of CRC cells. Skp2 deficiency enhances irradiation-induced intrinsic apoptosis by facilitating E3 ligase FBW7-mediated Mcl-1 ubiquitination and degradation. Knockout of Skp2 sensitizes CRC cells to irradiation treatments in vivo. Conclusion Our findings indicate that Skp2 stabilizes Mcl-1, and targeting Skp2 in combination with traditional radiotherapy might be efficacious in treating CRC.

Many vehicle and wheel detection methods based on convolutional neural networks suffer from challenges due to the lack of training data and the limitation on small object detection. To solve this problem, we present a novel optimized SSD algorithm with multi-concatenation modules, aiming to improve the performance of small object detection. In the multi-concatenation module, features from different layers are concatenated together, including feature map from shallow layer with more location information, feature map from intermediate layer, and feature map from deep layer with rich semantic information. SEBlock is employed to re-weight the new feature map to improve the quality of representation. Furthermore, to facilitate the study of vision-based vehicle and wheel detection, a large-scale benchmark dataset of 8209 images is established, comprising five object categories: truck, pickup, tractor, car, and wheel. On the Pascal VOC 2007 test set, our network achieves 78.7% mAP, which is higher than SSD by 1.5%. On KITTI dataset, the proposed method can reach 71.4% mAP, surpassing SSD by 3.5%. In addition, experimental results show that the proposed method results in better detection performance on small objects.

Water electrolysis was recognized as an effective method for new energy sources. In this work, an effective FexNiyOOH/ESS with high surface area and good catalytic activity was prepared for water electrolysis. Its morphologies at different ratio of Fe/Ni atoms were diverse, such as flower ball, flake, and block, etc. Test results showed that at 10 mA cm−2 and 300 mA cm−2, the hydrogen evolution overpotentials of Fe1.5Ni0.5OOH/ESS were 172 mV and 258 mV. The oxygen evolution overpotentials of Fe0.2Ni1.8OOH/ESS were 208 mV and 308 mV at 10 mA cm−2 and 600 mA cm−2. During the 136-h stability test, the oxygen evolution activity of Fe0.2Ni1.8OOH/ESS was basically unchanged. The Fe1.5Ni0.5OOH//Fe0.2Ni1.8OOH in alkaline conditions presented good performance for water electrolysis. Water electrolysis experiment was carried out at 1.58 V, and the current density reached to 10 mA cm−2. FexNiyOOH/ESS exhibited higher electrocatalytic activity and superior stability at high current density.

A nonmagnetic metal droplet with dynamic interfaces under a time-varying magnetic field was considered. Considering that the thermal effect of the magnetic field and the droplet evaporation were disregarded, we obtained the magnetically augmented Young–Laplace equation theoretically according to the normal stress balance principles. The droplet contact angle was further determined according to the droplet volume conservation. According to the curvature and contact angle, the droplet profile was mathematically determined. Results showed that a downward magnetic force caused droplet contraction and an upward force caused expansion. The increase in surface tension hindered the droplet spreading without affecting the change trend of droplet shape parameters. The increase in angular frequency (ω) decreased the variation amplitude of the droplet curvature and contact angle, and the increase in damping factor (τ) slowed down the decay of the droplet curvature and contact angle.

As an important aspect of epigenetics, DNA methylation has been proven to be suitable for forensic DNA analysis. By detecting changes in DNA methylation, it is desirable to construct a model of age patterns associated with it to infer the age of the individual. The hTERT gene methylation is closely related to tumors, but there are few reports on the relationship between hTERT gene promoter methylation and age. In this study, we utilized the methylation-specific polymerase chain reaction and real-time PCR (relative quantification and absolute quantification) approach to explore the connection between hTERT DNA methylation and age prediction. We fit three models for age prediction based on methylation assay for 90 blood samples from donors aged 1–79 years old. Among them, the model of absolute quantification of real-time enabled the age prediction with R2 = 0.9634. We verified the linear regression model with a validation set of 30 blood samples where prediction average error was 4.29 years. Generally, this reliable method improves the DNA methylation analysis of forensic samples.

Spatio-temporal patterns of drought from 1961 to 2013 over the Beijing-Tianjin-Hebei (BTH) region of China were analyzed using the Palmer Drought Severity index (PDSI) based on 21 meteorological stations. Overall, changes in the mean-state of drought detected in recent decades were due to decreases in precipitation and potential evapotranspiration. The Empirical Orthogonal Functions (EOF) method was used to decompose drought into spatio-temporal patterns, and the first two EOF modes were analyzed. According to the first leading EOF mode (48.5%), the temporal variability (Principal Components, PC1) was highly positively correlated with annual series of PDSI (r=+0.99). The variance decomposition method was further applied to explain the inter-decadal temporal and spatial variations of drought relative to the total variation. We find that 90% of total variance was explained by time variance, and both total and time variance dramatically decreased from 1982 to 2013. The total variance was consistent with extreme climate events at the inter-decadal scale (r=0.71, p

A new kind of bifunctional magnetic-fluorescent nanoparticles (NPs) with abundant carboxyls on the surface has been prepared by covalently combining glutathiose (GSH)-modified CdTe quantum dots (QDs) with Fe3O4@SiO2 NPs. The silica-coated Fe3O4 NPs were functionalized with amino groups by (3-aminopropyl)triethoxysilane to provide Fe3O4@SiO2-NH2 NPs, which was then chemically conjugated with GSH-modified CdTe QDs to form bifunctional magnetic-fluorescent NPs, Fe3O4@SiO2-NH-CO-CdTe-QDs NPs. The properties and morphologies of Fe3O4@SiO2-NH-CO-CdTe-QDs NPs were investigated by FTIR, X-ray diffraction, transmission electron microscopy (TEM), absorption and fluorescence spectroscopy and vibrating sample magnetometry. TEM images display that Fe3O4@SiO2-NH-CO-CdTe-QDs NPs possess spherical core-shell structure with a uniform size about 50 nm. The bifunctional NPs were found to exhibit good magnetic and strong fluorescent properties favorable for their application in the detection of latent fingerprints. Furthermore, the carboxyls on the surface of NPs have good absorptions with water in air and the residues of fingerprints so as to not only avoid dust flying to protect the health of operators, but also improve the efficiency of detection.

BackgroundDespite there is growing evidence focusing on health inequalities in China, socioeconomic inequalities in cognitive impairment among older adults have received little attention. This study aims to measure socioeconomic inequalities in cognitive impairment among Chinese older adults, and determine the contributing social factors to the inequalities.MethodsA cross-sectional analysis was performed using data from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 10,556 older adults aged 65 and over were included in the study. The prevalence of cognitive impairment was measured by using the Chinese version of the Mini-Mental State Examination. The socioeconomic inequalities in cognitive impairment were illustrated and quantified by the concentration curve and normalized concentration index. Multivariate logistic regression was conducted to identify the associated factors of cognitive impairment. And decomposition analysis was further applied to decompose the contribution of each determinant to the observed inequalities in cognitive impairment.ResultsThe study indicated that the prevalence of cognitive impairment among Chinese older adults was 18.95%. The overall concentration index for cognitive impairment was − 0.046, which suggested a higher concentration of cognitive impairment among socioeconomically disadvantaged older adults. The results showed the prevalence of cognitive impairment was associated with sex, age, marital status, education level, occupation, economic status, emotional support, financial support, living arrangement, and participation in informal activities. Decomposition results further revealed the contributions of the determinants to the inequalities in cognitive impairment. Specifically, age (131.61%), marital status (85.68%), emotional support (84.85%), education level (39.73%), occupation (21.24%), sex (17.25%), financial support (− 4.19%), economic status (1.02%), living arrangement (0.88%), and informal activities (0.30%) have varying degrees of contributions to the inequality in cognitive impairment.ConclusionThis study sheds light on the pro-rich inequality in cognitive impairment among older adults in China. It suggests that policymakers should pay more attention to older adults who are female, old-old, widowed, illiterate, economically disadvantaged, with no social support, and less socially involved. Also, more targeted interventions should be undertaken to improve the socioeconomic conditions of these vulnerable individuals and strengthen their ability to cope with the risk of cognitive impairment.

Adoptive transfer of γδ T cells is an attractive approach for cell-based immunotherapy in treatment of renal cell carcinoma (RCC). Interleukin-15 (IL-15) is the key physiological cytokine that regulates γδ T cell differentiation, proliferation and survival. In this work, we determined that IL-15 have the capacity to enhance the anti-tumoral functions of γδ T cells. IL-15 can induce the upregulation of cytotoxicity-associated molecules on the γδ T cell surface, incite γδ T cell proliferation and decrease apoptosis. Moreover, the enhanced cytotoxicity of IL-15-induced γδ T cell was dependent on the interaction of NKG2D and MICA. Most importantly, we found that IL-15-induced γδ T cells effectively suppressed the tumor growth in vivo and prolonged the survival time of RCC-bearing patient‑derived xenograft (PDX) mice. These results are important for the prospective use of γδ T cells in clinical practice when designing novel cell-based immunotherapies against RCC.

Background Aurora B kinase is aberrantly overexpressed in various tumors and shown to be a promising target for anti-cancer therapy. Methods A customized natural product library was used for natural compound screening through Molecular modeling. The expression of Aurora B in oral squamous cell carcinoma (OSCC) and the inhibitory effect of Tanshinone IIA (Tan IIA) on OSCC were examined by MTS and colony formation assays, immunoblot, immunofluorescence, immunohistochemical staining, and in vivo xenograft experiment. Results Aurora B is overexpressed in OSCC tumor tissues and cell lines. Knockdown of Aurora B inhibited the malignant phenotypes of OSCC cells in vitro and in vivo. With a molecular modeling screening of 74 commercially available natural products, we identified that Tan IIA, as a potential Aurora B kinase inhibitor. Tan IIA exhibited a significant anti-tumor effect on OSCC cells both in vitro and in vivo, including reduction of Aurora B and histone H3 phosphorylation, induction of G2/M cell cycle arrest, increase the population of polyploid cells, and promotion of apoptosis. The in vivo mouse model revealed that Tan IIA delayed tumor growth of OSCC cells. Tan IIA alone or in combination with radiation overcame radioresistance in OSCC xenograft tumors. Conclusion Our data indicates that targeting Aurora B kinase signaling is a promising anti-tumor strategy for OSCC treatment.

Background Coronavirus can cross the species barrier and infect humans with a severe respiratory syndrome. SARS-CoV-2 with potential origin of bat is still circulating in China. In this study, a prediction model is proposed to evaluate the infection risk of non-human-origin coronavirus for early warning. Methods The spike protein sequences of 2666 coronaviruses were collected from 2019 Novel Coronavirus Resource (2019nCoVR) Database of China National Genomics Data Center on Jan 29, 2020. A total of 507 human-origin viruses were regarded as positive samples, whereas 2159 non-human-origin viruses were regarded as negative. To capture the key information of the spike protein, three feature encoding algorithms (amino acid composition, AAC; parallel correlation-based pseudo-amino-acid composition, PC-PseAAC and G-gap dipeptide composition, GGAP) were used to train 41 random forest models. The optimal feature with the best performance was identified by the multidimensional scaling method, which was used to explore the pattern of human coronavirus. Results The 10-fold cross-validation results showed that well performance was achieved with the use of the GGAP (g = 3) feature. The predictive model achieved the maximum ACC of 98.18% coupled with the Matthews correlation coefficient (MCC) of 0.9638. Seven clusters for human coronaviruses (229E, NL63, OC43, HKU1, MERS-CoV, SARS-CoV, and SARS-CoV-2) were found. The cluster for SARS-CoV-2 was very close to that for SARS-CoV, which suggests that both of viruses have the same human receptor (angiotensin converting enzyme II). The big gap in the distance curve suggests that the origin of SARS-CoV-2 is not clear and further surveillance in the field should be made continuously. The smooth distance curve for SARS-CoV suggests that its close relatives still exist in nature and public health is challenged as usual. Conclusions The optimal feature (GGAP, g = 3) performed well in terms of predicting infection risk and could be used to explore the evolutionary dynamic in a simple, fast and large-scale manner. The study may be beneficial for the surveillance of the genome mutation of coronavirus in the field.

Northwest China is characterized by a high water deficit and regular water resource shortages. These issues have become limiting factors for agricultural and socioeconomic development. Based on a trend-preserving method of bias correction, we calibrated the maximum temperature and minimum temperature in four CMIP5 GCMs (CNRM, IPSL, BCC, and CMCC). Then, we investigated variations in the regional crop water requirement (CWR) in the total growth stages for five main crops (cotton, spring corn, summer corn, spring wheat, and winter wheat) in the past (1961–2005) and future (2006–2100). The results suggest that the MK test yielded insignificant decreasing CWR trends in the total growth stages of cotton (0.10 mm/year), spring corn (0.13 mm/year), and spring wheat (0.05 mm/year) and insignificant increasing trends for summer corn (0.02 mm/year) and winter wheat (0.32 mm/year) historically. In the future period, for the same type of crops (cotton), the CWRs in all scenarios (RCP 2.6, 4.5, and 8.5 scenarios) for all GCMs exhibited significant positive trends; for the same GCM (BCC), the CWRs projected for five major crops in the RCP 4.5 and 8.5 scenarios all exhibited extremely significant MK trends (99%); in addition, the CWRs’ rate increases of the five crops projected in RCP8.5 scenario by BCC exhibited the following order: winter wheat (1.25 mm/year), summer corn (1.15 mm/year), spring corn (1.02 mm/year), cotton (0.97 mm/year), and spring wheat (0.87 mm/year). The maximum CWRs of winter wheat were mainly observed in southeastern Northwest China, while those of the other four crops occurred in southern Xinjiang.

Rapid elevation-dependent warming (EDW) in high mountain environments can accelerate the rate of change in permafrost and further induce the degradation of alpine tundra systems. However, how changes in area of alpine tundra response to EDW is difficult to be directly quantified at regional scales. Here, we project future changes in areal extent of the Koppen “alpine tundra” climate type in the Tibetan Plateau (TP), which is a potential indicator describing the climate conditions for the development of alpine tundra system, based on a suite of latest Coupled Model Intercomparison Project Phase 5 (CMIP5) climate models under two emission scenarios (representative concentration pathways: RCP 4.5 and RCP 8.5). The results indicated that the Koppen “alpine tundra” climate type would gradually decrease in the TP for three future periods: 2011–2040, 2041–2070, and 2071–2100, especially under the RCP8.5 scenario. The decline in area of Koppen “alpine tundra” climate type mainly occurs above 2500 m above sea level (ASL) due to the EDW (> 10 °C) in the warmest months. The projected changes in area of “alpine tundra” climate type are overall consistent among different climate models, emission scenarios, and post-processing approaches (bias correction or not) used. The results obtained would thus deepen our understanding of future elevation-dependent warming and its potential influences on alpine tundra ecosystems in the Tibetan Plateau.

Micro-expression recognition (MER) is a growing field of research which is currently in its early stage of development. Unlike conventional macro-expressions, micro-expressions occur at a very short duration and are elicited in a spontaneous manner from emotional stimuli. While existing methods for solving MER are largely non-deep-learning-based methods, deep convolutional neural network (CNN) has shown to work very well on such as face recognition, facial expression recognition, and action recognition. In this article, we propose applying the 3D flow-based CNNs model for video-based micro-expression recognition, which extracts deeply learned features that are able to characterize fine motion flow arising from minute facial movements. Results from comprehensive experiments on three benchmark datasets—SMIC, CASME/CASME II, showed a marked improvement over state-of-the-art methods, hence proving the effectiveness of our fairly easy CNN model as the deep learning benchmark for facial MER.

Delay tolerant networks (DTNs) are a kind of sparse and highly mobile wireless networks, where no stable connectivity guarantee can be assumed. Most DTN users have several points of interest (PoIs), and they enjoy disseminating messages to the other users of the same PoI through WiFi. In DTNs, some time-sensitive messages (disaster warnings, search notices, etc.) need to be rapidly propagated among specific users or areas. Therefore, finding a path from the source to the destination with the shortest delay is the key problem. Taking the dissemination cost into consideration, we propose an efficient message dissemination strategy for minimizing delivery delay (MDMD) in DTNs, which first defines the user’s activeness according to the transiting habit among different PoIs. Furthermore, depending on the activeness, an optimal user in each PoI is selected to constitute the path with the shortest delay. Finally, the MDMD with inactive state (on the way between PoIs) is further proposed to enhance the applicability. Simulation results show that, compared with other dissemination strategies, MDMD achieves the lowest average delay, and the comparable average hopcounts, on the premise that the delivery ratio is guaranteed to be 100% by the sufficient simulation time.

In the December 2018 issue of the Journal of Biosciences, in the article titled ‘‘Protein-rich extract of Musca domestica larvae alleviated metabolic disorder in STZ-induced type 2 diabetic rat model via hepatoprotective and pancreatic β -cell protective activities’’ by Hanfang Mei et al. (DOI: 10.1007/s12038-018-9804-z; Vol. 43, No. 5, pp. 969–983), the affiliations of Hanfang Mei have been incompletely mentioned as

In this paper, we investigate a stochastic Galerkin approximation scheme for an optimal control problem governed by an elliptic PDE with random field in its coefficients. The optimal control minimizes the expectation of a cost functional with mean-state constraints. We first represent the stochastic elliptic PDE in terms of the generalized polynomial chaos expansion and obtain the parameterized optimal control problems. By applying the Slater condition in the subdifferential calculus, we obtain the necessary and sufficient optimality conditions for the state-constrained stochastic optimal control problem for the first time in the literature. We then establish a stochastic Galerkin scheme to approximate the optimality system in the spatial space and the probability space. Then the a priori error estimates are derived for the state, the co-state and the control variables. A projection algorithm is proposed and analyzed. Numerical examples are presented to illustrate our theoretical results.

Membrane bioreactor (MBR) and microbial fuel cell (MFC) are new technologies based on microbial process. MBR takes separation process as the core to achieve the high efficient separation and enrichment the beneficiation of microbes during the biological treatment. MFC is a novel technology based on electrochemical process to realize the mutual conversion between biomass energy and electric energy, in order to solve the problems of serious membrane fouling and low efficiency of denitrification in membrane bioreactor, the low power generation efficiency, and unavailability of bioelectric energy of MFC. In recent years, MFC-MBR coupling system emerged. It can effectively mitigate the membrane fouling and reduce the excess sludge production. Simultaneously, the electricity can be used effectively. The new coupling system has good prospects for development. In this paper, we summarized the research progresses of the two kinds of coupling systems in recent years and analyzed the coupling structure and forms. Based on the above, the future development fields of the MFC-MBR coupling system were prospected.

Zinc (Zn) is widely known as an essential trace element for fish and new ways to supply it to them are needed. Palygorskite (Pal) is a natural silicate clay mineral and the palygorskite structure contains nano-channels, which are filled with water and exchangeable ions. Zn-bearing palygorskites (Zn-Pal) prepared using ion exchange have attracted attention due to the durable antibacterial properties that limit pathogens and as a potential new Zn source for livestock. The present study was conducted to evaluate the effects of Zn-Pal supplementation on the growth performance, nutrient retention, meat quality, Zn accumulation, and intestinal Zn transporter protein gene expression in blunt snout bream Megalobrama amblycephala. The fish were fed a basal diet without an exogenous Zn source and the basal diet was supplemented with 125 mg/kg Zn as Zn sulfate (ZnSO4) or 35, 80, or 125 mg/kg Zn as Zn-Pal. Each diet was tested using three replicates for 7 weeks. The results showed that dietary Zn-Pal supplementation quadratically (P 0.05), increased mRNA expression of the metal-response element-binding transcription factor-1 in the intestine (P

The giant panda feeds almost exclusively on bamboo, a diet highly enriched in lignin and cellulose, but is characterized by a digestive tract similar to carnivores. It is still large unknown if and how the giant panda gut microbiota contributes to lignin and cellulose degradation. Here we show the giant pandas' gut microbiota does not significantly contribute to cellulose and lignin degradation. We found that no operational taxonomic unit had a nearest neighbor identified as a cellulolytic species or strain with a significant higher abundance in juvenile than cubs, a very low abundance of putative lignin and cellulose genes existed in part of analyzing samples but a significant higher abundance of genes involved in starch and hemicellulose degradation in juveniles than cubs. Moreover, a significant lower abundance of putative cellulolytic genes and a significant higher abundance of putative α-amylase and hemicellulase gene families were present in giant pandas than in omnivores or herbivores.

Red crucian carp (Carassius auratus red var.) is an ornamental fish with vivid red/orange color. It has been found that the adult body color of this strain forms a gray-to-red change. In this study, skin transcriptomes of red crucian carp are first obtained for three different stages of body color development, named by gray-color (GC), color-variation (CV), and red-color (RC) stages, respectively. From the skins of GC, CV, and RC, 103,229; 108,208; and 120,184 transcripts have been identified, respectively. Bioinformatics analysis reveals that 2483, 2967, and 4473 unigenes are differentially expressed between CV and GC, RC and CV, and RC and GC, respectively. A part of the differentially expressed genes (DEGs) are involved in the signaling pathway of pigment synthesis, such as the melanogenesis genes (Mitfa, Pax3a, Foxd3, Mc1r, Asip); tyrosine metabolism genes (Tyr, Dct, Tyrp1, Silva, Tat, Hpda); and pteridine metabolism genes (Gch, Xdh, Ptps, Tc). According to the data of transcriptome and quantitative PCR, the expression of Mitfa and its regulated genes which include the genes of Tyr, Tyrp1, Dct, Tfe3a, and Baxα, decreases with gray-to-red change. It is suggested that Mitfa and some genes, being related to melanin synthesis or melanophore development, are closely related to the gray-to-red body color transformation in the red crucian carp. Furthermore, the DEGs of cell apoptosis and autophagy pathway, such as Tfe3a, Baxα, Hsp70, Beclin1, Lc3, Atg9a, and Atg4a, might be involved in the melanocytes fade away of juvenile fish. These results shed light on the regulation mechanism of gray-to-red body color transformation in red crucian carp, and are helpful to the selective breeding of ornamental fish strains.

Drought is occurring with increased frequency under climate warming. To understand the behavior of drought and its variation in the future, current and future drought in the twenty-first century over China is discussed. The drought frequency and trend of drought intensity are assessed using the Palmer Drought Severity Index (PDSI), which is calculated based on historical meteorological observations and outputs of the fifth Coupled Model Intercomparison Project (CMIP5) under three representative concentration pathway (RCP) scenarios. The simulation results of drought period, defined by PDSI class, could capture more than 90% of historical drought events. Projection results indicate that drought frequency will increase over China in the twenty-first century under the RCP4.5 and RCP8.5 scenarios. In the mid-twenty-first century (2021–2050), similar patterns of drought frequency are found under the three emission scenarios, and annual drought duration would last 3.5–4 months. At the end of the twenty-first century (2071–2100), annual drought duration could exceed 5 months in northwestern China as well as coastal areas of eastern and southern China under the RCP8.5 scenario. Drought is slightly reduced over the entire twenty-first century under the RCP2.6 scenario, whereas drought hazards will be more serious in most regions of China under the RCP8.5 scenario.

Activating mutations of epidermal growth factor receptor (EGFR) play crucial roles in the oncogenesis of human non-small cell lung cancer (NSCLC). By screening 79 commercially available natural products, we found that the natural compound deguelin exhibited a profound anti-tumor effect on NSCLC via directly down-regulating of EGFR-signaling pathway. Deguelin potently inhibited in vitro EGFR kinase activity of wild type (WT), exon 19 deletion, and L858R/T790M-mutated EGFR. The in silico docking study indicated that deguelin was docked into the ATP-binding pocket of EGFRs. By suppression of EGFR signaling, deguelin inhibited anchorage-dependent, and independent growth of NSCLC cell lines, and significantly delayed tumorigenesis in vivo. Further study showed that deguelin inhibited EGFR and downstream kinase Akt, which resulted in the activation of GSK3β and eventually enhanced Mcl-1 phosphorylation at S159. Moreover, deguelin promoted the interaction between Mcl-1 and E3 ligase SCFFBW7, which enhanced FBW7-mediated Mcl-1 ubiquitination and degradation. Additionally, phosphorylation of Mcl-1 by GSK3β is a prerequisite for FBW7-mediated Mcl-1 destruction. Depletion or pharmacological inactivation of GSK3β compromised deguelin-induced Mcl-1 ubiquitination and reduction. Taken together, our data indicate that enhancement of ubiquitination-dependent Mcl-1 turnover might be a promising approach for cancer treatment.