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Summary: Background: Benefits of Intermittent fasting (IF) on health-related outcomes have been found in a range of randomised controlled trials (RCTs). Our umbrella review aimed to systematically analyze and synthesize the available causal evidence on IF and its impact on specific health-related outcomes while evaluating its evidence quality. Methods: We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane databases (from inception up to 8 January 2024) to identify related systematic reviews and meta-analyses of RCTs investigating the association between IF and human health outcomes. We recalculated the effect sizes for each meta-analysis as mean difference (MD) or standardized mean difference (SMD) with corresponding 95% confidence intervals (CIs). Subgroup analyses were performed for populations based on three specific status: diabetes, overweight or obesity, and metabolic syndrome. The quality of systematic reviews was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. This study is registered with PROSPERO (CRD42023382004). Findings: A total of 351 associations from 23 meta-analyses with 34 health outcomes were included in the study. A wide range of outcomes were investigated, including anthropometric measures (n = 155), lipid profiles (n = 83), glycemic profiles (n = 57), circulatory system index (n = 41), appetite (n = 9), and others (n = 6). Twenty-one (91%) meta-analyses with 346 associations were rated as high confidence according to the AMSTAR criteria. The summary effects estimates were significant at p

Visible Light Communication (VLC) has become an effective underwater communication technology due to its advantages such as fast transmission speed and strong confidentiality. When light propagates underwater, it is prone to scattering, resulting in a decrease in the energy of light propagation with the increase of transmission distance. Therefore, improving the responsiveness of the receiving end is the key technology to achieve underwater VLC. This article first designs a new holographic waveguide focusing system for the front end of the detector, which can effectively improve the signal-to-noise ratio of underwater detectors. Then, we construct a low-cost antimony sulfide thin film detector with weak light detection capability. Based on the built VLC system, the experimental results show that the dark current of the receiver detector is only 10-7 A/cm2, with a 3 dB bandwidth of 220 kHz, a response of 0.2 A/W, and an external quantum efficiency of over 70% in the blue green light band. Therefore, the new antimony sulfide thin film detector combined with a holographic waveguide focusing system can achieve weak light detection of visible light, making it a very effective underwater visible light receiving system.

Limb length discrepancy (LLD) is a common orthopedic condition that can result in significant functional impairment, pain, and cosmetic deformities. Current reconstructive techniques for severe LLD are primarily based on callus distraction, which is a time-consuming process that can lead to complications, such as significant infection, joint stiffness, and stress fractures. To reduce the therapeutic time and minimize the risk of complications, we investigated the use of vascularized bone flaps as a technical supplement to callus distraction in the reconstruction of short limbs. We present two cases of severe LLD in the upper and lower legs, in which a two-stage reconstruction approach was used. In the first stage, external fixation was applied to the affected limb to correct the soft tissue length and convert the short deformity into a bone defect. In the second stage, the bone defect was reconstructed using bilateral (patient A) or unilateral (patient B) free vascularized fibula bone grafts. Both patients had complete survival of the fibular grafts without stress fractures, and bone consolidation took 8 months (patient A) and 4 months (patient B). Compared to the traditional callus distraction, the two-stage approach was found to be more time-saving and reliable. The entire reconstructive scheme required 18 and 4 months for patients A and B, respectively, whereas the traditional callus distraction required 41 and 17 months, respectively. These findings suggest that the use of vascularized bone flaps as a technical supplement for callus distraction may provide an effective and efficient alternative for the treatment of severe LLD. Further studies are needed to validate these results and assess the long-term outcomes of this approach.

We aimed to identify co-stimulatory molecule clusters and explore their associations with immune infiltration and tumor mutation burden (TMB) in non-small cell lung cancer (NSCLC), using a systematic analysis based on RNA-seq and mutation data in TCGA database. Twelve immune-related prognostic co-stimulatory molecules were screened. Based on the expression of these molecules, all samples were divided into four clusters by Consensus clustering analysis. Clusters 2 and 4 were associated with worse survival and favorable prognosis, respectively. The proportion of patients with different age, Pathologic T and Pathologic stage among these four clusters showed significant differences. Cluster 4 was associated with a higher proportion of patients with pathological N0 and T1–2, as well as early tumors (stages I–II). Additionally, these clusters significantly differed in terms of immune infiltration of memory B cells, regulatory T cells, M2 macrophages, and activated memory CD4+ T cells, as well as the expression of six checkpoint genes. Worse survival was associated with a high rather than a low TMB; among the clusters, clusters 4 and 2 had the lowest and highest TMB, respectively. In conclusion, four co-stimulatory molecule clusters identified in NSCLC significantly differed in terms of survival, tumor stage, immune response, and TMB. Highlights Four co-stimulatory molecule clusters were identified that correlated differently with survival. Feature genes of four clusters were enriched in different functions. Four clusters significantly differed in terms of tumor stage, immune infiltration, and checkpoint gene expression. Worse survival was associated with high, compared with low TMB. Survival was better for cluster 4 than other clusters, and TMB was low.

Jin Ning Fang (JNF), a classic Chinese medicine formula, is widely used to treat lung cancer. However, its molecular mechanism remains unclear. Thus, we aimed to explore the pharmacological mechanisms of JNF against lung cancer. JNF targets and lung cancer-related genes were derived from public databases. Key compounds, potential therapeutic targets, and pathways were determined via bioinformatics analyses. Further, molecular docking, in vitro experiments, and real-time PCR were performed to verify the findings. A total of 27 active compounds and 25 genes were selected. Pharmacological network revealed that quercetin, calcium carbonate, and beta-sitosterol might be candidate agents; ESR1, AR, AKT1, FDPS, PIM1, VCAM1, SLC29A1, NQO1, and ANPEP could be potential drug targets. These genes were involved in apoptosis pathway. Docking analysis showed that beta-sitosterol combined well with AKT1, AR, and ESR1. In vitro experiments confirmed that JNF could inhibit proliferation and promote apoptosis of A549 cells. JNF treatment inhibited the level of FDPS, PIM1, VCAM1, SLC29A1, NQO1, and ESR1, while increased the level of AR and ANPEP. This study illuminated that JNF exerts anti-lung cancer effects through regulating multiple targets and pathways, and the identified genes may be used as potential therapeutic targets for lung cancer.

Natural gas is extensively used as a clean energy source in cities and industries; consequently, there are associated risks of accidental explosions. To reduce the hazards associated with natural gas explosions, it is important to study the inherent laws of natural gas blast loads in unconfined spaces and establish load models. Using experiments on natural gas explosions in unconfined spaces, this study demonstrates the influence of natural gas concentrations, propagation distances, and gas volumes upon explosion loads. A new load model was proposed for the overpressure–time history curves of natural-gas explosions in an unconfined space. A comparison with the empirical model indicated that the predictive effect was superior to that of previous models, such as the TNT equivalent model and the TNO multi-energy model.

ObjectiveTo determine the preventive effect of melatonin on delirium in the intensive care units.MethodsWe conducted a systematic search of the PubMed, Cochrane Library, Science, Embase, and CNKI databases, with retrieval dates ranging from the databases’ inception to September 2022. Controlled trials on melatonin and placebo for preventing delirium in the intensive care units were included. The meta-analysis was performed using Review Manager software (version 5.3) and Stata software (version 14.0).ResultsSix studies involving 2374 patients were included in the meta-analysis. The results of the meta-analysis showed that melatonin did not reduce the incidence of delirium in ICU patients (odds ratio [OR]: 0.71; 95% confidence interval [CI]: 0.46 to 1.12; p = 0.14). There was a strong hetero-geneity between the selected studies (I2 = 74%). Subgroup analysis results showed that melatonin reduced the incidence of delirium in cardiovascular care unit (CCU) patients (OR: 0.52; 95% CI: 0.37 to 0.73; p=0.0001), but did not in general intensive care unit (GICU) patients (OR: 1.14; 95% CI: 0.86 to 1.50; p=0.35). In terms of the secondary outcomes, there were no significant differences in all-cause mortality (OR: 0.85; 95% CI: 0.66 to 1.09; p=0.20), length of ICU stay (mean difference [MD]: 0.33; 95% CI: -0.53 to 1.18; p=0.45), or length of hospital stay (MD: 0.51; 95% CI: -1.17 to 2.19; p=0.55).ConclusionMelatonin reduced the incidence of delirium in CCU patients, but did not significantly reduce the incidence of delirium in GICU patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022367665.

Due to the influence of many factors, the overpressure–time history load model of vented gas explosions is difficult to describe and is not conducive to further structural design. Based on vented gas explosion test data, this paper obtains three typical overpressure-time history curves and puts forward a new semi-empirical model— double hump model that considers gas concentration and venting pressure, and gives a formula for peak pressure and overpressure–time history model. The scientificity of the model is then verified by the total impulse in the load. The model is able directly reflect the load characteristics, provide reference for calculating key parameters of a vented gas explosion and provide information on the structural response under the load. The model thereby has the potential to help reduce the impact of gas explosion disasters.

Understanding animal growth plays an important role in improving animal genetics and breeding. In order to explore the early growth and development law of Ashidan yak, the body weight (BW), wither height (WH), body oblique length (BL) and chest girth (CG) of 260 female Ashidan yaks were measured. These individuals grew under grazing conditions, and growth traits were measured at 6, 12, 18 and 30 months of age. Then the absolute growth and relative growth of Ashidan yak were calculated, and five nonlinear models (Logistic model, Gompertz model, Brody model, von Bertalanffy model and Richards model) were used to fit the growth curve of Ashidan yak. The fitting effect of the model was evaluated according to MSE, AIC and BIC. The results showed that the growth rate of Ashidan yak was the fastest from 12 to 18 months old, and the growth was slow or even stagnant from 6 to 12 months old. The AIC and BIC values of the Richards model were the lowest among the five models, with an AIC value of 4543.98 and a BIC value of 4563.19. The Richards model estimated body weight at 155.642 kg. In summary, the growth rate of female Ashidan yak changes with the seasons, growing faster in warm seasons and slower in cold seasons. Richards model is the best model to describe the growth curve of female Ashidan yak in five nonlinear models.

Tianzhu white yak is a rare local yak breed with a pure white coat in China. In recent years, breeders have discovered long-haired individuals characterized by long hair on the forehead in the Tianzhu white yak, and the length and density of the hair on these two parts of the body are higher than that of the normal Tianzhu white yak. To elucidate the genetic mechanism of hair length in Tianzhu white yak, we re-sequence the whole genome of long-haired Tianzhu White yak (LTWY) (n = 10) and normal Tianzhu White yak (NTWY) (n = 10). Then, fixation index (FST), θπ ratio, cross-population composite likelihood ratio (XP-CLR), integrated haplotype score (iHS), cross-population extended haplotype homozygosity (XP-EHH), and one composite method, the de-correlated composite of multiple signals (DCMS) were performed to discover the loci and genes related to long-haired traits. Based on five single methods, we found two hotspots of 0.2 and 1.1 MB in length on chromosome 6, annotating two (FGF5, CFAP299) and four genes (ATP8A1, SLC30A9, SHISA3, TMEM33), respectively. Function enrichment analysis of genes in two hotspots revealed Ras signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, and Rap1 signaling pathway were involved in the process of hair length differences. Besides, the DCMS method further found that four genes (ACOXL, PDPK1, MAGEL2, CDH1) were associated with hair follicle development. Henceforth, our work provides novel genetic insights into the mechanisms of hair growth in the LTWY.

Abstract Background Long non-coding RNA (lncRNA) as an important regulator has been demonstrated playing an indispensable role in the biological process of hair follicles (HFs) growth. However, their function and expression profile in the HFs cycle of yak are yet unknown. Only a few functional lncRNAs have been identified, partly due to the low sequence conservation and lack of identified conserved properties in lncRNAs. Here, lncRNA-seq was employed to detect the expression profile of lncRNAs during the HFs cycle of yak, and the sequence conservation of two datasets between yak and cashmere goat during the HFs cycle was analyzed. Results A total of 2884 lncRNAs were identified in 5 phases (Jan., Mar., Jun., Aug., and Oct.) during the HFs cycle of yak. Then, differential expression analysis between 3 phases (Jan., Mar., and Oct.) was performed, revealing that 198 differentially expressed lncRNAs (DELs) were obtained in the Oct.-vs-Jan. group, 280 DELs were obtained in the Jan.-vs-Mar. group, and 340 DELs were obtained in the Mar.-vs-Oct. group. Subsequently, the nearest genes of lncRNAs were searched as the potential target genes and used to explore the function of DELs by GO and KEGG enrichment analysis. Several critical pathways involved in HFs development such as Wnt signaling pathway, VEGF signaling pathway, and signaling pathways regulating pluripotency of stem cells, were enriched. To further screen key lncRNAs influencing the HFs cycle, 24 DELs with differ degree of sequence conservation were obtained via a comparative analysis of partial DELs with previously published lncRNA-seq data of cashmere goat in the HFs cycle using NCBI BLAST-2.9.0+, and 3 DELs of them were randomly selected for further detailed analysis of the sequence conservation properties. Conclusions This study revealed the expression pattern and potential function of lncRNAs during HFs cycle of yak, which would expand the knowledge about the role of lncRNAs in the HFs cycle. The findings related to sequence conservation properties of lncRNAs in the HFs cycle between the two species may provide valuable insights into the study of lncRNA functionality and mechanism.

Abstract Background Hypertension, a major risk factor of cardiovascular mortality, is a critical issue for public health. Although Baduanjin (Eight Brocades, EB), a traditional Chinese exercise, might influence blood pressure, glucose, and lipid status, the magnitude of true effects and subgroup differences remains unclear. Therefore, we performed a systematic review of relevant randomized controlled trials (RCTs) to evaluate the effect of EB on patient-important outcomes. Methods We systematically searched PubMed, the Cochrane Library, Web of Science, and Chinese databases since inception until March 30, 2020. Meta-analysis was carried out using “meta” package in R 3.4.3 software. A prespecified subgroup analysis was done according to the type of comparisons between groups, and the credibility of significant subgroup effects (P

Abstract Background To determine plasma ephrin-A1 and VEGF165 levels in a cohort of diabetic retinopathy patients. Methods Plasma ephrin-A1 and VEGF165 levels in fifty-five subjects including 19 individuals without diabetes (non-DM), 16 patients with diabetes (DM) but without diabetic retinopathy, and 20 patients with diabetic retinopathy (DR), were determined by ELISA. Serum creatinine, total cholesterol, fasting blood glucose and HbA1c were also measured. One-way ANOVA, Kruskal-Wallis Test, Mann-Whitney U Test corrected by Bonferroni, Pearson Correlation Analysis and Spearman Correlation Coefficient Analysis were used for data analysis. Results Ephrin-A1 expression could be detected in human plasma with an average of 1.52 ± 0.43 (mean ± SEM) ng/ml. In DR subjects, the plasma ephrin-A1concentration was 3.63 ± 4.63 ng/ml, which was significantly higher than that of the other two groups (non-DM: 0.27 ± 0.13 ng/ml, DM: 0.35 ± 0.34 ng/ml). The expression of VEGF165 in human plasma was 34.00 ± 42.55 pg/ml, with no statistical difference among the three groups. There was no correlation between ephrin-A1 and VEGF165 in human plasma, but there was a correlation between plasma ephrin-A1 and duration of diabetes. Conclusions Plasma ephrin-A1 was highly expressed in patients with diabetic retinopathy, and there was no difference of plasma VEGF165 expression in patients with diabetic retinopathy compared to the other two groups, suggesting that changes of plasma ephrin-A1 may be a more sensitive biomarker than plasma VEGF165 in detecting diabetic retinopathy.

The growth hormone receptor (GHR) is a member of the cytokine/hematopoietic factor receptor superfamily, which plays an important role in the growth and development, immunity, and metabolism of animals. This study identified a 246 bp deletion variant in the intronic region of the GHR gene, and three genotypes, including type II, type ID, and type DD, were observed. Genotype analysis of structural variation (SV) was performed on 585 individuals from 14 yak breeds, and it was found that 246 bp deletion was present in each breed. The II genotype was dominant in all yak breeds except for SB yak. The association analysis of gene polymorphisms and growth traits in the ASD yak population showed that the 246 bp SV was significantly associated with body length at 6 months (p < 0.05). GHR messenger RNA (mRNA) was expressed in all the tested tissues, with significantly higher levels in the liver, muscle, and fat than in other organs. The results of transcription activity showed that the luciferase activity of the pGL4.10-DD vector was significantly higher than that of the pGL4.10-II vector (p < 0.05). Additionally, the transcription-factor binding prediction results showed that the SV in the runt-related transcription factor 1 (Runx1) transcription-factor binding site may affect the transcriptional activity of the GHR gene, regulating yak growth and development. This study showed that the novel SV of the GHR gene could be used as a candidate molecular marker for the selection of the early growth trait in ASD yak.

Abstract Background Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease and has become a heavy economic and social burden due to its high prevalence and morbidity. The most effective strategy is that patients with DKD should be diagnosed and treated early. Preliminary studies showed that the Chinese herbal Tangshen Formula (TSF) may delay the progression of DKD, reducing microalbuminuria and macroalbuminuria and improving renal function. We designed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of TSF in patients with DKD. Methods/design This trial is a 13-center, randomized, double-blind, placebo-controlled study. A total of 632 participants will be randomized in a 1:1 ratio to an experiment group (TSF plus losartan) and a control group (placebo plus losartan). The trial cycle will last 24 weeks. The primary outcome will be the change in the urine microalbumin–creatinine ratio from baseline to week 24. The secondary outcome will be the change in the rate of progression to the clinical proteinuria period after intervention, the rate of urine microalbumin negative conversion, the rate of normal urinary microalbumin, the doubling rate of the baseline creatinine value and the glomerular filtration rate between the two groups. Safety in medication will also be evaluated. Discussion We hypothesize that patients with type 2 diabetes in the early stage of DKD will benefit from TSF. If successful, this study will provide evidence-based recommendations for clinicians. Trial registration ClinicalTrials.gov, NCT03009864. Registered January 2017.

Developing degradable bio-plastics has been considered feasible to lessen marine plastic pollution. However, unanimity is still elusive regarding the actual degradability of bio-plastics such as polylactide (PLA) and poly(hydroxybutyrate) (PHB). Thus, herein, we studied the degradability of fabrics made from PLA/PHB blends in marine seawater. The dry-mass percentage of the PLA/PHB fabrics decreased progressively from 100% to 85~90% after eight weeks of immersion. Two environmental aging parameters (UV irradiation and aerating) were also confirmed to accelerate the abiotic hydrolysis of the incubated fabrics. The variation in the molecular structure of the PLA/PHB polymers after the degradation process was investigated by electrospray ionization mass spectrometry (ESI-MS). However, the hydrolysis degradability of bulky PLA/PHB blends, which were used to produce such PLA/PHB fabrics, was negligible under identical conditions. There was no mass loss in these solid PLA/PHB plastics except for a decrease in their tensile strength. Finally, a deep learning artificial neural network model was proposed to model and predict the nonlinear abiotic hydrolysis behavior of PLA/PHB fabrics. The degradability of PLA/PHB fabrics in marine water under the synergistic destructive effects of seawater, UV, and dissolved oxygen provides a pathway for more sustainable textile fibers and apparel products.

Introduction: The role of intraoperative ventilation strategies in subjects undergoing surgery is still contested. This meta-analysis study was performed to assess the relationship between the low tidal volumes strategy and conventional mechanical ventilation in subjects undergoing surgery.Methods: A systematic literature search up to December 2020 was performed in OVID, Embase, Cochrane Library, PubMed, and Google scholar, and 28 studies including 11,846 subjects undergoing surgery at baseline and reporting a total of 2,638 receiving the low tidal volumes strategy and 3,632 receiving conventional mechanical ventilation, were found recording relationships between low tidal volumes strategy and conventional mechanical ventilation in subjects undergoing surgery. Odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CIs) were calculated between the low tidal volumes strategy vs. conventional mechanical ventilation using dichotomous and continuous methods with a random or fixed-effect model.Results: The low tidal volumes strategy during surgery was significantly related to a lower rate of postoperative pulmonary complications (OR, 0.60; 95% CI, 0.44–0.83, p < 0.001), aspiration pneumonitis (OR, 0.63; 95% CI, 0.46–0.86, p < 0.001), and pleural effusion (OR, 0.72; 95% CI, 0.56–0.92, p < 0.001) compared to conventional mechanical ventilation. However, the low tidal volumes strategy during surgery was not significantly correlated with length of hospital stay (MD, −0.48; 95% CI, −0.99–0.02, p = 0.06), short-term mortality (OR, 0.88; 95% CI, 0.70–1.10, p = 0.25), atelectasis (OR, 0.76; 95% CI, 0.57–1.01, p = 0.06), acute respiratory distress (OR, 1.06; 95% CI, 0.67–1.66, p = 0.81), pneumothorax (OR, 1.37; 95% CI, 0.88–2.15, p = 0.17), pulmonary edema (OR, 0.70; 95% CI, 0.38–1.26, p = 0.23), and pulmonary embolism (OR, 0.65; 95% CI, 0.26–1.60, p = 0.35) compared to conventional mechanical ventilation.Conclusions: The low tidal volumes strategy during surgery may have an independent relationship with lower postoperative pulmonary complications, aspiration pneumonitis, and pleural effusion compared to conventional mechanical ventilation. This relationship encouraged us to recommend the low tidal volumes strategy during surgery to avoid any possible complications.

Infectious microbial diseases are a major public health hazard, calling for more innovative antimicrobials. Herein, polylactic acid (PLA) oligomers have been explored and reported as a bio-safe and eco-friendly functional antimicrobial agent against pathogens, such as viruses (H1N1, H3N2, and SARS-CoV-2), bacteria (E. coli, S. aureus, K. pneumoniae, MRSA), and fungi (C. albicans). The PLA oligomers were prepared by direct catalyst-free condensation polymerization of l-lactic acid monomers and characterized by FT-IR and 1H-NMR. The antiviral results demonstrate that PLA oligomers possess robust (inhibiting rate > 99%) and rapid (−) and Gram positive (G+) bacteria. The PLA oligomers also perform efficiently in killing a large amount of C. albicans as high as 105 cfu/mL down to zero at the concentration of 10 mg/mL. Thus, the broad-spectrum antimicrobial activity endowed the PLA oligomers with a promising biocidal option, except antibiotics in a wide range of applications, such as medical textiles, food preservation, water disinfection, and personal hygiene, in light of their unique biodegradability and biocompatibility.

Although significant advancement has been made in the study of adipogenesis, knowledge about how chromatin accessibility regulates yak adipogenesis is lacking. We here described genome-wide dynamic chromatin accessibility in preadipocytes and adipocytes by using the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), and thus revealed the unique characteristics of open chromatin during yak adipocyte differentiation. The chromatin accessibility of preadipocytes and adipocytes exhibited a similar genomic distribution, displaying a preferential location within the intergenic region, intron, and promoter. The pathway enrichment analysis identified that genes with differential chromatin accessibility were involved in adipogenic metabolism regulation pathways, such as the peroxisome proliferator activated receptor-γ (PPAR) signaling pathway, wingless-type MMTV integration site (Wnt) signaling pathway, and extracellular matrix-receptor (ECM–receptor) interaction. Integration of ATAC-seq and mRNA-seq revealed that genes with a high expression were associated with high levels of chromatin accessibility, especially within 1 kb upstream and downstream of the transcription start site. In addition, we identified a series of transcription factors (TFs) related to adipogenesis and created the TF regulatory network, providing the possible interactions between TFs during yak adipogenesis. This study is crucial for advancing the understanding of transcriptional regulatory mechanisms of adipogenesis and provides valuable information for understanding the adaptation of plateau species to high-altitude environments by maintaining whole body homeostasis through fat metabolism.

Aluminum alloy is the preferred material for lightweight structure, and has broad application prospects in aerospace, transportation and ships. The additive manufacturing of aluminum alloy possesses outstanding advantages and potential on fabricating complicated three-dimensional precision structural parts. Furthermore, this method can be characterized by its high efficiency and excellent structural properties. With regard to the rapid development of the aluminum alloy additive manufacturing, the research status and latest achievements of aluminum alloy fabricated with additive manufacturing from the aspects of structure and performance, precision and quality, controlling of defects and numerical simulation, and the shortcomings of current research were summarized. Based on these, the key issues that will be focused were summarized at last, including realizing the control of the micro-structure, clarifying the forming mechanism of the stress, improving the forming accuracy, and studying the distribution law of the temperature field in the forming process.

Application of the organic fertilizers can improve soil properties and agricultural product quality, while the in-depth effect of organic fertilizer needs further exploration. In this study, the apple fruit (Malus pumila Mill.) quality, soil physicochemical characteristics, and microbial community under different fertilizers including control without fertilizer (CK), composted manure (CM), biogas slurry (BS), and chemical fertilizer (CF) were systematically investigated, and each treatment was repeated three times in completely random block plots with equal NPK content of fertilizer applied in each treatment. The CM treated apple fruit were observed with the best vertical diameter (78.72 ± 4.32 mm), transverse diameter (87.51 ± 1.3 mm), and color index (L* = 55.48 ± 5.48, b* = 18.96 ± 1.86). Meanwhile, the CM and BS treated apple fruit had higher flesh firmness than that of CK and CF treatment, implying that the organic fertilization can improve the storability and crispy taste apple fruit. Furthermore, the total sugars, essential amino acid, crude protein, total acids, and soluble solid contents of apple fruit were also significantly improved by using CM and BS fertilizer due to the resulting higher N, P, and organics content in soil. The application of organic fertilizer also dramatically enhanced the bacterial and fungi diversity, which may contribute to better soil respiration. The results obtained in this study reveals the insight effect of organic fertilizer on improvement of fruit quality and soil health and can supply technical assistance to organic cultivation of apple.

Triboelectric nanogenerators (TENGs) have attracted many researchers’ attention with their remarkable potential despite the fact that the practical implementation requires further improvement in their electric performance. In this work, a novel graphene phase two-dimension material, graphitic carbon nitride (g-C3N4), was employed for the development of a TENG material with enhanced features. An electrospun nanofibrous PA66 membrane doped with g-C3N4 was fabricated as a multifunctional TENG for harvesting different kinds of mechanical energy and detecting human motions. By utilizing the innovative 2D material in PA66 solution for electrospinning, the as-made TENG showed a two times enhancement in electrical performance as compared to the control device, and also had the advantages of lightweight, softness, high porosity, and rugged interface properties. The assembled TENG with 4 cm2 could light up 40 light-emitting diodes by gentle hand clapping and power electronic watches or calculators with charging capacitors. At a given impact force of 40 N and 3 Hz, the as-made TENG can generate an open-circuit voltage of 80 V, short current of ±3 µA, charge transfer of 50 nC, and a maximum power density of 45 mW/m2 at a load resistance of 500 MΩ. The UV light sensitivity of TENG was also improved via g-C3N4 doping, showing that charge transfer is very sensitive with a two times enhancement with dopant. For the demonstration of applications, the g-C3N4 doped TENG was fabricated into an energy flag to scavenge wind energy and sensor devices for detecting human motions.

Copy number variation (CNV) is a structural variant with significant impact on genetic diversity. CNV has been widely used in breeding for growth traits, meat production or quality, and coat color. SRY-like box genes (SOXs) are a class of transcription factors that play a regulatory role in cell fate specification and differentiation. SOX5 and SOX8 belong to subgroups D and E of the SOXs, respectively. Previous studies have shown that SOX5 and SOX8 are essential in the development of bones. In this study, we explored the association between the growth traits and CNVs of SOX5 and SOX8 in 326 Ashidan yaks and detected mRNA expression levels in different tissues. Our results illustrated that CNVs of SOX5 and SOX8 were significantly associated with withers height at 18 months of age and chest girth at 30 months of age (p < 0.05). The CNV combination of SOX5 and SOX8 was significantly associated with withers height at 18 months of age (p < 0.01). SOX5 expression in the lung was significantly higher than in the heart, spleen, kidney, and muscle (p < 0.05). SOX8 expression in the lung was significantly higher than in the liver and muscle (p < 0.05). Our results provide evidence that the CNVs of SOX5 and SOX8 genes could be used as new markers for the selection of yak growth traits.

Background: Diabetic retinopathy (DR) is one of the most common and severe microvascular complications of diabetes mellitus (DM), which results in blindness among adults worldwide. Presently, the efficacy of drug treatments for diabetic retinopathy (DR) is not satisfactory, thus urgently necessitating effective drug treatment measures. TangWang prescription (TWP) has been found to have retinal protection effects in previous clinical and basic research. However, there is a lack of rigorous, randomized, and controlled studies. This study aims to evaluate the efficacy and safety of TWP in delaying the development of DR.Methods: This study is a randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial, consisting of 384 participants to be randomized in a 1:1 ratio in the treatment and control groups. Furthermore, the treatment and control groups will be administered the TangWang prescription and the placebo, respectively, each at a dose of one bag twice a day. The study period will last for 48 weeks. The primary outcome measure will be the changes in the degree of retinal microvascular lesions before and after treatment. The secondary outcome will be changes in the degree of hemangioma, microvascular bleeding, microvascular leakage, macular edema, and vision. All statistical tests will be two-sided, and a p < 0.05 will be considered statistically significant.Discussion: We hypothesize that the patients with DR will benefit from TangWang prescription, and in addition to the central random system and platform of dynamic information collection, the patients’ conditions will be monitored, and the data collected for analysis. If successful, this study will provide evidence that the TWP formulation delays in the progression of DR.Trial registration: The design of this trial has been registered with the ClinicalTrials.gov (NCT03025399).

Marine plastic pollution is emerging as a potential hazard to global ecosystems and human health. Micro-fibers derived from synthetic textiles contribute a considerable proportion of plastic debris. Bio-polymers/bio-plastics have been proposed for the application of apparel products, yet their degradability, fate, durability and related environmental parameters are still elusive and need further exploration. Herein, we report the degradation behavior of poly(lactide acid)/poly(hydroxybutyrate) (PLA/PHB) fabrics, made from PLA/PHB multi-filament yarns, in subtropics marine seawater. The degradation experiments were performed under various parallel conditions including static seawater, aerobic seawater in dark box, aerobic seawater under sunlight, static seawater under ultra-violet light and aerobic seawater under ultra-violet light. Continuous mass loss of PLA/PHB fabrics as the immersion time in the seawater increased was confirmed. The hydrolysis rate of PLA/PHB fabrics accelerated in the presence of UV light and dissolved oxygen in the seawater. Moreover, the tensile strength of the PLA/PHB yarns dropped rapidly by 38.54–68.70% in spite of the mass loss percentage being from 9.57% to 14.48% after 2 weeks’ immersion. All the PLA/PHB fabrics after two weeks’ immersion exhibited similar ATR-IR spectra. Therefore, the degradability of PLA/PHB fabrics, in the marine surface water under the synergistic destructive effect of seawater, UV and dissolved oxygen, provides a pathway for more sustainable textile fibers and apparel products.

Although the inhibition of mTOR is a promising treatment for neuroendocrine tumors, several questions are still open for cell specificity and resistance. With the newly characterized gastric neuroendocrine tumor mouse model (CEA424-SV40 T antigen transgenic mice), the anti-tumor efficiency of RAD001 (Everolimus) was tested both in vitro and in vivo. Tumor samples were analyzed for the expression of RNA by cDNA microarrays and also signaling pathways to get more details on the local surviving or selected cells. RAD001 treatment dramatically slowed down tumor growth and prolonged the animals' survival. This inhibitory effect has a preference for tumor cells since gastrointestinal hormone and neuroendocrine tumor specific markers were more reduced than the epithelial ones. While phosphorylation of p70S6K was almost completely blocked both in vitro and in vivo, the phosphorylation of 4EBP1 was only partially inhibited in vitro and unaffected in vivo. RAD001 treatment induced feedback activation of metabolism related pathways like PI(3)K–Akt–mTOR and MEK/ERK signalings. An induction of senescence as well as differential expression of genes responsible for metabolism was also observed, which highlighted the contribution of metabolic molecular signatures to the escape of the tumor cells from the treatment. Together, our data revealed efficient anti-tumor ability of RAD001 in a new gastric neuroendocrine tumor mouse model system and offered new insights into the clinical aspects of the incomplete elimination of tumor cells in patients treated.

Abstract Background Diabetic distal symmetric polyneuropathy (DSPN) is one of the most common microvascular complications of diabetes mellitus, and it has become a major public health problem worldwide because of its high and increasing prevalence, morbidity, and disability rate. The current medications for DSPN are not entirely satisfactory. Preliminary studies indicated that the Chinese herbal TangBi Formula may alleviate signs and symptoms and improve the velocity of nerve conduction in patients with DSPN. This study was designed to determine if Chinese herbal medicine used in combination with conventional treatment is more effective than conventional treatment alone. Methods/design We are conducting a multicenter, placebo-controlled, double-blind, randomized, controlled clinical trial as a means of assessing the therapeutic effects of traditional Chinese medicine (TCM) treatment. A total of 188 patients will be randomized in a 1:1 ratio to a treatment group (TangBi Formula plus mecobalamin) and a control group (placebo plus mecobalamin). The test period lasts 6 months, during which all of the patients will be given standard medical care as recommended by established guidelines. The primary outcome will be development of differences in changes in clinical symptoms and signs in patients and changes in Michigan Diabetic Neuropathy Score (MDNS) between the two groups before and after treatment. The secondary outcome will be changes in nerve conduction velocity and in single clinical signs and symptoms. Safety assessments and adverse events will also be evaluated. Discussion We postulate that patients with DSPN will benefit from therapy that includes TCM. If successful, this work will provide an evidence-based complementary therapeutic approach for treatment of DSPN. Trial registration ClinicalTrials.gov, NCT03010241 . Registered on 2 January 2017

Three sampling strategies with a 16s rRNA high-throughput sequencing and gene expression assay (by RT-PCR) were designed, to better understand the host and probiotics effect on gut microbiota in sheep. Sampling: (1) colon contents and back-fat tissues from small-tailed Han sheep (SHS), big-tailed Hulun Buir sheep (BHBS), and short-tailed Steppe sheep (SHBS) (n = 12, 14, 12); (2) jejunum, cecum and colon contents, and feces from Tan sheep (TS, n = 6); (3) feces from TS at 4 time points (nonfeeding, 30 and 60 feeding days, and stop feeding 30 days) with probiotics supplementation (n = 7). The results indicated SHS had the highest Firmicutes abundance, the thinnest back-fat, and the lowest expression of C/EBPβ, C/EBPδ, ATGL, CFD, and SREBP1. Some bacteria orders and families could be potential biomarkers for sheep breeds with a distinct distribution of bacterial abundance, implying the host genotype is predominant in shaping unique microbiota under a shared environment. The microbiota diversity and Bifidobacterial populations significantly changed after 60 days of feeding but restored to its initial state, with mostly colonies, after 30 days ceased. The microbiota composition was greatly different between the small and large intestines, but somewhat different between the large intestine and feces; feces may be reliable for studying large intestinal microbiota in ruminants.

Abstract The purpose of this study was to testify the hypothesis that graphene oxide (GO) could act as an appropriate vehicle for the release of tissue inhibitors of metalloproteinase-1 (TIMP-1) protein in the context of skin repair. GO characteristics were observed by scanning electron microscopy, atomic force microscopy, and thermal gravimetric analysis. After TIMP-1 absorbing GO, the release profiles of various concentrations of TIMP-1 from GO were compared. GO biocompatibility with fibroblast viability was assessed by measuring cell cycle and apoptosis. In vivo wound healing assays were used to determine the effect of TIMP-1-GO on skin regeneration. The greatest intensity of GO was 1140 nm, and the most intensity volume was 10,674.1 nm (nanometer). TIMP-1 was shown to be continuously released for at least 40 days from GO. The proliferation and viability of rat fibroblasts cultured with TIMP-1-GO were not significantly different as compared with the cells grown in GO or TIMP-1 alone (p > 0.05). Skin defect of rats treated with TIMP-1 and TIMP-1-GO showed significant differences in histological and immunohistochemical scores (p

As technologies used to study the gut microbiota have improved, the relationship between the gut microbiota and health has become increasingly obvious. Herbal medicines have been used for thousands of years, and are known to be “simple, convenient, cheap, and effective”. However, due to many factors, such as their complex composition, unclear active compounds, and poor knowledge of their underlying mechanisms, the clinical applications of herbal medicines are not widely recognized. Recently, there have been an increasing number of studies which have investigated the interaction between the gut microbiota and herbal medicines. We have found that interactions between the gut microbiota and herbal medicines occur primarily through two pathways. One pathway is that the gut microbiota “digests” the herbal medicines into absorbable active small molecules, which enter the body and induce physiological changes. The other is that herbal medicines regulate the composition of the gut microbiota and its secretions, thereby changed gut microbiota and its secretions inducing physiological changes. In summary, the interactions between the gut microbiota and herbal medicines can be attributed to absorbable active small molecules and changed gut microbiota and its secretions. Our findings will aid the exploration of the mechanisms and pathways underlying the function of herbal medicines in the future. This review also summarizes the direction of future research and the main problems faced by the current researchers.

Melanoma is one common skin cancer. In the present study, the potential anti-melanoma activity by a liposomal C6 ceramide was tested in vitro. We showed that the liposomal C6 (ceramide) was cytotoxic and anti-proliferative against a panel of human melanoma cell lines (SK-Mel2, WM-266.4 and A-375 and WM-115). In addition, liposomal C6 induced caspase-dependent apoptotic death in the melanoma cells. Reversely, its cytotoxicity was attenuated by several caspase inhibitors. Intriguingly, liposomal C6 was non-cytotoxic to B10BR mouse melanocytes and primary human melanocytes. Molecularly, liposomal C6 activated protein phosphatase 1 (PP1) to inactivate Akt-mammalian target of rapamycin (mTOR) signaling in melanoma cells. On the other hand, PP1 shRNA knockdown or exogenous expression of constitutively activate Akt1 (CA-Akt1) restored Akt-mTOR activation and significantly attenuated liposomal C6-mediated cytotoxicity and apoptosis in melanoma cells. Our results suggest that liposomal C6 activates PP1 to inhibit melanoma cells.

Melanomas cause over 76% of skin cancer deaths annually. Phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) signaling pathway is important for melanoma initiation and progression. In the current study, we evaluated the potential anti-melanoma effect of VS-5584, a novel and highly potent PI3K-mTOR dual inhibitor. We demonstrated that VS-5584 potently inhibited survival and proliferation of established (A375, A-2058 and SK-MEL-3 lines) and primary human melanoma cells, but was non-cytotoxic to non-cancerous human skin keratinocytes and B10BR murine melanocytes. At the meantime, VS-5584 induced caspase-dependent apoptotic death in melanoma cells, and its cytotoxicity was alleviated by the caspase inhibitors. At the molecular level, VS-5584 blocked AKT-mTOR activation and downregulated cyclin D1 expression in melanoma cells, while the expressions of Bcl-xL and Bcl-2 were not affected by VS-5584 treatment. On the other hand, a BH-3 mimetic Bcl-xL/Bcl-2 inhibitor ABT-737, as well as siRNA-mediated knockdown of Bcl-xL or Bcl-2, enhanced the activity of VS-5584 in melanoma cells. In vivo, oral administration of VS-5584 suppressed A375 melanoma xenograft growth in nude mice, and its activity was further enhanced by co-administration of ABT-737. These results provide the rationale for the clinical assessment of VS-5584 in melanoma patients and development of ABT-737 and other Bcl-xL/Bcl-2 inhibitors as the possible adjuvants.

Physiology constants of adolescents are important to understand growing living systems and are a useful reference in clinical and epidemiological research. Until recently, physiology constants were not available in China and therefore most physiologists, physicians, and nutritionists had to use data from abroad for reference. However, the very difference between the Eastern and Western races casts doubt on the usefulness of overseas data. We have therefore created a database system to provide a repository for the storage of physiology constants of teen-agers in Beijing. The several thousands of pieces of data are now divided into hematological biochemistry, lung function, and cardiac function with all data manually checked before being transferred into the database. The database was accomplished through the development of a web interface, scripts, and a relational database. The physiology data were integrated into the relational database system to provide flexible facilities by using combinations of various terms and parameters. A web browser interface was designed for the users to facilitate their searching. The database is available on the web. The statistical table, scatter diagram, and histogram of the data are available for both anonym and user according to queries, while only the user can achieve detail, including download data and advanced search.

Nrf2, a central regulator of the cellular defense against oxidative stress and inflammation, participates in modulating hepatocyte proliferation during liver regeneration. It is not clear, however, whether Nrf2 regulates hepatocyte growth, an important cellular mechanism to regain the lost liver mass after partial hepatectomy (PH). To determine this, various analyses were performed in wild-type and Nrf2-null mice following PH. We found that, at 60 h post-PH, the vast majority of hepatocytes lacking Nrf2 reduced their sizes, activated hepatic progenitor markers (CD133, TWEAK receptor, and trefoil factor family 3), depleted HNF4α protein, and downregulated the expression of a group of genes critical for their functions. Thus, the identity of hepatocytes deficient in Nrf2 was transiently but massively impaired in response to liver mass loss. This event was associated with the coupling of protein depletion of hepatic HNF4α, a master regulator of hepatocyte differentiation, and concomitant inactivation of hepatic Akt1 and p70S6K, critical hepatocyte growth signaling molecules. We conclude that Nrf2 participates in maintaining newly regenerated hepatocytes in a fully differentiated state by ensuring proper regulation of HNF4α, Akt1, and p70S6K during liver regeneration.

Partial hepatectomy (PH) triggers hepatocyte proliferation-mediated liver repair and is widely used to study the mechanisms governing liver regeneration in mice. However, the dynamics of the hepatocyte proliferative response to PH remain unclear. We found that PH-induced mouse liver regrowth was driven by four consecutive waves of hepatocyte replication. The first wave exhibited the highest magnitude followed by two moderate waves and one minor wave. Underlying this continuous hepatocyte replication was persistent activation of cell cycle components throughout the period of liver regeneration. Hepatocyte mitotic activity in the first three proliferative cycles showed a circadian rhythm manifested by three corresponding mitosis peaks, which were always observed at Zeitgeber time 0. The Bmal1-Clock/Wee1/Cdc2 pathway has been proposed by others to govern the circadian rhythm of hepatocyte mitosis during liver regeneration. However, we did not observe the correlations in the expression or phosphorylation of these proteins in regenerating livers. Notably, Bmal1 protein displayed frequent changes in hepatic distribution and cellular localization as the liver regrowth progressed. Further, three waves of hepatic fat accumulation occurred during hepatic regeneration. The first started before and lasted through the first round of hepatocyte proliferation, whereas the second and third occurred concomitantly with the second and third mitotic peaks, respectively.PH-induced liver regeneration consists of four continuous waves of hepatocyte proliferation coupled with three waves of hepatic fat accumulation. Bmal1, Wee1, and Cdc2 may not form a pathway regulating the circadian rhythm of hepatocyte mitosis during liver regeneration.

Abstract Background Alteration in gene expression resulting from allopolyploidization is a prominent feature in plants, but its spectrum and extent are not fully known. Common wheat (Triticum aestivum) was formed via allohexaploidization about 10,000 years ago, and became the most important crop plant. To gain further insights into the genome-wide transcriptional dynamics associated with the onset of common wheat formation, we conducted microarray-based genome-wide gene expression analysis on two newly synthesized allohexaploid wheat lines with chromosomal stability and a genome constitution analogous to that of the present-day common wheat. Results Multi-color GISH (genomic in situ hybridization) was used to identify individual plants from two nascent allohexaploid wheat lines between Triticum turgidum (2n = 4x = 28; genome BBAA) and Aegilops tauschii (2n = 2x = 14; genome DD), which had a stable chromosomal constitution analogous to that of common wheat (2n = 6x = 42; genome BBAADD). Genome-wide analysis of gene expression was performed for these allohexaploid lines along with their parental plants from T. turgidum and Ae. tauschii, using the Affymetrix Gene Chip Wheat Genome-Array. Comparison with the parental plants coupled with inclusion of empirical mid-parent values (MPVs) revealed that whereas the great majority of genes showed the expected parental additivity, two major patterns of alteration in gene expression in the allohexaploid lines were identified: parental dominance expression and non-additive expression. Genes involved in each of the two altered expression patterns could be classified into three distinct groups, stochastic, heritable and persistent, based on their transgenerational heritability and inter-line conservation. Strikingly, whereas both altered patterns of gene expression showed a propensity of inheritance, identity of the involved genes was highly stochastic, consistent with the involvement of diverse Gene Ontology (GO) terms. Nonetheless, those genes showing non-additive expression exhibited a significant enrichment for vesicle-function. Conclusions Our results show that two patterns of global alteration in gene expression are conditioned by allohexaploidization in wheat, that is, parental dominance expression and non-additive expression. Both altered patterns of gene expression but not the identity of the genes involved are likely to play functional roles in stabilization and establishment of the newly formed allohexaploid plants, and hence, relevant to speciation and evolution of T. aestivum.

Lyophyllum consists of rare edible and medicinal mushrooms. Considering this group's economic and ecological significance, understanding its biodiversity could be strategically important. Our analysis involved an extensive examination of publicly available ITS sequences from NCBI-GenBank and fungal amplicon sequencing data obtained from NCBI-SRA. At a 98% sequence similarity level, we deliminated 88 Lyophyllum OTUs, 49 of which were not categorized as 'known species'. The diversity of Lyophyllum is predominantly concentrated in the Northern Hemisphere and tends to display endemic distribution, and Europe is particularly notable for its high diversity of Lyophyllum. Given the escalating volume of data produced by amplicon sequencing, employing the amplicon dataset can facilitate an accurate survey of species diversity in Lyophyllum taxonomy. By using data from amplicon datasets, the fieldwork time and research funding for taxonomists can be saved, thereby significantly advancing the progress of the entire field of biodiversity research. [ABSTRACT FROM AUTHOR]

This article defines two common q-orthogonal polynomials: homogeneous q-Laguerre polynomials and homogeneous little q-Jacobi polynomials. They can be viewed separately as solutions to two q-partial differential equations. Furthermore, an analytic function satisfies a certain system of q partial differential equations if and only if it can be expanded in terms of homogeneous q-Laguerre polynomials or homogeneous little q-Jacobi polynomials. As applications, several generalized Ramanujan q-beta integrals and Andrews-Askey integrals are obtained. [ABSTRACT FROM AUTHOR]