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The maturity and patency of arteriovenous fistula (AVF) are essential for patients undergoing hemodialysis. Dysfunction of AVF due to neointimal hyperplasia (NIH) presents a significant clinical challenge. While balloon dilation therapy and open surgery can address this issue, they are associated with a higher likelihood of restenosis and reduced long-term durability. Therefore, there is an urgent need to establish a new method for inhibiting NIH to prolong the patency of AVF treatment. In this study, we developed a local vascular-encapsulated sustained-release drug delivery system containing degradable rapamycin nanofiber membrane patches (R-NFMs). During surgery, R-NFMs were wrapped around the anastomotic site of the AVF and the venous outflow tract. In vitro assessments demonstrated the consistent and stable release of rapamycin from the R-NFMs, confirming the material’s non-toxicity and its support of healthy cellular morphology. Animal studies further revealed that the experimental group showed significant reductions in neointimal and medial hyperplasia, as well as decreased expression of α-SMA, compared to controls. In conclusion, these findings suggest that R-NFMs are effective in inhibiting NIH and may serve as an innovative preventative approach to this pervasive issue.

Abstract Traditional eye drops are administered via topical instillation. However, frequent dosing is needed due to their relatively rapid precorneal removal and low ocular bioavailability. To address these issues, stearoyl L-carnitine-modified nanoemulsions (SC-NEs) were fabricated. The physicochemical properties of SC-NEs in terms of size, morphology, zeta potential, encapsulation efficiency, and in vitro drug release behavior were characterized. The cellular uptake and mechanisms of SC-NEs were comprehensively studied in human corneal epithelial cells and the stearoyl L-carnitine ratio in SC-NEs was optimized. The optimized SC-NEs could target the novel organic cation/carnitine transporter 2 (OCTN2) and amino acid transporter B (0 +) (ATB0,+) on the corneal epithelium, which led to superior corneal permeation, ocular surface retention ability, ocular bioavailability. Furthermore, SC-NEs showed excellent in vivo anti-inflammatory efficacy in a rabbit model of endotoxin-induced uveitis. The ocular safety test indicated that the SC-NEs were biocompatible. In general, the current study demonstrated that OCTN2 and ATB0,+-targeted nanoemulsions were promising ophthalmologic drug delivery systems that can improve ocular drug bioavailability and boost the therapeutic effects of drugs for eye diseases. Graphical Abstract

Abstract Counterfeiting has become a serious global problem, causing worldwide losses and disrupting the normal order of society. Physical unclonable functions are promising hardware-based cryptographic primitives, especially those generated by chemical processes showing a massive challenge-response pair space. However, current chemical-based physical unclonable function devices typically require complex fabrication processes or sophisticated characterization methods with only binary (bit) keys, limiting their practical applications and security properties. Here, we report a flexible laser printing method to synthesize unclonable electronics with high randomness, uniqueness, and repeatability. Hexadecimal resistive keys and binary optical keys can be obtained by the challenge with an ohmmeter and an optical microscope. These readout methods not only make the identification process available to general end users without professional expertise, but also guarantee device complexity and data capacity. An adopted open-source deep learning model guarantees precise identification with high reliability. The electrodes and connection wires are directly printed during laser writing, which allows electronics with different structures to be realized through free design. Meanwhile, the electronics exhibit excellent mechanical and thermal stability. The high physical unclonable function performance and the widely accessible readout methods, together with the flexibility and stability, make this synthesis strategy extremely attractive for practical applications.

Abstract The ongoing mutations of the SARS‐CoV‐2 pose serious challenges to the efficacy of the available antiviral drugs, and new drugs with fantastic efficacy are always deserved investigation. Here, a nanobody called IBT‐CoV144 is reported, which exhibits broad neutralizing activity against SARS‐CoV‐2 by inducing the conformation of spike trimer dimers. IBT‐CoV144 was isolated from an immunized alpaca using the RBD of wild‐type SARS‐CoV‐2, and it showed strong cross‐reactive binding and neutralizing potency against diverse SARS‐CoV‐2 variants, including Omicron subvariants. Moreover, the prophylactically and therapeutically intranasal administration of IBT‐CoV144 confers fantastic protective efficacy against the challenge of Omicron BA.1 variant in BALB/c mice model. The structure analysis of the complex between spike (S) protein, conducted using Cryo‐EM, revealed a special conformation known as the trimer dimers. This conformation is formed by two trimers, with six RBDs in the “up” state and bound by six VHHs. IBT‐CoV144 binds to the lateral region of the RBD on the S protein, facilitating the aggregation of S proteins. This aggregation results in steric hindrance, which disrupts the recognition of the virus by ACE2 on host cells. The discovery of IBT‐CoV144 will provide valuable insights for the development of advanced therapeutics and the design of next‐generation vaccines.

Objective: To explore the prognostic role of frailty in patients with abdominal aortic aneurysm (AAA) by conducting this systematic review and meta-analysis Methods: We conducted an extensive literature search on PubMed, Web of Sciences, and Embase databases to identify studies that reported the association of frailty with postoperative complications, reintervention, or all-cause mortality in patients with AAA after surgery. Short-term mortality was defined by a combination of in-hospital and 30-day death. Results: Seven cohort studies reporting on 9 articles with 323,788 AAA patients were included. The reported prevalence of frailty in AAA patients ranged between 2.3% and 34.6%. Pooling the results revealed that frailty was significantly associated with a higher risk of short-term all-cause mortality (adjusted risk ratios [RR] 3.20; 95% confidence intervals [CI] 1.95–5.26), long-term all-cause mortality (adjusted RR 2.86; 95% CI 2.57–3.17), and postoperative complications (adjusted RR 2.19; 95% CI 1.50–3.20) compared to non-frail individuals. However, there was no clear association between frailty and reintervention (HR 1.44; 95% CI 0.97–2.16). Conclusions: Frailty independently predicts the short and long-term survival as well as postoperative complications in patients with AAA undergoing surgery. Assessing frail status may potentially enhance surgical decision-making for these patients.

Abstract Organic semiconductors, such as carbon nitride, when employed as powders, show attractive photocatalytic properties, but their photoelectrochemical performance suffers from low charge transport capability, charge carrier recombination, and self-oxidation. High film-substrate affinity and well-designed heterojunction structures may address these issues, achieved through advanced film generation techniques. Here, we introduce a spin coating pretreatment of a conductive substrate with a multipurpose polymer and a supramolecular precursor, followed by chemical vapor deposition for the synthesis of dual-layer carbon nitride photoelectrodes. These photoelectrodes are composed of a porous microtubular top layer and an interlayer between the porous film and the conductive substrate. The polymer improves the polymerization degree of carbon nitride and introduces C-C bonds to increase its electrical conductivity. These carbon nitride photoelectrodes exhibit state-of-the-art photoelectrochemical performance and achieve high yield in C-H functionalization. This carbon nitride photoelectrode synthesis strategy may be readily adapted to other reported processes to optimize their performance.

Lysine-specific demethylase 4A (KDM4A) catalyzes demethylation of histone lysine residues, which regulates chromatin state and transcription. In drosophila and mice, KDM4A plays an important role in multiple biological processes including development, aging, metabolism, and immunity, however the functions of KDM4A in fish are still unclear. There are two copies of the kdm4a gene in zebrafish, namely kdm4aa and kdm4ab, kdm4aa was edited using CRISPR/Cas9 technology in the present study, then homozygous kdm4aa mutants (kdm4aa−/−) were obtained, and loss of kdm4aa was confirmed by sequencing and increased H3K9me3. Whole-mount in situ hybridization showed that kdm4aa is widely expressed during the embryonic development of zebrafish. Compared with WT zebrafish, kdm4aa−/− zebrafish showed no significant difference in gamete formation and fertilization, but the survival rate of kdm4aa−/− embryos dramatically reduced to 21% at 26 hpf. Further observation showed that about 80% of survived kdm4aa−/− zebrafish experienced disruption in stripe formation, and 10% of survived kdm4aa−/− zebrafish underwent vertebral malformation. Alizarin red S staining demonstrated the abnormal spinal development in kdm4aa−/− zebrafish. These results indicated that kdm4aa is required for normal embryonic development of zebrafish, loss of kdm4aa function leads to decreased survival during the early stages of zebrafish development and morphological variation in adult zebrafish.

Abstract This paper developed XJCT-3D, a simulation software for cooling tower wet plume dispersion. By coupling it with the Open GIS component Dotspatial, we have achieved geospatial visual representation of the calculation results, which has solved the problems of low calculation efficiency and insufficient visual representation of the traditional CFD software in the calculation of cooling tower wet plume dispersion. In order to verify the validity of the XJCT-3D software simulation results, we have conducted tracer experimental data from the ChalkPoint power plant. XJCT-3D accurately models wet plume deposition during cooling tower operation. From the XJCT-3D calculation results, we have observed that the maximum value of the cooling tower thermal plume wet deposition occurs near 610 m with a maximum value of 6.9E−07 kg/m2 s. This finding suggests that the cooling tower emissions carry a significant load of particles or droplets that have settled on surfaces at this particular altitude. It provides insights into potential environmental and human health impacts and helps in identifying and assessing areas at relatively higher risk of deposition, such as nearby ecosystems, farmland, or urban areas. This information can contribute to the development of effective mitigation strategies and the implementation of appropriate measures to minimize the impact of cooling tower emissions.

Abstract Aims Coronary artery disease (CAD) is the most common cause of heart failure (HF). This study aimed to identify cytokine biomarkers for predicting HF in patients with CAD. Methods and results Twelve patients with CAD without HF (CAD‐non HF), 12 patients with CAD complicated with HF (CAD‐HF), and 12 healthy controls were enrolled for Human Cytokine Antibody Array, which were used as the training dataset. Then, differentially expressed cytokines among the different groups were identified, and crucial characteristic proteins related to CAD‐HF were screened using a combination of the least absolute shrinkage and selection operator, recursive feature elimination, and random forest methods. A support vector machine (SVM) diagnostic model was constructed based on crucial characteristic proteins, followed by receiver operating characteristic curve analysis. Finally, two validation datasets, GSE20681 and GSE59867, were downloaded to verify the diagnostic performance of the SVM model and expression of crucial proteins, as well as enzyme‐linked immunosorbent assay was also used to verify the levels of crucial proteins in blood samples. In total, 12 differentially expressed proteins were overlapped in the three comparison groups, and then four optimal characteristic proteins were identified, including VEGFR2, FLRG, IL‐23, and FGF‐21. After that, the area under the receiver operating characteristic curve of the constructed SVM classification model for the training dataset was 0.944. The accuracy of the SVM classification model was validated using the GSE20681 and GSE59867 datasets, with area under the receiver operating characteristic curve values of 0.773 and 0.745, respectively. The expression trends of the four crucial proteins in the training dataset were consistent with those in the validation dataset and those determined by enzyme‐linked immunosorbent assay. Conclusions The combination of VEGFR2, FLRG, IL‐23, and FGF‐21 can be used as a candidate biomarker for the prediction and prevention of HF in patients with CAD.

Introduction: Factors associated with incident infarcts after stroke are unclear. We aimed to determine whether subsequent incident infarcts continue to develop one year post-stroke and how incident infarcts relate to baseline imaging features, vascular risks, and cognitive outcomes. Methods: We recruited patients with non-disabling stroke. After diagnostic MRI, we repeated MRI at 3-6 monthly intervals for 12 months, visually assessing incident infarcts on DWI or FLAIR. We used logistic regression to determine associations with incident infarcts, including baseline vascular risks, SVD score, and index stroke subtype. We quantified 7-level ordinal cognitive outcome status at one year, using MoCA/telephone MoCA and modified Rankin Scale.[1,2] We used ordinal regression to determine whether cognitive outcomes associated with incident infarcts and baseline age, mRS, MoCA, and WMH volume. Results: We recruited 229 participants, mean age 65.9 (SD 11.1) years; 77/229 (33.6%) female; 130/229 (56.8%) index lacunar stroke. From baseline to one-year MRI, we detected 117 incident infarcts in n=57/229 participants at 80 visits. Most were small subcortical infarcts: 86/117 (73.5%) infarcts in n=38/57 (66%). N=39 participants had incident infarcts at one visit; n=14 at two visits; n=3 at three visits, and n=1 at four visits. Nineteen participants had multiple incident infarcts at a single visit. Baseline summary SVD score was the strongest predictor of incident infarcts (aOR 1.74, 95%CI 1.29-2.41, Figure 1). At one year, 10/218 (4.6%) participants met criteria for single-domain and 62/218 (28.4%) for multi-domain neurocognitive disorder; 15/218 (6.8%) for mild dementia; 2/218 (0.9%) for moderate dementia; none severe; 3/229 (1.3%) had died. Participants’ odds of impaired one-year cognition increased for every one-unit increment in baseline mRS (aOR=2.03 [1.30-3.10]) and decreased for every one-unit increment in baseline MoCA (aOR=0.78 [0.71-0.85]). For participants with incident small subcortical infarcts, the odds of impaired cognition were 23% higher than for incident cortical infarcts, though not statistically significant (aOR 1.23 [0.55-2.1])(Figure 2). Discussion: In a mild stroke population, incident infarcts, mostly small subcortical, occur in one quarter and associate with worse baseline SVD. Minor neurocognitive disorder occurs in one third and associates with baseline mRS, MoCA, and trends towards incident small subcortical rather than cortical infarcts.

Abstract Objective: To assess the association between the risk of malnutrition, as estimated by the Patient-Generated Subjective Global Assessment (PG-SGA) numerical scores, and adverse outcomes in oncology patients. Design: Systematic review and meta-analysis. Settings: A comprehensive search was conducted in PubMed, Web of Science, Embase, CKNI, VIP, Sinomed and Wanfang databases. Studies that examined the association between the risk of malnutrition, as estimated by the PG-SGA numerical scores, and overall survival (OS) or postoperative complications in oncology patients were included. Patients were classified as low risk (PG-SGA ≤ 3), medium risk (PG-SGA 4–8) and high risk of malnutrition (PG-SGA > 8). Subject: Nineteen studies reporting on twenty articles (n 9286 patients). Results: The prevalence of medium and high risk of malnutrition ranged from 16·0 % to 71·6 %. A meta-analysis showed that cancer patients with medium and high risk of malnutrition had a poorer OS (adjusted hazard ratios (HR) 1·98; 95 % CI 1·77, 2·21) compared with those with a low risk of malnutrition. Stratified analysis revealed that the pooled HR was 1·55 (95 % CI 1·17, 2·06) for medium risk of malnutrition and 2·65 (95 % CI 1·90, 3·70) for high risk of malnutrition. Additionally, the pooled adjusted OR for postoperative complications was 4·65 (95 % CI 1·61, 13·44) for patients at medium and high risk of malnutrition. Conclusions: The presence of medium and high risk of malnutrition, as estimated by the PG-SGA numerical scores, is significantly linked to poorer OS and an increased risk of postoperative complications in oncology patients.

Hydrogel sensors have drawn tremendous attention due to the combination of stretchability, biocompatibility, and convenient production. The integration of high mechanical strength, stretchability and a wide working range towards various application environment is still a great challenge. Herein, both the tough and highly stretchable hydrogel sensor was developed and showed large working range and good sensing capability towards various deformation and underwater motions. The hydrogel was constructed by the polymerization of acrylic acid, acrylamide and N, N-dimethyl acrylamide, and crosslinked by the zirconium hydroxide. The obtained hydrogel exhibits high mechanical strength (∼1.5 MPa), strain (∼1400%) with good toughness (∼12 MJ/m−3), recovery properties and high elasticity (G’∼23 KPa) which was beneficial for the stable sensing performance. It also showed high sensitivity in a wide working range (0–1300%), and exhibited stretching-dependent resistance signal monitoring capability on large, small, cyclic deformations, and various human motions (wrist, finger bending and swallowing). Moreover, it can detect various motions underwater, even monitor the pulse beating for healthcare in the liquid environment. This hydrogel with these comprehensive mechanical and sensing performances has great potential in the fields of artificial intelligence and electric skins, and further applied in the aquatic environment.

Abstract Chronic morphine administration alters gene expression in different brain regions, an effect which may contribute to plastic changes associated with addictive behavior. This change in gene expression is most possibly mediated by addictive drug-induced epigenetic remodeling of gene expression programs. Our previous studies showed that chronic morphine-induced decrease of miR-105 in the medial prefrontal cortex (mPFC) contributed to context-induced retrieval of morphine withdrawal memory. However, how chronic morphine treatment decreases miR-105 in the mPFC still remains unknown. The present study shows that chronic morphine induces addiction-related change in miR-105 in the mPFC via two kinds of transcription factors: the first transcription factor is CREB activated by mu receptors-ERK-p90RSK signaling pathway and the second transcription factor is glucocorticoid receptor (GR), which as a negative transcription factor, mediates chronic morphine-induced decrease in miR-105 in the mPFC of rats.

The present study employs the k-epsilon turbulence model to investigate the influence of stable stratification with different Richardson numbers (Rib) on flow patterns and pollutant dispersion near tall buildings. The results show that thermal stratification significantly affects the flow pattern around buildings. As Rib increases, the leeward stagnation point gradually shifts upward toward the top of the building, while the recirculation region on the top of the building moves downward, and the length of the recirculation region on the windward side initially increases and then decreases. The vortex position gradually moves above the building. The region with high TKE/uH2 is primarily concentrated on the top of the building and within the downwind recirculation area. As Rib increases, the TKE/uH2 decreases in the top and wake regions of the building. With increasing Rib, the ground-level pollutant concentration first increases and then decreases, the height of the downwind plume gradually reduces, while the maximum concentration in the plume rises.

Porosity is considered to be one of the key factors affecting the structural properties of porous lattices, but in fact, pore size also plays an important role, and it has great potential to adjust pore size and porosity independently to improve structural properties. In this work, by adjusting the sheet thickness of the triply periodic minimal surface (TPMS) lattice structures and adjusting the height of the single row structure according to linear and constant laws, the TPMS lattice structures with given porosity and adjustable pore size are designed, and the mechanical response is investigated. Based on preparing samples by Ti6Al4V laser powder bed fusion, the results of the tests show that the elastic modulus ranges of linear change TPMS (LC-TPMS) and constant TPMS (C-TPMS) lattice structures are 3625.6 MPa–4575.1 MPa and 3820.0 MPa–4509.1 MPa, respectively. In the plateau stage, the LC-TPMS lattice structures have a longer and more stable plateau stage, higher yield stress and better energy absorption capacity than the C-TPMS lattice structures. The maximum energy absorption difference is 62.7 MJ/mm3 and the maximum energy absorption efficiency difference is 0.12. The LC-TPMS lattice structures can also obtain a larger damping ratio under larger compressive strain.

Background: Traditional Chinese eight brocade exercise (TCEBE) with same cycle and frequency and different durations has an effect on patients with chronic heart failure (CHF). However, relevant reports on the topic are lacking. Objective: This study aims to explore the differences of rehabilitation effect by conducting TCEBE with the same cycle and frequency and different single exercise time for patients with CHF. Methods: A total of 103 patients with CHF were randomly divided into long-time group (LTG), short-time group (STG) and control group (CG). The subjects in the three groups were given corresponding routine treatment. In addition, under the guidance of professional TCEBE coaches and nurses, TCEBE was conducted for 12 weeks (3 times/week) for LTG (60 min/time) and STG (30 min/time). Minnesota living with heart failure questionnaire (MLHFQ) was used, and 6-min walk (6MWK) and brain nautical peptide (BNP) were tested. Results: 1) At 12 weeks, the comparison between groups obtained the following results: For the LTG, MLHFQ was less than that of the CG (P

IntroductionThis study examined the impact of parental involvement on the psychological adjustment of children with autism spectrum disorder (ASD), and the role of parenting self-efficacy and parenting stress in the transition from kindergarten to primary school.MethodsUsing the questionnaires, we collected data from 237 Chinese parents of children with ASD.ResultsMediation analyses showed that parental involvement partially promoted the psychological adjustment of children with ASD, which was reflected in the fact that parental involvement promoted children’s prosocial behavior but did not reduce their emotional/behavioral problems. Mediation analyses also revealed the role of the mediator in parenting stress between parental involvement and the psychological adjustment of children. Additionally, the results suggested that parenting self-efficacy and parenting stress played a chain-mediating role in the association between parental involvement and psychological adjustment in children with ASD.DiscussionThese findings enhance our understanding of the mechanisms underlying the relationship between parental involvement and psychological adjustment in children with ASD in the transition from kindergarten to primary school.

The transportation was simulated of aerosol particles released from point-source over the typical hilly terrain in a wind tunnel. The Particle Dynamic Analysis technique (PDA) was used to investigate the effects of wind speed (1 m/s, 2 m/s), particle size (0.1~2, 2~4, 4~6 μm), and terrain conditions (different height of peaks) on the migration behavior of particles in the range of roughness sub-layers. It was found that the longitudinal velocity and vertical velocity probability distribution of particles in the range of roughness sub-layer are in accordance with the Gaussian distribution. Smaller particles display larger correlation coefficients and so better Gaussian fittings. It is showed that increasing wind speed could make the longitudinal motion of particles more dispersed, and the vertical motion of particles is the joint action of wind speed and terrain. By comparing the mean longitudinal and vertical velocity of particles in the range of roughness sub-layer between smooth surface and hilly terrain, it was found that the mean longitudinal velocities of particles over peaks are smaller than those over smooth surface. It is indicated that the airflow can be hindered in the range of roughness sub-layer by the peaks. The above results provide data basis and support for the study of the migration behavior of aerosol particles in the range of roughness sub-layer.

Objective The objective of this experiment was to investigate the effect of dietary glucose oxidase (GOD), catalase (CAT), or both supplementation on reproductive performance, oxidative stress, and apoptosis in sows. Methods A total of 104 multiparous sows were randomly assigned to four groups (n = 26) with each group given a basal diet, basal diet plus GOD at 60 U/kg, basal diet plus CAT at 75 U/kg, and basal diet plus GOD at 60 U/kg and CAT at 75 U/kg. Sows were fed the experimental diets throughout gestation and lactation. Results Dietary GOD supplementation increased average daily feed intake of sows and litter weight at weaning (p

Background: Bladder urothelial carcinoma (BLCA) is a malignancy with a high incidence worldwide. One-third of patients may experience aggressive progression later on, and 70% of patients who have undergone surgical intervention will still suffer from metastasis. Materials and Methods: RNA sequencing profiles of BLCA samples were obtained from The Cancer Genome Atlas (TCGA) database. Differential expression and univariate Cox regression analyses were performed to identify prognosis-related differentially expressed immune genes (DEIGs). Subsequently, a proportional hazards model of DEIGs was then constructed by univariate regression analysis. Differential expression and correlation analyses, CIBERSORT, Single Sample Gene Set Enrichment Analysis (ssGSEA), GSVA were conducted on transcription factors (TFs), immune cells/pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The regulation network was then constructed. Eventually, ATAC-seq, ChIP-seq, scRNA-seq, and multiple online databases were employed for further validation. Results: A proportional hazards model of 31 DEIGs was constructed and risk score was calculated and proven to be a independent prognostic factor. Then 5 immune genes were characterized to be significantly correlated with bone metastasis, stage and TF expression simultaneously. 4 TFs were identified to be significantly correlated with prognosis and RBP7 expression. 5 immune cells/pathways were revealed to be significantly correlated with RBP7 expression. Only 1 KEGG pathway was identified to be significant in Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) analyses. The regulatory relationship was then constructed, in which the correlation between EBF1 and RBP7 (R = 0.677, p < 0.001), Th2 cells and RBP7 (R = 0.23, p < 0.001), the oocyte meiosis pathway and RBP7 (R = 0.14, p = 0.042) were the most statistically significant. The results were further confirmed by Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq), Chromatin Immunoprecipitation sequencing (ChIP-seq), single-cell RNA sequencing (scRNA-seq), and multiple online databases validation. Conclusions: This study revealed that the EBF1-RBP7 regulatory relationship had potential importance in the bone metastasis in BLCA through Th2 cells and the oocyte meiosis pathway.

Triacylglycerol (TGA) is the primary component of intramuscular fat. Expression of diacylglyceryl transferase (DGAT) determines the polyester differentiation ability of precursor adipocytes. The two DGAT isoforms (DGAT1 and DGAT2) play different roles in TAG metabolism. This study investigates the roles of DGAT1 and DGAT2 in signaling pathways related to differentiation and lipid metabolism in Yanbian bovine preadipocytes. sh-DGAT1 (sh-1), sh-DGAT2 (sh-2), and sh-DGAT1 + sh-DGAT2 (sh-1 + 2) were prepared using short interfering RNA (siRNA) interference technique targeting DGAT1 and DGAT2 genes and infected bovine preadipocytes. Molecular and transcriptomic techniques, including differentially expressed genes (DEGs) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis, were used to investigate the effects on the differentiation of Yanbian bovine preadipocytes. After interference with DGAT1 and DGAT2 genes, the contents of TAG and adiponectin were decreased. The TAG content in the sh-2 and sh-1 + 2 groups was significantly lower than that in the sh-NC group. RNA sequencing (RNA-seq) results showed 2070, 2242, and 2446 DEGs in the sh-1, sh-2, and sh-1 + 2 groups, respectively. The DEGs of the sh-2 group were mainly concentrated in the PPAR, AMPK, and Wnt signaling pathways associated with adipocyte proliferation and differentiation. These results demonstrated that at the mRNA level, DGAT2 plays a more important role in lipid metabolism than DGAT1.

Ciglitazone is a member of the thiazolidinedione family, and specifically binds to peroxisome proliferator-activated receptor-γ (PPARγ), thereby promoting adipocyte differentiation. We hypothesized that ciglitazone as a PPARγ ligand in the absence of an adipocyte differentiation cocktail would increase adiponectin and adipogenic gene expression in bovine satellite cells (BSC). Muscle-derived BSCs were isolated from six, 18-month-old Yanbian Yellow Cattle. The BSC were cultured for 96 h in differentiation medium containing 5 µM ciglitazone (CL), 10 µM ciglitazone (CM), or 20 µM ciglitazone (CH). Control (CON) BSC were cultured only in a differentiation medium (containing 2% horse serum). The presence of myogenin, desmin, and paired box 7 (Pax7) proteins was confirmed in the BSC by immunofluorescence staining. The CL, CM, and CH treatments produced higher concentrations of triacylglycerol and lipid droplet accumulation in myotubes than those of the CON treatment. Ciglitazone treatments significantly increased the relative expression of PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα), C/EBPβ, fatty acid synthase, stearoyl-CoA desaturase, and perilipin 2. Ciglitazone treatments increased gene expression of Pax3 and Pax7 and decreased expression of myogenic differentiation-1, myogenin, myogenic regulatory factor-5, and myogenin-4 (p < 0.01). Adiponectin concentration caused by ciglitazone treatments was significantly greater than CON (p < 0.01). RNA sequencing showed that 281 differentially expressed genes (DEGs) were found in the treatments of ciglitazone. DEGs gene ontology (GO) analysis showed that the top 10 GO enrichment significantly changed the biological processes such as protein trimerization, negative regulation of cell proliferation, adipocytes differentiation, and cellular response to external stimulus. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that DEGs were involved in the p53 signaling pathway, PPAR signaling pathway, biosynthesis of amino acids, tumor necrosis factor signaling pathway, non-alcoholic fatty liver disease, PI3K-Akt signaling pathway, and Wnt signaling pathway. These results indicate that ciglitazone acts as PPARγ agonist, effectively increases the adiponectin concentration and adipogenic gene expression, and stimulates the conversion of BSC to adipocyte-like cells in the absence of adipocyte differentiation cocktail.

We hypothesized that the unsaturated fatty acid palmitoleic acid (POA) could promote the expression of adipogenic/lipogenic genes in bovine skeletal muscle satellite cells (BSCs). The BSCs were cultured in a growth medium containing 10% fetal bovine serum. When the cells reached 80%–90% confluence, we used the differentiation medium with 5% horse serum for differentiation for 96 h. The differentiation medium contained 50 µM, 100 µM and 200 µM POA. Control BSC were cultured only in differentiation media. Compared with the control BSC, the POA BSC significantly up-regulated the expression of paired box 3 (Pax3) and paired box 7 (Pax7) and down-regulated myogenin gene expression (p < 0.01), which indicates a depression in muscle fiber development. However, all POA treatments up-regulated the expression of the adipocyte transcription factors peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein alpha and beta (C/EBP α and C/EBP β), and other genes (p < 0.01) and increased the expression of PAT-family proteins and the concentration of adiponectin in the media. These results indicate that POA can convert part of BSCs into adipocytes.

Lattice structures’ performance is directly determined by the topological structure and arrangement of cells. Here, we propose a lattice structure design approach that generates predictable mechanical properties by adjusting the three-dimensional posture and mirror arrays of cells. Specifically, the Euler angle (α β γ) is introduced to accurately control the three rotational degrees of freedom of the orthogonal unit cell. Then, a new unit cell with symmetric characteristics composed of multiple primitive rotation units is constructed by mirror operation, which is called super variable pose Octahedral Structures (SVPOS). The mathematical model of SVPOS topological structure is established, the mapping relationship between Euler Angle and relative density is deduced, and the mechanical response of structures with different Euler angles is studied. The results show that Structure of α = β = γ = 30˚ obtained the best performance, and the elastic modulus, compressive strength, and energy absorption at 50% strain of it are 553.1%, 471.9% and 529% of that of the octahedral, respectively. The new lattice structure can be obtained by adjusting the Euler Angle, its relative density and performance can be better predicted, which can provide experimental and theoretical basis for the design of lattice structures that meet different requirements.

The flow and diffusion around a building under neutral (Rib=0) and stable stratification (Rib=0.057) conditions were investigated by wind tunnel experiment. The mean flow and turbulent structure around the building were measured by a combination of hot wire and cold wire. The characteristics of pollutant concentration distribution under neutral and stable stratification conditions were investigated by using tracer experiments. The results indicate that when atmospheric stratification is stable, the longitudinal velocity and turbulence intensity are lower than under neutral conditions. Different thermal stratification has different effect on the diffusion around a building. Stable thermal stratification inhibits the diffusion of pollutants in the vertical direction, which causes an increase in concentrations. The maximum normalized concentration appears near the building (x/H=1/3, z/H=1.2). The maximum normalized concentration is 11 for the stable condition and 7 for the neutral condition. As the downwind distance increases, the height of the concentration peak decreases. Compared with neutral thermal stratification, stable thermal stratification gives a lower concentration peak value.

Fabrication of hybrid photoelectrodes on a subsecond timescale with low energy consumption remains a challenge. Here, the authors report a modular approach, laser-driven transfer synthesis, to build a library of structurally defined transition metal oxide composite films, enabling the creation of materials for diverse applications.

Normal heart development is vital for maintaining its function, and the development process is involved in complex interactions between different cell lineages. How mammalian hearts develop differently is still not fully understood. In this study, we identified several major types of cardiac cells, including cardiomyocytes (CMs), fibroblasts (FBs), endothelial cells (ECs), ECs/FBs, epicardial cells (EPs), and immune cells (macrophage/monocyte cluster, MACs/MONOs), based on single-cell transcriptome data from embryonic hearts of both human and mouse. Then, species-shared and species-specific marker genes were determined in the same cell type between the two species, and the genes with consistent and different expression patterns were also selected by constructing the developmental trajectories. Through a comparison of the development stage similarity of CMs, FBs, and ECs/FBs between humans and mice, it is revealed that CMs at e9.5 and e10.5 of mice are most similar to those of humans at 7 W and 9 W, respectively. Mouse FBs at e10.5, e13.5, and e14.5 are correspondingly more like the same human cells at 6, 7, and 9 W. Moreover, the e9.5-ECs/FBs of mice are most similar to that of humans at 10W. These results provide a resource for understudying cardiac cell types and the crucial markers able to trace developmental trajectories among the species, which is beneficial for finding suitable mouse models to detect human cardiac physiology and related diseases.

The advantages of “printing the right material in the right position” and “printing the unique structure for unique function” in additive manufacturing make the design of biomimetic graded scaffold of bone tissue engineering possible. Here, under different porosities, we propose a biomimetic graded TPMS scaffold design with adjustable graded pore size, providing guidance for designing porous bone implants without the characteristics of stress concentration, stress shielding and barrier mass transport. Specifically, the structural characteristics of TPMS can be achieved without stress concentration. By adjusting the porosity, the elastic modulus of Ti6Al4V samples can be adjusted in the range of 1158–4567 MPa, which can match the individual selection of mechanical properties of the biological bone. Since the TPMS scaffold is designed by layer-by-layer splicing, through adjusting the height parameters of the single-layer structure, the selective pore size variation can be realized to further match mass transport of biological bone. Then, the in vitro culture experiments have been conducted and the maximum cell survival rate of the scaffold with an offset constant 0.4 is 85.44%, which can meet the mass transport of bone implants. As such, the proposed graded scaffold design in this paper shows excellent potential for orthopedic implants.

Functionally graded lattice structures are gaining increasing attention due to their potential to enable the customization of the structural response and development of multi-functional applications. However, some grading methods may lead to weak layers or discontinuous unit cells. These problems can be overcome by varying the morphology, but the mechanical performance is only slightly improved, limiting the application of lattice structures. This work proposes a bidirectionally graded lattice structure, wherein the gradient design is simultaneously implemented in parallel and perpendicularly to the load direction. Experimental samples fabricated through laser powder bed fusion (L-PBF) and using PA2200 as the matrix material, were subjected to quasi-static compression tests. The results showed that the bidirectionally graded lattice structure attains a significantly higher compressive modulus, yield stress, and plateau stress (59.8%, 43.0%, and 33.9% higher, respectively) compared with a unidirectionally graded lattice structure. Moreover, a proposed stiffness prediction method was appropriate for effectively estimating the modulus of graded body-centered cubic lattice structures, which combined with the understanding of the influence of gradient parameters, allows the realization of a tailored structural performance. In conclusion, the proposed bidirectionally graded strategy and experimental findings provide an effective reference for the design of multi-functional lightweight additive manufactured parts.

Abstract Long non-coding RNAs (lncRNAs) play key roles in colorectal carcinogenesis. Here, we aimed to identify the risk SNP-induced lncRNAs and to investigate their roles in colorectal carcinogenesis. First, we identified rs6695584 as the causative SNP in 1q41 locus. The A>G mutation of rs6695584 created a protein-binding motif of BATF, altered the enhancer activity, and subsequently activated lncSLCC1 expression. Further validation in two independent CRC cohorts confirmed the upregulation of lncSLCC1 in CRC tissues, and revealed that increased lncSLCC1 expression was associated with poor survival in CRC patients. Mechanistically, lncRNA-SLCC1 interacted with AHR and transcriptionally activated HK2 expression, the crucial enzyme in glucose metabolism, thereby driving the glycolysis pathway and accelerating CRC tumor growth. The functional assays revealed that lncSLCC1 induced glycolysis activation and tumor growth in CRC mediated by HK2. In addition, HK2 was upregulated in colorectal cancer tissues and positively correlated with lncSLCC1 expression and patient survival. Taken together, our findings reveal a risk SNP-mediated oncogene lncRNA-SLCC1 promotes CRC through activating the glycolysis pathway.

Abstract MYB plays vital roles in regulating proliferation and differentiation of hematopoietic progenitor cells, dysregulation of MYB has been implicated in the pathogenesis of leukemia. Although the transcription of MYB has been well studied, its detailed underlying regulatory mechanisms still remain elusive. Here, we detected the long-range interaction between the upstream regions, −34k and −88k, and the MYB promoter in K562, U937, and HL-60 cells using circularized chromosome conformation capture (4C) assay, which declined when MYB was downregulated during chemical-induced differentiation. The enrichment of enhancer markers, H3K4me1 and H3K27ac, and enhancer activity at the −34k and −88k regions were confirmed by ChIP-qPCR and luciferase assay respectively. ChIP-qPCR showed the dynamic binding of GATA1, TAL1, and CCAAT/enhancer-binding protein (C/EBPβ) at −34k and −88k during differentiation of K562 cells. Epigenome editing by a CRISPR-Cas9-based method showed that H3K27ac at −34k enhanced TF binding and MYB expression, while DNA methylation inhibited MYB expression. Taken together, our data revealed that enhancer elements at −34k are required for MYB expression, TF binding, and epigenetic modification are closely involved in this process in human myeloid leukemia cells.

Poor quality straw can be made more digestible and palatable through delignification using white rot fungi as a biological treatment in SSF. The decomposition of organic matter by white rot fungi is improved when a carbon source is added. Reducing the fermentation cycle can also help retain more nutrients in straw feed. To increase rumen digestibility and nutrient utilization, corn straw and rice straw were subjected to SSF with white rot fungi (Phanerochaete chrysosporium) for 21 days. The type of carbon source (glucose, sucrose, molasses, or soluble starch) was optimized, and the nutrient composition and in vitro fermentation parameters of the fermented straw were assessed. In the fermented corn straw and rice straw supplemented with different carbon sources, the results showed a decrease in lignin content, dry matter, cellulose, and hemicellulose loss, and an increase in crude protein content after 21 days. Total volatile fatty acid and ammonium nitrogen concentrations increased significantly (p < 0.01) during in vitro fermentation. Overall, the most enhanced nutritional values for corn straw and rice straw were observed after 14 days of SSF in the groups using molasses or glucose as a carbon source.

Purpose. To identify the ability of releasing and uptaking exosomes in rat lens and characterize the exosomal microRNA profile of lens-derived exosomes. Methods. The rat lenses were cultured ex vivo and the medium was collected. The exosomes were isolated from medium and measured in size and concentration by nanoflow cytometry (nFCM) and transmission electron microscopy (TEM) and verified with CD63 and TSG101 by Western blot. The miRNAs in exosomes released from lens epithelial cells (LECs) were sequenced. The plasma exosomes labeled by PKH26 were used to verify the exosomes uptake LECs, and their colocalized fluorescence was imaged by confocal microscopy. Results. LECs released numerous exosomes into the medium through the capsule, which contained abundant miRNAs. The most abundant miRNAs included miR-184, let-7c-5p, let-7a-5p, let-7b-5p, let-7f-5p, miR-125a-5p, miR-204-5p, miR-125b-5p, miR-1b, and miR-23a-3p. The LECs but not the lens fibre cells showed exosome uptake. The LECs uptake more PKH26-labeled exosomes at day 7 than day 3 and day 14. Conclusions. Our results suggested that LECs can release and uptake exosomes through the capsule. Exosomes may be an important way for the lens to communicate among LECs, aqueous humour, vitreous body, and other ocular tissues.

Cardiomyocyte differentiation derived from embryonic stem cells (ESCs) is a complex process involving molecular regulation of multiple levels. In this study, we first identify and compare differentially expressed gene (DEG) signatures of ESC-derived cardiomyocyte differentiation (ESCDCD) in humans and mice. Then, the multiscale embedded gene co-expression network analysis (MEGENA) of the human ESCDCD dataset is performed to identify 212 significantly co-expressed gene modules, which capture well the regulatory information of cardiomyocyte differentiation. Three modules respectively involved in the regulation of stem cell pluripotency, Wnt, and calcium pathways are enriched in the DEG signatures of the differentiation phase transition in the two species. Three human-specific cardiomyocyte differentiation phase transition modules are identified. Moreover, the potential regulation mechanisms of transcription factors during cardiomyocyte differentiation are also illustrated. Finally, several novel key drivers of ESCDCD are identified with the evidence of their expression during mouse embryonic cardiomyocyte differentiation. Using an integrative network analysis, the core molecular signatures and gene subnetworks (modules) underlying cardiomyocyte lineage commitment are identified in both humans and mice. Our findings provide a global picture of gene-gene co-regulation and identify key regulators during ESCDCD.

A porous lattice structure with highly controllable mechanical properties, low weight, and high strength is the most promising option for many fields, such as the aerospace, automobile, and biomedical industries. However, the most common and critical issue is the excessively high stress concentration at the struts’ nodes when the lattice structure is loaded. Thus, a curving lattice design strategy is proposed, maintaining a light structure, through which either a circular or elliptical arc is used in the lattice struts to obtain new forms of curving lattice structures. By establishing theoretical models and preparing samples by laser powder bed fusion (L-PBF), combined with scanning electron microscopy (SEM), quasi-static uniaxial compressive experiments, finite element analysis (FEA), and Gibson-Ashby models, excellent results were obtained. The stress distribution of the original under the loads was altered in the curving lattice structure and the stress concentration at the nodes of the struts was effectively relieved, dramatically improving its mechanical properties. Compared with the original structure, the specific elastic modulus and specific compressive strength of curving lattice structures were maximally increased by 213.7% and 126.2%, respectively. Meanwhile, the curving lattice structure had a superior energy absorption capacity, with a significant increase of 92.9%.

(1) Background: Non-small cell lung cancer (NSCLC) is the most common lung cancer. Enhancer RNA (eRNA) has potential utility in the diagnosis, prognosis and treatment of cancer, but the role of eRNAs in NSCLC metastasis is not clear; (2) Methods: Differentially expressed transcription factors (DETFs), enhancer RNAs (DEEs), and target genes (DETGs) between primary NSCLC and metastatic NSCLC were identified. Prognostic DEEs (PDEEs) were screened by Cox regression analyses and a predicting model for metastatic NSCLC was constructed. We identified DEE interactions with DETFs, DETGs, reverse phase protein arrays (RPPA) protein chips, immunocytes, and pathways to construct a regulation network using Pearson correlation. Finally, the mechanisms and clinical significance were explained using multi-dimensional validation unambiguously; (3) Results: A total of 255 DEEs were identified, and 24 PDEEs were selected into the multivariate Cox regression model (AUC = 0.699). Additionally, the NSCLC metastasis-specific regulation network was constructed, and six key PDEEs were defined (ANXA8L1, CASTOR2, CYP4B1, GTF2H2C, PSMF1 and TNS4); (4) Conclusions: This study focused on the exploration of the prognostic value of eRNAs in the metastasis of NSCLC. Finally, six eRNAs were identified as potential markers for the prediction of metastasis of NSCLC.

This paper introduces a novel variational inference (VI) method with Bayesian and gradient descent techniques. To facilitate the approximation of the posterior distributions for the parameters of the models, the Stein method has been used in Bayesian variational inference algorithms in recent years. Unfortunately, previous methods fail to either explicitly describe the influence of its history in the tracing of particles (Q(x) in this paper) in the approximation, which is important information in the search for particles. In our paper, Q(x) is considered in design of the operator Bp, but the chance of jumping out of the local optimum may be increased, especially in the case of complex distribution. To address the existing issues, a modified Stein variational inference algorithm is proposed, which can make the gradient descent of Kullback–Leibler (KL) divergence more random. In our method, a group of particles are used to approximate target distribution by minimizing the KL divergence, which changes according to the newly defined kernelized Stein discrepancy. Furthermore, the usefulness of the suggested technique is demonstrated by using four data sets. Bayesian logistic regression is considered for classification. Statistical studies such as parameter estimate classification accuracy, F1, NRMSE, and others are used to validate the algorithm’s performance.

Accumulating evidence indicates that heat shock protein 90 (HSP90) plays essential roles in modulation of phenotypic plasticity in vertebrate development, however, the roles of HSP90 in modulation of cold tolerance capacity in fish are still unclear. In the present study, we showed that transient inhibition of embryonic HSP90 function by a chemical inhibitor or low conductivity stress promoted variation of cold tolerance capacity in adult zebrafish. Further work showed that embryonic HSP90 inhibition enhanced cold tolerance in adult zebrafish could be transmitted to their offspring. RNA-seq data showed that embryonic HSP90 inhibition enhanced cold tolerance involves variation of gene expression related to proteasome, lysosome, autophagy, and ribosome. Experiments with zebrafish ZF4 cells showed that two differentially expressed genes atg9b and psmd12 were up-regulated by radicicol treatment and provided protective roles for cells under cold stress, indicating that up-regulation of autophagy and proteasome function contributes to enhanced cold tolerance. The present work sheds a light on the roles of HSP90 in regulation of phenotypic plasticity associated with thermal adaptation in fish.

Background: MicroRNAs (miRNAs) have an increasing functional role in some neurodegenerative diseases. Autophagy, the degradation of bulk protein in the cytoplasm, is the quality control function of protein and has a protective role in the survival of neural cells. miR-433 may play a regulatory role in neurodegenerative diseases. Many aspects underlying the mechanism of miR-433 in neural development and neurodegeneration are not clear.Methods: In this study, we established stable cell lines expressing miR-433 by infecting mouse hippocampal neural cell line (HT-22) cells with rLV-miR-433 and the control rLV-miR. Pre-miR-433 expression was analyzed using polymerase chain reaction (PCR). Mature miR-433 expression was measured using quantitative PCR (qPCR). The effect of miR-433 overexpression on cell proliferation was determined using a CCK-8 assay and flow cytometry. RNA interference was used to analyze the function of Cdk12 in mediating the effect of miR-433 on cell proliferation. The effect of miR-433 overexpression on cell apoptosis was determined by flow cytometry. Autophagy-related genes Atg4a, LC3B, and Beclin-1 were determined using qPCR, Western blot, or immunofluorescence. In addition, RNA interference was used to analyze the effect of Atg4a on the induction of autophagy. TargetScan 7.2 was used to predict the target genes of miR-433, and Smad9 was determined using qPCR.Results: Our results indicated that miR-433 increased the expression of Atg4a and induced autophagy by increasing the expression of LC3B-Ⅱ and Beclin-1 in an Atg4a-dependent manner. In addition, miR-433 upregulated the expression of Cdk12 and inhibited cell proliferation in a Cdk12-dependent manner and promoted apoptosis in HT-22 cells under the treatment of 10-hydroxycamptothecin.Conclusion: The results of our study suggest that miR-433 may regulate neuronal growth by promoting autophagy and attenuating cell proliferation. This might be a potential therapeutic intervention in neurodegenerative diseases.

As the most common cause of progressive cognitive decline in humans, Alzheimer's disease (AD) has been intensively studied, but the mechanisms underlying its profound synaptic dysfunction remain unclear. Here we confirm that exposing wild-type mice to an enriched environment (EE) facilitates signaling in the hippocampus that promotes long-term potentiation (LTP). Exposing the hippocampus of mice kept in standard housing to soluble Aβ oligomers impairs LTP, but EE can fully prevent this. Mechanistically, the key molecular features of the EE benefit are an upregulation of miRNA-132 and an inhibition of histone deacetylase (HDAC) signaling. Specifically, soluble Aβ oligomers decreased miR-132 expression and increased HDAC3 levels in cultured primary neurons. Further, we provide evidence that HDAC3 is a direct target of miR-132. Overexpressing miR-132 or injecting an HDAC3 inhibitor into mice in standard housing mimics the benefits of EE in enhancing hippocampal LTP and preventing hippocampal impairment by Aβ oligomers in vivo. We conclude that EE enhances hippocampal synaptic plasticity by upregulating miRNA-132 and reducing HDAC3 signaling in a way that counteracts the synaptotoxicity of human Aβ oligomers. Our findings provide a rationale for prolonged exposure to cognitive novelty and/or epigenetic modulation to lessen the progressive effects of Aβ accumulation during human brain aging.

BackgroundAlternative splicing (AS) modifies 92-94% human genes, abnormal splicing events might relate to tumor development and invasion. Glioblastoma Multiforme (GBM) is a fatal, invasive, and malignant tumor in nervous system. The recurrence and development leads to poor prognosis. However, few studies have focused on AS in GBM.MethodsRNA-seq and Alternative splicing events (ASEs) data of GBM samples were downloaded from The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases, respectively. Firstly, the Cox regression analysis was utilized to identify the overall survival splicing events (OS-SEs). Secondly, a multivariable model was applied to access the prognostic value of risk score. Then, we constructed a co-expressed network between splicing factors (SFs) and overall survival alternative splicing events (OS-SEs). Additionally, to explore the relationship between the potential prognostic signaling pathways and OS-SEs, we constructed a network between these pathways and OS-SEs. Ultimately, to better explain the results, validations from multi-dimension platforms were applied.ResultsIn the first step, 1,062 OS-SEs were selected by Cox regression. Then, 11 OS-SEs were integrated in a multivariate model by Lasso regression. The area under the curve (AUC) of receiver operator characteristic (ROC) curve was 0.861. In addition, the risk score generated from the multivariate model was confirmed to be an independent prognostic factor (P < 0.001). What's more, in the network of SFs and ASEs, CELF5 significantly regulated GSG1L|35696|AP and GSG1L|35698|AP (P < 0.001, R = 0.511 and = -0.492). Additionally, GSG1L|35696|AP (P = 0.006) and GSG1L|35698|AP (P = 0.007) showed a significant relationship with cancer status. Eventually, KEGG pathways related to prognosis of GBM were selected by GSVA. The primary bile acid synthesis (P < 0.001, R = 0.420) was the significant pathway co-expressed with Germ Cell-Specific Gene 1-Like Protein (GSG1L).ConclusionsBased on the comprehensive bioinformatics analysis, we proposed that aberrant splicing factor CUGBP Elav-like family member 5 (CELF5) significantly, positively and negatively, regulated ASE of GSG1L, and the primary bile acid synthesis pathway might play an important role in tumorigenesis and prognosis of GBM.

MicroRNAs (miRNAs) play vital roles in various biological processes under multiple stress conditions by leading to mRNA cleavage or translational repression. However, the detailed roles of miRNAs in cold acclimation in fish are still unclear. In the present study, high-throughput sequencing was performed to identify miRNAs from 6 small RNA libraries from the zebrafish embryonic fibroblast ZF4 cells under control (28°C, 30 days) and cold-acclimation (18°C, 30 days) conditions. A total of 414 miRNAs, 349 known and 65 novel, were identified. Among those miRNAs, 24 (19 known and 5 novel) were up-regulated, and 23 (9 known and 14 novel) were down-regulated in cold acclimated cells. The Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses indicated that the target genes of known differentially expressed miRNAs (DE-miRNA) are involved in cold acclimation by regulation of phosphorylation, cell junction, intracellular signal transduction, ECM-receptor interaction and so on. Moreover, both miR-100-3p inhibitor and miR-16b mimics could protect ZF4 cells under cold stress, indicating the involvement of miRNA in cold acclimation. Further study showed that miR-100-3p and miR-16b could regulate inversely the expression of their target gene (atad5a, cyp2ae1, lamp1, rilp, atxn7, tnika, btbd9), and that overexpression of miR-100-3p disturbed the early embryonic development of zebrafish. In summary, the present data show that miRNAs are closely involved in cold acclimation in zebrafish ZF4 cells and provide information for further understanding of the roles of miRNAs in cold acclimation in fish.

Abstract Background Drug addiction is a chronic brain disorder characterized by the compulsive use of drugs. The study of chronic morphine-induced adaptation in the brain and its functional significance is of importance to understand the mechanism of morphine addiction. Previous studies have found a number of chronic morphine-induced adaptive changes at molecular levels in the brain. A study from our lab showed that chronic morphine-induced increases in the expression of D1 receptors at presynaptic terminals coming from other structures to the basolateral amygdala (BLA) played an important role in environmental cue-induced retrieval of morphine withdrawal memory. However, the neurocircuitry where the increased D1 receptors are located and how chronic morphine increases D1 receptor expression in specific neurocircuits remain to be elucidated. Results Our results show that chronic morphine induces a persistent increase in D1 receptor expression in glutamatergic terminals of projection neurons from the medial prefrontal cortex (mPFC) to the BLA, but has no influence on D1 receptor expression in projection neurons from the hippocampus or the thalamus to the BLA. This adaptation to chronic morphine is mediated by reduced expression of miR-105 in the mPFC, which results in enhanced D1 receptor expression in glutamatergic terminals of projection neurons from the mPFC to the BLA. Ex vivo optogenetic experiments show that a chronic morphine-induced increase in D1 receptor expression in glutamatergic terminals of projection neurons from the mPFC to the BLA results in sensitization of the effect of D1 receptor agonist on presynaptic glutamate release. mPFC to BLA projection neurons are activated by withdrawal-associated environmental cues in morphine-withdrawal rats, and overexpression of miR-105 in the mPFC leads to reduced D1 receptor induction in response to chronic morphine in glutamatergic terminals of the projection neurons from the mPFC to the BLA, and a reduction in place aversion conditioned by morphine withdrawal. Conclusions These results suggest that chronic morphine use induces a persistent increase in D1 receptors in glutamatergic terminals of projection neurons from the mPFC to the BLA via downregulation of miR-105 in the mPFC, and that these adaptive changes contribute to environmental cue-induced retrieval of morphine withdrawal memory.

During power system restoration following a blackout, it is necessary to quickly restore as many generator units as possible to accelerate the speed of the system restoration. Considering that wind power of large capacity has the advantages of fast start-up speed, flexible access method etc., its participation in power system restoration can speed up grid recovery. However, due to wind power fluctuations, the integration of wind power during system restoration may impact the frequency of the restored system. In severe cases, the frequency of the restored system will exceed the limit, which will threaten the safety of the restored system. Consequently, the power reference of the wind farm needs to be optimised during the system restoration. Therefore, an optimisation model of power reference of the wind farm in power restoration based on the fuzzy chance constraints model was proposed in this study. The model maximises the power support of a wind farm on the basis of the safety of the restored system. Simulation results show that this method can provide more power under the condition that the system safety is guaranteed.

Depression is a common neuropsychiatric disorder and new anti-depressive treatments are still in urgent demand. Fast Green FCF, a safe biocompatible color additive, has been suggested to mitigate chronic pain. However, Fast green FCF’s effect on depression is unknown. We aimed to investigate Fast green FCF’s effect on lipopolysaccharide (LPS)-induced depressive-like behavior and the underlying mechanisms. Pretreatment of Fast green FCF (100 mg/kg, i.p. daily for 7 days) alleviated depressive-like behavior in LPS-treated mice. Fast green FCF suppressed the LPS-induced microglial and astrocyte activation in the hippocampus. Fast green FCF decreased the mRNA and protein levels of Toll-like receptor 4 (TLR4) and Myeloid differentiation primary response 88 (Myd88) and suppressed the phosphorylation of nuclear factor-κB (NF-κB) in the hippocampus of LPS-treated mice. Fast green FCF also downregulated hippocampal tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, but did not alter the level of the brain-derived neurotrophic factor (BDNF) in the hippocampus of LPS-treated mice. The molecular docking simulation predicts that Fast green FCF may interact with TLR4 and interrupt the formation of the TLR4-MD2 complex. In conclusion, the anti-depressive action of Fast green FCF in LPS-treated mice may involve the suppression of neuroinflammation and the downregulation of TLR4/Myd88/NF-κB signal pathway in mouse hippocampus. Our findings indicate the potential of Fast green FCF for controlling depressive symptoms.

Fast Green FCF (FGF), a biocompatible dye, recently drew attention as a potential drug to treat amyloid-deposit diseases due to its effects against amyloid fibrillogenesis in vitro and a high degree of safety. However, its role in inflammatory pain is unknown. Our study aimed to investigate the effect of FGF in the inflammatory pain model induced by complete Freund’s adjuvant (CFA) and to identify the associated mechanisms. We found that systemic administration of FGF reversed mechanical and thermal pain hypersensitivity evoked by CFA in a dose-dependent manner. FGF treatment decreased purinergic spinal P2X4 expression in the spinal cord of CFA-inflamed mice. FGF also down-regulated spinal and peripheral pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)], but did not alter the spinal level of nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF). In conclusion, our results suggest the potential of FGF for controlling the progress of inflammatory pain.

Age-related cataract (ARC) is a leading cause of visual impairment and blindness worldwide. DNA damage and malfunction of DNA repair are believed to contribute to the pathogenesis of ARC. Aside from increasing age, the risk factors for ARC appear to be rather complex, and one or more gene variations could play critical roles in the diverse processes of ARC progression. This study aimed to investigate the combined effects of different genetic variants on ARC risk.A cohort of 789 ARC patients and 531 normal controls from the Jiangsu Eye Study was included in this study. Genotyping of 18 single-nucleotide polymorphisms (SNPs) in 4 DNA damage/repair genes was performed using TaqMan SNP assays. SNP-SNP interactions were analyzed via multifactor dimensionality reduction (MDR), classification and regression tree (CART) and genetic risk score (GRS) analyses.Based on single-locus analyses of the 18 SNPs examined, WRN-rs11574311 (T>C) was associated with ARC risk. However, in MDR, the gene-gene interaction among the five SNPs (WRN-rs4733220 (G>A), WRN-rs1801195 (T>G), OGG1-rs2072668 (G>C) and OGG1-rs2304277 (A>G)) on ARC risk was significant (OR = 5.03, 95% CI: 3.54~7.13). CART analyses also revealed that the combination of five SNPs above was the best polymorphic signature for discriminating between the cases and the controls. The overall odds ratio for CART ranged from 4.56 to 7.90 showing an incremental risk for ARC. This result indicated that these critical SNPs participate in complex interactions. The GRS results showed an increased risk for ARC among individuals with the SNPs in this polymorphic signature.The use of multifactorial analysis (or an integrated approach) rather than a single methodology could be an improved strategy for identifying complex gene interactions. The multifactorial approach used in this study has the potential to identify complex biological relationships among ARC-related genes and processes. This approach will lead to the discovery of novel biological information, ultimately improving ARC risk management.

Long non-coding RNAs (lncRNAs) are increasingly regarded as a key role in regulating diverse biological processes in various tissues and species. Although the cold responsive lncRNAs have been reported in plants, no data is available on screening and functional prediction of lncRNAs in cold acclimation in fish so far. Here we compared the expression profile of lncRNAs in cold acclimated zebrafish embryonic fibroblast cells (ZF4) cultured at 18°C for 30 days with that of cells cultured at 28°C as control by high-throughput sequencing. Totally 8,363 novel lncRNAs were identified. Including known and novel lncRNAs, there are 347 lncRNAs up-regulated and 342 lncRNAs down-regulated in cold acclimated cells. Among the differentially expressed lncRNAs, 74 and 61 were detected only in control cells or cold-acclimated cells, respectively. The Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses of adjacent genes to the differentially expressed lncRNAs showed that the enriched genes are involved in electron transport, cell adhesion, oxidation-reduction process, and so on. We also predicted the target genes of the differentially expressed lncRNAs by looking for interactions between lncRNAs and mRNAs, and constructed an interaction network. In summary, our genome-wide systematic identification and functional prediction of cold responsive lncRNAs in zebrafish cells suggests a crucial role of lincRNAs in cold acclimation in fish.

Bisphenol-A (BPA), a widely used synthetic compound in plastics, disrupts endocrine function and interferes with physiological actions of endogenous gonadal hormones. Chronic effects of BPA on reproductive function, learning and memory, brain structure, and social behavior have been intensively investigated. However, less is known about the influence of BPA on long-term potentiation (LTP), one of the major cellular mechanisms that underlie learning and memory. In the present study, for the first time we investigated the effect of different doses of BPA on hippocampal LTP in rat brain slices. We found a biphasic effect of BPA on LTP in the dentate gyrus: exposure to BPA at a low dose (100 nM) enhanced LTP and exposure to BPA at a high dose (1000 nM) inhibited LTP compared with vehicle controls. The rapid facilitatory effect of low-dose BPA on hippocampal LTP required membrane-associated estrogen receptor (ER) and involved activation of the extracellular signal-regulated kinase (ERK) signaling pathway. Coadministration of 17β-estradiol (E2, the primary estrogen hormone) and BPA (100 nM) abolished both the BPA-induced enhancement of LTP and the E2-induced enhancement of baseline fEPSP, suggesting a complex interaction between BPA- and E2-mediated signaling pathways. Our investigation implies that even nanomolar levels of endocrine disrupters (e.g., BPA) can induce significant effects on hippocampal LTP.