Search

Abstract Ischaemic bowel disease (ICBD) is a group of intestinal ischaemia syndromes caused by various aetiologies of reduced intestinal blood flow or vascular occlusion. ICBD can present as abdominal pain, bloody stool, and diarrhoea. This disease often occurs in middle-aged and elderly individuals with cardiovascular and cerebrovascular diseases. The incidence of ischaemic bowel disease has been increasing for decades, and it is difficult to diagnose, resulting in rapid disease progression and a high mortality rate. Therefore, fully understanding this disease, improving the diagnosis rate of this disease, and finding appropriate treatment methods are urgently needed to improve the condition and prognosis of patients. Umbilical cord blood stem cells are accessible, have weak immunogenicity, and have various biological functions, such as angiogenesis, inflammation and immune regulation. Many studies have confirmed that cord blood stem cells can relieve ischaemia, and these cells have attracted tremendous amounts of attention in regenerative medicine in recent years. In this paper, we discuss the clinical characteristics of ICBD, analyse the characteristics of human umbilical cord blood mononuclear cells (HUCB-MNCs), and use its to treat ischaemic bowel disease. Additionally, we compare the clinical manifestations and related indicators before and after treatment to evaluate the efficacy and safety of these methods.

Abstract Non-small cell lung cancer (NSCLC) ranks as one of the leading causes of cancer-related deaths worldwide. Despite the prominence and effectiveness of kinase-target therapies in NSCLC treatment, these drugs are suitable for and beneficial to a mere ~30% of NSCLC patients. Consequently, the need for novel strategies addressing NSCLC remains pressing. Deubiquitinases (DUBs), a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic targets. Nevertheless, the mechanisms by which DUBs promote NSCLC remain poorly understood. Through a global analysis of the 97 DUBs’ contribution to NSCLC survival possibilities using The Cancer Genome Atlas (TCGA) database, we found that high expression of Josephin Domain-containing protein 2 (JOSD2) predicted the poor prognosis of patients. Depletion of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in vivo. Mechanically, we found that JOSD2 restricts the kinase activity of LKB1, an important tumor suppressor generally inactivated in NSCLC, by removing K6-linked polyubiquitination, an action vital for maintaining the integrity of the LKB1-STRAD-MO25 complex. Notably, we identified the first small-molecule inhibitor of JOSD2, and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in vivo. Our findings highlight the vital role of JOSD2 in hindering LKB1 activity, underscoring the therapeutic potential of targeting JOSD2 in NSCLC, especially in those with inactivated LKB1, and presenting its inhibitors as a promising strategy for NSCLC treatment.

The independent effects of hedgerow or grass ditches on the migration of runoff, sediment and nutrients are well known; however, the effects of combined hedgerow–grass ditch systems have rarely been assessed. Vegetation stem diameter (VSD) is an essential variable that changes the effectiveness of a hedgerow–grass ditch system in reducing runoff and sediment yield on sloping lands. A hedgerow–grass ditch system was simulated to interpret the effects of varied VSDs [i.e., 0 (control), 0.1, 0.2, 0.4 and 0.8 cm] in hedgerow on runoff and sediment yield by laboratory rainfall simulation. Compared to the control, the time to runoff initiation presented a 43.3% delay in 0.8 cm VSD (p < 0.05), and the runoff rate was significantly reduced by 16.6% in the 0.2 cm VSD and by 17.0% in the 0.8 cm VSD, respectively (p < 0.05). The sediment yield rate decreased by 74.2% and 85.8% relative to that of the control, respectively (p < 0.05). The reduction was 5.3–17.0% for the runoff rate and 3.5–85.8% for the sediment yield rate with varied VSDs relative to the control. The sediment yield rate decreased remarkably as an exponential function with increased stem diameter (p < 0.05). Our results have great significance for creating strategies for soil and water conservation on sloping lands.

Background and objectives: The purpose of this research was to develop and validate the first prognostic nomograms for 3-, 5-, and 10-year cancer-specific survival (CSS) and overall survival (OS) in patients diagnosed with locally advanced thyroid cancer (LATC) by evaluating independent predictors of prognosis in a population of LATC patients. Methods: Demographics, clinicopathologic characteristics, treatment, and follow-up of 2396 LATC patients in the surveillance, epidemiology, and end results database from 2004 to 2015 were retrospectively analyzed and compared with patients with LATC according to staging. We randomized all LATC patients into training and validation groups in a 7:3 ratio. Cox regression analyses helped us to derive independent prognostic factors for LATC patients. According to these results, we established and validated the first prognostic nomograms and risk stratification. Results: In our research, the clinical information of LATC patients was compared and significant differences were found in the relevant variables including CSS and OS (P

The icing of wind turbine blades can cause changes in airfoil shape, which in turn significantly reduces the aerodynamic performance and affects the power generation efficiency of a wind turbine. In this paper, the iced airfoil shape of wind turbine blades with different positions, masses, and angles of attack icing was measured and modeled using 3D scanning technology, and changes in airfoil shape parameters under different icing conditions were obtained. The numerical simulations of icing blades were carried out to investigate the effect of blade icing on aerodynamic characteristics. The results show that ice accumulation thickness tends to increase nonlinearly along the spanwise direction and chord length for both windward and leeward icing. The airfoil angle of attack affects the trend of ice accumulation changes. As shown by the numerical simulation of the aerodynamic characteristic, blade icing changes the airfoil shape, which changes the pressure difference between the leading edge and trailing edge, affects the size and number of the wake vortex structures, and further changes the aerodynamic characteristics of the blade.

Knockout of the transcriptional repressor Trctf1 is known to enhance the yield of cellulose-induced cellulase synthesis in Trichoderma reesei. However, different inducers possess distinct induction mechanisms, and the effect of Trctf1 on cellulase synthesis with soluble inducers remains unknown. To evaluate the effect of the Trctf1 gene on cellulase synthesis and develop a high-yielding cellulase strain, we established a CRISPR–Cas9 genome editing system in T. reesei Rut C30 using codon-optimized Cas9 protein and in vitro transcribed RNA. This study demonstrated that T. reesei ΔTrctf1 with the Trctf1 gene knocked out showed no statistically significant differences in cellulase, cellobiohydrolase, endoglucanase, and β−glucosidase production when induced with MGD (the mixture of glucose and sophorose). However, when induced with lactose, the activities of these enzymes increased by 20.2%, 12.4%, and 12.9%, respectively, with no statistically significant differences in β−glucosidase activity. The hydrolysis efficiency on corn stover of cellulases produced by T. reesei ΔTrctf1 under different inducers was not significantly different from that of wild-type cellulases, indicating that Trctf1 gene deletion has little effect on the cellulase cocktail. These findings contribute to a better understanding of the molecular mechanisms underlying the regulation of T. reesei cellulase synthesis by different soluble inducers, as well as the construction of high-yield cellulase gene−engineered strains.

Abstract Enkurin, TRPC Channel Interacting Protein (ENKUR) was shown as a suppressor in some tumors. However, the biological role of ENKUR on gastric cancer (GC) and its related molecular mechanisms is not clear. Here, we first observed that ENKUR significantly inhibited cell migration, invasion, and metastasis in GC. The molecular basis showed β‐catenin‐mediated epithelial‐mesenchymal transition (EMT) signaling was inactivated in ENKUR‐overexpressing GC cells. In addition, ENKUR knockdown markedly restored cell migration and invasion. Subsequently, ENKUR bound to MYH9 and decreased its protein expression by recruiting E3 ubiquitin ligase F‐Box And WD Repeat Domain Containing 7 (FBXW7) to form an ubiquitinated degradation complex. The downregulated Myosin Heavy Chain 9 (MYH9) protein weakened the recruitment of the deubiquitinase USP2 and thus promoted the degradation of β‐catenin protein, which finally suppressed EMT signaling. Finally, the oncogenic transcription factor c‐Jun bound to ENKUR promoter and reduced its expression in GC. In clinical samples, decreased ENKUR expression promoted the unfavorable prognosis of GC. Our data proved the vital role of ENKUR on suppressing cell migration, invasion, and metastasis and demonstrated its potential as a therapeutic target for GC.

Abstract The mixture of glucose and β-disaccharide (MGD) synthesized by transglycosylation of glucose as a low-cost soluble carbon source can efficiently induce cellulase production in Trichoderma reesei, which holds potential for the biorefining of lignocellulosic biomass. However, it is not yet fully understood how MGD induces T. reesei cellulase. In this study, transcriptomic analyses were conducted to investigate the molecular basis of MGD for lignocellulose-degrading enzyme production of T. reesei Rut C30 compared with that on lactose. Particular attention was paid to CAZymes, transcription factors, transporters and other protein processing pathways related to lignocellulose degradation. As a result, MGD can elicit transcription of GH5-, GH6- and GH7-encoding cellulases that is up to 1.4-fold higher than that induced by lactose, but GH11- and GH74-encoding xylanases are downregulated by 1.7- and 4.4-fold, respectively. Gene expression profiles suggest that the transcription activators xyr1 and vib1 are significantly upregulated and that the mitogen-activated protein kinase pathway is strengthened compared to the case of lactose induction. In addition, hac1-encoding UPR-specific transcription factors are significantly upregulated by MGD, which may be enhanced due to proper folding and processing of nascent proteins. These findings provide a theoretical basis for further understanding the characterization of efficient cellulase production using MGD as an inducer in T. reesei and offer potential strategies for strain improvement.

Nasopharyngeal carcinoma (NPC) is prevalent in East and Southeast Asia. In a previous study, Epstein-Barr virus (EBV)-miR-BART22 induces tumor metastasis and stemness and is significantly involved in NPC progression. In the present study, we observed that miR-4721 is induced by EBV-miR-BART22 through phosphatidylinositol 3-kinase (PI3K)/AKT/c-JUN/Sp1 signaling to promote its transcription. In a subsequent study, we observed that miR-4721 serves as a potential oncogenic factor promoting NPC cell cycle progression and cell proliferation in vitro and in vivo. Mechanism analysis indicated that miR-4721 directly targetes GSK3β and reduces its expression, which therefore elevates β-catenin intra-nuclear aggregation and activates its downstream cell cycle factors, including CCND1 and c-MYC. In clinical samples, miR-4721 and GSK3β are respectively observed to be upregulated and downregulated in NPC progression. Elevated expression of miR-4721 is positively associated with clinical progression and poor prognosis. Our study first demonstrated that miR-4721 as an oncogene is induced by EBV-miR-BART22 via modulating PI3K/AKT/c-JUN/Sp1 signaling to target GSK3β, which thus activates the WNT/β-catenin-stimulated cell cycle signal and enhances the tumorigenic capacity in NPC. miR-4721 may be a potential biomarker or therapeutic target in NPC treatment in the future.

Growth hormone receptor (GHR), a member of the class I cytokine receptor family, plays key roles in cancer progression. Recently, GHR has been reported to be associated with breast cancer development, but the molecular mechanism of GHR in this malignancy is not fully understood. To investigate this issue, we stably inhibited GHR in breast cancer cell lines, which were observed to reduce cell proliferation, tumor growth and induction of apoptosis, and arrest the cell‐cycle arrest at the G1–S phase transition. In addition, GHR silencing suppressed the protein levels of B‐Raf proto‐oncogene, serine/threonine kinase (BRAF), Mitogen‐activated protein kinase kinase (MEK) and Extracellular regulated protein kinases (ERK). These findings suggest that GHR may mediate breast cell progression and apoptosis through control of the cell cycle via the BRAF/MEK/ERK signaling pathway.

Abstract Background Acute glaucoma, characterized by a sudden elevation in intraocular pressure (IOP) and retinal ganglion cells (RGCs) death, is a major cause of irreversible blindness worldwide that lacks approved effective therapies, validated treatment targets and clear molecular mechanisms. We sought to explore the potential molecular mechanisms underlying the causal link between high IOP and glaucomatous RGCs death. Methods A murine retinal ischemia/ reperfusion (RIR) model and an in vitro oxygen and glucose deprivation/reoxygenation (OGDR) model were used to investigate the pathogenic mechanisms of acute glaucoma. Results Our findings reveal a novel mechanism of microglia-induced pyroptosis-mediated RGCs death associated with glaucomatous vision loss. Genetic deletion of gasdermin D (GSDMD), the effector of pyroptosis, markedly ameliorated the RGCs death and retinal tissue damage in acute glaucoma. Moreover, GSDMD cleavage of microglial cells was dependent on caspase-8 (CASP8)-hypoxia-inducible factor-1α (HIF-1α) signaling. Mechanistically, the newly identified nucleotide-binding leucine-rich repeat-containing receptor (NLR) family pyrin domain-containing 12 (NLRP12) collaborated with NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing protein 4 (NLRC4) downstream of the CASP8-HIF-1α axis, to elicit pyroptotic processes and interleukin-1β (IL-1β) maturation through caspase-1 activation, facilitating pyroptosis and neuroinflammation in acute glaucoma. Interestingly, processing of IL-1β in turn magnified the CASP8-HIF-1α-NLRP12/NLRP3/NLRC4-pyroptosis circuit to accelerate inflammatory cascades. Conclusions These data not only indicate that the collaborative effects of NLRP12, NLRP3 and NLRC4 on pyroptosis are responsible for RGCs death, but also shed novel mechanistic insights into microglial pyroptosis, paving novel therapeutic avenues for the treatment of glaucoma-induced irreversible vision loss through simultaneously targeting of pyroptosis.

Recent years, multi-label feature selection has gradually attracted significant attentions from machine learning, statistical computing and related communities and has been widely applied to diverse problems from music recognition to text mining, image annotation, etc. However, traditional multi-label feature selection methods employ cumulative summation strategy to design methods, which suffers from the problem of overestimation the redundancy of some candidate features. Additionally, the cumulative summation strategy will lead to the high value of the goal function when one candidate feature is completed related with one or few already-selected features, but it is almost independent from the majority of already-selected features. To address these issues, we propose a new multi-label feature selection method named Feature Redundancy Maximization (FRM), which combines the cumulative summation of conditional mutual information with the `maximum of the minimum' criterion. Additionally, FRM can be rewritten as another form of multi-label feature selection method that employs interaction information as a measure of feature redundancy that obtains an accurate score of feature redundancy as the number of already-selected features increases. Finally, extensive experiments are implemented on fourteen benchmark multi-label data sets in comparison to six state-of-the-art methods. The experimental results demonstrate the superiority of the proposed method.

Background. Parathyroid tumors are common endocrine neoplasias associated with primary hyperparathyroidism. Although numerous studies have studied the subject, the predictive value of gene biomarkers nevertheless remains low. Methods. In this study, we performed genomic analysis of abnormal DNA methylation in parathyroid tumors. After data preprocessing, differentially methylated genes were extracted from patients with parathyroid tumors by using t-tests. Results. After refinement of the basic differential methylation, 28241 unique CpGs (634 genes) were identified to be methylated. The methylated genes were primarily involved in 7 GO terms, and the top 3 terms were associated with cyst morphogenesis, ion transport, and GTPase signal. Following pathway enrichment analyses, a total of 10 significant pathways were enriched; notably, the top 3 pathways were cholinergic synapses, glutamatergic synapses, and oxytocin signaling pathways. Based on PPIN and ego-net analysis, 67 ego genes were found which could completely separate the diseased group from the normal group. The 10 most prominent genes included POLA1, FAM155 B, AMMECR1, THOC2, CCND1, CLDN11, IDS, TST, RBPJ, and GNA11. SVM analysis confirmed that this grouping approach was precise. Conclusions. This research provides useful data to further explore novel genes and pathways as therapeutic targets for parathyroid tumors.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high infectivity, pathogenicity, and variability, is a global pandemic that severely affected public health and the world economy. The development of safe and effective vaccines is crucial to the prevention and control of an epidemic. As an emerging technology, mRNA vaccine is widely used for infectious disease prevention and control and has significant safety, efficacy, and high production. It has received support and funding from many pharmaceutical enterprises and becomes one of the main technologies for preventing COVID-19. This review introduces the current status of SARS-CoV-2 vaccines, specifically mRNA vaccines, focusing on the challenges of developing mRNA vaccines against SARS-CoV-2, and discusses the relevant strategies.

Thermal management systems for lithium-ion batteries based on the cooling and heating of phase change materials have become a popular research topic. However, the low thermal conductivity, flame resistance, high and low temperature adaptability of phase change materials, as well as the thermal runaway mechanisms and lightweight design of phase change material-based systems remain to be explored. The aim of this paper is to conduct a publication-wide macro bibliometric review on thermal management systems for lithium-ion batteries based on phase change material to date. Total of 583 associated publications were retrieved from the Web of Science Core Collection database for the period 2006–2022. A bibliometric study was conducted through the visualization software VOSviewer. The findings were derived from annual publication trends, geographical and institutional distribution, authors and their collaborative networks, keyword network analysis and analysis of highly cited publications as well as reference co-citation analysis. The findings provide a comprehensive overview of the evolution of research hotspots in the field and can help researchers who would like to work in the field to quickly grasp the research frontiers and the overall picture. Furthermore, some suggestions for future work are summarized.

The performance of engineered cementitious composites (ECCs) under coupled salt freezing and loaded conditions is important for its application on the transportation infrastructure. However, in most of the studies, the specimens were generally loaded prior to the freezing. The influence of sustained load was merely considered. To this end, four sustained deflection levels, i.e., 0%, 10%, 30% and 50% of the deflection at the ultimate flexural strength, and three salt concentrations (1%, 3% and 5%) were applied. Prior to the salt frost resistance test, the fluid absorption of ECC specimens under various conditions were measured. The changes in relative dynamic elastic modulus (RDEM) during the freeze–thaw cycles were captured. The depth and the content profile of free chloride were measured after the coupled sustained load and freezing and thawing cycles. It is shown that 3% NaCl solution leads to the largest deterioration in all cases. There is no visible flaking or damage occurring on the surface. The relationships between locally sustained flexural stress and RDEM loss and also locally sustained flexural stress and free chloride penetration depth were proposed and showed satisfactory results. It is concluded that when ECC is subjected to the FTCs under 1% de-ice salt solution, no depassivation of the steel is expected even under a large deflection level. In terms of 3% and 5% salt solution, the thickness of cover should be no less than 20 mm when a deflection level of 0.5 is applied.

Molecular probes based on the excited-state intramolecular proton-transfer (ESIPT) mechanism have emerged to be attractive candidates for various applications. Although the steady-state fluorescence mechanisms of these ESIPT-based probes have been reported extensively, less information is available about the fluorescence lifetime characteristics of newly developed NIR-emitting dyes. In this study, four NIR-emitting ESIPT dyes with different cyanine terminal groups were investigated to evaluate their fluorescence lifetime characteristics in a polar aprotic solvent such as CH2Cl2. By using the time-correlated single-photon counting (TCSPC) method, these ESIPT-based dyes revealed a two-component exponential decay (τ1 and τ2) in about 2–4 nanoseconds (ns). These two components could be related to the excited keto tautomers. With the aid of model compounds (5 and 6) and low-temperature fluorescence spectroscopy (at −189 ℃), this study identified the intramolecular charge transfer (ICT) as one of the major factors that influenced the τ values. The results of this study also revealed that both fluorescence lifetimes and fractional contributions of each component were significantly affected by the probe structures.

More and more wind turbines are installed in cold regions because of better wind resources. In these regions, the high humidity and low temperatures in winter will lead to ice accumulation on the wind turbine impeller. A different icing location or mass will lead to different natural frequency variations of the impeller. In order to monitor the icing situation in time and in advance, a method based on depth neural network technology to predict the icing mass is explored and proposed. Natural-environment icing experiments and iced-impeller modal experiments are carried out, aiming at a 600 W wind turbine, respectively. The mapping relationship between the change rate of the natural frequency of the iced impeller at different icing positions and the icing mass is obtained, and the correlation coefficients are all above 0.93. A deep neural network (DNN) prediction model of ice-coating quality for the impeller was constructed with the change rate of the first six-order natural frequencies as the input factor. The results show that the MAE and MSE of the trained model are close to 0. The average prediction error of the DNN model is 4.79%, 9.35%, 3.62%, 1.63%, respectively, under different icing states of the impeller. It can be seen that the DNN shows the best prediction ability among other methods. The smaller the actual ice-covered mass of the impeller, the larger the relative error of the ice-covered mass predicted by the DNN model. In the same ice-covered state, the relative error will decrease gradually with the increase in ice-covered mass. In a word, using the natural frequency change rate to predict the icing quality is feasible and accurate. The research achievements shown here can provide a new idea for wind farms to realize efficient and intelligent icing monitoring and prediction, provide engineering guidance for the wind turbine blade anti-icing and deicing field, and further reduce the negative impact of icing on wind power generation.

Accurate determination of Cu2+ in solution is crucial for preventing several disease conditions. Spectroscopy-based techniques for metal ion detection are promising methods due to their excellent sensitivity and rapid response time. In this work, we are reporting a newly synthesized 2-(2′-Hydroxyphenyl) benzoxazole-based compound, probe 2, by incorporating a vinyl pyridinium segment into the bis(HBO) 4 system. Probe 2 exhibited excellent specificity toward Cu2+ in solution. The ratiometric absorbance (λ440/λ370) and the quenching of fluorescence at λem ≈585 nm exhibited an excellent linear correlation. The formation of the 2-Cu complex can be utilized as a highly sensitive spectroscopic method for the detection of Cu2+ in solution with a detection limit of 0.15 µM. In addition, Cu2+-induced fluorescence quenching in probe 2 occurs mainly via a static quenching mechanism by forming a 2-Cu complex, and the stability constant for the 2-Cu complex was calculated based on spectroscopic measurements.

Mesobuthus martensii, a famous and important Traditional Chinese Medicine has a long medical history and unique functions. It is the first scorpion species whose whole genome was sequenced worldwide. In addition, it is the most widespread and infamous poisonous animal in northern China with complex habitats. It possesses several kinds of toxins that can regulate different ion channels and serve as crucial natural drug resources. Extensive and in-depth studies have been performed on the structures and functions of toxins of M. martensii. In this research, we compared the morphology of M. martensii populations from different localities and calculated the COI genetic distance to determine intraspecific variations. Transcriptome sequencing by RNA-sequencing of the venom glands of M. martensii from ten localities and M. eupeus from one locality was analyzed. The results revealed intraspecific variation in the expression of sodium channel toxin genes, potassium channel toxin genes, calcium channel toxin genes, chloride channel toxin genes, and defensin genes that could be related to the habitats in which these populations are distributed, except the genetic relationships. However, it is not the same in different toxin families. M. martensii and M. eupeus exhibit sexual dimorphism under the expression of toxin genes, which also vary in different toxin families. The following order was recorded in the difference of expression of sodium channel toxin genes: interspecific difference; differences among different populations of the same species; differences between sexes in the same population, whereas the order in the difference of expression of potassium channel toxin genes was interspecific difference; differences between both sexes of same populations; differences among the same sex in different populations of the same species. In addition, there existed fewer expressed genes of calcium channel toxins, chloride channel toxins, and defensins (no more than four members in each family), and their expression differences were not distinct. Interestingly, the expression of two calcium channel toxin genes showed a preference for males and certain populations. We found a difference in the expression of sodium channel toxin genes, potassium channel toxin genes, and chloride channel toxin genes between M. martensii and M. eupeus. In most cases, the expression of one member of the toxin gene clusters distributed in series on the genome were close in different populations and genders, and the members of most clusters expressed in same population and gender tended to be the different. Twenty-one toxin genes were found with the MS/MS identification evidence of M. martensii venom. Since scorpions were not subjected to electrical stimulation or other special treatments before conducting the transcriptome extraction experiment, the results suggested the presence of intraspecific variation and sexual dimorphism of toxin components which revealed the expression characteristics of toxin and defensin genes in M. martensii. We believe this study will promote further in-depth research and use of scorpions and their toxin resources, which in turn will be helpful in standardizing the identification and medical applications of Quanxie in traditional Chinese medicine.

In this article, the abundant wave solutions of Boussinesq equations are obtained, which are very important to investigate the waves propagation of shallow water. Firstly, we establish the time-fractional form of (1 + 1) dimensional Boussinesq equations to describe the shallow water waves more accurately. Furthermore, by applying the complete discrimination system for polynomial method, all the possible wave solutions are revealed. Finally, in order to analysis the fractionalize effects efficaciously, the numerical simulations for different type of solutions is carried out and the corresponding graphs are obtained. The whole of the solutions presented in this paper consist of all the results in the published literatures, especially the elliptic functions solutions, which are initially shown. In addition, according to the results obtained by advanced fractional method in mathematical physics, the nature of rich wave propagation patterns could be seen clearly.

Trichoderma reesei is a high-yield producer of cellulase for applications in lignocellulosic biomass conversion, but its cellulase production requires induction. A mixture of glucose and β-disaccharide has been demonstrated to achieve high-level cellulase production. However, as inducers, β-disaccharides are prone to be hydrolyzed by β-glucosidase (BGL) during fermentation, therefore β-disaccharides need to be supplemented through feeding to overcome this problem. Here, miglitol, an α-glucosidase inhibitor, was investigated as a BGL inhibitor, and exhibited an IC50 value of 2.93 μg/mL. The cellulase titer was more than two-fold when miglitol was added to the fermentation medium of T. reesei. This method was similar to the prokaryotic expression system using unmetabolized isopropyl-β-D-thiogalactopyranoside (IPTG) as the inducer instead of lactose to continuously induce gene expression. However, cellulase activity was not enhanced with BGL inhibition when lactose or cellulose was used as an inducer, which demonstrated that the transglycosidase activity of BGL is important for the inducible activity of lactose and cellulose. This novel method demonstrates potential in stimulating cellulase production and provides a promising system for T. reesei protein expression.

The aim of this work is to evaluate the effects of glucose and corn syrup on the physical characteristics and whipping properties of whipped creams. The interfacial protein concentration and apparent viscosity of emulsions increased with an increasing sugar concentration. In whipped creams, a shorter optimum whipping time (top), higher fat coalescence degree, higher firmness and higher stability were detected as sugar concentration increased. The partial coalescence degree, overrun and firmness of whipped cream with 30 wt% glucose reached 76.49%, 306% and 3.82 N, respectively, significantly (p < 0.05) higher than those (67.15%, 235% and 3.19 N) with 30 wt% corn syrup. Compared with glucose at the same sugar concentration, higher interfacial protein concentration and less-shaped aggregates and coalescences were observed for the emulsions upon the addition of corn syrup, which caused a lower degree of fat coalescence and a lower firmness of whipped cream. The differences could be explained by the presence of maltodextrin (MDX) in corn syrup, which protects absorbed protein throughout freezing and retards the formation of a continuous network during whipping. As a result, the addition of sugars could well improve stability of emulsion, firmness and foam stability of whipped cream efficiently. With a 25–30 wt% sugar addition, even if there was a lower partial coalescence degree and firmness compared with glucose, whipped cream with corn syrup exhibited relatively good stability. These results suggest that MDX improves the stability of emulsion and, thus, has a potential use in low-sugar whipped cream.

FAM83A is part of an 8-member protein family of unknown function and is reported to be a cancer-promoting and treatment-resistance factor in several cancers. However, its role in hepatocellular carcinoma (HCC) remains unclear. Analysis of the Cancer Genome Atlas (TCGA) showed that FAM83A mRNA expression is upregulated in HCC, as are the protein expression levels in both HCC cell lines and tissues. Clinical data have demonstrated that high FAM83A expression is positively correlated with poor progression-free survival time, thus suggesting its cancer-promoting potential. Functional analyses showed that FAM83A overexpression promoted HCC cell migration and invasion in vitro and suppressed sorafenib sensitivity. Inhibiting FAM83A reversed these results. A pulmonary metastasis model further confirmed that FAM83A promoted HCC cell metastasis in vivo. Mechanistic analyses indicated that FAM83A activated the PI3K/AKT signaling pathway, its downstream c-JUN protein, and epithelial-to-mesenchymal transition (EMT)-related protein levels, including downregulation of E-cadherin and upregulation of Vimentin and N-cadherin. Interestingly, c-JUN induced FAM83A expression by directly binding to its promoter region and thus forming a positive-feedback loop for FAM83A/PI3K/AKT/c-JUN. In conclusion, we demonstrated that FAM83A, as a cancer-metastasis promoter, accelerates migration, invasion and metastasis by activating the PI3K/AKT/c-JUN pathway and inducing its self-expression via feedback, thus forming a FAM83A/PI3K/AKT/c-JUN positive-feedback loop to activate EMT signaling and finally promote HCC migration, invasion and metastasis.

Abstract Background Subfoveal choroidal thickness (SFCT) in highly myopic eyes was found to be correlated with increasing age, refractive error (spherical equivalent), and axial length. Which factor is the most significant predictor of SFCT remains controversial. Methods A hospital-based cohort of highly myopic eyes (with spherical equivalent equal to or over 6.00 diopter) were retrospectively screened. Data from only right eye in those bilateral high myopia, and unilateral high myopia in any eye, were used for analysis. Correlations among the four biometric factors were analyzed. Linear correlation was performed to analyze the predictors of SFCT. Results A cohort of 312 eyes from 312 adults (98 men) was enrolled. Statistical analysis showed that axial length (R = − 0.592), spherical equivalent (R = − 0.471), and age (R = − 0.296) were significantly correlated with SFCT (P

With the rapid growth of the Internet, the curse of dimensionality caused by massive multi-label data has attracted extensive attention. Feature selection plays an indispensable role in dimensionality reduction processing. Many researchers have focused on this subject based on information theory. Here, to evaluate feature relevance, a novel feature relevance term (FR) that employs three incremental information terms to comprehensively consider three key aspects (candidate features, selected features, and label correlations) is designed. A thorough examination of the three key aspects of FR outlined above is more favorable to capturing the optimal features. Moreover, we employ label-related feature redundancy as the label-related feature redundancy term (LR) to reduce unnecessary redundancy. Therefore, a designed multi-label feature selection method that integrates FR with LR is proposed, namely, Feature Selection combining three types of Conditional Relevance (TCRFS). Numerous experiments indicate that TCRFS outperforms the other 6 state-of-the-art multi-label approaches on 13 multi-label benchmark data sets from 4 domains.

Based on analysis of horizontal well data characteristics, the differences of data distribution and variogram between vertical and horizontal wells in MPE3 oil field of Orinoco heavy oil belt were compared, and modeling strategies were proposed to cope with the big data paradox when data of horizontal wells was used directly into geologic modeling. The study shows the horizontal wells in the study area contain a large quantity of information, strong directionality of well trajectories and high drilling ratio of sandstone, causing variogram analysis result unconformable to the geologic understanding, and in turn making errors in the modeling of sedimentary microfacies and reservoir physical properties and prediction of probabilistic reserves. Firstly, the distributary channel distribution variogram was analyzed with data of vertical wells, and then the lithofacies framework was established under the control of the sedimentary facies and seismic data. After that, the horizontal wells data revealing high heterogeneity accuracy of reservoir, was combined with the vertical wells data to analyze argillaceous interlayer variograms and the corresponding reservoir lithofacies models were constructed. Finally, reservoir physical property models were generated and the geological reserves were calculated by wellblocks. This reservoir modeling method does not only reflect the geologic features underground, but also improve the accuracy of inter-well sand body prediction, and enhance the reliability of reservoir geologic model ultimately. Key words: horizontal well, geological modeling, big data paradox, big data analysis, variogram

Abstract Background Mammalian folliculogenesis, maturation of the ovarian follicles, require both growth factors derived from oocyte and surrounding cells, including stromal cells. However, the mechanism by which stromal cells and derived factors regulate oocyte development remains unclear. Results We observed that SENP1, a small ubiquitin-related modifier (SUMO)-specific isopeptidase, was expressed in sm22α-positive stromal cells of mouse ovary. The sm22α-positive stromal cells tightly associated with follicle maturation. By using the sm22α-specific Cre system, we show that mice with a stromal cell-specific deletion of SENP1 exhibit attenuated stroma-follicle association, delayed oocyte growth and follicle maturation with reduced follicle number and size at early oocyte development, leading to premature ovarian failure at late stages of ovulating life. Mechanistic studies suggest that stromal SENP1 deficiency induces down-regulation of BMP4 in stromal cells concomitant with decreased expression of BMP4 receptor BMPR1b and BMPR2 on oocytes. Conclusions Our data support that protein SUMOylation-regulating enzyme SENP1 plays a critical role in early ovarian follicle development by regulating gene expression of BMP4 in stroma and stroma-oocyte communication.

Abstract Background Transscleral tunnel incisions are commonly made to avoid postoperative leakage in small gauge sutureless vitrectomy. We present an unreported intraoperative complication, tunnel incision related arterial hemorrhage from sclerotomy, in 23-gauge (23G) vitrectomy. Case presentation Two cases of intraocular arterial hemorrhage from superonasal sclerotomy were observed at the beginning of vitrectomy. The bleeding filled the vitreous cavity quickly and gushed out from the incision port after the involved supronasal cannula was removed. The active bleeding seemed not to stop spontaneously. We controlled the active bleeding by relocating the involved cannula, elevating the intraocular pressure and compressing the sclera wound. Post-operative intraocular hemorrhage from the sclerotomy was not found in any of the two cases. Conclusions We suggest that the bleeding was from injured ciliary artery when the incision crossed 3 or 9 o’clock accidently. Surgeons might avoid this complication by locating the superior incisions away from the horizontal axis, and should be aware the proper management.

Multi-label data often involve features with high dimensionality and complicated label correlations, resulting in a great challenge for multi-label learning. Feature selection plays an important role in multi-label learning to address multi-label data. Exploring label correlations is crucial for multi-label feature selection. Previous information-theoretical-based methods employ the strategy of cumulative summation approximation to evaluate candidate features, which merely considers low-order label correlations. In fact, there exist high-order label correlations in label set, labels naturally cluster into several groups, similar labels intend to cluster into the same group, different labels belong to different groups. However, the strategy of cumulative summation approximation tends to select the features related to the groups containing more labels while ignoring the classification information of groups containing less labels. Therefore, many features related to similar labels are selected, which leads to poor classification performance. To this end, Max-Correlation term considering high-order label correlations is proposed. Additionally, we combine the Max-Correlation term with feature redundancy term to ensure that selected features are relevant to different label groups. Finally, a new method named Multi-label Feature Selection considering Max-Correlation (MCMFS) is proposed. Experimental results demonstrate the classification superiority of MCMFS in comparison to eight state-of-the-art multi-label feature selection methods.

Background: Studies have shown that mini-αA can protect retinal pigment epithelium (RPE) cells from apoptosis. However, no in vivo study concerning the anti-apoptotic function of mini-αA has been conducted yet. Methods: MTT assay, HE staining and TUNEL assay were used to assess levels of cells, and an animal model was established to examine the protective effects of mini-αA against NaIO3-induced RPE cell apoptosis. Western blot analysis and RT-qPCR were performed to explore the possible mechanism of mini-αA’s protective function against NaIO3-induced RPE cell apoptosis. Results: Results from in vivo and animal experiments showed that mini-αA antagonized NaIO3-induced RPE cell apoptosis. Further investigation into how mini-αA provided protection against NaIO3-induced RPE cell apoptosis showed that mini-αA reduced NaIO3-induced RPE cell apoptosis and autophagy. In addition, unfolded protein response was also involved in the protective effects of mini-αA against NaIO3-induced RPE cell apoptosis. Conclusions: mini-αA can antagonize RPE cell apoptosis induced by NaIO3. A possible mechanism is by inhibition of apoptosis by repressing autophagy and endoplasmic reticulum stress.

This study aims to evaluate the efficacy of ketorolac with local anesthesia compared to local anesthesia alone for perioperative pain control in day care retinal detachment surgery. The randomized controlled trial included 59 eyes of 59 participants for retinal detachment surgery who were randomly assigned (1 : 1) into the ketorolac (K) group and control (C) group. All participants underwent conventional local anesthesia while patients in the K group received an extra administration of preoperative ketorolac. Participants in the K group had a statistically significantly lower intraoperative NRS score (median 1.0 versus 3.0, P=0.003), lower postoperative NRS score (median 0 versus 1.0, P=0.035), fewer proportion of rescue analgesic requirement (10% versus 34.5%, P=0.023), and lower incidence of postoperative nausea and vomiting (13.3% versus 41.4%, P=0.015) compared to the C group. Intraocular pressure (IOP) changes (△IOP) were significantly reduced in the K group (median 1.9 versus 3.0, P=0.038) compared to the C group 24 hours postoperatively. In conclusion, the combination of local anesthesia with ketorolac provides better pain control in retinal detachment surgery compared to local anesthesia alone. The beneficial effect of ketorolac with local anesthesia may contribute to a wider-spread adoption of day care retinal detachment surgery. This trial is registered with ClinicalTrials.gov NCT02729285.

Recent reform of medical education highlights the growing concerns about the capability of the current educational model to equip medical school students with essential skills for future career development. In the field of ophthalmology, although many attempts have been made to address the problem of the decreasing teaching time and the increasing load of course content, a growing body of literature indicates the need to reform the current ophthalmology teaching strategies. Flipped classroom is a new pedagogical model in which students develop a basic understanding of the course materials before class, and use in-class time for learner-centered activities, such as group discussion and presentation. However, few studies have evaluated the effectiveness of the flipped classroom in ophthalmology education. This study, for the first time, assesses the use of flipped classroom in ophthalmology, specifically glaucoma and ocular trauma clerkship teaching. A total number of 44 international medical school students from diverse background were enrolled in this study, and randomly divided into two groups. One group took the flipped glaucoma classroom and lecture-based ocular trauma classroom, while the other group took the flipped ocular trauma classroom and lecture-based glaucoma classroom. In the traditional lecture-based classroom, students attended the didactic lecture and did the homework after class. In the flipped classroom, students were asked to watch the prerecorded lectures before the class, and use the class time for homework discussion. Both the teachers and students were asked to complete feedback questionnaires after the classroom. We found that the two groups did not show differences in the final exam scores. However, the flipped classroom helped students to develop skills in problem solving, creative thinking and team working. Also, compared to the lecture-based classroom, both teachers and students were more satisfied with the flipped classroom. Interestingly, students had a more positive attitude towards the flipped ocular trauma classroom than the flipped glaucoma classroom regarding the teaching process, the course materials, and the value of the classroom. Therefore, the flipped classroom model in ophthalmology teaching showed promise as an effective approach to promote active learning.

The anticancer agent 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (laromustine), upon decomposition in situ, yields methyl isocyanate and the chloroethylating species 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine (90CE). 90CE has been shown to kill tumor cells via a proposed mechanism that involves interstrand DNA cross-linking. However, the role of methyl isocyanate in the antineoplastic function of laromustine has not been delineated. Herein, we show that 1,2-bis(methylsulfonyl)-1-[(methylamino)carbonyl]hydrazine (101MDCE), an analog of laromustine that generates only methyl isocyanate, activates ASK1-JNK/p38 signaling in endothelial cells (EC). We have previously shown that ASK1 forms a complex with reduced thioredoxin (Trx1) in resting EC, and that the Cys residues in ASK1 and Trx1 are critical for their interaction. 101MDCE dissociated ASK1 from Trx1, but not from the phosphoserine-binding inhibitor 14-3-3, in whole cells and in cell lysates, consistent with the known ability of methyl isocyanate to carbamoylate free thiol groups of proteins. 101MDCE had no effect on the kinase activity of purified ASK1, JNK, or the catalytic activity of Trx1. However, 101MDCE, but not 90CE, significantly decreased the activity of Trx reductase-1 (TrxR1). We conclude that methyl isocyanate induces dissociation of ASK1 from Trx1 either directly by carbamoylating the critical Cys groups in the ASK1-Trx1 complex or indirectly by inhibiting TrxR1. Furthermore, 101MDCE (but not 90CE) induced EC death through a non-apoptotic (necroptotic) pathway leading to inhibition of angiogenesis in vitro. Our study has identified methyl isocyanates may contribute to the anticancer activity in part by interfering with tumor angiogenesis.