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Background: Encouraging antitumor activity of nab-paclitaxel plus S-1 (AS) has been shown in several small-scale studies. This study compared the efficacy and safety of AS versus standard-of-care nab-paclitaxel plus gemcitabine (AG) as a first-line treatment for advanced pancreatic cancer (PC)., Methods: In this multicenter, randomized, phase II trial, eligible patients with unresectable, locally advanced, or metastatic PC were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 125 mg/m2 on days 1 and 8; S-1 twice daily on days 1 through 14) or AG (nab-paclitaxel 125 mg/m2 on days 1 and 8; gemcitabine 1000 mg/m2 on days 1 and 8) for 6 cycles. The primary endpoint was progression-free survival (PFS)., Results: Between July 16, 2019, and September 9, 2022, 62 patients (AS, n = 32; AG, n = 30) were treated and evaluated. With a median follow-up of 8.36 months at preplanned interim analysis (data cutoff, March 24, 2023), the median PFS (8.48 vs 4.47 months; hazard ratio [HR], 0.402; P = .002) and overall survival (OS; 13.73 vs 9.59 months; HR, 0.226; P < .001) in the AS group were significantly longer compared to the AG group. More patients had objective response in the AS group than AG group (37.50% vs 6.67%; P = .005). The most common grade 3-4 adverse events were neutropenia and leucopenia in both groups, and gamma glutamyl transferase increase was observed only in the AG group., Conclusion: The first-line AS regimen significantly extended both PFS and OS of Chinese patients with advanced PC when compared with the AG regimen, with a comparable safety profile. (ClinicalTrials.gov Identifier: NCT03636308)., (© The Author(s) 2024. Published by Oxford University Press.)

Human cortical neurons (hCNs) exhibit high dendritic complexity and synaptic density, and the maturation process is greatly protracted. However, the molecular mechanism governing these specific features remains unclear. Here, we report that the hominoid-specific gene TBC1D3 promotes dendritic arborization and protracts the pace of synaptogenesis. Ablation of TBC1D3 in induced hCNs causes reduction of dendritic growth and precocious synaptic maturation. Forced expression of TBC1D3 in the mouse cortex protracts synaptic maturation while increasing dendritic growth. Mechanistically, TBC1D3 functions via interaction with MICAL1, a monooxygenase that mediates oxidation of actin filament. At the early stage of differentiation, the TBC1D3/MICAL1 interaction in the cytosol promotes dendritic growth via F-actin oxidation and enhanced actin dynamics. At late stages, TBC1D3 escorts MICAL1 into the nucleus and downregulates the expression of genes related with synaptic maturation through interaction with the chromatin remodeling factor ATRX. Thus, this study delineates the molecular mechanisms underlying human neuron development., Competing Interests: Declaration of interests The authors have no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The regenerative potential of injured axons displays considerable heterogeneity. However, the molecular mechanisms underlying the heterogeneity have not been fully elucidated. Here, we establish a method that can separate spinal motor neurons (spMNs) with low and high regenerative capacities and identify a set of transcripts revealing differential expression between two groups of neurons. Interestingly, oligodendrocyte transcription factor 1 (Olig1), which regulates the differentiation of various neuronal progenitors, exhibits recurrent expression in spMNs with enhanced regenerative capabilities. Furthermore, overexpression of Olig1 (Olig1 OE) facilitates axonal regeneration in various models, and down-regulation or deletion of Olig1 exhibits an opposite effect. By analyzing the overlapped differentially expressed genes after expressing individual Olig factor and functional validation, we find that the role of Olig1 is at least partially through the neurite extension factor 1 (Nrsn1). We therefore identify Olig1 as an intrinsic factor that promotes regenerative capacity of injured axons., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The zinc finger DHHC-type containing 1 (ZDHHC1) gene is implicated in the pathogenesis and progression of various malignant tumors, but its precise involvement in uterine corpus endometrial carcinoma (UCEC) remains unknown. Thus, this study investigated ZDHHC1 expression in UCEC using publicly available TCGA and Xena databases and elucidated the functions and mechanisms of the ZDHHC1 gene in UCEC progression using bioinformatics and in vitro experiments. The correlation between ZDHHC1 expression and prognosis, clinical features, immune cells, and RNA modifications of UCEC was evaluated using nomograms, correlation, ROC, and survival analyses. The impacts of ZDHHC1 overexpression on UCEC progression and mechanisms were explored with bioinformatics and in vitro experiments. Our study revealed that ZDHHC1 expression was significantly downregulated in UCEC and correlated with poor prognosis, cancer diagnosis, clinical stage, age, weight, body mass index, histological subtypes, residual tumor, tumor grade, and tumor invasion. Notably, Cox regression analysis and constructed nomograms showed that downregulated ZDHHC1 expression was a prognostic factor associated with poor prognosis in patients with UCEC. Conversely, above-normal ZDHHC1 expression inhibited the cell growth, cell cycle transition, migration, and invasion of UCEC cells, which may be related to the cell cycle, DNA replication, PI3K-AKT, and other pathways that promote tumor progression. Altered ZDHHC1 expression in UCEC was significantly associated with RNA modifications and the changes in cancer immune cell populations, such as CD56 bright NK cells, eosinophils, Th2 cells, and cell markers. In conclusion, considerably reduced ZDHHC1 expression in UCEC is associated with cancer cell growth, metastasis, poor prognosis, immune infiltration, and RNA modifications, revealing the promising potential of ZDHHC1 as a prognostic marker for UCEC.

Deciphering patterns of connectivity between neurons in the brain is a critical step toward understanding brain function. Imaging-based neuroanatomical tracing identifies area-to-area or sparse neuron-to-neuron connectivity patterns, but with limited throughput. Barcode-based connectomics maps large numbers of single-neuron projections, but remains a challenge for jointly analyzing single-cell transcriptomics. Here, we established a rAAV2-retro barcode-based multiplexed tracing method that simultaneously characterizes the projectome and transcriptome at the single neuron level. We uncovered dedicated and collateral projection patterns of ventromedial prefrontal cortex (vmPFC) neurons to five downstream targets and found that projection-defined vmPFC neurons are molecularly heterogeneous. We identified transcriptional signatures of projection-specific vmPFC neurons, and verified Pou3f1 as a marker gene enriched in neurons projecting to the lateral hypothalamus, denoting a distinct subset with collateral projections to both dorsomedial striatum and lateral hypothalamus. In summary, we have developed a new multiplexed technique whose paired connectome and gene expression data can help reveal organizational principles that form neural circuits and process information., Competing Interests: PX, JP, TY, ZC, HH, ZW, TL, XL, LW, LG, JY, WW, CL, ZL, YC No competing interests declared, (© 2024, Xu, Peng, Yuan et al.)

Brain organoids have been widely used to study diseases and the development of the nervous system. Many reports have investigated the application of brain organoids, but most of these models lack vascular structures, which play essential roles in brain development and neurological diseases. The brain and blood vessels originate from two different germ layers, making it difficult to induce vascularized brain organoids in vitro. We developed this protocol to generate brain-specific blood vessel and cerebral organoids and then fused them at a specific developmental time point. The fused cerebral organoids exhibited robust vascular network-like structures, which allows simulating the in vivo developmental processes of the brain for further applications in various neurological diseases. Key Features • Culturing vascularized brain organoids using human embryonic stem cells (hESCs). • The new approach generates not only neural cells and vessel-like networks but also brain-resident microglia immune cells in a single organoid., Competing Interests: Competing interestsThe authors declare no competing interests., (©Copyright : © 2023 The Authors; This is an open access article under the CC BY license.)

Amyotrophic lateral sclerosis (ALS) is a uniformly lethal neurodegenerative disease characterized by progressive deterioration of motor neurons and neuromuscular denervation. Adeno-associated virus (AAV)-mediated delivery of trophic factors is being considered as a potential disease-modifying therapeutic avenue. Here we show a marked effect of AAV-mediated over-expression of neuron-derived neurotrophic factor (NDNF) on SOD1 G93A ALS model mice. First, we adopt AAV-PHP.eB capsid to enable widespread expression of target proteins in the brain and spinal cord when delivered intrathecally. Then we tested the effects of AAV-NDNF on SOD1 G93A mice at different stages of disease. Interestingly, AAV-NDNF markedly improved motor performance and alleviated weight loss when delivered at early post-symptomatic stage. Injection in the middle post-symptomatic stages still improved the locomotion ability, although it did not alleviate the loss of body weight. Injection in the late stage also extended the life span of SOD1 G93A mice. Furthermore, NDNF expression promoted the survival of spinal motoneurons, reduced abnormal protein aggregation, and preserved the innervated neuromuscular functions. We further analyzed the signaling pathways of NDNF expression and found that it activates cell survival and growth-associated mammalian target of rapamycin signaling pathway and downregulates apoptosis-related pathways. Thus, intrathecally AAV-NDNF delivery has provided a potential strategy for the treatment of ALS., Competing Interests: Declaration of interests A related patent pertaining to the application of NDNF on ALS treatment has been filed (patent applicant: ShanghaiTech University, inventors: Z.G.L. and W.C., application number: 202310546009.1, status: pending)., (Copyright © 2023 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Understanding the fundamental processes of human brain development and diseases is of great importance for our health. However, existing research models such as non-human primate and mouse models remain limited due to their developmental discrepancies compared with humans. Over the past years, an emerging model, the "brain organoid" integrated from human pluripotent stem cells, has been developed to mimic developmental processes of the human brain and disease-associated phenotypes to some extent, making it possible to better understand the complex structures and functions of the human brain. In this review, we summarize recent advances in brain organoid technologies and their applications in brain development and diseases, including neurodevelopmental, neurodegenerative, psychiatric diseases, and brain tumors. Finally, we also discuss current limitations and the potential of brain organoids., (© 2023. The Author(s).)

The Suntuan mining area of Huaibei is a typical coal resource mining base in the Huainan-Huaibei areas in North China. Previous environmental studies related to surface dust in coal mining areas mainly focused on heavy metals and water-soluble ions, with little research on polycyclic aromatic compounds (PACs). In this study, gas chromatography-triple tandem quadrupole mass spectrometry (GC-MS/MS) was used to determine the contents of 16 parent polycyclic aromatic hydrocarbons (16PAHs), alkyl polycyclic aromatic hydrocarbons (aPAHs), and some oxygenated polycyclic aromatic hydrocarbons (OPAHs) in surface dust from the Suntuan mining area and surrounding environment. The results showed that the ΣPACs concentration range of surface dust in the Suntuan mining area was 283.8-36852.5 μg·kg -1 (mean:4114.2 μg·kg -1 ). ΣaPAHs (mean:2593.8 μg·kg -1 ) was 2.4 times higher than Σ16PAHs (mean:1074.9 μg·kg -1 ), which was the main contributor to PAC pollution. The composition of 16PAHs and aPAHs in surface dust was dominated by low molecular polycyclic aromatic hydrocarbons. The average OPAH content was 445.6 μg·kg -1 . At the same time, PAC pollution was mainly concentrated around the mining area and near the road of a coal gangue landfill. Based on the positive matrix factor (PMF) analysis, it was inferred that the study area was mainly affected by petroleum sources, followed by coal and biomass combustion, and traffic sources and petroleum product leakage accounted for a relatively small proportion. Based on the ratio and distribution pattern of 16PAHs and aPAHs, it was inferred that when Σ16PAHs/ΣPACs<0.25, it was mainly polluted by the coal mining area. The results of PMF combined with lifetime carcinogenic risk (ILCR) showed that there were potential carcinogenic risks for children near the study area, mainly from coal and biomass burning and coal mining. There are many coal mining areas in Huaihe River Basin in China. The results of this study can provide reference for pollution prevention and control of PACs in these coal mining areas.

Metformin (MTF) and berberine (BBR) share several therapeutic benefits in treating metabolic-related disorders. However, as the two agents have very different chemical structure and bioavailability in oral route, the goal of this study is to learn their characteristics in treating metabolic disorders. The therapeutic efficacy of BBR and MTF was systemically investigated in the high fat diet feeding hamsters and/or ApoE (-/-) mice; in parallel, gut microbiota related mechanisms were studied for both agents. We discovered that, although both two drugs had almost identical effects on reducing fatty liver, inflammation and atherosclerosis, BBR appeared to be superior over MTF in alleviating hyperlipidemia and obesity, but MTF was more effective than BBR for the control of blood glucose. Association analysis revealed that the modulation of intestinal microenvironment played a crucial role in the pharmacodynamics of both drugs, in which their respective superiority on the regulation of gut microbiota composition and intestinal bile acids might contribute to their own merits on lowering glucose or lipids. This study shows that BBR may be a good alternative for MTF in treating diabetic patients, especially for those complicated with dyslipidemia and obesity., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The efficiency of homology-directed repair (HDR) plays a crucial role in the development of animal models and gene therapy. We demonstrate that microhomology-mediated end-joining (MMEJ) constitutes a substantial proportion of DNA repair during CRISPR-mediated gene editing. Using CasRx to downregulate a key MMEJ factor, Polymerase Q (Polq), we improve the targeted integration efficiency of linearized DNA fragments and single-strand oligonucleotides (ssODN) in mouse embryos and offspring. CasRX-assisted targeted integration (CATI) also leads to substantial improvements in HDR efficiency during the CRISPR/Cas9 editing of monkey embryos. We present a promising tool for generating monkey models and developing gene therapies for clinical trials., (© 2023. The Author(s).)

To develop recyclable biocatalyst used in Pickering interfacial systems, the pH-responsive monomer [2-(dimethylamine)ethyl methacrylate] (DMAEMA) was grafted onto the maize starch molecule via free radical polymerization. Subsequently, combined with the gelatinization-ethanol precipitation and lipase (Candida rugosa) absorption process, an enzyme-loaded starch nanoparticle with DMAEMA grafting (D-SNP@CRL) was tailor-made, showing a nanometer size and regular sphere. X-ray photoelectron spectroscopy and confocal laser scanning microscopy confirmed a concentration-induced enzyme distribution within D-SNP@CRL, thereof the outside-to-inside enzyme distribution was proved to be optimum in achieving the highest catalytic efficiency. Benefited from the tunable wettability and size of D-SNP@CRL under pH variation, the generated Pickering emulsion could be readily applied as the recyclable microreactors for the n-butanol/vinyl acetate transesterification. This catalysis exhibited both highly catalytic activity and good recyclability, making the enzyme-loaded starch particle a promising green and sustainable biocatalyst in the Pickering interfacial system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The nervous system is composed of a variety of neurons and glial cells with different morphology and functions. In the mammalian peripheral nervous system (PNS) or the lower vertebrate central nervous system (CNS), most neurons can regenerate extensively after axotomy, while the neurons in the mammalian CNS possess only limited regenerative ability. This heterogeneity is common within and across species. The studies about the transcriptomes after nerve injury in different animal models have revealed a series of molecular and cellular events that occurred in neurons after axotomy. However, responses of various types of neurons located in different positions of individuals were different remarkably. Thus, researchers aim to find the key factors that are conducive to regeneration, so as to provide the molecular basis for solving the regeneration difficulties after CNS injury. Here we review the heterogeneity of axonal regeneration among different cell subtypes in different animal models or the same organ, emphasizing the importance of comparative studies within and across species., (© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Brain organoids have been used to recapitulate the processes of brain development and related diseases. However, the lack of vasculatures, which regulate neurogenesis and brain disorders, limits the utility of brain organoids. In this study, we induced vessel and brain organoids, respectively, and then fused two types of organoids together to obtain vascularized brain organoids. The fused brain organoids were engrafted with robust vascular network-like structures and exhibited increased number of neural progenitors, in line with the possibility that vessels regulate neural development. Fusion organoids also contained functional blood-brain barrier-like structures, as well as microglial cells, a specific population of immune cells in the brain. The incorporated microglia responded actively to immune stimuli to the fused brain organoids and showed ability of engulfing synapses. Thus, the fusion organoids established in this study allow modeling interactions between the neuronal and non-neuronal components in vitro, particularly the vasculature and microglia niche., Competing Interests: XS, XJ, YL, PZ, JW, YZ, LS, JD, YC, ZL No competing interests declared, (© 2022, Sun et al.)

Oxidized gellan gum (OGG) hydrogel beads as delivery systems for resveratrol were fabricated by ionic cross-linking with calcium chloride (CaCl 2 ). The degree of oxidation (DO) and CaCl 2 concentration had significant influences on the formation and functional properties of hydrogel beads. The resveratrol encapsulation efficiency (66.43%-79.84%) and loading capacity (4.15%-5.05%) of OGG hydrogel beads were enhanced as DO increased. The hydrogel beads exhibited a uniform spherical shape as observed by scanning electron microscope. Fourier transform infrared spectroscopy analysis confirmed that hydrogen bonds and ionic interaction participated in the formation of hydrogel beads. X-ray diffraction analysis revealed that the physical state of resveratrol was changed from crystalline to amorphous form after encapsulation. Furthermore, the physical stability and antioxidant capacity evaluation demonstrated that the hydrogel bead fabricated with DO80 OGG and CaCl 2 concentration of 1.0 M could provide high protection for resveratrol against degradation by environmental stresses and maintain its antioxidant capacity. The DO and CaCl 2 concentrations could modulate the in-vitro release behaviors of hydrogel beads and obtain a good small intestinal-targeted release of resveratrol at high DO and medium CaCl 2 concentration. These findings suggested that a promising delivery system for encapsulating bioactive ingredients can be fabricated by rational design., (Copyright © 2021. Published by Elsevier B.V.)

The prevailing coronavirus disease-19 (COVID-19) caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has presented some neurological manifestations including hyposmia, hypogeusia, headache, stroke, encephalitis, Guillain-Barre syndrome, and some neuropsychiatric disorders. Although several cell types in the brain express angiotensin-converting enzyme-2 (ACE2), the main SARS-CoV-2 receptor, and other related proteins, it remains unclear whether the observed neurological manifestations are attributed to virus invasion into the brain or just comorbidities caused by dysregulation of systemic factors. Here, we briefly review the neurological manifestations of SARS-CoV-2, summarize recent evidence for the potential neurotropism of SARS-CoV-2, and discuss the potential mechanisms of COVID-19-associated neurological diseases., (© The Author(s) (2021). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)

Russula virescens is an edible wild mushroom that is widely distributed in south of China. This research aimed to analyze the structure characterization and evaluate the hypoglycemic, anticancer and immunological activities of two water soluble polysaccharides RVP-1 and RVP-2 from R. virescens. The results showed RVP-1 and RVP-2 were non-triple helix structured hetero-polysaccharides with different weight-average molecular weight 14,883 and 13,301 Da, respectively. Both RVP-1 and RVP-2 were composed of galactose, glucose, mannose and fructose, and the sugar residues were mainly linked by 1,6→, 1,2→, 1→ and 1,3,6→ glycosidic bonds. Moreover, the antidiabetic, anticancer and immune activities of RVP-1 and RVP-2 were explored in vitro methods. The two polysaccharides have potential for inhibiting α-glucosidase and α-amylase activities, suppressing HepG-2, A549 and MCF-7 cancer cells proliferation, and activating macrophage RAW 264.7 cells to secret immune cytokines for mediating cellular immune response. These findings provided a scientific basis for further utilization of polysaccharide from R. virescens., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Fusion transcripts or RNAs have been found in both disordered and healthy human tissues and cells; however, their physiological functions in the brain development remain unknown. In the analysis of deposited RNA-sequence libraries covering early to middle embryonic stages, we identify 1,055 fusion transcripts present in the developing neocortex. Interestingly, 98 fusion transcripts exhibit distinct expression patterns in various neural progenitors (NPs) or neurons. We focus on CTNNBIP1-CLSTN1 (CTCL), which is enriched in outer radial glial cells that contribute to cortex expansion during human evolution. Intriguingly, downregulation of CTCL in cultured human cerebral organoids causes marked reduction in NPs and precocious neuronal differentiation, leading to impairment of organoid growth. Furthermore, the expression of CTCL fine-tunes Wnt/β-catenin signaling that controls cortex patterning. Together, this work provides evidence indicating important roles of fusion transcript in human brain development and evolution., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The 2019 novel coronavirus has spread rapidly around the world. Cancer patients seem to be more susceptible to infection and disease deterioration, but the factors affecting the deterioration remain unclear. We aimed to develop an individualized model for prediction of coronavirus disease (COVID-19) deterioration in cancer patients. The clinical data of 276 cancer patients diagnosed with COVID-19 in 33 designated hospitals of Hubei, China from December 21, 2019 to March 18, 2020, were collected and randomly divided into a training and a validation cohort by a ratio of 2:1. Cox stepwise regression analysis was carried out to select prognostic factors. The prediction model was developed in the training cohort. The predictive accuracy of the model was quantified by C-index and time-dependent area under the receiver operating characteristic curve (t-AUC). Internal validation was assessed by the validation cohort. Risk stratification based on the model was carried out. Decision curve analysis (DCA) were used to evaluate the clinical usefulness of the model. We found age, cancer type, computed tomography baseline image features (ground glass opacity and consolidation), laboratory findings (lymphocyte count, serum levels of C-reactive protein, aspartate aminotransferase, direct bilirubin, urea, and d-dimer) were significantly associated with symptomatic deterioration. The C-index of the model was 0.755 in the training cohort and 0.779 in the validation cohort. The t-AUC values were above 0.7 within 8 weeks both in the training and validation cohorts. Patients were divided into two risk groups based on the nomogram: low-risk (total points ≤ 9.98) and high-risk (total points > 9.98) group. The Kaplan-Meier deterioration-free survival of COVID-19 curves presented significant discrimination between the two risk groups in both training and validation cohorts. The model indicated good clinical applicability by DCA curves. This study presents an individualized nomogram model to individually predict the possibility of symptomatic deterioration of COVID-19 in patients with cancer., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Hydrogel beads composed of oxidized gellan gum (OGG) and resistant starch (RS) were successfully fabricated by ionic cross-linking and used as delivery carriers for resveratrol. Firstly, OGG with different degrees of oxidation were prepared through 2, 2, 6, 6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation, and characterized by Fourier transform infrared spectroscopy and carbon-13 nuclear magnetic resonance to prove that carboxyl groups were successfully introduced into the gellan gum molecules. Molecular weight, thermal stability, zeta potential and gelation temperature of OGG were also investigated. Subsequently, resveratrol was encapsulated into OGG/RS hydrogel beads in the form of resveratrol/β-cyclodextrins inclusion complexes. The addition of RS significantly influenced the morphological structure and swelling capacity of OGG/RS hydrogel beads. The OGG/RS hydrogel beads exhibited a pH-sensitivity and high encapsulation efficiency of resveratrol (84.95 %-90.73 %). Furthermore, the in-vitro release behaviors demonstrated that OGG/RS hydrogel beads showed good stability in simulated gastric fluids and sustained release of resveratrol in simulated intestinal fluids. The obtained results indicate that OGG/RS hydrogel beads show a potential as delivery system for resveratrol in the food industry., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Pullulanase (EC 3.2.1.41) is a starch-debranching enzyme in the α-amylase family and specifically cleaves α-1,6-glycosidic linkages in starch-type polysaccharides, such as pullulan, β-limited dextrin, glycogen, and amylopectin. It plays a key role in debranching and hydrolyzing starch completely, thus bring improved product quality, increased productivity, and reduced production cost in producing resistant starch, sugar syrup, and beer. Plenty of researches have been made with respects to the discovery of either thermophilic or mesophilic pullulanases, however, few examples meet the demand of industrial application. This review presents the progress made in the recent years from the first aspect of characteristics of pullulanases. The heterologous expression of pullulanases in different microbial hosts and the methods used to improve the expression effectiveness and the regulation of enzyme production are also described. Then, the function evolution of pullulanases from a protein engineering view is discussed. In addition, the immobilization strategy using novel materials is introduced to improve the recyclability of pullulanases. At the same time, we indicate the trends in the future research to facilitate the industrial application of pullulanases.

Background: Chronic fatigue syndrome (CFS) is a relatively complex and disabling illness with a substantial economic burden and functional impairment. Until now, many CFS patients lack appropriate healthcare. Acupoint catgut embedding is an effective and emerging alternative therapy for CFE. With this research, we endeavor to investigate the effect and safety of ACE for CFS., Methods: Eight databases will be searched from inception to December 2020: PubMed, EMBASE, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chong-Qing VIP database, and Wan-fang database. We regard studies as eligible for inclusion if they were RCTs done in CFS patients, compare acupoint catgut embedding to another treatment strategy, and report fatigue changes at the end of the intervention period. Two independent reviewers complete the study selection, data extraction, and the risk of bias assessment. We assess pooled data using a random-effects model through Revman software (v.5.3) and Stata (version 15.0)., Ethics and Dissemination: Ethics approval is not required because the individual patient data will not be involved, with no privacy concerns. This systematic review and meta-analysis will provide a reference for CFS patients and clinicians on the non-drug interventions. We will publish and disseminate the results of this review in a peer-reviewed journal or relevant conference., Osf Registration Number: 10.17605/OSF.IO/7SHD9 (https://osf.io/7shd9)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Genomic changes during human linage evolution contribute to the expansion of the cerebral cortex to allow more advanced thought processes. The hominoid-specific gene TBC1D3 displays robust capacity of promoting the generation and proliferation of neural progenitors (NPs), which are thought to contribute to cortical expansion. However, the underlying mechanisms remain unclear. Here, we found that TBC1D3 interacts with G9a, a euchromatic histone lysine N -methyltransferase, which mediates dimethylation of histone 3 in lysine 9 (H3K9me2), a suppressive mark for gene expression. TBC1D3 displayed an inhibitory role in G9a's histone methyltransferase activity. Treatment with G9a inhibitor markedly increased NP proliferation and promoted human cerebral organoid expansion, mimicking the effects caused by TBC1D3 up-regulation. By contrast, blockade of TBC1D3/G9a interaction to disinhibit G9a caused up-regulation of H3K9me2, suppressed NP proliferation, and impaired organoid development. Together, this study has demonstrated a mechanism underlying the role of a hominoid-specific gene in promoting cortical expansion., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

In this work, spiral dextrin/resveratrol (SD/Res) crystal, a new colon-specific drug-delivery system, was established by a novel method of encapsulation and cocrystallization to improve the antidigestion ability compared with the SD/Res inclusion complex (SD/Res IC) prepared by encapsulation and coprecipitation. X-ray diffraction (XRD) and scanning electron microscopy (SEM) revealed that the SD/Res crystal formed a more regular and perfect crystallite than SD/Res IC. Moreover, the encapsulation ability and thermostability of the SD/Res crystal were enhanced as the chain length of SD was increased. In vitro digestion indicated that SD/Res IC merely achieved small intestine-targeted release of resveratrol, while the SD/Res crystal could act as a colon-specific delivery system to protect resveratrol from degradation by gastric acid and pancreatic enzymes. The SD-1/Res crystal presented much higher thermal stability and stronger gastrointestinal stability than other SD/Res crystals and SD/Res ICs, which facilitated its application as a novel colon-target delivery system for resveratrol.

Context: Curcumin has shown efficacy in promoting radiosensitivity combined with radiotherapy. However, the role and mechanism of curcumin on radiosensitivity in laryngeal squamous cell cancer (LSCC) is largely unknown. Objective: The aim of our study is to explore the role of IKKγ-NF-κB signaling in curcumin enhancing LSCC cell radiosensitivity in vitro . Materials and methods: Curcumin and X-ray were used to induce cell DNA damage and apoptosis, or inhibit cell clone formation. IKKγ siRNA and plasmid were used to change IKKγ expression. The CCK8 assay was used to detect cell viability. Clone formation ability was analyzed using a clonogenic assay, cell apoptosis was examined using flow cytometry, an immunofluorescence assay was used to detect DNA damage, while mRNA and protein levels were assayed using real time PCR and western blotting, respectively. Results: Curcumin significantly enhanced irradiation-induced DNA damage and apoptosis, while weakening clone-forming abilities of LSCC cell line Hep2 and Hep2-max. Compared to Hep2 cells, Hep2-max cells are more sensitive to curcumin post-irradiation. Curcumin suppressed irradiation-induced NF-κB activation by suppressing IKKγ expression, but not IKKα and IKKβ. Overexpression of IKKγ decreased irradiation-induced DNA damage and apoptosis, while promoting clone-forming abilities of Hep2 and Hep2-max cells. IKKγ overexpression further increased expression of NF-κB downstream genes, Bcl-XL, Bcl-2, and cyclin D1. Conversely, IKKγ silencing enhanced irradiation-induced DNA damage and apoptosis, but promoted clone formation in Hep2 and Hep2-max cells. Additionally, IKKγ silencing inhibited expression of Bcl-XL, Bcl-2, and cyclin D1. Conclusions: Curcumin enhances LSCC radiosensitivity via NF-ΚB inhibition by suppressing IKKγ expression.

Vitamin C (VC) and β-Carotene (βC) were selected to produce co-encapsulated liposomes using hydrophilic and hydrophobic cavities simultaneously by ethanol injection method. The results of liposomal structure characterized by particle size, polydispersity index, zeta-potential and transmission electron microscope showed that the microstructure of all liposomal samples was spherical without adhesion or break and the size of VC-βC-loaded liposome (L-VC-βC) was bigger than VC-loaded liposome (L-VC) or βC-loaded liposome (L-βC). The encapsulation efficiency (EE) of VC in L-VC-βC was significantly higher than that in L-VC, and the EE of βC in L-VC-βC had no significant change compared with that in L-βC. The free radical scavenging rate of L-VC-βC was significantly higher than that of L-βC, while it had no significant change compared with that of L-VC. In addition, the storage stability of βC in L-VC-βC improved greatly compared with that in L-βC. Furthermore, the zero order model was applied to understand the release kinetics of βC from L-βC and L-VC-βC in the stomach, whereas the Korsmeyr-Peppas model was chosen to describe the release of βC from two types of liposome in small intestine and their release mechanisms were mainly dominated by Fickian diffusion. It was significant to provide a new idea for using hydrophilic and hydrophobic cavities simultaneously in liposomes to design the multicomponent nutrient delivery system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Nucleobindin 2 (NUCB-2) is a multifunctional protein that contains several functional domains and is associated with a wide variety of biological processes, such as food intake and energy homeostasis. NUCB-2 has been demonstrated to be associated with worse malignant outcomes and cell migration in breast and prostate cancer. However, to the best of our knowledge, its clinical and biological significance in renal cell carcinoma remains unknown. In the present study, tissue specimens from 68 patients with renal cell carcinoma and 10 normal controls were collected for NUCB-2 mRNA and protein assays. The NUCB-2 level in the patients with renal cell cancer was significantly increased compared with the normal control patients. NUCB-2-knockout in the renal cancer cell line SK-RC-52 inhibited migration and invasion. In addition, the expression levels of molecules associated with epithelial-mesenchymal transition (EMT), including E-cadherin, β-catenin, Slug and Twist, were affected by NUCB-2 suppression and the zinc finger E-box binding to homeobox 1 (ZEB1)-dependent pathway. The AMP-dependent protein kinase (AMPK)/target of rapamycin complex (mTORC) 1 signaling pathway participates in the regulation of NUCB-2-mediated metastasis and EMT. Suppression of NUCB-2 also inhibited tumor nodule formation in a murine renal cell carcinoma tumor model. In summary, NUCB-2 increased migration, invasion and EMT in renal cell carcinoma cells through the AMPK/TORC1/ZEB1 pathway in vitro and in vivo ., (Copyright: © Tao et al.)

Cortex development is controlled by temporal patterning of neural progenitor (NP) competence with sequential generation of deep and superficial layer neurons, but underlying mechanisms remain elusive. Here, we report a role for heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) in regulating the division of early cortical NPs that mainly give rise to deep-layer neurons via direct neurogenesis. HNRNPA3 is expressed at high levels in NPs of mouse and human cortex at early stages, with a unique peri-chromosome pattern. Intriguingly, downregulation of HNRNPA3 caused chromosome disarrangement, which hindered normal separation of chromosomes during NP division, leading to mitotic delay. Furthermore, HNRNPA3 is associated with the cohesin-core subunit SMC1A and controls its association with chromosomes, implicating a mechanism for the role of HNRNPA3 in regulating chromosome segregation in dividing NPs. Hnrnpa3 -deficient mice exhibited reduced cortical thickness, especially of deep layers. Moreover, downregulation of HNRNPA3 in cultured human cerebral organoids led to marked reduction in NPs and deep-layer neurons. Thus, this study has identified a crucial role for HNRNPA3 in NP division and highlighted the relationship between mitosis progression and early neurogenesis., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Objective: To explore an effective method for inducing a rat model with hyperuricemia in a short period and assess the effects of the model. Methods: Sprague-Dawley rats were adopted as donors and randomly divided into control group (CT group, n=6) and 5 model groups (M1-M5 groups, n=8 in each group). M1 group (gavage with 10 g/kg yeast extracts and 100 mg/kg adenine, twice per day, 300 mg/kg oxonic acid potassium by intraperitoneal injection, in the 7 th day of model inducing), M2 group (gavage with 10 g/kg yeast extracts and 100 mg/kg adenine, twice per day, 300 mg/kg oxonic acid potassium by intraperitoneal injection, in the 1 st , 3 rd and 7 th day of model inducing),M3 group (gavage with 10 g/kg yeast extracts and 100 mg/kg adenine, twice per day, 300 mg/kg oxonic acid potassium by intraperitoneal injection, once per day during the model inducing), M4 group (gavage with 20 g/kg yeast extracts and 100 mg/kg adenine, twice per day, 300 mg/kg oxonic acid potassium by intraperitoneal injection, once per day during the model inducing), M5 group (gavage with 30 g/kg yeast extracts and 100 mg/kg adenine, twice per day, 300 mg/kg oxonic acid potassium by intraperitoneal injection, once per day during the model inducing), and group CT (gavaged with equal volume sterilized water and intraperitoneal injected with normal saline according to the weight and at the same frequency as the model groups). The model inducing lasted for 7 days. After the inducing was finished, blood and 24-hour urine were sampled for uric acid and creatinine determination. Then rats were maintained for 2 weeks and blood and 24-hour urine samples were collected, the concentration of uric acid and creatinine were detected. The kidney and stomach were weighed,morphological changes in kidney were observed. Results: After model inducing, the body weight of rats in all model groups was lower than that of the control group (P＜0.01). Deaths occurred in all the rats with model treatments except M2. M4 and M5 groups were failed to be analyzed because of the high mortality, model 1 and 3 groups had 4 and 2 deaths, respectively. The uric acid levels in blood and urine of the model groups were significantly elevated (P＜ 0.01) at the end of model inducing. The model 2 group's blood uric acid was highest among the model groups (P＜0.05). It sustained a higher concentration than CT group in the three model groups after 2 weeks feeding (P＜0.05). The kidneys in model groups obviously swelling and were heavier than CT group (P＜0.01). The inflammation and structural damages were observed in kidneys of all model groups. Conclusion: The yeast extract (10 g/kg), adenine (100 mg/kg) gavage combined with intraperitoneal injections(the 1 st , 3 rd , 7 th day during inducing) of potassium oxonate can be an rapid and effective method for inducing the rat model with hyperuricemia, which can be suggested to the related research.

During the development of mammalian neuromuscular junction (NMJ), the original supernumerary axon inputs are gradually eliminated, finally leaving each muscle fiber innervated by a single axon terminal. However, the molecular cues that mediate the elimination of redundant axon inputs remain unclear. Here we show that tumor necrosis factor-α (TNFα) expressed in postsynaptic muscle cells plays an important role in presynaptic axonal elimination at the NMJ. We found that intramuscular injection of TNFα into the levator auris longus (LAL) muscles caused disassociation of presynaptic nerve terminals from the postsynaptic acetylcholine receptor (AChR) clusters. By contrast, genetic ablation of TNFα globally or specifically in skeletal muscle cells, but not in motoneurons or Schwann cells, delayed the synaptic elimination. Moreover, ablation of TNFα in muscle cells attenuated the tendency of activity-dependent competition in a motoneuron-muscle coculture system. These results suggest a role of postsynaptic TNFα in the elimination of redundant synaptic inputs., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

The modified rice starches by octenyl succinic anhydride (OS-RSs) with the same degree of substitution of 0.033 were prepared in aqueous solution using 3% or 20% (w/w) NaOH as a catalyst (OS-RS 3 or OS-RS 20). The results indicated that 20% of NaOH could destroy the structure of starch more seriously and led to more OS groups travelling to interior of starch granules. Furthermore, the storage stability and rheological properties of Pickering emulsions formulated by RS, OS-RS 3 and OS-RS 20 were investigated. Emulsion index of OS-RS 20 were always lower than OS-RS 3 during the storage time, while G', G" and viscosity of O/W Pickering emulsion formulated by OS-RS 20 particles were greater than those of OS-RS 3. OS-RS 3 with more hydrophobic groups in the granule surface could form more compact oil/water layers which contributed greater to the storage stability of Pickering emulsion due to the formation of more compact oil/water layers. However, OS-RS 20 with homogeneous distribution of OS groups in the whole particles resulted in the formation of a tighter droplet network structure that was more resistant to external impacts, which showed OS-RS 20 could improve the shear stability of Pickering emulsion., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The cerebellum is critical for controlling motor and non-motor functions via cerebellar circuit that is composed of defined cell types, which approximately account for more than half of neurons in mammals. The molecular mechanisms controlling developmental progression and maturation processes of various cerebellar cell types need systematic investigation. Here, we analyzed transcriptome profiles of 21119 single cells of the postnatal mouse cerebellum and identified eight main cell clusters. Functional annotation of differentially expressed genes revealed trajectory hierarchies of granule cells (GCs) at various states and implied roles of mitochondrion and ATPases in the maturation of Purkinje cells (PCs), the sole output cells of the cerebellar cortex. Furthermore, we analyzed gene expression patterns and co-expression networks of 28 ataxia risk genes, and found that most of them are related with biological process of mitochondrion and around half of them are enriched in PCs. Our results also suggested core transcription factors that are correlated with interneuron differentiation and characteristics for the expression of secretory proteins in glia cells, which may participate in neuronal modulation. Thus, this study presents a systematic landscape of cerebellar gene expression in defined cell types and a general gene expression framework for cerebellar development and dysfunction., (© The Author(s) (2019). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.)

A series of novel 4″- O -desosaminyl clarithromycin derivatives with 11, 12-arylalkyl side chains was synthesized by coupling 6-deoxy-desosamine donors ( 18 , 19 ) with 4″-OH of compounds 5a - c . The activities of the target compounds were tested against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed activities against macrolide sensitive and resistant pathogens, and compounds 21d and 21e displayed significant improvement of activities against resistant pathogens.

In this study, the structure characteristics and the hypoglycemic and antioxidant activities of mulberry fruit polysaccharides obtained by the commonly used hot water (MFPh)-, ultrasonic (MFPu)-, acid (MFPc)- and alkali (MFPa)-assisted extraction methods were investigated. NMR analysis indicated that the four polysaccharides had similar glycosidic linkage patterns. Scanning electron microscopy analyses showed that the surface morphology of the polysaccharides was greatly affected by the extraction methods. The results of the bioactivity assays indicated that MFPh exhibited stronger antioxidant and α-amylase inhibitory activities than the other polysaccharides. Moreover, all the polysaccharides showed good α-glucosidase inhibitory activities except for MFPu with the lowest molecular weight. These results suggested that acid, alkali, and ultrasonic-assisted extractions have different effects on the degradation of polysaccharides without changing the main structure compared with hot water extraction. In addition, the molecular weight of polysaccharides plays a key role in the bioactivity of the mulberry fruit polysaccharides.

Competing Interests: None

Objective: To investigate the infection of reproductive Mycoplasma genitalium (MG) detected by real-time fluorescence constant-temperature simultaneous amplification and testing (SAT) of nucleic acid among patients present at the clinics of urology, gynecology or venereal diseases., Methods: We retrospectively analyzed the clinical data on 5 711 patients with suspected genitourinary tract (GUT) infection present at the clinics of urology, gynecology or sexually transmitted diseases in Hangzhou Third People's Hospital, Shaoxing People's Hospital and General Hospital of Eastern Theater Command from January 2018 to December 2018. The patients were aged 16－73 (38.77 ± 11.32) years, 3 425 males and 2 286 females. We collected urine samples from 3 666, GUT secretion samples from 2 095, and both urine and GUT samples from 50 of the patients. Using the SAT technique, we detected the infections of MG, Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG) in the patients., Results: Of the 5 711 patients, 294 (5.15%) were found MG-positive, with a significantly higher positive rate in the males than in the females (5.96% ［206/3 425］ vs 3.85% ［88/2 286］, P < 0.05). The laboratory results with the urine and GUT secretion samples from 50 of the cases showed a consistency rate of 100%. Simple MG infection accounted for 52.04% in the 294 MG-positive cases, 63.11% in the 206 MG-positive males, and 26.13% in the 88 females, with a significantly higher positive rate in the males than in the females (P < 0.05). MG combined with UU infection had the highest rate among the mixed infections in both the males and females and in those aged ≤20 years, even higher in the females than in the males (P < 0.05) and in the ≤20-year-old males than in the ≤20-year-old females (8.65% ［9/104］ vs 5.13% ［4/78］, P < 0.05). There were statistically significant differences in the MG-positive rate among different age groups (χ2 = 32.74, P < 0.05)., Conclusions: Among patients with suspected GUT infection, the MG-positive rate is higher in men than in women, with MG + UU-positive as the most common mixed infection, and it decreases with the increase of age. The results of SAT of urine and GUT secretion have a high consistency rate.

A series of novel 5-O-(4',6'-O-dimodified)-mycaminose 14-membered ketolides were assessed for their in vitro antibacterial activities against a panel of sensitive and resistant pathogens. Compound 1 and compound 2, two ester analogs, showed the best antibacterial activities against several macrolide-sensitive and macrolide-resistant strains. These results indicated that introducing ester to 6-OH and a small volume ether substituent to the 4-OH of mycaminose could improve the antibacterial activities of ketolides.

Background: Chronic active Esptein-Barr virus (CAEBV) enteritis if rarely observed in immunocompetent patients and can be often misdiagnosed as inflammatory bowel disease., Case: We hereby present a case of CAEBV enteritis diagnosed with double-balloon enteroscopy and EBER in-situ hybridization., Conclusion: This case demonstrates the clinical presentation and diagnosis of CAEBV enteritis and highlights the importance of early recognition of the disease., (Copyright © 2019. Published by Elsevier Ltd.)

Cardiovascular and metabolic disease (CMD) remains a main cause of premature death worldwide. Berberine (BBR), a lipid-lowering botanic compound with diversified potency against metabolic disorders, is a promising candidate for ameliorating CMD. The liver is the target of BBR so that liver-site accumulation could be important for fulfilling its therapeutic effect. In this study a rational designed micelle (CTA-Mic) consisting of α-tocopheryl hydrophobic core and on-site detachable polyethylene glycol-thiol shell is developed for effective liver deposition of BBR. The bio-distribution analysis proves that the accumulation of BBR in liver is increased by 248.8% assisted by micelles. Up-regulation of a range of energy-related genes is detectable in the HepG2 cells and in vivo. In the high fat diet-fed mice, BBR-CTA-Mic intervention remarkably improves metabolic profiles and reduces the formation of aortic arch plaque. Our results provide proof-of-concept for a liver-targeting strategy to ameliorate CMD using natural medicines facilitated by Nano-technology.

As a simple and effective physical method, ultrasound irradiation has been used to modify starch. Native waxy corn starch was treated by ultrasound irradiation at 100 and 400 W in this study. Compared with native waxy corn starch, lower proportion of B 1 , B 2 , and B 3 , higher proportion of A chain were observed in ultrasonicated waxy corn starch. 1 H NMR combined with HPSEC-MALLS-RI data showed that lower degree of branching was observed in ultrasonicated waxy corn starch, and α-1,4 glycosidic linkages were more stable than α-1,6 glycosidic linkages in waxy corn starches. 13 C NMR data indicated that the content of double helices was decreased, and single helix and amorphous components were increased after ultrasound irradiation. The A-type crystal structure was scarcely affected according to X-ray diffraction (XRD) analysis. The granule surface of ultrasonicated waxy corn starch became notch and rough fragment, and lower particle diameter was observed in ultrasonicated waxy corn starch. These results demonstrated that ultrasound irradiation affected chain length distribution, double helices, single helices and amorphous state, especially α-1,4 glycosidic linkages and α-1,6 glycosidic linkages, of waxy corn starch., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Globally, heat stress seriously threatens productivity of cattle. The objective of this study was to identify novel miRNAs that regulated heat stress in feedlot cattle. Experiment was conducted under heat stress and normal conditions. With profiling miRNAs of each feedlot cattle, our results showed the level of miR-1246 was significantly increased in these heat-stressed cattle (P < 0.05). Furthermore, by using bioinformatics analysis and luciferase reporter assays combined with qPCR and western blot, we found miR-1246 negatively regulated poly (C) binding protein 2 (PCBP2) and cAMP response element binding protein-like 2 (CREBL2) mRNA and protein levels through binding to the 3'-UTR region (P < 0.05); further, it inhibited heat-induced apoptosis in lung cells. Finally, our results suggested that miR-1246 plays an important role in heat stress and it has the potential to be a novel modulation factor for heat stress in feedlot cattle.

Spiral dextrin subfraction (SD-40) obtained through enzyme debranching and gradient ethanol precipitation could interact with vitamin E (VE) or soy isoflavone (SIO) to form V-type inclusion complexes. The formation of two inclusion complexes was confirmed by Fourier transform-infrared spectroscopy, atomic force microscopy, and differential scanning calorimetry. In this study, an in vitro gastrointestinal model was used to investigate the breakdown of inclusion complexes and release behavior of bioactive compounds. The results indicated that the two inclusion complexes exhibited a controlled and sustained release behavior during digestion. In addition, the SD-40/VE inclusion complex presented higher stability and stronger antioxidant capacity than the SD-40/SIO inclusion complex. Furthermore, the first and zero order models were applied to understand the release kinetics of VE and SIO from inclusion complexes in the stomach, whereas the first order model was chosen to describe the release of VE and SIO from inclusion complexes in the intestine.

As highly tissue-specific genes, it is increasingly recognized that long non-coding RNAs (lncRNAs) are considered as promising prognostic biomarkers for multiple human cancers. However, lack of tissue-specific lncRNAs in gastric cancer (GC) still exist. In this study, we identified a novel lncRNA LINC01939 which showed the largest fold change in GC than other human cancers from lnCAR database by bioinformatic analysis. Reverse transcription quantitative polymerase chain reaction (qPCR) assay confirmed that LINC01939 was significantly downregulated in GC tissues compared with matched normal tissues. Low expression of LINC01939 was positively associated with advanced TNM stage and lymphatic metastasis. Patients with low LINC01939 expression have remarkably shorter overall survival (OS) and progression-free survival (PFS) than those with high LINC01939 expression. Univariate and multivariate analysis showed that LINC01939 is an independent protective predictor of OS and PFS in GC patients. Therefore, our data suggest that the newly identified lncRNA LINC01939 might act as a potential prognostic biomarker for GC., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

The development of multilayered interfacial engineering on the emulsion freeze-thaw properties has recently attracted widespread attention, because of the essential freeze-thaw storage process in some emulsion-matrix food products. In this research, we studied the role of salt concentration on the freeze-thaw properties of quinoa protein (QPI) nanoparticles-stabilized Pickering emulsions. The QPI nanoparticles (particle concentration c = 2%, w/v) with increasing particle size and surface hydrophobicity ( H 0 ) were fabricated by ultrasound treatment at 100 W for 20 min, by varying the NaCl addition (salt concentrations, 0-500 mM). The sonicated QPI nanoparticles with increasing salt concentrations showed higher β-sheet structure contents and stronger hydrophobic interactions, which were attributed to the decreasing charged groups and particle aggregation by electrostatic interactions. As compared to the sonicated QPI nanoparticles-stabilized Pickering emulsions ( c = 2%, oil fraction φ = 0.5) without salt accretion, the emulsions with salt accretion exhibited better freeze-thaw properties after three freeze-thaw circulations, which might be mainly caused by the generation of gel-like three-dimensional structure and multilayered network at the droplets' interface with smaller droplet sizes. Increasing the salt concentration progressively enhanced the freeze-thaw properties of sonicated QPI nanoparticles-stabilized Pickering emulsions probably due to the inhibit formation of ice crystal by the "salting-out" effects. The results of this study would provide great significance to investigate the role of salt concentration in the freeze-thaw properties of protein-stabilized Pickering emulsions.