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This study was aimed at preparing chitosan (CS)-phenolic acids copolymers to obtain better preservation effect in marine products. In this work, CS was grafted onto phenolic acids such as gallic acid (GA) and protocatechuic acid (PA) by a carbodiimide coupling method. The copolymers (CS-grafted-GA (CS-g-GA) and CS-grafted-PA (CS-g-PA)) were further confirmed through physicochemical properties including ultraviolet–visible (UV–Vis) spectrophotography, fourier transform infrared (FTIR) spectrometry, differential scanning calorimetry (DSC) thermogram, rheological behaviour, scanning electron microscope (SEM) and antioxidant activity analysis. Subsequently, the effects of copolymers on preservation of refrigerated sea bass (Lateolabrax japonicus) fillets were investigated. The results showed that the CS-g-GA (110.82 mg GA/g) exhibited higher grafting rate than CS-g-PA (62.63 mg PA/g). According to the assessment of UV–Vis and FTIR spectrometry, both the GA and PA were grafted onto CS successfully. SEM analysis demonstrated that the microstructure of copolymers became irregular. Meanwhile, both the CS-g-GA and CS-g-PA copolymers displayed superior thermal stability, rheological properties and antioxidant capacity than the pure CS. Furthermore, the copolymers also revealed a significantly stronger preservation effect on sea bass fillets including inhibiting microbial growth and delaying the deterioration of color, texture and sensory quality. Therefore, CS-g-GA and CS-g-PA could be used as promising preservatives for seafood.

Reducing treatment burden is a priority for people with cystic fibrosis, whose health has benefited from using new modulators that substantially increase CFTR protein function. The SIMPLIFY study aimed to assess the effects of discontinuing nebulised hypertonic saline or dornase alfa in individuals using the CFTR modulator elexacaftor plus tezacaftor plus ivacaftor (ETI).The SIMPLIFY study included two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials at 80 participating clinics across the USA in the Cystic Fibrosis Therapeutics Development Network. We included individuals with cystic fibrosis aged 12-17 years with percent predicted FEVFrom Aug 25, 2020, to May 25, 2022, a total of 672 unique participants were screened for eligibility for one or both trials, resulting in 847 total random assignments across both trials with 594 unique participants. 370 participants were randomly assigned in the hypertonic saline trial and 477 in the dornase alfa trial. Participants across both trials had an average ppFEVIn individuals with cystic fibrosis on ETI with relatively well preserved pulmonary function, discontinuing daily hypertonic saline or dornase alfa for 6 weeks did not result in clinically meaningful differences in pulmonary function when compared with continuing treatment.

Observational epidemiologic studies have associated vitamin D deficiency with cholestasis. It has been reported by our laboratory that the vitamin D/vitamin D receptor (VDR) axis activation in cholangiocytes mitigates cholestatic liver injury by remodeling the damaged bile duct. However, the function of VDR in hepatocytes during cholestasis remains unclear.Paricalcitol (VDR agonist, 200 ng/kg) was injected intraperitoneally into bile duct-ligated mice every other day for 5 days. Primary hepatocytes and HepG2 cells were transfected with Vdr short hairpin RNA, control short hairpin RNA, Vdr plasmid, control vector, Atg5 small interfering RNA (siRNA), and control siRNA. Liver histology, cell proliferation, and autophagy were evaluated.Treatment with the VDR agonist paricalcitol improved bile duct-ligated mouse liver injury by up-regulating VDR expression in hepatocytes, which in turn reduced hepatocyte apoptosis by inhibiting reactive oxygen species (ROS) generation via suppressing the Ras-related C3 botulinum toxin substrate 1/reduced nicotinamide adenine dinucleotide phosphate oxidase 1 pathway. Mechanistically, upon exposure to the ROS-inducing compound, Vdr siRNA contributed to apoptosis events, whereas the Vdr plasmid led to apoptosis resistance. Interestingly, up-regulated VDR expression also appeared to increase autophagosome generation and macroautophagic/autophagic flux, which was the underlying mechanism for VDR activation-inhibited apoptosis. Autophagy depletion completely impaired the up-regulated VDR-inhibited apoptosis events, whereas autophagy induction showed a synergistic effect with VDR overexpression. Importantly, up-regulation of VDR promoted autophagy activation by suppressing the activation of the extracellular signal-regulated kinase (ERK)/p38 mitogen-activated protein kinase (p38MAPK) pathway. The p38MAPK inhibitor abrogated the Vdr siRNA-induced decrease in autophagy and the Vdr siRNA-induced increase in apoptosis. In contrast, the MEK/ERK activator prevented the Vdr plasmid-enhanced autophagy and decreased apoptosis. Moreover, the ROS inhibitor NAC blocked Vdr siRNA-enhanced activation of the ERK/p38MAPK pathway.VDR activation mitigated liver cholestatic injury by reducing autophagy-dependent hepatocyte apoptosis and suppressing the activation of the ROS-dependent ERK/p38MAPK pathway. Thus, VDR activation may be a potential target for the treatment of cholestatic liver disease.

Starch microspherical aerogel (SMA) prepared by enzymatic hydrolysis of starch with α-amylase was demonstrated to be higher adsorption capacity for methylene blue. Proper cleavage of α-1,4 glycosidic bonds could enhance the adsorption capacity of SMA, while the cleavage of α-1,6 glycosidic bonds showed an opposite effect. Compared with tapioca starch (TS), α-amylase hydrolyzed starch exhibited a 9.46 % decrease in amylose content, a 25.40 % increase in adsorbability, and significant decreases in weight-average molecular weight (Mw) of different amylases. When the Mw of enzymolysis starch was 6.39 × 10

To visualize the course of the tympanic segment of chorda tympani nerve (CTN) using ultra-high-resolution computed tomography.A hundred and fourteen ears with no evident otologic pathologies were included. The tympanic segment of CTN was divided into 4 portions as follows: periannular, posteromalleal, malleal, and anteromalleal. The length of the periannular portion running along the tympanic annulus was recorded. Four points of interest (the beginning and end of the posteromalleal and anteromalleal portions) were selected to perform distance measurements relative to the tip of the malleus manubrium. Differences in lengths and distances were compared in terms of ear sides and sexes.The length of the periannular portion was 2.49 ± 1.16 mm. The beginning of the posteromalleal portion was located more laterally on the right side than on the left side (mean: 4.09 mm vs. 3.92 mm;, P = 0.016). The end of the posteromalleal portion was located more inferiorly on the right (mean: 2.11 mm vs. 2.26 mm; P = 0.018). The beginning of the anteromalleal portion on the right was located more laterally than that on the left (mean: 2.60 mm vs. 2.45 mm; P = 0.027). The start and end of the anteromalleal portion were more posteriorly located in women than in men (both Ps 0.001).The course of the tympanic segment of normal CTN was comprehensively visualized by ultra-high-resolution computed tomography. Preoperative evaluation of the tympanic segment of CTN might be helpful in avoiding iatrogenic injury during middle ear surgery.

Microdroplets and their dispersion, with a large specific surface area and a short diffusion distance, have been applied in various unit operations and reaction processes. However, it is still a challenge to control the size and size distribution of microdroplets, especially for high-throughput generation. In this work, a novel ultra-high speed rotating packed bed (UHS-RPB) was invented, in which rotating foam packing with a speed of 4000–12000 r·min–1 provides microfluidic channels to disperse liquid into microdroplets with high throughput. Then generated microdroplets can be directly dispersed into a continuous falling film for obtaining a mixture of microdroplet dispersion. In this UHS-RPB, the effects of rotational speed, liquid initial velocity, liquid viscosity, liquid surface tension and packing pore size on the average size (d32) and size distribution of microdroplets were systematically investigated. Results showed that the UHS-RPB could produce microdroplets with a d32 of 25–63 μm at a liquid flow rate of 1025 L·h–1, and the size distribution of the microdroplets accords well with Rosin–Rammler distribution model. In addition, a correlation was established for the prediction of d32, and the predicted d32 was in good agreement with the experimental data with a deviation within ±15%. These results demonstrated that UHS-RPB could be a promising candidate for controllable preparation of uniform microdroplets.

Introduction Although researchers have done intensive research on depression, its pathogenesis is still not fully explained. More and more evidence suggests that gut microbiota is closely related to the onset of depression; but its specific functional ways are not clearly identified. Objectives The purpose of our work was to find out how the gut microbiota was involved in the onset of depression, and to identify the potential ways to link the gut and brain in mice with depressive-like behaviors (DLB). Methods We used the chronic restraint stress (CRS)-induced depression model here. Gut microbiota compositions in fecal samples, lipid metabolism (in fecal, serum and hippocampus samples) and neurotransmitters in hippocampus samples were detected. Results We found that the 7 of 13 differential genera that significantly correlated with DLB belonged to phylum Firmicutes. The differential lipid metabolites in fecal samples mainly belonged to glycerophospholipids (GP) and fatty acids (FA) metabolism, and three important “metabolite type-bacterial taxa” correlated pairs were identified: “FA/GP-Firmicutes”, “FA/GP-Akkermansia”, and “FA/GP-Bifidobacterium”. The key differential lipid metabolites significantly correlated with DLB mainly belonged to FA and GP, and the DLB-related metagenomic genes were consistently enriched in GP metabolism and FA metabolism. Three significantly changed short-chain fatty acids (SCFAs) were significantly correlated with the majority of differential genera. Meanwhile, we found that the differential lipid metabolites in serum and hippocampus samples were mainly mapped into the GP metabolism, and there were four differential neurotransmitters from the tryptophan pathway in hippocampus samples. Conclusion Together, our findings could provide novel insights into the role of “microbiota-gut-brain” (MGB) axis in depression, and indicate that the gut microbiota might have a vital role in the onset of DLB by affecting the peripheral/central GP metabolism and tryptophan pathway. The “Firmicutes-SCFAs-GP metabolism-Tryptophan pathway” might be a possible way to link the gut and brain in depressed mice.

Since the gene encoding mobilised colistin resistance (mcr-1) was first reported in China in 2015, it has been reported in various Enterobacteriaceae worldwide. Escherichia coli, one of the main pathogens causing diarrhoea, is the most prevalent, clinically identified species carrying mcr-1. This study aimed to investigate the epidemiologic and genomic characteristics of mcr-1 in Escherichia coli from patients in Shanghai.Faecal samples were collected from hospitals in Shanghai between 2012 and 2015. Polymerase chain reaction was performed to detect mcr-1, and molecular characteristics of the mcr-1-positive E. coli was determined by antimicrobial susceptibility testing and whole-genome sequencing.We detected 40 (3.9%) mcr-1-positive E. coli strains from faecal samples in clinical settings between 2012 and 2015 in Shanghai. Mcr-1 was detected in 4 types of E. coli, including atypical enteropathogenic E. coli (aEPEC), enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), and enteroaggregative E. coli (EAEC). Most strains harbouring mcr-1 were isolated from children aged7 years. Whole-genome sequencing revealed that nearly half of the strains that carried quinolone resistance- or β-lactam resistance-related genes were multidrug-resistant. IncX4 was the predominant type in mcr-1-positive E. coli in Shanghai, but the other types of mcr-1-harbouring plasmids are highly diverse in genetic context.These data suggest that mcr-1 is prevalent in E. coli strains, especially those identified in diarrhoeal patients in Shanghai, and strengthening the surveillance of mcr-1 transmission, especially in children, is essential.

Natural gas hydrate (NGH) holds great promise as a source of clean energy. It is critical for acquiring the largest possible in situ NGH core for NGH eigen features and resource assessment. However, the existing NGH coring technology has limitations, such as temperature increments, limited coring diameters, low coring rates, and complex coring structures. Therefore, this study designs and proposes an NGH freezing coring (NGHFC) method and verifies the freezing and coring capacities of the NGHFC method in laboratories and experimental wells. Results suggest that NGHFC shows good freezing and heat-retention properties. A freezing core heat transfer model is developed. According to the actual air temperature and operating time, the optimum initial temperature of the cold source can be determined using this model. The average coring rate of NGHFC can reach 77.86 %. The research results will provide a new idea of coring gas hydrates.

Background To analyze the long-term outcomes and prognostic value of hematological parameters in anal cancer patients receiving intensity-modulated radiation therapy (IMRT). Materials Hospital records of consecutive patients with anal squamous cell carcinoma who received curative-intent IMRT according to a standardized contouring protocol between 2010 and 2020 were reviewed. Locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Coverage of locoregional recurrences by the initial IMRT volumes were assessed. The prognostic value of pretreatment blood counts for PFS and OS were determined using Cox regression analysis. Results A total of 166 patients were analyzed with a median follow-up of 3.3 years. Forty-six percent and 54% of patients had Stage I-II and IIIA-B cancers, respectively. The 5-year LRFS, DMFS, PFS and OS were 81%, 89%, 65% and 76% respectively. Grade ≥ 3 toxicity occurred in 5% of patients. Of all patients who relapsed, 70% had only locoregional recurrence as first site of failure. Ninety percent of locoregional recurrences were in-field. Hemoglobin, neutrophil and platelet counts were associated with PFS on univariable analysis, but only cancer stage and p16 status remained prognostic on multivariable analysis. Patients with more advanced cancer stages also had higher baseline neutrophil counts. Performance status and neutrophil counts were prognostic for OS on multivariable analysis. Conclusion This study affirms the long-term efficacy and safety of IMRT. Treatment resistance, rather than radiation geographic miss, is a major issue underpinning locoregional recurrences. Pretreatment blood counts were not validated to be independently prognostic for disease recurrence.

The problem of sliding mode control for a class of Takagi–Sugeno fuzzy model-based nonlinear one-sided Lipschitz systems is investigated in the paper. Due to the state components are not available, a state observer is designed based on an event-triggering mechanism. Meanwhile, the output measurements transmitted through the communication channels suffer from signal delays. Based on the estimated state, an integral sliding surface is proposed. Then, the sliding mode dynamics is obtained by virtue of equivalent control principle. Further, by constructing appropriate sliding mode controller, the finite-time reachability of predefined sliding surface is surely guaranteed. Moreover, the stability with an H ∞ performance analysis of sliding mode dynamics is undertaken via Lyapunov function theory and the criteria are established in terms of LMI. Finally, numerical examples are provided to demonstrate the effectiveness of the proposed method.

Surface modification by hydrophilic functional group have a tremendous influence on the catalytic activity of photocatalyst, however, there are few reports on improving piezoelectric catalytic performance through surface functionalization. Herein, OH-modified SrTiO3 was successfully obtained via a novel low-temperature solid-state precursor method and employed as a catalyst for photocatalytic, piezocatalytic and piezo-photocatalytic hydrogen production. Thanks to the super hydrophilic that is facilitating the contact of catalyst and water molecular and the more oxygen vacancies that can promote electron-hole separation, the photocatalytic, piezocatalytic and piezo-photocatalytic hydrogen generation of OH-modified SrTiO3 (OH-STO) is about two times higher than pristine SrTiO3 (STO). It is worth mentioning that the optimal piezo-photocatalytic hydrogen evolution rate of OH-STO (701.2 µmol h-1 g-1) is 5.3 times higher than the photocatalytic hydrogen evolution process of STO. This study presents a low-energy approach to the rational design of functional group modification nanomaterials that possess excellent piezo-photocatalytic performance.

The freemium pricing model has become mainstream in the software industry. A large user base can induce positive network effects while expanding security risks associated with unpatched users. This study explores a two-stage decision problem faced by software vendors that involves a freemium versioning strategy and a subsequent security-patching strategy when taking both the positive network externality and negative security externality into consideration. It is noteworthy that a joint effect of the two externalities on the vendor’s management decisions exists. First, we analytically derive three patching strategies for the vendor: P S 1 (rebates all users), P S 2 (rebates only freeware users), and P S 3 (rebates no users). Our results indicate that, if the strength of the positive network externality is relatively low, the optimal security-patching strategy will be significantly affected by the negative security externality. Specifically, when the intensity of the negative security externality is low, the vendor’s optimal patching strategy will be P S 1 . However, with the increase in the negative security externality, the optimal patching strategy changes to P S 2 and then to P S 3 , whereas the strategy spaces of P S 1 and P S 2 decrease in the positive network externality to zero. Nevertheless, if the strength of the positive network externality is relatively high, the vendor is better off selecting P S 1 when the negative security externality is low. However, when the negative security externality is high, P S 3 is optimal. Furthermore, based on optimal patching strategies, we reveal the optimal conditions required for the vendor to adopt the freemium model compared with commercial only. Of interest, we find that the vendor adopting the freemium version is also influenced by the interaction of the two externalities. Finally, through numerical experiments, we find that the vendor and social planner’s interests can be aligned under certain conditions. However, this is not always the case.

Summary Conventional aqueous electrolytes suffer from a narrow voltage window due to water decomposition. Highly concentrated electrolytes expand the voltage window; however, they are limited by high cost and potential toxicity. Here, we develop a hydrogen bond-anchored electrolyte by introducing sulfolane as hydrogen bond acceptor to limit water activity. The designed electrolyte expands the voltage window to 3.4 V (1.3–4.7 V versus Li+/Li) and forms a hierarchical anode-electrolyte interphase to suppress the hydrogen evolution reaction. An aqueous Li4Ti5O12/LiMn2O4 full cell achieved 141 W h kg−1 for 300 cycles at 1 C and 125 W h kg−1 for 1,000 cycles at 5 C with a high Coulombic efficiency of 99.5%–99.9%. On-line electrochemical mass spectroscopy shows negligible hydrogen/oxygen gas evolution upon cycling, further confirming the stability of the designed electrolyte. This work demonstrates a rational and effective approach to suppress the hydrogen evolution reaction and achieve stable high-voltage aqueous batteries.

Background Vestibular schwannoma is the third most common benign intracranial tumor that can occur sporadically or be associated with neurofibromatosis type 2 (neurofibromatosis type 2 vestibular schwannoma [NF2-VS]). The aim of this study is to provide a comprehensive bioinformatic analysis of methylated-differentially expressed genes (MDEGs) in NF2-VS. Methods Transcriptional sequencing datasets (GSE141801 and GSE108524) and gene methylation microarrays (GSE56598) from the Gene Expression Omnibus database were used to identify and analyze MDEGs in NF2-VS. A protein–protein interaction (PPI) network was built, and the hub genes and modules were identified. Finally, potential pharmacotherapy targeting MDEGs were extracted for NF2-VS. Results A total of 57 hypermethylation–low expression genes and 88 hypomethylation–high expression genes were identified. Pathways associated with aberrantly MDEGs included P13K-AKT, MAPK, and Ras, which were also involved in NF2-VS. Six hub genes (EGFR, CCND1, CD53, CSF1R, PLAU, and FGFR1) were identified from the PPI network. Modification of the aforementioned genes altered cell-to-cell communication, response to stimulus, cellular regulation, and membrane and protein bindings. Thirty drugs targeting these pathways were selected based on the hub genes. Conclusions Analysis of MDEGs may enrich the understanding of the molecular mechanisms of NF2-VS pathogenesis and lay the groundwork for potential biomarkers and therapeutic targets for NF2-VS.

Frozen aquatic products undergo unavoidable quality changes owing to temperature fluctuations during frozen storage and distribution. This study investigated the effects of 1% cellobiose (CB), and 0.5 and 1% carboxylated cellulose nanofibers (CNF) on ice crystal growth and recrystallization of frozen large yellow croaker fillets exposed to temperature fluctuations. Denser and more uniformly distributed ice crystals were observed in the CB- and CNF-treated samples than in the water-treated samples. Furthermore, the addition of CB and CNF suppressed the conversion of bound water to frozen water in the samples during temperature fluctuation cycles, played a positive role in fixing the ionic and hydrogen bonds that stabilize the protein structure, limited the conformational transition from α-helix to β-sheet, and improved protein thermal stability. Based on turbidity, zeta potential, and confocal laser scanning microscopy (CLSM) analyses, the presence of CB and CNF restricted the protein aggregation. Compared with CB, CNF molecules with abundant carboxyl functional groups and longer morphology exhibited better cryoprotective effects. Moreover, the fillets were more improved protected from mechanical damage induced by large ice crystals at a higher CNF concentration. This study reveals the potential of CB and CNF as novel cryoprotectants.

Pancreatic cancer is a highly aggressive cancer with an exceedingly low rate of response to treatments, which calls for comprehensive molecular characterization of pancreatic cancer cell lines (PCCLs). We screened multi-layer molecular data of 36 PCCLs, including gene mutation, gene expression, microRNA (miRNA) expression, and protein profiles. Our comparative analysis of genomic mutations found that PCCLs recapitulated genomic alterations of the primary tumor and suggested potential therapeutic strategies for clinical interventions. The panel of 36 PCCLs was classified into 2 subgroups based on transcriptomic mRNA expression, wherein the C1 subgroup was characterized with differentiation, whereas C2 cell lines were featured with immunity, angiogenesis, epidermis, and proliferation. Transcriptomic classification was further recapitulated by miRNA and protein expression. Additionally, the differential proteins between C1 and C2 subgroups were prominently involved in epidermal growth factor receptor (EGFR) signaling, phosphatidylinositol 3-kinase (PI3K) signaling, and mitogen-activated protein kinase (MAPK) signaling pathways. Tumor samples from different subgroups exhibited distinct infiltration of CD4 naive cells and monocytes. Remarkably, patients in subgroups C1 showed longer survival, whereas those in C2 had worse clinical outcome. Further integrative analysis revealed that temozolomide and NVP-TAE684 showed higher sensitivity in the C1 subgroup, whereas the C2 cell lines were more sensitive to SR1001 and SRT-1720. Our results also showed that PCCLs with mutations in CDKN2A, TP53, and SMAD4 were more sensitive to certain anti-cancer drugs. Our integrative analysis identified molecular features of pancreatic cancer that were associated with clinical significance and drug sensitivity, providing potentially effective strategies for precision treatments of patients with pancreatic cancer., Graphical abstract, This study provides a comprehensive characterization of multiple pancreatic cancer cell lines, which are divided into 2 subgroups that showed therapeutic differences.

An efficient and environment-friendly method for simultaneous determination of 13 typical derivatives of polycyclic aromatic hydrocarbon (PAH) in petroleum-polluted soil with nitro-, oxy- and alkyl-functional group was developed using supercritical fluid extraction (SFE) followed by ultra-high performance supercritical fluid chromatography (UHPSFC). Parameters of UHPSFC, including type of stationary phase and mobile phase modifiers, gradient elution process, backpressure, column temperature, and the flow rate of mobile phase, were systematically optimized, achieving a fast separation within 4.2 min. Limits of detection (LOD) were 0.005–0.1 μg mL−1 or 0.1–2.0 ng g−1, respectively, with a good repeatability (RSD