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To clarify the effect of lipid peroxyl radicals on the structure and processing properties of egg yolk protein, peroxyl radicals produced at different concentrations of 2,2'-Azobis (2-methylpropylimide) dihydrochloride (AAPH) was applied to egg yolk proteins under aerobic conditions to study the changes of structure, physicochemical properties and functional properties of egg yolk protein. The results showed that the carbonyl content of egg yolk protein was significantly increased (P

Abstract Recent observations have revealed upregulation of H3K27cr in colorectal cancer (CRC) tissues; however, the underlying cause remains elusive. This study aimed to investigate the mechanism of H3K27cr upregulation and its roles in CRC metastasis. Clinically, our findings showed that H3K27cr served as a highly accurate diagnostic marker to distinguish CRC tissues from healthy controls. Elevated levels of LINC00887 and H3K27cr were associated with a poorer prognosis in CRC patients. Functionally, LINC00887 and H3K27cr facilitated the migration and invasion of CRC cells. Mechanistically, LINC00887 interacted with SIRT3 protein. Overexpressed of LINC00887 obstructed the enrichment of SIRT3 within GCN5 promoter, thereby elevating H3K27ac but not H3K27cr level within this region, subsequently activating GCN5 expression. This activation increased the global level of H3K27cr, promoting the enrichment of GCN5, H3K27cr, and YEATS2 within ETS1 promoter, activating ETS1 transcription and ultimately promoting the metastasis of CRC. The in vivo study demonstrated that inhibition of LINC00887 suppressed CRC metastasis, but this inhibitory effect was nullified when mice were treated with NaCr. In conclusion, our results confirmed the diagnostic biomarker potential of H3K27cr in individuals with CRC, and proposed a functional model to elucidate the involvement of LINC00887 in promoting CRC metastasis by elevating H3K27cr level.

To investigate the effects of epigallocatechin-3-gallate-bovine bone protein (EGCG-BBP) on the protein structure and storage oxidative stability of emulsified meat products, the effects of adding different concentrations of EGCG-BBP on the physicochemical and structural properties of myofibrillar protein (MP) in raw meat, and on the oxidative stability of meatballs were investigated. The results showed that the addition of 0.8% EGCG-BBP resulted in the highest content of sulfhydryl group of MP (4.06 nmol/mg protein) in the minced meat, while the carbonyl group and surface hydrophobicity values were lowest, effectively improving the antioxidant capacity of the emulsified meat products. Fourier-transform infrared spectroscopy analysis showed that the wave number corresponding to the peak of the amide A band of MP was significantly increased in the minced meat supplemented with EGCG-BBP compared with the control group, indicating corresponding changes in the secondary structure of MP. The fluorescence spectra showed that there was a significant red shift in the strongest MP wavelength in the control group with a prolongation of the storage time. However, this shift was significantly reduced as the concentration of EGCC-BBP increased. This suggested that the addition of EGCG-BBP changed the tertiary structure of MP. Furthermore, analysis of oxidation indices during storage of the emulsified meatballs showed that the addition of 0.8% EGCG-BBP significantly reduced the values of both PV values and TBARS in the meatballs, thereby improving their oxidative stability. In summary, EGCG-BBP can significantly alter both the secondary and tertiary structures of MP and has good oxidation resistance. This indicates its potential to enhance the quality of emulsified meat products and provides a new choice for the application of antioxidant emulsifiers in meat products.

Abstract Background Post-extubation dysphagia (PED) emerges as a frequent complication following endotracheal intubation within the intensive care unit (ICU). PED has been strongly linked to adverse outcomes, including aspiration, pneumonia, malnutrition, heightened mortality rates, and prolonged hospitalization, resulting in escalated healthcare expenditures. Nevertheless, the reported incidence of PED varies substantially across the existing body of literature. Therefore, the principal objective of this review was to provide a comprehensive estimate of PED incidence in ICU patients undergoing orotracheal intubation. Methods We searched Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science, Technology Journal Database (VIP), and SinoMed databases from inception to August 2023. Two reviewers independently screened studies and extracted data. Subsequently, a random-effects model was employed for meta-statistical analysis utilizing the “meta prop” command within Stata SE version 15.0 to ascertain the incidence of PED. In addition, we performed subgroup analyses and meta-regression to elucidate potential sources of heterogeneity among the included studies. Results Of 4144 studies, 30 studies were included in this review. The overall pooled incidence of PED was 36% (95% confidence interval [CI] 29–44%). Subgroup analyses unveiled that the pooled incidence of PED, stratified by assessment time (≤ 3 h, 4–6 h, ≤ 24 h, and ≤ 48 h), was as follows: 31.0% (95% CI 8.0–59.0%), 28% (95% CI 22.0–35.0%), 41% (95% CI 33.0–49.0%), and 49.0% (95% CI 34.0–63.0%), respectively. When sample size was 100

BackgroundHealth care professionals use mobile apps to support patients’ rehabilitation after total hip or knee arthroplasty. Understanding patient engagement in such mobile health interventions can help tailor these interventions to better support patients. ObjectiveThis study aimed to investigate patient engagement in a mobile app–based arthroplasty rehabilitation program and to investigate the association between patient engagement and their characteristics. MethodsData were extracted from a pool of 42 participants in the experimental arm of a randomized controlled trial that used a mobile app (WeChat [Tencent Holdings Limited])–based program to support patients’ rehabilitation after total hip or knee arthroplasty. The primary outcomes were the number of days the participants accessed the program and completed recommended rehabilitation tasks. Secondary outcomes included data on the participants’ posts on a discussion forum, messages sent by the participants, access to the program components, and reading and sharing the program content. Generalized linear models were used to analyze the association between patient engagement and personal characteristics. ResultsThe participants reported in a rehabilitation diary accessing the program on a mean of 5.2 (SD 2) days per week and completing recommended rehabilitation tasks on a mean of 6.5 (SD 0.8) days per week. The majority (31/42, 74%) posted on the discussion forum, with a mean of 18.1 (SD 21.2) posts. Most participants (37/42, 88%) sent messages to health care professionals, with a mean of 14 (SD 15.9) messages. The program components were visited for a total of 525 times. The program content was read 898 times and shared 82 times in total. Generalized linear models showed that both primary outcomes, the number of days the participants accessed the program (B=6.46, 95% CI 1.98-15.35; χ21=11.1, P=.001) and the number of days they completed rehabilitation tasks (B=2.65, 95% CI 0.45-5.48; χ21=5.7, P=.02), were positively associated with having a high school education or above. In addition, the number of posts on the discussion forum was positively associated with living with family, having a high school education or above, undergoing total knee arthroplasty, having comorbidities, and the score of self-efficacy but was negatively associated with age. The number of messages sent by the participants was positively associated with having a high school education or above, having comorbidities, and the score of self-efficacy. ConclusionsPatient engagement in mobile arthroplasty rehabilitation is associated with their education level, cohabitation status, age, type of surgery, presence of comorbidities, and sense of self-efficacy. Program developers can consider these characteristics and use strategies, such as family involvement, in the design of mobile arthroplasty rehabilitation programs to enhance patient engagement in such interventions. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12621000867897; https://tinyurl.com/mtdw25fp

IntroductionLow temperature inhibits the growth of most microorganisms. However, some microbes can grow well in a low temperature, even a freezing temperature.MethodsIn this study, the mechanisms conferring cold resistance in the cryophylactic yeast Metschnikowia (M.) pulcherrima MS612, an isolate of the epidermis of ice grapes, were investigated based on comparative transcriptome analysis.ResultsA total of 6018 genes and 374 differentially expressed genes (> 2-fold, p < 0.05) were identified using RNA-Seq. The differentially expressed genes were mainly involved in carbohydrate and energy metabolism, transport mechanisms, antifreeze protection, lipid synthesis, and signal transduction. M. pulcherrima MS612 maintained normal growth at low temperature (5°C) by enhancing energy metabolism, sterol synthesis, metal ion homeostasis, amino acid and MDR transport, while increased synthesis of glycerol and proline transport to improve its resistance to the freezing temperature (−5°C). Furthermore, cAMP-PKA and ERAD signaling pathways contribute to resist the low temperature and the freezing temperature, respectively.ConclusionThis study provides new insights into cold resistance in cryophylactic microorganisms for maneuvering various metabolism to resist different cold environment.

Drimane-type sesquiterpenoids (DMTs) are characterized by a distinctive 6/6 bicyclic skeleton comprising the A and B rings. While DMTs are commonly found in fungi and plants, their presence in bacteria has not been reported. Moreover, the biosynthetic pathways for DMTs have been primarily elucidated in fungi, with identified P450s only acting on the B ring. In this study, we isolated and characterized three bacterial DMTs, namely 3β-hydroxydrimenol (2), 2α-hydroxydrimenol (3), and 3-ketodrimenol (4), from Streptomyces clavuligerus. Through genome mining and heterologous expression, we identified a cav biosynthetic gene cluster responsible for the biosynthesis of DMTs 2–4, along with a P450, CavA, responsible for introducing the C-2 and C-3 hydroxy groups. Furthermore, the substrate scope of CavA revealed its ability to hydroxylate drimenol analogs. This discovery not only broadens the known chemical diversity of DMTs from bacteria, but also provides new insights into DMT biosynthesis in bacteria.

Three different emulsions of myofibrillar protein (MP), soy protein isolate (SPI) and egg white protein isolate (EPI) were individually mixed with MP sol to form composite gels. N-ethylmaleimide (NEM) was used as a sulfhydryl group blocker to evaluate the effects of sulfhydryl and disulfide bonds on the properties of different protein–emulsion composite gels. The results show that the disulfide bond contents in the MP (SPI, EPI) emulsion composite gel decreased from the initial 2.4 ± 0.1, (2.3 ± 0.2, 1.8 ± 0.4) mol/kg to 0.6 ± 0.1, (0.5 ± 0.3, 0.7 ± 0.1) mol/kg with the NEM content increased. In addition, the microstructure showed that the interfacial protein membrane of the emulsion globules were broken in different degrees, indicating that the interaction between the emulsion and the gel matrix was weakened. Meanwhile, gel strength, water distribution and elastic modulus of the composite gels were reduced with NEM contents increased.

The large molecular weight and high viscosity of natural konjac glucomannan (KGM) limit its industrial application. Microbial degradation of low-molecular-weight KGM has health benefits and various biological functions; however, the available KGM strains used in the industry have microbial contamination and low degradation efficiencies. Therefore, exploring novelly adaptable strains is critical for industrial processes. Here, the Bacillus licheniformis Z7-1 strain isolated from decaying konjac showed high efficiency for KGM degradation. The monosaccharide composition of the degradation products had a reduced molar ratio of mannose to glucose, indicating that Z7-1 preferentially degraded glucose in KGM. The degraded component was further characterized by ESI-MS, Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM), and it also exhibited good antibacterial activity against various food-spoilage bacteria. Genome sequencing and zymolytic analysis revealed that abundant carbohydrate-active enzymes exist in the Z7-1 genome, with at least five types of extracellular enzymes responsible for KGM degradation, manifesting multi-enzyme synergetic action. The extracellular enzymes had significant thermal stability, indicating their potential application in industry. This study provides an alternative method for obtaining low-molecular-weight KGM with antibacterial functions and supports foundational knowledge for its development as a biocatalyst for the direct conversion of biomass polysaccharides into functional components.

Abstract Background An increasing number of patients are discharged from a total hip or knee arthroplasty with a short length of hospital stay. Technologies, such as mobile applications, are used to provide remote support to patients’ postoperative rehabilitation. Patients’ experiences of receiving mobile application-based rehabilitation after total hip or knee arthroplasty have not been investigated extensively. Methods This was a qualitative descriptive study. Twenty-five participants who had completed a mobile application-based rehabilitation programme for total hip or knee arthroplasty were recruited. Semi-structured interviews were conducted via telephone between July 2021 and January 2022 regarding the participants’ experiences using the programme. All interviews were audio-recorded and verbatim transcribed. Data were analysed using inductive content analysis. The reporting of this study followed the Consolidated Criteria for Reporting Qualitative Research. Results Data analysis revealed five categories: (a) improved access to health care, (b) encouraged postoperative recovery, (c) established supportive relationships, (d) facilitated learning, and (e) future directions. Conclusion The theory-underpinned mobile application-based rehabilitation programme demonstrated potential value in supporting patients’ rehabilitation after arthroplasty. Nurses can consider using mobile technologies to expand their role in arthroplasty rehabilitation and improve the quality of rehabilitation care.

Three kinds of phenolic acids: ferulic acid (FA), caffeic acid (CA), and gallic acid (GA) with different chemical structures were individually grafted onto Arabic gum (AG) via a laccase mediated method, and their roles in stabilizing o/w emulsions were evaluated. The total phenolic content in modified AG increased from 2.7 ± 0.2 to 18.7 ± 0.2, 19.8 ± 0.6, 22.4 ± 0.8 mg/g after 4 h of laccase catalysis, respectively. FTIR spectra of modified AGs exhibited additional phenolic characteristics, revealing the successful grafting of phenolic acids to AG structure. Compared with natural AG, modified AGs showed remarkably enhanced thermal stability, as well as antioxidant capacity in an order of gallic acid > caffeic acid > ferulic acid. The incorporation of phenolic acids into AG dramatically improved its emulsification performance. Herein, gallic acid-modified AG evinced up to 17.6 % and 12.6 % increments in emulsifying activity and emulsion stability relative to natural AG, respectively. Moreover, the oxidative stability of AG emulsions was pronouncedly meliorated by the introduced phenolic acids, especially gallic acid, as manifested by the suppressed production of primary and secondary oxidation products.

Stenotrophomonas maltophilia is a major threat to the food industry and human health owing to its strong protease production and biofilm formation abilities. However, information regarding regulatory factors or potential mechanisms is limited. Herein, we observed that temperature differentially regulates biofilm formation and protease production, and a cAMP receptor-like protein (Clp) negatively regulates thermosensor biofilm formation, in contrast to protease synthesis. Among four c-di-GMP-related two-component systems (TCSs), promoter fusion analysis revealed that clp transcription levels were predominantly controlled by LotS/LotR, partially controlled by both RpfC/RpfG and a novel TCS Sm0738/Sm0737, with no obvious effect caused by Sm1912/Sm1911. Biofilm formation in Δclp and ΔTCSs strains suggested that LotS/LotR controlled biofilm formation in a Clp-mediated manner, whereas both RpfC/RpfG and Sm0738/Sm0737 may occur in a distinct pathway. Furthermore, enzymatic activity analysis combined with c-di-GMP level indicated that the enzymatic activity of c-di-GMP-related metabolism proteins may not be a vital contributor to changes in c-di-GMP level, thus influencing physiological functions. Our findings elucidate that the regulatory pathway of c-di-GMP-related TCSs and Clp in controlling spoilage or the formation of potentially pathogenic factors in Stenotrophomonas expand the understanding of c-di-GMP metabolism and provide clues to control risk factors of S. maltophilia in food safety.

Abstract Background Toxoplasma gondii (T. gondii) is a neuroinvasive parasite causing neuroinflammation, which in turn is associated with a higher risk for several psycho-behavioral disorders. There is an urgent need to identify drugs capable of improving cognitive deficits induced by T. gondii infection. β-Glucan, an active ingredient in mushrooms, could significantly enhance immunity. However, the effects of β-glucan against neuroinflammation and cognitive decline induced by T. gondii infection remain unknown. The present study aimed to investigate the neuroprotective effect of β-glucan on goal-directed behavior of mice chronically infected by T. gondii Wh6 strain. Methods A mice model of chronic T. gondii Wh6 infection was established by infecting mice by oral gavage with 10 cysts of T. gondii Wh6. Intraperitoneal injection of β-glucan was manipulated 2 weeks before T. gondii infection. Performance of the infected mice on the Y-maze test and temporal order memory (TOM) test was used to assess the goal-directed behavior. Golgi-Cox staining, transmission electron microscopy, immunofluorescence, real-time PCR and western blot assays were used to detect prefrontal cortex-associated pathological change and neuroinflammation. Results The administration of β-glucan significantly prevented T. gondii Wh6-induced goal-directed behavioral impairment as assessed behaviorally by the Y-maze test and TOM test. In the prefrontal cortex, β-glucan was able to counter T. gondii Wh6-induced degeneration of neurites, impairment of synaptic ultrastructure and decrease of pre- and postsynaptic protein levels. Also, β-glucan significantly prevented the hyperactivation of pro-inflammatory microglia and astrocytes, as well as the upregulation of proinflammatory cytokines caused by chronic T. gondii Wh6 infection. Conclusions This study revealed that β-glucan prevents goal-directed behavioral impairment induced by chronic T. gondii infection in mice. These findings suggest that β-glucan may be an effective drug candidate to prevent T. gondii-associated psycho-behavioral disorders including goal-directed behavioral injury. Graphical Abstract

Abstract Background Cholangiocarcinoma is a kind of invasive malignant tumor followed by hepatocellular carcinoma. miR-451 was suggested to function as regulator in various human tumors, but its role in mediating tumor progression and predicting the prognosis of cholangiocarcinoma remains unknown. The clinical significance and biological function of miR-451 in cholangiocarcinoma were assessed in this study. Results The tissue and serum expression of miR-451 was decreased in cholangiocarcinoma compared with corresponding normal samples. The downregulation of miR-451 was associated with the progressive TNM stage and positive lymph node metastasis of patients. miR-451 was identified to be an indicator of the diagnosis and prognosis of cholangiocarcinoma distinguishing cholangiocarcinoma patients from healthy volunteers and predicting the poor outcome of patients. miR-451 also served as a tumor suppressor negatively regulating the cellular processes of cholangiocarcinoma. Conclusions miR-451 played a vital role in the early detection and risk prediction of cholangiocarcinoma. miR-451 also suppressed the progression of cholangiocarcinoma, which provides a potential therapeutical target for cholangiocarcinoma treatment.

ABSTRACT: Galactooligosaccharides are composed mainly of galactosyl lactose, which is important for infant growth and as a functional food additive. Although galactosyl lactose is abundant in goat milk, its complex structure has hindered the separation and analysis of its isomers. In this study, 5 isomers of goat milk galactosyl lactose were separated by HPLC: β6′-galactosyl lactose (β6′-GL), α6′-galactosyl lactose (α6′-GL), β4′-galactosyl lactose (β4′-GL), α3′-galactosyl lactose (α3′-GL), and β3′-galactosyl lactose (β3′-GL). This composition differs from that of commercial galactooligosaccharide products, which comprise mainly β-configuration oligosaccharides. The isomers were then qualitatively and quantitatively compared at different lactation stages using online HPLC-mass spectrometry. Relative quantitative analysis showed that the total content of the 5 galactosyl lactose isomers was highest in transitional goat milk. Specifically, β3′-GL was the main isomer in colostrum and α3′-GL was the main isomer in transitional and mature milk. β6′-Galactosyl lactose and β4′-GL tended to increase and then decrease during lactation. Moreover, α3′-GL content was 2 times higher than in colostrum and 10 times higher in transitional milk than in mature milk; in contrast, for β3′-GL, the values were 5 and 2 times higher, respectively. Absolute quantitative analysis revealed that β3′-GL was the most abundant isomers in colostrum (32.3 mg/L), and α3′-GL was the most abundant in transitional milk (88.1 mg/L) and mature milk (36.3 mg/L). These findings provide an important quantitative basis for understanding the relationship between structure and function of galactosyl lactose in goat milk, as well as its exploitation as a functional food.

In this paper, a finite-time, active fault-tolerant control (AFTC) scheme is proposed for a class of autonomous surface vehicles (ASVs) with component faults. The designed AFTC framework is based on an integrated design of fault detection (FD), fault estimation (FE), and controller reconfiguration. First, a nominal controller based on the Barrier Lyapunov function is presented, which guarantees that the tracking error converges to the predefined performance constraints within a settling time. Then, a performance-based monitoring function with low complexity is designed to supervise the tracking behaviors and detect the fault. Different from existing results where the fault is bounded by a known scalar, the FE in this study is implemented by a finite-time estimator without requiring any prioir information of fault. Furthermore, under the proposed finite-time AFTC scheme, both the transient and steady-state performance of the ASV can be guaranteed regardless of the occurrence of faults. Finally, a simulation example on CyberShip II is given to confirm the effectiveness of the proposed AFTC method.

The objective of this study was to investigate the effect of pork oxidation through modified atmosphere packaging (MAP) on gel characteristics of myofibrillar proteins (MP) during the heat-induced gelation process. The pork longissimus thoracis (LT) was treated by MAP at varying oxygen concentrations (0, 20, 40, 60, and 80% O2) with a 5-day storage at 4 °C for the detection of MP oxidation and gel properties. The findings showed the rise of O2 concentration resulted in a significant increase of carbonyl content, disulfide bond, and particle size, and a decrease of sulfhydryl content and MP solubility (p < 0.05). The gel textural properties and water retention ability were significantly improved in MAP treatments of 0–60% O2 (p < 0.05), but deteriorated at 80% O2 level. As the concentration of O2 increased, there was a marked decrease in the α-helix content within the gel, accompanied by a simultaneous increase in β-sheet content (p < 0.05). Additionally, a judicious oxidation treatment (60% O2 in MAP) proved beneficial for crafting dense and uniform gel networks. Our data suggest that the oxidation treatment of pork mediated by O2 concentration in MAP is capable of reinforcing protein hydrophobic interaction and disulfide bond formation, thus contributing to the construction of superior gel structures and properties.

Bone is the main by-product of animal after slaughtering and is rich in collagen. First, the preparation of bone collagen, involved pretreatment of bone raw materials, extraction, isolation and purification of bone collagen, are introduced. Then its application in food industry including functional food and food packaging, are reviewed in this article from the aspects of structure and properties of bone collagen. This paper will provide ideas for the efficient utilization of animal bone collagen.

Abstract Background The global increase in total hip or knee arthroplasty has led to concern about the provision of postoperative rehabilitation. Telerehabilitation may be a strategy to meet the patients’ requirements for rehabilitation after arthroplasty. This study aims to investigate the effectiveness of a telerehabilitation programme delivered via the mobile application WeChat in patients after total hip or knee arthroplasty on the following outcomes: self-efficacy, physical function, pain, depression, anxiety and health-related quality of life. Methods This is a single-centre, single-blinded, parallel-group, superiority randomised controlled trial conducted in Shanghai, China. Eighty-four eligible participants who undergo primary total hip or knee arthroplasty will be recruited preoperatively in a university teaching hospital and randomly assigned to the experimental or control group with their informed consent. Once discharged, the control group (n = 42) will receive the usual care provided by the hospital. The experimental group (n = 42) will receive usual care and a 6-week mobile application rehabilitation programme that consists of physical exercises and techniques for enhancing participants’ self-efficacy for rehabilitation. Baseline assessments will be conducted on the day before hospital discharge, and outcome assessments will be conducted 6 and 10 weeks postoperatively. The primary outcomes are changes in self-efficacy and physical function 6 weeks postoperatively, and the secondary outcomes include pain, depression, anxiety and health-related quality of life. The approach of a generalised estimating equation will be used to analyse the effect of the intervention on outcomes at a significance level of 0.05. Discussion This study is the first of its kind conducted in China to incorporate self-efficacy and learning theories as a framework to guide the development of a mobile application rehabilitation programme after arthroplasty. This study will contribute to the knowledge about the effectiveness of mobile application-based rehabilitation among patients after total hip or knee arthroplasty. If the findings are positive, they will support the implementation of mobile application-based rehabilitation in practice, which may potentially increase the accessibility of rehabilitation services as well as patient adherence to rehabilitation. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12621000867897 . Retrospectively registered on July 6, 2021

Effects of the incorporation of ultrasound with varied intensities (0–800 W) into the thermal-induced gelation process on the gelling properties of myofibrillar protein (MP) were explored. In comparison with single heating, ultrasound-assisted heating (

Abstract ORP5, a lipid transporter, has been reported to increase the metastasis of several cancers. However, the potential mechanisms of ORP5 in renal cell carcinoma (RCC) remain unclear. In this study, we demonstrated that ORP5 was commonly overexpressed in tumor cells and tissues of RCC, and associated with tumor progression. Overexpression of ORP5 could promote RCC cells migration and invasion. In addition, the results suggested that the expression of ORP5 was favorably associated with c-Met expression, and ORP5 promoted RCC cells metastasis by upregulating c-Met in vitro and in vivo. Mechanistically, ORP5 facilitated the ubiquitination and degradation of c-Cbl (the E3 ligase of c-Met), and thus inhibited c-Met lysosomal degradation, which resulted in the stabilization of c-Met. In general, these findings revealed the role of ORP5 in contributing to tumorigenesis via upregulating c-Met in RCC.

Anomaly detection of high-dimensional data is a challenge because the sparsity of the data distribution caused by high dimensionality hardly provides rich information distinguishing anomalous instances from normal instances. To address this, this article proposes an anomaly detection method combining an autoencoder and a sparse weighted least squares-support vector machine. First, the autoencoder is used to extract those low-dimensional features of high-dimensional data, thus reducing the dimension and the complexity of the searching space. Then, in the low-dimensional feature space obtained by the autoencoder, the sparse weighted least squares-support vector machine separates anomalous and normal features. Finally, the learned class labels to be used to distinguish normal instances and abnormal instances are outputed, thus achieving anomaly detection of high-dimensional data. The experiment results on real high-dimensional datasets show that the proposed method wins over competing methods in terms of anomaly detection ability. For high-dimensional data, using deep methods can reconstruct the layered feature space, which is beneficial for gaining those advanced anomaly detection results.

Background: Guishaozichuan (GSZC) granules are a traditional Chinese medicine formulation created by Professor Li (Chinese–Japanese Friendship Hospital, Beijing, China) we studied the effect of GSZC granules in rats suffering from asthma.Methods: Specific pathogen-free Sprague–Dawley rats were divided randomly into seven groups. Ovalbumin (OVA) and Al (OH)3 gel were used to create an asthma model. On day 1, rats were injected with OVA (10 mg) and an Al(OH)3 gel suspension (100 mg). One week later, rats were sensitized again. On day 15, rats were given aerosolized OVA (1%) for 30 min/day for 10 days. Gastric administration of OVA was 1 h before nebulization. At 24 h after the last stimulation, changes in airway resistance (RI) and dynamic compliance (Cdyn) in rat lungs were measured after challenge with methacholine at increasing concentrations. The contents of immunoglobulin (Ig)E, interleukin (IL)-4, IL-5, IL-13, and IL-17 in serum were measured by enzyme-linked immunosorbent assays. The percentage of eosinophils (EOS) and the white blood cell (WBC) count in bronchoalveolar lavage fluid (BALF) were counted under an optical microscope. Pathologic alterations in lung tissue were evaluated by optical microscopy, and lung injury score calculated. Expression of mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) and epidermal growth factor receptor (EGFR) in lung tissue was measured by immunohistochemistry. mRNA expression of MUC5AC and EGFR in lung tissue was measured by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR).Results: GSZC granules reduced RI markedly and improved Cdyn, decreased serum levels of IgE, IL-4, IL-5, IL-13, IL-17, %EOS and the WBC count in BALF. GSZC granules alleviated lung-tissue damage, diminished the Inflammation Score, and reduced mRNA and protein expression of MUC5AC and EGFR in lung tissue.Conclusion: GSZC granules could improve bronchial hyperresponsiveness, bronchial inflammation, and histopathologic damage in the lungs of rats suffering from asthma. This phenomenon may be related to its regulation of cytokine levels and the MUC5AC/EGFR signaling pathway.

We present new LA-ICP-MS detrital zircon U-Pb age and trace element data of the Late Mesozoic sedimentary sequences from the western Shandong and Tanlu fault zone, with the aim to constrain the depositional ages and sedimentary sources. The samples from the western Shandong have similar U-Pb age spectra, which can be divided into three major age groups, peaking age at circa 2,475–2,540 Ma, 1820–1870 Ma and 257–285 Ma, with minor Mesoproterozoic, Neoproterozoic and Paleozoic detrital zircon grains. The sample JN recovered from the Tanlu fault zone has an overwhelming majority of the Early Cretaceous detrital zircons with the age peak at circa 125 Ma, whereas the Archean and Paleoproterozoic detrital zircons are subordinate. The weighted average age of the youngest zircons show that the Santai Formation probably had begun deposition at circa 158 Ma and terminated deposition at circa 150 Ma, and the Tianjialou Formation of the Dasheng Group had begun deposition at circa 122 Ma. Our study indicates that the activity of the dinosaurs might occur during the Late Jurassic rather than the Cretaceous in the Shandong province. In addition, most detrital zircons of the studied samples are characterized by the high Th/U ratios and left-inclined REE patterns, revealing a magmatic origin. Morphologically, most detrital zircon grains characterized by angular to sub-rounded shapes indicate a middle-short distance transport from the source regions, whereas minor detrital zircon grains show rounded shapes, indicating a long-distance transport or multiphase recycling. According to detrital age populations in this study, combined with previously published data, we conclude that depositional provenances of the Santai Formation were mainly derived from the western Shandong and Jiao-Liao Belt, and minor detritus were derived from the northern part of the North China Craton and Xing-Meng orogenic belt. The sediments deposited in the Tanlu fault zone were mainly derived from the volcanic and subvolcanic rocks of the Qingshan period in the eastern Shandong, and subordinate depositional sources were from the Jiao-Liao and the basement uplift of the western Shandong, with minor supplier being derived from the Yinshan-Yanshan orogenic belt. The detrital provenance of the Santai Formation indicates that extension of the eastern NCC occurred during the Late Jurassic. The Neoproterozoic detrital zircons play a minor role in the studied strata, indicating that the large sinistral movement of the Tanlu fault zone might have occurred at the Early-Middle Jurassic and formed a paleogeographic separation of the western Shandong and eastern Shandong (Sulu orogenic belt).

Abstract Aim This study aimed to establish a risk model of hub genes to evaluate the prognosis of patients with cervical cancer. Methods Based on TCGA and GTEx databases, the differentially expressed genes (DEGs) were screened and then analyzed using GO and KEGG analyses. The weighted gene co-expression network (WGCNA) was then used to perform modular analysis of DEGs. Univariate Cox regression analysis combined with LASSO and Cox-pH was used to select the prognostic genes. Then, multivariate Cox regression analysis was used to screen the hub genes. The risk model was established based on hub genes and evaluated by risk curve, survival state, Kaplan-Meier curve, and receiver operating characteristic (ROC) curve. Results We screened 1265 DEGs between cervical cancer and normal samples, of which 620 were downregulated and 645 were upregulated. GO and KEGG analyses revealed that most of the upregulated genes were related to the metastasis of cancer cells, while the downregulated genes mostly acted on the cell cycle. Then, WGCNA mined six modules (red, blue, green, brown, yellow, and gray), and the brown module with the most DEGs and related to multiple cancers was selected for the follow-up study. Eight genes were identified by univariate Cox regression analysis combined with the LASSO Cox-pH model. Then, six hub genes (SLC25A5, ENO1, ANLN, RIBC2, PTTG1, and MCM5) were screened by multivariate Cox regression analysis, and SLC25A5, ANLN, RIBC2, and PTTG1 could be used as independent prognostic factors. Finally, we determined that the risk model established by the six hub genes was effective and stable. Conclusions This study supplies the prognostic value of the risk model and the new promising targets for the cervical cancer treatment, and their biological functions need to be further explored.

Introduction: Phosphatase and tensin (PTEN) is a multifunctional gene associated with the normal development and physiological function of various tissues including the kidney. However, its role in renal tubular reabsorption function has not been well elucidated. Methods: We generated a renal tubule-specific Pten knockout mouse model by crossing Ptenfl/fl mice with Ksp-Cre transgenic mice, evaluated the effect of Pten loss on renal tubular function, and investigated the underlying mechanisms. Results: Pten loss resulted in abnormal renal structure and function and water retention in multiple organs. Our results also demonstrated that aquaporin-2 AQP2, an important water channel protein, was upregulated and concentrated on the apical plasma membrane of collecting duct cells, which could be responsible for the impaired water balance in Pten loss mice. The regulation of Pten loss on AQP2 was mediated by Protein kinase B (AKT) activation. Discussion/Conclusions: Our results reveal a connection between PTEN gene inactivation and water retention, suggesting the importance of PTEN in normal kidney development and function.

The Gangdese magmatic belt of southern Tibet is an ideal place to study Neo-Tethyan subduction, continental crustal growth and reworking. However, there are still controversies with regard to the evolution of the Neo-Tethys Ocean, the magma source and the detailed diagenetic processes of igneous rocks in the Gangdese belt. The Early Cretaceous magmatic exposures are sporadic in the Gangdese magmatic belt. Thus the finding of the new exposure is key to understanding the scenarios of the Neo-Tethys Ocean and geological background of southern Tibet during the Early Cretaceous. In this contribution, we undertook systematic geochronology, whole-rock geochemistry and zircon Lu-Hf isotopic studies on a newly identified granitic pluton in the middle Gangdese belt (Quesang area), southern Tibet. The results show that zircon U-Pb dating of three representative samples yielded a weighted age of 120 ± 1.4 Ma, 117.3 ± 2.5 Ma and 114.0 ± 1.3 Ma, respectively, which indicate the emplacement and crystallization age belonging to the Aptian stage of the Early Cretaceous in response to the northward subduction of the Neo-Tethyan oceanic lithosphere beneath the Lhasa terrane. In situ zircon Lu-Hf isotopic analyses indicate that ƐHf(t) values of the studied granitic pluton are predominantly positive ranging from 7.2 to 11.4, and one zircon shows negative ƐHf(t) value (−6.26), implying that a small amount of ancient continental crustal materials might have participated in the magma evolution. Geochemically, the granite samples are enriched in large ion lithophile elements (LILE) and light rare earth elements (LREE), but depleted in heavy rare earth elements (HREE), indicating arc-type geochemical characteristics or subduction-related tectonic setting. In addition, combined with mineral assemblages, zircon Lu-Hf isotopic features and low molar Al2O3/(CaO+Na2O+K2O) (A/CNK) ratios of 0.91–1.10, the studied samples show a close affinity with I-type granites. Moreover, zircon oxygen fugacity results show that Ce4+/Ce3+ values range from 185 to 12, with a mean value of 78, indicating a low oxygen fugacity setting similar to the Chile ore-barren granitic plutons. In combination with published data, we argue that the Gangdese magmatic belt may have developed continuous magmatism (145–105 Ma), and the notion of magmatic lull might deserve more consideration during the Early Cretaceous. In this study, the Early Cretaceous granitic pluton might be the result of the northward subduction of Neo-Tethys oceanic lithosphere beneath the Lhasa terrane at a normal angle.

Abstract This paper investigates the formation control of connected autonomous vehicle (CAV) platoons moving in multi lanes using distance‐based formation control techniques based on rigid graphs and V2V communication. A hierarchical architecture is proposed to decompose the cooperative control into velocity planning and vehicle dynamic control. A new velocity planning method is first developed via a distributed distance‐based formation controller so that each vehicle can keep platoon and change lane. Then, for the vehicle dynamics with nonlinearities and bounded disturbances, an adaptive controller is designed for regulating driving/braking torque to achieve the longitudinal velocity output of the velocity planner. The steering controller is designed to adjust the yaw angle of each vehicle to track and change lanes. Furthermore, stability analysis is conducted based on the Lyapunov theory. Finally, the applications of the proposed control designs to various of automated highway system (AHS) scenarios including lane‐change, curve lane and platoon overtaking, are simulated and numerically analysed to validate the effectiveness of theoretical results.

Many domestic animals, among them dogs, have been infected with SARS-CoV-2 during the COVID-19 pandemic. Here, the authors present the crystal structure of the SARS-CoV-2 spike protein receptor binding domain (RBD) bound to its receptor, dog angiotensin-converting enzyme 2 (dACE2), and show that the RBD N501Y mutation increases the infectivity and host range of SARS-CoV-2, which highlights the need to monitor emerging SARS-CoV-2 mutations in domestic animals.

Background and AimFew non-invasive models were established to identify patients with non-alcoholic steatohepatitis (NASH). Liver biopsy remains the gold standard in the clinic. Decreased serum ceruloplasmin (CP) is reported in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to develop a non-invasive model incorporating CP for identifying NASH from NAFLD without type 2 diabetes mellitus (T2DM).MethodsA total of 138 biopsy-proven patients with NAFLD without T2DM were enrolled. The CP ratio was calculated for standardization as the CP value divided by the lower limit of normal. The clinical, anthropometric, biochemical, and histological parameters were compared between the low and high CP ratio groups divided by the median value. Multivariate logistic regression analysis was performed to develop a model for identifying NASH in patients with NAFLD.ResultsThe medians of the high (n = 69) and low (n = 69) CP ratio groups were 1.43 (1.28–1.61) and 1.03 (0.94–1.12), respectively. A comparison of the two groups showed that the severity of steatosis, hepatocellular ballooning, inflammation activity, fibrosis, and liver iron deposition decreased along with the CP ratio (p < 0.05). The median CP ratio of patients with NASH was significantly lower than those with NAFL [1.15 (1.01–1.41) vs. 1.33 (1.24–1.54), p = 0.001]. A novel model which consists of the CP ratio, BMI, and aspartate aminotransferase (AST) was developed. The AUCs of the model in discriminating NASH from NAFLD was 0.796 (0.694–0.899) and 0.849 (0.713–0.984) in the training and validation groups, and 0.836 (0.659–1.000), 0.833 (0.705–0.962), and 0.821 (0.612–1.000) in patients with normal serum alanine aminotransferase, AST, and both levels, respectively.ConclusionsDecreased CP ratio is associated with more severe histological activity, a diagnosis of NASH, and hepatic iron deposition among patients with NAFLD without T2DM. The CP ratio model could be served as a non-invasive approach to identifying patients with NASH, which might reduce the need for liver biopsy.

Circular RNAs (circRNAs), a class of endogenous RNA molecules, are produced by alternative splicing of precursor RNA and are covalently linked at the 5′ and 3′ ends. Recent studies have revealed that dysregulated circRNAs are closely related to the occurrence and progression of gastrointestinal malignancies. Accumulating evidence indicates that circRNAs, including circPVT1, circLARP4, circ-SFMBT2, cir-ITCH, circRNA_100782, circ_100395, circ-DONSON, hsa_circ_0001368, circNRIP1, circFAT1(e2), circCCDC66, circSMARCA5, circ-ZNF652, and circ_0030235 play important roles in the proliferation, differentiation, invasion, and metastasis of cancer cells through a variety of mechanisms, such as acting as microRNA sponges, interacting with RNA-binding proteins, regulating gene transcription and alternative splicing, and being translated into proteins. With the characteristics of high abundance, high stability, extensive functions, and certain tissue-, time- and disease-specific expressions, circRNAs are expected to provide novel perspectives for the diagnoses and treatments of gastrointestinal malignancies.

Evidence from epidemiological studies suggests that chronic arsenic exposure may be associated with a higher incidence of hypertension in the population. However, the effect of arsenic exposure on blood pressure remains unexplored in different populations, regions, and regarding arsenic biomarkers. This study investigated 233 arsenicosis patients and 84 participants from a non-arsenic-exposed area to explore the relationship between arsenic exposure and blood pressure and the occurrence of hypertension and wide pulse pressure (WPP) in patients with coal-burning arsenicosis. The results show that arsenic exposure is related to an increased incidence of hypertension and WPP in the arsenicosis population, primarily due to an induced increase in systolic blood pressure (SBP) and pulse pressure (PP) (OR = 1.47, 1.65, all p < 0.05). The dose–effect relationships between monomethylated arsenicals (MMA), trivalent arsenic (As3+), hypertension, and WWP were characterized following trend analyses (all p-trend < 0.05) in the coal-burning arsenicosis population. After adjusting for age, gender, body mass index (BMI), smoking, and alcohol usage, compared with low-level exposure, the high level of MMA exposure increases the risk of hypertension by 1.99 times (CI: 1.04–3.80) and the WPP by 2.42 times (CI: 1.23–4.72). Similarly, the high level of As3+ exposure increases the hypertension risk by 3.68 times (CI: 1.86–7.30) and the WPP by 3.84 times (CI: 1.93–7.64). Together, the results revealed that urinary MMA and As3+ levels are mainly associated with increased SBP and induce a higher incidence of hypertension and WPP. This study provides preliminary population evidence that cardiovascular-related adverse events such as hypertension and WPP ought to be noticed in the coal-burning arsenicosis population.

This paper develops an integral reinforcement learning (IRL) controller for a class of high-order multivariable nonlinear systems with unknown control coefficients (UCCs). A new long-term performance index is first presented, and then the critic neural network (NN) and the action NN are presented to estimate the unobtainable long-term performance index and the unknown drift of systems, respectively. By combining the critic and action NNs with Nussbaum-type functions, the IRL controllers for high-order, nonsquare multivariable systems are proposed to cope with the problem of UCCs. The analysis are given to illustrate that the stability of the closed-loop system can be obtained, and the signals of the closed-loop systems are semiglobally uniformly ultimately bounded (UUB). Finally, one simulation example is provided to show the effectiveness of the proposed IRL controllers.

Existing results on dealing with unknown high-frequency gain signs (UHFGSs) mainly adopt the Nussbaum-type functions. A new kind of control algorithms with nonlinear PI functions are presented to cope with UHFGSs. It is rigorously proven that the proposed algorithms with properly selected nonlinear PI functions can guarantee consensus for high-order multi-agent systems (MASs) under switching topologies with uniformly quasi-strongly $\delta $ -connected graphs (UQSGs). Furthermore, we also investigate the output leaderless consensus of heterogeneous agents with UHFGSs. Finally, the numerical examples are illustrated to show the validity of the proposed results.

Polypharmacy is an increasing health concern among older adults and results in many health risks. Nurses have an important role to play in supporting medication management and promoting medication safety across different settings. This study aims to provide a meta-synthesis of qualitative studies investigating the perceptions and experiences of nurses in caring for older adults with polypharmacy. Electronic databases including PsycArticles, CINAHL Complete, MEDLINE, and ERIC were searched between September 2001 and July 2022. Potential studies were checked against inclusion and exclusion criteria. We included peer-reviewed studies reporting data on the experiences of nursing staff across different settings. Studies unitizing any qualitative approach were included, and the included studies were reviewed and analyzed using a thematic synthesis approach. Study quality was examined using the Critical Appraisal Skills Programme checklist for qualitative research. A total of nine studies with 91 nurses were included. Four major themes emerged: older adults suffering from polypharmacy, the importance of multidisciplinary teams, nursing roles in caring for older adults, and the complexity and barriers of implementing polypharmacy management. Healthcare professionals should pay attention to the impacts of polypharmacy in older adults’ lives and should acknowledge the importance of team-based polypharmacy care in supporting older adults. Nurses play a key role in caring for older adults with polypharmacy, therefore, they should be empowered and be involved in medication management.

Gut microbiota dysbiosis plays an important role in the progression of non-alcoholic fatty liver disease (NAFLD), and no approved drugs are available for NAFLD treatment. In this study, we aimed to explore the dynamic changes of gut microbiota at the different stages of NAFLD and determine whether ursodeoxycholic acid (UDCA) could improve liver histopathological features of non-alcoholic steatohepatitis (NASH) mice induced by a high-fat high-cholesterol (HFHC) diet and its impact on gut microbiota. 6-week-old male C57BL/6 mice were fed with a HFHC or normal diet for 12, 18, and 24 weeks, respectively, to simulate the different stages of NAFLD. 16s ribosomal RNA genes from mice fecal samples at the different time points were sequenced to evaluate the dynamic changes of the gut microbiota. Then, C57BL/6 mice were fed with a HFHC diet for 24 weeks to establish the NASH model. Different doses of UDCA were administered intragastrically for additional 4 weeks. Normal diet–fed mice were taken as control. Serum samples, liver, and intestine tissues were harvested for biochemical tests and histopathological examinations. 16s ribosomal RNA genes from mice fecal samples were sequenced to assess the structural changes of gut microbiota. HFHC diet–fed mice developed simple steatosis, steatohepatitis, and fibrosis at 12, 18, and 24 weeks, respectively. The profile of gut microbiota dynamically changed with the different stages of NAFLD. NASH mice had significantly higher abundance of Fecalibaculum, Coriobacteriaceae_UCG-002, and Enterorhabdus, and lower abundance of norank_f_Muribaculaceae, Bacteroides, and Alistipes, which were partially restored by UDCA treatment. UDCA treatment significantly attenuated hepatic inflammation of NASH mice as indicated by the sum of ballooning and lobular inflammation of the NALFD activity score (3.2 ± 0.8 vs 1.8 ± 0.8, p = 0.029), and partially restored gut microbiota dysbiosis, and increased the expression of Claudin-1 and ZO-1 in the intestine, but did not activate the suppressed Farnesoid X receptor signal pathway. Conclusions: The gut microbiota dynamically changes with the different stages of NAFLD. UDCA treatment (120 mg/kg) could partially restore gut microbiota, repair gut barrier integrity, and attenuate hepatic inflammation in the NASH mouse model.

A TCM formula has played an important role in the treatment of COVID-19 in China. However, the mechanism of TCM action is still unclear.

Background: Currently, most arsenic (As) studies in populations are concerned with water-borne arsenicosis. However, residents in Xingren County of Guizhou Province, Southwest of China, represent a unique case of arsenicosis which is related to indoor combustion of high As-containing coal. This study aimed to assess the alterations of As levels and its risk factors in coal-borne arsenicosis residents during the past 20 years. Methods: Four follow-up investigations in Xingren County were selected from the year 1998 to 2017, a total of 245, 272, 584, and 309 residents were involved in the four investigations, respectively. Local external environmental medium (coal, soil, water, air, rice, corn and chili peppers) and biological samples (urine, hair) were collected at each time of investigation for total As analysis. Sociodemographics and lifestyles variables were extracted from the questionnaire investigation. Both univariate and multivariate unconditional logistic regression models were performed to analyze the variation of risk factors for coal-borne arsenicosis. Results: A substantial reduction of total As levels was observed both in external environmental medium and biological samples in the unique coal-borne arsenicosis region, especially since the year 2006. In addition, age, duration of consuming high As-containing coal and smoking status were found to be the most significant risk factors for coal-borne arsenicosis during the past 20 years by both two different logistic regression models. Room ventilation and grain drying modes were no longer to be risk factors since 1998 survey. Annual household income had always been an important protective factor for coal-borne arsenicosis in recent 20 years by both two different logistic regression models. Grain storage modes had become significant protective factor in 2014 and 2017 survey. A certain correlation between sex, education and coal-borne arsenicosis was observed by univariate logistic regression model but no clear links were found by multivariate logistic regression model. Conclusions: Considerable efforts to blocking As exposure from burning coal and As contaminated foods in this region are observed over the study period. Further practical health education programs may need to target individuals with long-term of As exposure, lower socioeconomic status and smoking in order to better prevent and control the occurrence and development of coal-borne arsenicosis. Keywords: Coal, Guizhou, Arsenic, Arsenicosis, Risk factors

In this paper,a novel multi-mobile robots formation control algorithm based on ultra-wideband (UWB) location technology was proposed.UWB location technology is relatively mature but is less applied to formation control problem.The framework of systems and hardware design of mobile multi-robot systems were first presented.Then,the systems model was established and the corresponding distributed control algorithm was proposed.Finally,the stability of multi-robot systems was proved and one simulation example was given to show the effectiveness of the proposed formation control algorithm.

Abstract Background The pro-oncogenic anterior gradient 2 (AGR2) is involved in tumor growth and drug resistance of breast cancer. Mechanisms that regulate expression of AGR2 still need to be elucidated. Methods In this study, expression levels of AGR2 and miR-135b-5p were analyzed in different breast cancer cell lines as well as in clinical breast cancer tissues. The in vitro and in vivo functional effect of AGR2 and miR-135b-5p were also investigated. A luciferase reporter assay was applied to confirm the interaction between miR-135b-5p and AGR2 mRNA. Results We identified AGR2 as a target of miR-135b-5p. Expression of AGR2 was up-regulated in doxorubicin-resistant breast cancer cells. AGR2 mediated doxorubicin-sensitivity of breast cancer cells both in vitro and in vivo. miR-135b-5p negatively regulated AGR2-expression of breast cancer cells increasing doxorubicin-sensitivity. However, miR-135b-5p was down-regulated in doxorubicin-resistant breast cancer cells as well as during treatment with doxorubicin, which might be a probable reason for over-expression of AGR2. Up-regulation of miR-135b-5p increased doxorubicin-sensitivity of breast cancer cells in vivo. In addition, levels of AGR2 negatively correlated with levels of miR-135b-5p in clinical breast cancer tissue samples. Conclusion Our results highlight the potential of miR-135b-5p as a target for treating AGR2-expressing breast cancer with doxorubicin-resistance.

Six biota species were collected from Qilianyu Island, South China Sea to determine the bioaccumulation and biomagnification of polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane and its metabolites (DDTs). Concentrations of ΣPCBs and ΣDDTs in biota from Qilianyu Island ranged from 6.88 to 519.1 ng/g lipid weight (lw) and 7.0 to 19,413 ng/g lw, respectively. Significant differences for PCBs and DDTs concentrations were found among the six biota species from Qilianyu Island. The levels of PCBs and DDTs in intermediate egret were significantly higher than the other five biota species, which can be attributed to their different feeding and living habits. Significantly negative relationships between concentrations of PCBs and DDTs and δ13C values in the six biota species confirmed that dietary source is an important factor to determine the levels of PCBs and DDTs in biota species. ΣPCBs, ΣDDTs, PCB 28/31, PCB 52, and p,p′-DDE were biomagnified in the biota species from Qilianyu Island, and native species are suitable for studying the biomagnification of the contaminants. The toxic equivalent concentrations in birds from Qilianyu Island were significantly and positively correlated with PCBs concentrations, indicating that high concentrations of non- and mono-ortho-PCB congeners may induce adverse effects on bird species.

The COVID-19 has emerged as an epidemic, causing severe pneumonia with a high infection rate globally. To better understand the pathogenesis caused by SARS-CoV-2, we developed a rhesus macaque model to mimic natural infection via the nasal route, resulting in the SARS-CoV-2 virus shedding in the nose and stool up to 27 days. Importantly, we observed the pathological progression of marked interstitial pneumonia in the infected animals on 5-7 dpi, with virus dissemination widely occurring in the lower respiratory tract and lymph nodes, and viral RNA was consistently detected from 5 to 21 dpi. During the infection period, the kinetics response of T cells was revealed to contribute to COVID-19 progression. Our findings implied that the antiviral response of T cells was suppressed after 3 days post infection, which might be related to increases in the Treg cell population in PBMCs. Moreover, two waves of the enhanced production of cytokines (TGF-α, IL-4, IL-6, GM-CSF, IL-10, IL-15, IL-1β), chemokines (MCP-1/CCL2, IL-8/CXCL8, and MIP-1β/CCL4) were detected in lung tissue. Our data collected from this model suggested that T cell response and cytokine/chemokine changes in lung should be considered as evaluation parameters for COVID-19 treatment and vaccine development, besides of observation of virus shedding and pathological analysis.

This study adopted widely targeted high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) metabolomics and multivariate data analysis methods to evaluate the correlation between changes in metabolites and their taste formation in dry-cured beef during processing. The physicochemical profile changed significantly in the maturity period (RG), especially due to the continuous hydrolysis and oxidation of proteins. The sensory characteristic of dry-cured beef was highest in saltiness, umami, overall taste, and after-taste in RG. Overall, 400 metabolites were mainly identified, including amino acids, peptides, organic acids, and their derivatives, nucleotides, and their metabolites, as well as carbohydrates. Cysteine and succinic acid were significantly up-regulated during the process of dry-curing beef compared to the control group (CG). Moreover, glutamine and glutathione were significantly down-regulated in the fermentation period (FG) and in RG. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that glyoxylate and dicarboxylate metabolism, glutathione metabolism, alanine, aspartate, and glutamate metabolism, arginine biosynthesis, taurine, and hypotaurine metabolism were the main metabolic pathways influencing the taste of dry-cured beef during processing. Results of correlation analysis revealed that umami is positively correlated with salty, L-cysteine, L-arginine, inosine, creatinine, and succinic acid. Our study results provide a better understanding of the changes in taste substances and will contribute to quality evaluation of dry-cured beef.

This study aimed to evaluate the efficiency of microencapsulated apple polyphenols (MAP) in controlling cathepsin activity and texture, as well as inhibiting protein oxidation and metmyoglobin formation in lamb meat during frozen storage at −18 °C for 40 weeks. The effects of degradation in vitro on cathepsin and the microstructure in lamb were also evaluated. Results indicated that relative to the control group, the lamb treated with MAP exhibited increased cathepsin activity and inhibited metmyoglobin production. Textural characteristics, such as hardness and springiness, significantly changed (p < 0.05). Treatment with 0.2–1.6 mg/mL of MAP effectively reduced the mean particle size, increasing the zeta potential, delaying the conversion of α-helices to random coils, and maintaining the integrity of the tissue structure. However, treatment with 3.2 mg/mL of MAP damaged the protein structure. Degradation in vitro indicated that protein oxidation hindered the effect of cathepsin and was a dominant factor affecting protein during the frozen storage. These results demonstrated that microencapsulation can potentially be used for meat preservation and replace chemical antioxidants in the meat industry.

Proteins and peptides when forming complexes with zinc can increase zinc bioavailability. Such complexation was investigated on hemp protein hydrolysates (HPHs) in the present study using Pepsin, Alcalase, Flavourzyme, Papain, Protamex, and Trypsin. Two solubility fractions of Zn2+–HPH complexes, i.e., P1 (water-insoluble large peptides) and P2 (water-soluble small peptides, precipitable by ethanol), were collected. The FTIR analysis on Pepsin-HPH suggested that P1 and P2 peptides had different Zn2+-binding sites where NH and CO were the primary sites in P1 and P2, respectively. Although the Zn2+-binding capacity (P1 and P2 combined) of HPHs was lower than that of nonhydrolyzed hemp protein, the P2-bound Zn2+ was more abundant in HPHs (up to 63.4%) than in nonhydrlyzed protein (29.6%). Isothermal titration calorimetry corroborated with Zn2+-binding capacity for different HPH samples. Peptides produced with Flavourzyme had the highest Zn2+-binding activity (88.8%) while those with Pepsin exhibited the maximum solubility.

To investigate the role of sulfhydryl groups and disulfide bonds in different protein-stabilized emulsions, N-ethylmaleimide (NEM) was used as a sulfhydryl-blocking agent added in the emulsion. The addition of NEM to block the sulfhydryl groups resulted in a reduction in disulfide bond formation, which enabled the internal structure of the protein molecule to be destroyed, and then decreased the restriction of protein membrane on the oil droplets. Furthermore, with the NEM content increasing in the emulsion, a reduction in the protein emulsifying activity and emulsion stability also occurred. At the same time, the intermolecular interaction of the protein on the oil droplet interface membrane was destroyed, and the emulsion droplet size increased with the NEM content in the emulsion. Although NEM blocking sulfhydryl groups from forming disulfide bonds has similar effects on three types of protein emulsion, the degree of myofibrillar protein (MP), egg-white protein isolate (EPI), and soybean protein isolate (SPI) used as emulsifiers had a subtle difference.

The aim of this study was to investigate lipolysis and lipid oxidation of stored eggs at different temperatures (4 and 22°C) by evaluating the changes in physicochemical index, lipid profiles, enzymatic activity, and oxidative index. The results showed that the changes in physicochemical index were more significant at 22°C than at 4°C. Weight loss, moisture content, and pH of egg yolk increased significantly (P < 0.05), whereas the yolk index decreased during storage. However, there was no significant difference in lipid profiles between 4 and 22°C storage temperature. The lipid composition analysis demonstrated that lipid hydrolysis took place during egg storage and resulted in a marked decrease of PL and increase of FFA. It was also found that the content of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) decreased significantly during storage. The correlation analysis showed that the lipid degradation is significantly positively related to lipase activity (P < 0.05), and the marked changes of lipid fractions are results of both hydrolysis and oxidation. It can be concluded that the egg physicochemical index and lipase activity were greatly influenced by temperature during storage, but the yolk lipid stability was not significantly influenced by storage temperature.

Background and objective Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance significantly limits its use in clinical practice. Study found that TRIM24 was overexpressed in non-small cell lung cancer (NSCLC) tissues and regulate cell growth, cell cycle and apoptosis in lung cell lines. The aim of this study is to explore the mechanism of TRIM24 to regulate resistance of Gefitinib in NSCLC cells. Methods MTT and apoptosis were used to detect the change of cell grow and cell apoptosis with down-expression TRIM24 and ShTRIM24 with presence of Gefitinib. Meanwhile, Western blot was used to detect the expression of protein related to apoptosis and AKT signal path. Results TRIM24 interference could improve the effect of gefitinib on cell growth inhibition and upregulate the cell apoptosis in A549 cell. Down-regulated of endogenous TRIM24 and ShTRIM24 with Gifitinib could also reduce the protein related apoptosis, such as p-BAD and Bcl-2, and the protein PIK3CA related AKT signal path in A549 cell. Conclusion TRIM24 could regulate required resistance to Gefitinib via Akt pathway in NSCLC.

Background and objective Metastasis-associated protein 3 (MTA3) was originally found as a member of a small protein family (including MTA1, MTA2 and MTA3), and it has been proven that MTA3 had different roles in different types of human cancers. The aim of this study is to explore the function of MTA3 to regulate the cell apoptosis in lung cancer. Methods Western blot and Real-time PCR were used to detect the expression level of MTA3 after transfection in non-small cell lung cancer (NSCLC) cells A549 and H157. Apoptosis analysis was used to detect the change of cell apoptosis with upregulated/downregulated of MTA3, and Western blot was used to detect the the expression of the protein related with apoptosis, while downregulate the expression of MTA3 in NSCLC cells A549 and H157. Results Downregulated of endogenous MTA3 could promote apoptosis in NSCLC cells, meanwhile, siMTA3 could upregulate the protein of BAX, Cleved-Caspase-3, p-PARP, and dowmregulate the protein of Bcl-2. Conclusion The data we present here indicate that MTA3 suppress apoptosis of A549 an H157 cells by inhibiting BAX, PARP expression.

This paper presents results concerning the global external stochastic stabilization for linear systems with input saturation and stochastic external disturbances under random Gaussian distributed initial conditions. The objective is to construct a class of control laws that achieve global asymptotic stability in the absence of disturbances, while guaranteeing a bounded variance of the state for all the time in the presence of disturbances. By using an alternative approach, a new class of scheduled control laws are proposed, and the global external stochastic stabilization problem can be solved only through some routine manipulations. Furthermore, the reported approach allows a larger range of the design parameter. Finally, two numerical examples are provided to validate the theoretical results.