Search

Abstract Background Quercetin is a flavonol compound widely distributed in plants that possesses diverse biological properties, including antioxidative, anti-inflammatory, anticancer, neuroprotective and senescent cell-clearing activities. It has been shown to effectively alleviate neurodegenerative diseases and enhance cognitive functions in various models. The immune system has been implicated in the regulation of brain function and cognitive abilities. However, it remains unclear whether quercetin enhances cognitive functions by interacting with the immune system. Results In this study, middle-aged female mice were administered quercetin via tail vein injection. Quercetin increased the proportion of NK cells, without affecting T or B cells, and improved cognitive performance. Depletion of NK cells significantly reduces cognitive ability in mice. RNA-seq analysis revealed that quercetin modulated the RNA profile of hippocampal tissues in aging animals towards a more youthful state. In vitro, quercetin significantly inhibited the differentiation of Lin−CD117+ hematopoietic stem cells into NK cells. Furthermore, quercetin promoted the proportion and maturation of NK cells by binding to the MYH9 protein. Conclusions In summary, our findings suggest that quercetin promotes the proportion and maturation of NK cells by binding to the MYH9 protein, thereby improving cognitive performance in middle-aged mice. Graphical abstract

Background & Aims: The lymphatic system plays crucial roles in maintaining fluid balance and immune regulation. Studying the liver lymphatics has been considered challenging, as common lymphatic endothelial cell (LyEC) markers are expressed by other liver cells. Additionally, isolation of sufficient numbers of LyECs has been challenging because of their extremely low abundance (

Different patients have different rehabilitation requirements. It is essential to ensure the safety and comfort of patients at different recovery stages during rehabilitation training. This study proposes a multi-mode adaptive control method to achieve a safe and compliant rehabilitation training strategy. First, patients’ motion intention and motor ability are evaluated based on the average human–robot interaction force per task cycle. Second, three kinds of rehabilitation training modes—robot-dominant, patient-dominant, and safety-stop—are established, and the adaptive controller can dexterously switch between the three training modes. In the robot-dominant mode, based on the motion errors, the patient’s motor ability, and motion intention, the controller can adaptively adjust its assistance level and impedance parameters to help patients complete rehabilitation tasks and encourage them to actively participate. In the patient-dominant mode, the controller only adjusts the training speed. When the trajectory error is too large, the controller switches to the safety-stop mode to ensure patient safety. The stabilities of the adaptive controller under three training modes are then proven using Lyapunov theory. Finally, the effectiveness of the multi-mode adaptive controller is verified by simulation results.

The self-aligning capability of an exoskeleton is important to ensure wearing comfort, and the delicate motion ability of the exoskeleton is essential for motion assistance. Designing a self-aligning exoskeleton that offers improved wearing comfort and enhanced motion-assistance functions remains a challenge. This paper proposes a novel spatial self-aligning mechanism for a knee exoskeleton to enable simultaneous assistance in the flexion and extension (FE) of the knee joint and the internal and external rotation (IER) of the hip joint. Additionally, considering the misalignment of the human-robot joint axes, a kinematic model of the knee exoskeleton is established and analyzed to demonstrate the kinematic compatibility of the exoskeleton. Furthermore, a global torque manipulability (GTM) index is proposed to evaluate the effects of dimensional parameters on the exoskeleton’s performance, and then the knee exoskeleton is optimized according to the GTM index. Finally, experiments are conducted to validate the performance of the proposed exoskeleton. The experimental results show that during knee FE and hip IER, the proposed exoskeleton exhibits lower interaction forces and torques than existing exoskeletons.

Three types of starch with different amylose content were esterified and blended with polybutylene succinate (PBS) to obtain esterified manioc starch/PBS (EMS/PBS), esterified corn starch/PBS (ECS/PBS), and esterified waxy corn starch/PBS (EWS/PBS) composites. The EMS/PBS and ECS/PBS composites with high amylose content displayed typical V-type crystal structures. The original crystals of EWS, which had low amylose content, were disrupted during the esterification process. EWS exhibited the strongest interaction with PBS and the most favorable interface compatibility. The pyrolysis temperature was in order of EMS/PBS < ECS/PBS < EWS/PBS. The elongation at break of the three blends was higher than that of pure PBS. The esterification and plasticization of the EWS/PBS composite were the most comprehensive. The EWS/PBS composite showed the lowest storage modulus (G’) and complex viscosity (η*). The interfacial bonding force of the composite materials increased with more amylopectin, decreasing intermolecular forces and destroying crystal structures, which decreased G’ and η* and increased toughness. The EWS/PBS composite, with the least amylose content, had the best hydrophobicity and degradation performance.

Abstract Background Glycyrrhizic acid (GA), a saponin compound often used as a flavoring agent, can elicit anti-inflammatory and anti-tumor effects, and alleviate aging. However, the specific mechanism by which GA alters immune cell populations to produce these beneficial effects is currently unclear. Results In this study, we systematically analyzed single-cell sequencing data of peripheral blood mononuclear cells from young mice, aged mice, and GA-treated aged mice. Our in vivo results show that GA reduced senescence-induced increases in macrophages and neutrophils, and increased numbers of lymphoid lineage subpopulations specifically reduced by senescence. In vitro, GA significantly promoted differentiation of Lin−CD117+ hematopoietic stem cells toward lymphoid lineages, especially CD8+ T cells. Moreover, GA inhibited differentiation of CD4+ T cells and myeloid (CD11b+) cells by binding to S100 calcium-binding protein 8 (S100A8) protein. Overexpression of S100A8 in Lin− CD117+ hematopoietic stem cells enhanced cognition in aged mice and the immune reconstitution of severely immunodeficient B-NDG (NOD.CB17-Prkdcscid/l2rgtm1/Bcgen) mice. Conclusions Collectively, GA exerts anti-aging effects by binding to S100A8 to remodel the immune system of aged mice.

Artemisia sphaerocephala Krasch gum (ASKG) can be carboxymethylated and greasy-based emulsified to improve its water solubility and emulsifying property, while the effect of modified ASKG on wheat flour processing as a gluten enhancer remains largely unknown. In this study, we investigated the gluten-increasing effect of ASKG in the formation of wheat flour dough and the production of greasy dough through its carboxymethylation and emulsification modification. The results showed that the carboxymethylation could reduce the optimum addition amount of ASKG from 1.0% to 0.4% in wheat flour. Carboxymethyl ASKG (C-ASKG) increased the wet gluten content, gluten index, water absorption, dough development time, dough stability time, and reduced the weakening degree. However, C-ASKG did not show better reinforcement in greasy dough than ASKG. In comparison, ASKG emulsified (E-ASKG) by wheat germ oil and palm stearin fat was shown to be more suitable for greasy dough modulation. The addition of 1.0% of ASKG and 5% of oil or fat in flour by emulsification manner reduced the difference between the oil and fat during the formation of gluten and improve the evaluation indexes of dough texture. This study demonstrated that carboxymethylation could reduce the dosage of ASKG used in wheat flour as a gluten enhancer, while emulsive ASKG was suitable for the gluten reinforcement of water-oiled dough.

Background: Flexible fiberoptic bronchoscopy (FFB) for children is widely performed under sedation. Currently, the optimal sedation regimen remains unclear. Esketamine is an N-methyl-D-aspartic acid (NMDA) receptor antagonist, which has stronger sedative and analgesic effects and exerts less cardiorespiratory depression than other sedatives. The purpose of this study was to evaluate whether a subanesthetic dose of esketamine as an adjuvant to propofol/remifentanil and spontaneous ventilation compared with control reduces the procedural and anesthesia-related complications of FFB in children.Materials and methods: Seventy-two children ≤ 12 years of age who were scheduled for FFB were randomly assigned, in a 1:1 ratio, to the esketamine-propofol/remifentanil (Group S, n = 36) or to the propofol/remifentanil group (Group C, n = 36). All children were retained spontaneous ventilation. The primary outcome was the incidence of oxygen desaturation (respiratory depression). Perioperative hemodynamic variables, blood oxygen saturation (SPO2), end-tidal partial pressure of carbon dioxide (PetCO2), respiratory rate (R), and the Bispectral index (BIS), induction time, procedural time, recovery time, the time to the ward from the recovery room, consumption of propofol and remifentanil during the procedure and the appearance of adverse events, including paradoxical agitation following midazolam administration, injection pain, laryngospasm, bronchospasm, PONV, vertigo, and hallucination were also compared.Results: The incidence of oxygen desaturation was significantly lower in Group S (8.3%) compared to Group C (36.1%, p = 0.005). The perioperative hemodynamic profile including SBP, DBP, and HR were more stable in Group S than that in Group C (p < 0.05). Consumption of propofol and remifentanil was lower in Group S than in Group C (p < 0.05). Furthermore, PAED scores, cough scores and injection pain were lower in the Group S than in Group C (p < 0.05). The recovery time of Group S was slightly longer than that of Group C (p < 0.05). Nobody happened paradoxical agitation following midazolam administration, PONV, vertigo, and hallucinations in both groups (p > 0.05).Conclusion: Our findings indicate that a subanesthetic dose of esketamine as an adjuvant to propofol/remifentanil and spontaneous respiration is an effective regimen for children undergoing FFB. Our findings will provide a reference for clinical sedation practice during these procedures in children.Clinical Trail Registration: Chinese clinicaltrials.gov registry (identifier: ChiCTR2100053302).

Abstract Background Sepsis is still a major public health concern and a medical emergency due to its high morbidity and mortality. Accurate and timely etiology diagnosis is crucial for sepsis management. As an emerging rapid and sensitive pathogen detection tool, digital droplet PCR (ddPCR) has shown promising potential in rapid identification of pathogens and antimicrobial resistance genes. However, the diagnostic value and clinical impact of ddPCR tests remains to be studied in patients with suspected sepsis. PROGRESS trial is aimed to evaluate the clinical effectiveness of a novel ddPCR assay compared with standard practice. Methods PROGRESS is a multicenter, open-label, pragmatic randomized controlled trial (pRCT) set in ten hospitals, including departments of infectious disease and intensive care units. In this study, a total of 2292 patients with suspected sepsis will be randomly assigned to two arms: the ddPCR group and the control group with a ratio of 3:1. The primary outcome is the diagnostic efficacy, that is, the sensitivity and specificity of the ddPCR assay compared with the synchronous blood culture. Secondary outcomes include the mortality rates and the mean Sequential Organ Failure Assessment (SOFA) score at follow-up time points, the length of stay in the hospital, the time to directed antimicrobial therapy, duration of broad-spectrum antibiotic use, and the EQ-5D-5L score on day 90. Discussion It is the first multicenter pragmatic RCT to explore the diagnostic efficacy and clinical impact of the ddPCR assay in patients with suspected sepsis, taking advantage of both RCT’s ability to establish causality and the feasibility of pragmatic approaches in real-world studies (RWS). This trial will help us to get a comprehensive view of the assay’s capacity for precise diagnosis and treatment of sepsis. It has the potential to monitor the pathogen load change and to guide the antimicrobial therapy, making a beneficial impact on the prognosis of sepsis patients. Trial registration: ClinicalTrial.gov, NCT05190861. Registered January 13, 2022—‘Retrospectively registered’, https://clinicaltrials.gov/ct2/show/NCT05190861 .

Abstract Klinotaxis is a strategy of chemotaxis behavior in Caenorhabditis elegans (C. elegans), and random walking is evident during its locomotion. As yet, the understanding of the neural mechanisms underlying these behaviors has remained limited. In this study, we present a connectome-based simulation model of C. elegans to concurrently realize realistic klinotaxis and random walk behaviors and explore their neural mechanisms. First, input to the model is derived from an ASE sensory neuron model in which the all-or-none depolarization characteristic of ASEL neuron is incorporated for the first time. Then, the neural network is evolved by an evolutionary algorithm; klinotaxis emerged spontaneously. We identify a plausible mechanism of klinotaxis in this model. Next, we propose the liquid synapse according to the stochastic nature of biological synapses and introduce it into the model. Adopting this, the random walk is generated autonomously by the neural network, providing a new hypothesis as to the neural mechanism underlying the random walk. Finally, simulated ablation results are fairly consistent with the biological conclusion, suggesting the similarity between our model and the biological network. Our study is a useful step forward in behavioral simulation and understanding the neural mechanisms of behaviors in C. elegans.

With the advent of the digital age, traditional lifestyle activities, such as reading books, referencing recipes, and enjoying music, have progressively transitioned from offline to online. However, numerous issues plague the conventional approach to digital copyright protection. This is especially true in the realm of recipe protection, where the rights and interests of original creators are inadequately safeguarded due to the widespread dissemination of a large number of recipes on the Internet. This primarily stems from the high costs of gathering evidence, incomplete coverage of evidence collection, and the inability to identify and halt infringement activities in a timely manner during the process of traditional digital copyright protection. Therefore, this study designs and implements a blockchain-based digital recipe copyright protection scheme to address the issues of insufficient legal evidence and cumbersome processes in traditional digital copyright protection. First, we enhance standard short text similarity calculation method SimHash, boosting the accuracy of text similarity detection. We then utilize the decentralization, immutability, time-stamping, traceability, and smart contract features of blockchain technology for data privacy protection. We employ the Interplanetary File System (IPFS) to store raw data, thereby ensuring user privacy and security. Lastly, we improve the proxy voting node selection in the existing delegated proof of stake (DPOS) consensus mechanism. According thorough evaluation and empirical analysis, the scheme effectively improves the accuracy of text similarity detection. Simultaneously, the enhanced DPOS mechanism effectively rewards nodes with excellent performance and penalizes nodes exhibiting malicious behavior. In this study, we successfully designed and implemented an innovative digital recipe copyright protection scheme. This scheme effectively enhances the accuracy of text similarity detection; ensures the privacy and security of user data; and, through an enhanced DPOS mechanism, rewards well-performing nodes while penalizing those exhibiting malicious behavior.

Abstract Background Gallbladder cancer (GBC) is the most common biliary tract malignancy and has a poor prognosis in patients with GBC. CircRNA TP63 (circTP63) has been implicated in cell proliferation and invasion in some tumor progress. The study aims to investigate the clinical significance and functional role of circTP63 expression in GBC. Methods The expression of circTP63 in GBC tissues or cells was detected by qRT-PCR and the association between circTP63 expression and prognosis of GBC patients was analyzed. CCK8 assay, flow cytometry analysis, transwell assay and in vivo studies were used to evaluate the cell proliferation and invasion abilities after circTP63 knockdown in GBC cells. Luciferase reporter assays and RNA pull-down assay were used to determine the correlation between circTP63 and miR-217 expression. Besides, western blot analysis was also performed. Results In the present study, we showed that circTP63 expression was upregulated in GBC tissues and cells. Higher circTP63 expression was associated with lymph node metastasis and short overall survival (OS) in patients with GBC. In vitro, knockdown of circTP63 significantly inhibited cell proliferation, cell cycle progression, migration and invasion abilities in GBC. Besides, we demonstrated that knockdown of circTP63 inhibited GBC cells Epithelial-Mesenchymal Transition (EMT) process. In vivo, knockdown of circTP63 inhibited tumor growth in GBC. Mechanistically, we demonstrated that circTP63 competitively bind to miR-217 and promoted EZH2 expression and finally facilitated tumor progression. Conclusions Our findings demonstrated that circTP63 sponged to miR-217 and regulated EZH2 expression and finally facilitated tumor progression in GBC. Thus, targeting circTP63 may be a therapeutic strategy for the treatment of GBC.

Abstract Gallbladder cancer (GBC) is the most malignant cancer of the biliary tract cancer and presents poor prognosis. CircRNAs have been identified as critical regulators of multiple stages in tumor progression. In the study, we first demonstrated that circular RNA circβ-catenin expression was upregulated in GBC tissues when compared to adjacent normal tissues and associated with advanced clinical stage and poor prognosis in GBC patients. Silencing of circβ-catenin obviously suppressed GBC cell proliferation and cell cycle progression in vitro, but circβ-catenin overexpression had the opposite effects. In vivo, silencing of circβ-catenin inhibited tumor growth. Furthermore, we also found that circβ-catenin promoted GBC cell lactate production, pyruvate production, ATP quantity, and extracellular acidification rate (ECAR), which suggested that circβ-catenin regulated Warburg effect in GBC. Mechanistic analysis further highlighted that circβ-catenin promoted Stathmin 1 (STMN1) expression through sponging miR-223 in GBC progression. In addition, knockdown of STMN1 inhibited cell growth and Warburg effect in GBC. In summary, our findings indicated that circβ-catenin/miR-223/STMN1 axis could regulate cell growth and Warburg effect in GBC. Targeting circβ-catenin might be a potential therapeutic strategy for GBC.

Phenolic ingredients of Hippophae tibetana (Tib) and H. rhamnoides ssp. sinensis (Rha) berry from Qinghai-Tibet Plateau were identified by Ultra Performance Liquid Chromatography-triple Quadrupole Tandem Mass Spectrometry. Results demonstrated that both of them possessed high levels of total phenolic and flavonoid, and compared to Tib, Rha berry exhibited higher contents. Moreover, flavonols was the most predominant subclass in Rha berry, flavonols and flavanols were the two most abundant subclasses in Tib berry. Among them, rutin and narcissin were present in the most abundant amounts in Rha berry, while (−)-epigallocatechin was the richest substance in Tib berry. Furthermore, both phenolic extracts of sea buckthorn berry exhibited strong in vitro and cellular antioxidant properties. Rha berry extract exhibited much stronger effects because of its higher levels of phenolic and flavonoid profiles. This finding proved that the Rha berry could serve as a food source for better health with great potential antioxidant activity.

Buckwheat has beneficial effects on human intestinal health, which is often compounded with wheat to make food. Therefore, the effect of cereals mixture via in vitro fermentation on gut microbes and short-chain fatty acids (SCFAs) were investigated in this study. The mixture of wheat and tartary buckwheat (WT) produced more lactate and acetate, and the mixture of wheat and sweet buckwheat (WE) produced more propionate and butyrate. Compared with wheat (WA), the relative abundance of some beneficial bacteria significantly increased, such as Sutterella in WT and Faecalibacterium in WE. Cereals mixture also affected the expression of functional genes, involved in metabolic pathways and carbohydrate-active enzymes (CAZymes) that modulated SCFAs generation. This study provides new insights into the effects of sweet and tartary buckwheat on intestinal function, which is beneficial to applying both types of buckwheat in practical.

With the large-scale access of renewable energy, the randomness, fluctuation and intermittency of renewable energy have great influence on the stable operation of a power system. Energy storage is considered to be an important flexible resource to enhance the flexibility of the power grid, absorb a high proportion of new energy and satisfy the dynamic balance between the supply and demand of a system. At present, the cost of energy storage is still high, and how to achieve the optimal energy storage configuration is the primary problem to be solved. Therefore, the current research progress in energy storage application scenarios, modeling method and optimal configuration strategies on the power generation side, grid side and user side are summarized in this paper. On this basis, the shortcomings that still exist of energy storage configuration research are summarized, and the future research direction for energy storage configuration is prospected. This review can provide reference for the latest development and future research and innovation direction for energy storage configuration.

Abstract Background Acute kidney injury (AKI) is a prevalent and severe complication of sepsis contributing to high morbidity and mortality among critically ill patients. In this retrospective study, we develop a novel risk-predicted nomogram of sepsis associated-AKI (SA-AKI). Methods A total of 2,871 patients from the Medical Information Mart for Intensive Care III (MIMIC-III) critical care database were randomly assigned to primary (2,012 patients) and validation (859 patients) cohorts. A risk-predicted nomogram for SA-AKI was developed through multivariate logistic regression analysis in the primary cohort while the nomogram was evaluated in the validation cohort. Nomogram discrimination and calibration were assessed using C-index and calibration curves in the primary and external validation cohorts. The clinical utility of the final nomogram was evaluated using decision curve analysis. Results Risk predictors included in the prediction nomogram included length of stay in intensive care unit (LOS in ICU), baseline serum creatinine (SCr), glucose, anemia, and vasoactive drugs. Nomogram revealed moderate discrimination and calibration in estimating the risk of SA-AKI, with an unadjusted C-index of 0.752, 95 %Cl (0.730–0.774), and a bootstrap-corrected C index of 0.749. Application of the nomogram in the validation cohort provided moderate discrimination (C-index, 0.757 [95 % CI, 0.724–0.790]) and good calibration. Besides, the decision curve analysis (DCA) confirmed the clinical usefulness of the nomogram. Conclusions This study developed and validated an AKI risk prediction nomogram applied to critically ill patients with sepsis, which may help identify reasonable risk judgments and treatment strategies to a certain extent. Nevertheless, further verification using external data is essential to enhance its applicability in clinical practice.

With the development of materials science and biomedicine, the application of nanomaterials in the medical field is further promoted. In the process of the diagnosis and treatment of diseases, a variety of drugs need to be used. It is an ideal state to make these drugs arrive at a specific location at a specific time and release at a specific speed, which can improve the bioavailability of drugs and reduce the adverse effects of drugs on normal tissues. Traditional drug delivery methods such as tablets, capsules, syrups, and ointments have certain limitations. The emergence of a new nano-drug delivery system further improves the accuracy of drug delivery and the efficacy of drugs. It is well known that the development of the cancer of the stomach is the most serious consequence for the infection of Helicobacter pylori. For the patients who are suffering from gastric cancer, the treatments are mainly surgery, chemotherapy, targeted and immune therapy, and other comprehensive treatments. Although great progress has been made, the diagnosis and prognosis of gastric cancer are still poor with patients usually diagnosed with cancer at an advanced stage. Current treatments are of limited benefits for patients, resulting in a poor 5-year survival rate. Nanomaterials may play a critical role in early diagnosis. A nano-drug delivery system can significantly improve the chemotherapy, targeted therapy, and immunotherapy of advanced gastric cancer, reduce the side effects of the original treatment plan and provide patients with better benefits. It is a promising treatment for gastric cancer. This article introduces the application of nanomaterials in the diagnosis and treatment of H. pylori and gastric cancer.

It has been nearly 60 years since the introduction of the Gough–Stewart manipulator (GSM). With the advantages of superior load capacity and high precision, the GSM still plays an important role in many fields. However, the GSM has limitations such as a small workspace and complex singularities. To overcome these problems, a novel kinematically redundant parallel robot is designed with three redundant actuators added on the basis of the GSM. First, the structure of the proposed robot is introduced, and the kinematics of the proposed robot is established. Second, the workspaces of the proposed robot are analyzed, and the results show that the position workspace volume and the maximum torsion and orientation angles of the proposed robot can be improved effectively. Third, the singularities of the proposed robot and the GSM are compared based on the Jacobian matrices. Finally, the multi-parameter, multi-objective optimization is used to optimize the geometric parameters of the proposed robot, and an experimental prototype of the proposed robot is designed based on the optimization results.

Alcohol has been demonstrated to disrupt intestinal barrier integrity. Some flavonoid compounds that exert antioxidant activity have a protective effect on intestinal barrier function. As an important medicinal and edible plant, sea buckthorn (Hippophae) seeds are rich in flavonoids, but their protective effect on the intestinal barrier has not been reported. In our research, 76 kinds of flavonoids were identified in Hippophae rhamnoides ssp. sinensis seed residue flavonoids (HRSF) by ultra-performance liquid chromatography–tandem mass spectrometry. Kaempferol-3-O-rutinoside, isorhamnetin-3-O-rutinoside, kaempferol-3-O-robinoside-7-O-rhamnoside, isorhamnetin-3-O-2G-rhamnosylrutinoside, quercetin-3-O-rutinoside, (−)-epigallocatechin, and B type of procyanidin were the most abundant substances, accounting for 15.276%, 15.128%, 18.328%, 10.904%, 4.596%, 5.082%, and 10.079% of all identified flavonoids, respectively. Meanwhile, pre-treatment with HRSF was able to prevent alcohol-induced disruption of intestinal barrier integrity through elevating the transepithelial monolayer resistance value, inhibiting the flux of fluorescein isothiocyanate-dextran, and upregulating the mRNA and protein level of TJs (occludin and ZO-1). Furthermore, it was also able to reverse alcohol-induced oxidative stress through suppressing the accumulation of reactive oxygen species and malondialdehyde, improving the glutathione level and superoxide dismutase activity. Finally, the results showed that HRSF pre-treatment effectively elevated the erythroid-related factor 2 mRNA and protein level compared with the alcohol-alone treatment group. Our research was the first to demonstrate that HRSF could prevent alcohol-induced intestinal barrier dysfunction through regulating the Nrf2-mediated pathway in order to attenuate oxidative stress and enhance TJ expression.

Background: Dysfunction of liver sinusoidal endothelial cells (LSECs) is permissive for the progression of liver fibrosis and cirrhosis and responsible for its clinical complications. Here, we have mapped the spatial distribution of heterogeneous liver ECs in normal vs cirrhotic mouse livers and identified zone-specific transcriptomic changes of LSECs associated with liver cirrhosis using scRNA-seq technology. Approach & Results: Cirrhosis was generated in endothelial specific green fluorescent protein (GFP) reporter mice through carbon tetrachloride inhalation for 12 weeks. GFP-positive liver EC populations were isolated from control and cirrhotic mice by FACS. We identified 6 clusters of liver EC populations including 3 clusters of LSECs, 2 clusters of vascular ECs and 1 cluster of lymphatic ECs. Based on previously reported LSEC-landmarks, we mapped the 3 clusters of LSECs in zones 1, 2, and 3, and determined phenotypic changes in each zone between control and cirrhotic mice. We found genes representing capillarization of LSECs (eg, CD34) as well as extracellular matrix genes were most upregulated in LSECs of zone 3 in cirrhotic mice, which may contribute to the development of basement membranes. LSECs in cirrhotic mice also demonstrated decreased expression of endocytic receptors, most remarkably in zone 3. Transcription factors (Klf2 [Kruppel-like factor-2], Klf4 [Kruppel-like factor-4], and AP-1) that induce nitric oxide production in response to shear stress were downregulated in LSECs of all zones in cirrhotic mice, implying increased intrahepatic vascular resistance. Conclusion: This study deepens our knowledge of the pathogenesis of liver cirrhosis at a spatial, cell-specific level, which is indispensable for the development of novel therapeutic strategies to target the most dysfunctional liver ECs.

Poly(hexylene succinate) (PHS), poly(ethylene succinate) (PES), and their random copolyesters, poly(hexylene succinate-co-ethylene succinate) ((P(HS-co-ES)), were synthesized by melting polycondensation. Simply varying the ratios of HS/ES afforded control over the copolymer crystallinity, thermal and mechanical properties, wettability, and enzymatic hydrolyzability as shown by X-ray diffraction (XRD), differential scanning calorimetry (DSC), tensile tests, and water contact angle (WCA) measurements. The enzymatic hydrolysis rates of all prepared copolyesters were higher than those of the corresponding homopolyesters. The hydrolysis rates were affected by crystallinity, melting temperature, and hydrophobicity of the copolyesters, and therefore, the degradation rates could be tuned along with the ES content. The library of copolymers prepared here with tunable degradation rates, ranging from HS-enriched to ES-enriched copolyesters, is promising for a variety of different applications. The P(HS-co-ES51) copolyester that did not fully degrade is particularly promising for use in long-term storage applications, whereas P(HS-co-ES13) and P(HS-co-ES76) that rapidly degrade are good for use in very short-term applications.

Aiming at the situation that the structural parameters of the general manipulators are uncertain, a time-varying impedance controller based on model reference adaptive control (MRAC) is proposed in this article. The proposed controller does not need to use acceleration-based feedback or to measure external loads and can tolerate considerable structure parameter errors. The global uniform asymptotic stability of the time-varying closed-loop system is analyzed, and a selection approach for control parameters is presented. It is demonstrated that, by using the proposed control parameter selection approach, the closed-loop system under the adaptive controller is equivalent to an existing result. The feasibility of the presented controller for the general manipulators is demonstrated by some numerical simulations.

The enrichment of Fusobacterium nucleatum (Fn) has been identified in CRC patients and associated with worse outcomes. However, whether Fn was involved in the metastasis of CRC was not well determined. Here, we found that the abundance of Fn was significantly increased in CRC patients with lymph nodes metastasis. To further clarify the role of Fn in CRC metastasis, we performed transwell and wound healing assays after incubating CRC cell lines with or without Fn and injected Fn-treated or untreated CRC cells into nude mice via tail vein. The results indicated that Fn infection promoted CRC cells migration in vitro, as well as lung metastasis in vivo. Interestingly, colonization of Fn was detected in metastatic lung lesions of nude mice by fluorescence in situ hybridization. Mechanistically, RNA sequencing and validation study revealed that Fn significantly upregulated the expression of long non-coding RNA Keratin7-antisense (KRT7-AS) and Keratin7 (KRT7) in CRC cells. Importantly, Fn-induced CRC lung metastasis was attenuated by the depletion of KRT7-AS. In addition, KRT7-AS facilitated CRC cells migration by upregulating KRT7. Subsequently, we found that NF-κB signaling pathway was involved in the upregulation of KRT7-AS upon Fn infection. In conclusion, Fn infection upregulated KRT7-AS/KRT7 by activating NF-κB pathway, which promoted CRC cell migration in vitro and metastasis in vivo.

Abstract Background The purpose of this study was to assess the efficacy and safety of cisplatin-based chemotherapy with or without bevacizumab (BEV) in Chinese women with advanced cervical cancer (ACC). Methods For this observational study, we analysed the data of 316 Chinese women with ACC who were treated at the Henan provincial people’s hospital between Jan 1, 2014, and Dec 31, 2018, with cisplatin-based chemotherapy plus BEV (CB) or cisplatin-based chemotherapy alone (CA) until disease progression, unacceptable toxicity, or death. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS); the secondary endpoint was the occurrence of adverse events (AEs). Results A total of 264 patients with ACC were included in the assessment (CB, n = 130 and CA, n = 134). At a median follow-up of 38 months (IQR 36–40), the median OS in the CB cohort was significantly longer than that in the CA cohort (hazard ratio [HR] 1.21, 95% confidence interval[CI] 1.14–1.73; p = 0.002); additionally, the median PFS was 345 days (95% CI, 318–372) for CB and 261 days (95% CI, 165–357) for CA(HR 1.61, 95% CI 1.12–2.17; p = 0.000). Significant differences were noted between groups in terms of thrombosis/embolism, neutropenia, and febrile neutropenia. Conclusions In Chinese women with ACC, cisplatin-based chemotherapy plus BEV is associated with improved survival compared to cisplatin-based chemotherapy alone. This finding suggests a positive survival benefit of anti-angiogenesis therapy in this population.

Forest ecosystems are crucial to the survival and development of human societies. Urbanization is expected to impact forest landscape patterns and consequently the supply of forest ecosystem services. However, the specific ways by which such impacts manifest are unclear. Therefore, to discuss the relationship between them is of great significance for realizing regional sustainable development. Here, we quantitatively assess the intensity of forest ecosystem service functions and forest landscape patterns in Renqiu City of China's Hebei Province in 2019 using ArcGIS and FRAGSTATS. We characterize the relationships between forest ecosystem service capacity and landscape patterns, and identify strategies for the spatial optimization of forests. We find that the ecosystem service intensity of forests are significantly correlated with their spatial distribution, forest area ratio, and landscape patterns. Specifically, the percentage of landscape (PLAND) index, landscape shape index (LSI), and contagion (CONTAG) index indices display second-order polynomial relationships with various forest ecosystem service functions, with critical values of 80, 5, and 70, respectively. We propose that forest ecosystem functions can be optimized by optimizing forest landscape patterns. Specifically, to maximize the function of forest ecosystem services, managers should consider the integrity of forest ecosystems, optimize their ability to self-succession, repair service functions of key nodes within forests, enhance forests' structural stability, optimize forest quality and community structure, and strengthen the efficiency of functional transformation per unit area. Finally, we propose a strategy for the spatial optimization of forests in Renqiu to optimize their associated ecosystem services. This involves protecting important areas for forest ecosystems, rationally organizing different ecological patches such as forests and water bodies to maximize their functions, strengthening the connectivity of scattered forests, and supplementing woodland areas.

The Qinghai–Tibet Plateau is the main production area of Hippophae rhamnoides ssp. sinensis (Rha) and H. tibetana (Tib), but studies on the types and contents of soluble sugars, organic acids, free phenolics, bound phenolics, vitamin C (VC), tocopherol (VE) and carotenoids of the two sea buckthorn berries from this region have not been reported. In this paper, we found that the soluble sugars in Rha and Tib were mainly glucose and fructose; Rha exhibited a higher content of total sugar and fructose compared to Tib. The organic acids were mainly quinic acid and malic acid; Rha exhibited a higher content of total acids and quinic acid, but lower tartaric acid and citric acid compared to Tib. Rha also possessed a higher total (free and bound) phenolic as well as total (free and bound) flavonoid content than those in Tib; twelve phenolic compounds were analyzed, among which flavonols were dominant. Catechin, isorhamnetin and quercetin were the main phenolic substances. VC and VE (γ-tocopherol (γ-VE) and δ-tocopherol (δ-VE)) were higher in Rha than Tib. The total carotenoid, lutein, β-carotene and lycopene content of Tib was remarkably higher than that in Rha. Moreover, both Rha and Tib showed good in vitro and cellular antioxidant activities, and Rha had a stronger antioxidant activity. Taken together, Rha had a higher antioxidant activity, which may be due to its higher content of phenolics, flavonoids, VC and VE.

Senescent microenvironments play an important role in tumor progression. Here, we report that doxorubicin (DOX)‐pretreated or replicative senescent stromal cells (WI‐38 and HUVEC) promote colorectal cancer (CRC) cell growth and invasion in vitro and in vivo. These pro‐tumorigenic effects were attenuated by exogenous administration of Klotho, an anti‐aging factor. We subsequently identified several senescence‐associated secretory phenotype (SASP)‐associated genes, including CCL2, which were significantly upregulated in both types of senescent stromal cells during replication and DNA damage‐induced senescence. Importantly, we found that the secretion of CCL2 by senescent stromal cells was significantly higher than that seen in nonsenescent cells or in senescent cells pretreated with Klotho. Notably, CCL2 was found to accelerate CRC cell proliferation and invasion, while this effect could be blocked by administration of a specific CCR2 antagonist. We further show that Klotho can suppress NF‐κB activation during DOX‐induced senescence and thus block CCL2 transcription. Low expression of Klotho, or high expression of CCL2 in patient tumor tissues, correlated with poor overall survival of CRC patients. Collectively, our findings suggest that senescent stromal cells are linked to progression of CRC. Klotho can suppress the senescent stromal cell‐associated triggering of CRC progression by inhibiting the expression of SASP factors including CCL2. The identification of key SASP factors such as CCL2 may provide potential therapeutic targets for improving CRC therapy.

Background: Risk management strategies play a significant role in genetic counseling, which involves lifestyle modification with respect to nutrition and unhealthy living habits, enhanced screening imaging, endocrine therapy, and following the physician’s advice etc. This study aimed to describe the health-promoting lifestyle of breast cancer patients and their family members in a Chinese genetic counseling clinic, and to explore its various levels encompassing different socio-economic variables. Methods: This was a cross-sectional study. The participants in this study originated from a genetic counseling clinic of a cancer center in Shanghai, China. Two hundred and fifty nine patients conforming to the inclusion and exclusion criteria were screened from November 2019 to March 2022. Participants agreeing to participate were sent a questionnaire web-link with an invitation to finish this survey. Two questionnaires were included in the link, one referring to socio-economic information and the other referring to the health-promoting lifestyle. Chinese Health-promoting lifestyle profile-Ⅱ (HPLP-Ⅱ) was used to evaluate the health-promoting lifestyle. Results: One hundred and forty participants were finally included in this study. The mean scores for health-promoting lifestyle was 141.22 ± 19.77, and multiple liner regression revealed monthly family income to be a statistically significant predictor of health-promoting lifestyle (p < 0.05). In the six subscales, health responsibility got the highest score (26.43 ± 4.40), and nutrition received the lowest score (17.81 ± 4.73). Self-actualization was 25.84 ± 4.19, physical activity 24.02 ± 4.97, interpersonal relationship 22.21 ± 4.42, and stress management 24.91 ± 4.39. Conclusions: A representative level of health-promoting lifestyle of breast cancer patients and family members in a Chinese genetic counseling clinic were acquired. More education and intervention should be tailored to enhance and encourage health-promoting lifestyle behaviors in participants with low monthly family income. Additionally, developing nutritional curriculum and strengthening the publicity of nutritional popular science are priorities for future improvement measures.

Caenorhabditis elegans (C. elegans) exhibits sophisticated chemotaxis behavior with a unique locomotion pattern using a simple nervous system only and is, therefore, well suited to inspire simple, cost-effective robotic navigation schemes. Chemotaxis in C. elegans involves two complementary strategies: klinokinesis, which allows reorientation by sharp turns when moving away from targets; and klinotaxis, which gradually adjusts the direction of motion toward the preferred side throughout the movement. In this study, we developed an autonomous search model with undulatory locomotion that combines these two C. elegans chemotaxis strategies with its body undulatory locomotion. To search for peaks in environmental variables such as chemical concentrations and radiation in directions close to the steepest gradients, only one sensor is needed. To develop our model, we first evolved a central pattern generator and designed a minimal network unit with proprioceptive feedback to encode and propagate rhythmic signals; hence, we realized realistic undulatory locomotion. We then constructed adaptive sensory neuron models following real electrophysiological characteristics and incorporated a state-dependent gating mechanism, enabling the model to execute the two orientation strategies simultaneously according to information from a single sensor. Simulation results verified the effectiveness, superiority, and realness of the model. Our simply structured model exploits multiple biological mechanisms to search for the shortest-path concentration peak over a wide range of gradients and can serve as a theoretical prototype for worm-like navigation robots.

Polystyrene (PS) is a widely used petroleum-based plastic, that pollutes the environment because it is difficult to degrade. In this study, a PS degrading bacterium identified as Massilia sp. FS1903 was successfully isolated from the gut of Galleria mellonella (Lepidoptera: Pyralidae) larvae that were fed with PS foam. Scanning electron microscopy and X-ray energy dispersive spectrometry showed that the structure and morphology of the PS film was destroyed by FS 1903, and that more oxygen appeared on the degraded PS film. A water contact angle assay verified the chemical change of the PS film from initially hydrophobic to hydrophilic after degradation. X-ray photoelectron spectroscopy further demonstrated that more oxygen-containing functional groups were generated during PS degradation. After 30 days of bacterial stain incubation with 0.15 g PS, 80 ml MSM, 30°C and PS of Mn 64400 and Mw 144400 Da, the weight of the PS film significantly decreased, with 12.97 ± 1.05% weight loss. This amount of degradation exceeds or is comparable to that previously reported for other species of bacteria reported to degrade PS. These results show that Massilia sp. FS1903 can potentially be used to degrade PS waste.

Sucrose non-fermenting 1 (SNF1)-related protein kinase (SnRK) is a large family of protein kinases that play a significant role in plant stress responses. Although intensive studies have been conducted on SnRK members in some crops, little is known about the SnRK in barley. Using phylogenetic and conserved motif analyses, we discovered 46 SnRK members scattered across barley’s 7 chromosomes and classified them into 3 sub-families. The gene structures of HvSnRKs showed the divergence among three subfamilies. Gene duplication and synteny analyses on the genomes of barley and rice revealed the evolutionary features of HvSnRKs. The promoter regions of HvSnRK family genes contained many ABRE, MBS and LTR elements responding to abiotic stresses, and their expression patterns varied with different plant tissues and abiotic stresses. HvSnRKs could interact with the components of ABA signaling pathway to respond to abiotic stress. Moreover, the haplotypes of HvSnRK2.5 closely associated with drought tolerance were detected in a barley core collection. The current results could be helpful for further exploration of the HvSnRK genes responding to abiotic stress tolerance in barley.

Convolutional neural networks (CNNs) have significantly promoted the development of speaker verification (SV) systems because of their powerful deep feature learning capability. In CNN-based SV systems, utterance-level aggregation is an important component, and it compresses the frame-level features generated by the CNN frontend into an utterance-level representation. However, most of the existing aggregation methods aggregate the extracted features across time and cannot capture the speaker-dependent information contained in the frequency domain. To handle this problem, this paper proposes a novel attention-based frequency aggregation method, which focuses on the key frequency bands that provide more information for utterance-level representation. Meanwhile, two more effective temporal-frequency aggregation methods are proposed in combination with the existing temporal aggregation methods. The two proposed methods can capture the speaker-dependent information contained in both the time domain and frequency domain of frame-level features, thus improving the discriminability of speaker embedding. Besides, a powerful CNN-based SV system is developed and evaluated on the TIMIT and Voxceleb datasets. The experimental results indicate that the CNN-based SV system using the temporal-frequency aggregation method achieves a superior equal error rate of 5.96% on Voxceleb compared with the state-of-the-art baseline models.

Background: Helicobacter pylori (H. pylori) infection is associated with remodeling of gastric microbiota. However, comprehensive analyses of the impact of H. pylori infection, eradication therapy and probiotic supplementation on gut microbiota are still lacking. We aimed to provide evidence for clinical decision making. Methods: Seventy H. pylori-positive and 35 H. pylori-negative patients (group C) were enrolled. H. pylori-positive patients were randomly assigned to group A (14-day bismuth-containing quadruple therapy) and group B (quadruple therapy supplemented with Clostridium butyricum). Stool samples of group A and B were collected on day 0, 14 and 56 while stool samples of group C were collected on day 0. Gut microbiota was investigated by 16S rRNA sequencing. Findings: The Sobs index (richness estimator) was significantly higher in H. pylori-positive samples than H. pylori-negative samples (p

Si2N2O matrix composites were fabricated by solid/gas reaction in air or N2 atmosphere. The effects of atmosphere on the phase and microstructure of the composites were investigated. The reaction mechanism of Si2N2O system was discussed by analysing the variation of the Gibbs free energy with temperature. The effect of N2 and air on sintering of Si2N2O matrix composites was discussed in relation to observed kinetics and thermodynamic calculations. The results showed that gradient structure of Si2N2O matrix composites were obtained in N2 atmosphere. While high N2 concentration was useful for the formation of the pure β-Si3N4 ceramics, low N2 concentration was proposed to form the pure Si2N2O ceramics. However, in the air atmosphere, structure of the Si3N4/SiO2 composites is homogeneous without the gradient structure appearing. Its composition is a little different as the O2 concentration changes.

In this paper, a time-optimal trajectory planning method based on quintic PythagoreanHodograph (PH) curves is proposed to realize the smooth and stable high-speed operation of the Delta parallel robot. The trajectory is determined by applying the quintic PH curves to the transition segments in the pick-and-place operation trajectory and the 3-4-5 polynomial motion law to the trajectory. The quintic PH curves are optimized to reduce the cycle time of the pick-and-place operation. In addition, a comparison between different trajectory planning methods has been implemented so as to observe the performance of the obtained results. The MATLAB simulation results reveal that compared with the trajectory planning based on vertical and horizontal motion superposition, the trajectory planning based on quintic PH curves is completed with a shorter motion cycle time and more stable motion performance, with the velocities, accelerations, and jerks in joint space bounded and continuous. Experiments carried out on the prototype also confirm that the trajectory planning based on quintic PH curves has a shorter cycle time, which is of great importance to high-speed operations of Delta parallel robots.

Plastic waste pollution and its difficult degradation process have aroused widespread concern. Research has demonstrated that the larvae of Tenebrio molitor (yellow mealworm), Galleria mellonella (greater wax moth), and Zophobas atratus (superworm) possess a biodegradation ability for polystyrene (PS) within the gut microbiota of these organisms. In this study, the difference in PS degradation and the changes of the gut microbiota were compared before and after feeding PS. The results showed that superworm had the strongest PS consumption capacity and the highest survival rate during the 30 d experiment period. They all could degrade PS to different degrees. Superworm showed the highest ability to degrade PS into low-molecular-weight substances, while yellow mealworm depolymerized PS strongly by destroying the benzene ring. The changes of the intestinal microbiome caused by feeding PS showed that after ingesting PS, there was a decrease in community diversity in superworm and yellow mealworm, but an increase in greater wax moth. Meanwhile, Enterococcus and Enterobacteriaceae, found in all three species’ larvae upon 20 d of PS feeding, might play an important role in PS degradation. The results will provide more accurate PS degradation comparative data of the three species’ larvae and theoretical guidance for further research on the efficient PS biodegradations.

Genipin was used as a crosslinking agent to prepare magnetic genipin-crosslinked chitosan beads, which were then used as a carrier for immobilizing recombinant cutinase from Fusarium solani (FSC) to obtain immobilized FSC. The optimal temperature for the immobilized FSC was 55 °C, which was 5 °C higher than that of the free enzyme, whereas its optimal pH was increased from 8.0 to 9.0; this indicates that the immobilized FSC had improved pH and thermal stability. After repeated use for 10 cycles, the activity of the immobilized FSC remained at more than 50%; after being stored at 4 °C for 30 days, its activity was still approximately 88%. We also found that the Km of the immobilized FSC was higher than that of the free enzyme. These results indicate that the performance of FSC was improved after immobilization, which is an important basis for the subsequent application of FSC in industrial production.

This article presents a strategy for efficient sorting path planning and trajectory optimization with multiple constraints. The proposed strategy is applicable to typical high-density sorting applications. It plans the sorting path while optimizing each trajectory. The total stroke traveled by the end effector to complete the sorting task is shortened, and the efficiency of the production line is correspondingly facilitated. Thus, this article designs bow-shaped trajectories by analyzing the work process of the production line to ensure the smooth transition of the end effector and bow-shaped trajectories are based on the starting point and the end point of each sorting action. The modified trapezoidal acceleration and deceleration algorithm is used to optimize each sorting trajectory, which ensures that each sorting action is executed quickly and stably. Simultaneously, the greedy strategy is applied to plan the sorting task, which further shortens the total stroke of the end effector and improves the efficiency of the production line. A specific cost function is also designed to improve the planning strategy to prevent the occurrence of missing materials and enhance the adaptability of the sorting system. In consideration of the efficiency of the sorting system is significantly improved by this approach, the effectiveness of the proposed strategy in this article is thus verified compared with existing ones by experiments. In addition, the impact of the conveyor speed on the sorting system is also discussed.

Alterations in gut microbiota are postulated to be an etiologic factor in the pathogenesis of irritable bowel syndrome (IBS). To determine whether IBS patients in China exhibited differences in their gut microbial composition, fecal samples were collected from diarrhea-predominant IBS (IBS-D) and healthy controls and evaluated by 16S ribosomal RNA gene sequence and quantitative real-time PCR. A mouse model of postinfectious IBS (PI-IBS) was established to determine whether the altered gut microbiota was associated with increased visceral hypersensitivity. The results indicated that there were significant differences in the bacterial community profiles between IBS-D patients and healthy controls. Prevotella was more abundant in fecal samples from IBS-D patients compared with healthy controls (p

Locomotion systems with variant constraints are familiar in real world applications, but the dynamics and control issues of variant constraint systems have not been sufficiently discussed to date. From the viewpoint of Lagrange−d’Alembert equations with additional variable constraints, this paper investigates the modeling approaches of a class of hybrid dynamical systems (HDS) with instantaneously variant constraints and the switching control techniques of stabilizing the HDS to given periodic orbits. It is shown that under certain conditions there possibly exist zero impact periodic orbits in the HDS, and the HDS can be stabilized to the period-one orbits by a linear controller with only partial state feedback, even though the HDS are generally underactuated nonholonomic systems. As an example, a one-legged planar hopping robot is employed to demonstrate the main results of modeling and control of a class of HDS.

A new trajectory planning approach on the basis of the quintic Pythagorean−Hodograph (PH) curve is presented and applied to Delta robot for implementing pick-and-place operation (PPO). To satisfy a prescribed geometrical constraint, which indicates the distance between the transition segment curve and right angle of PPO trajectory is no greater than a prescribed value, the quintic PH curve is used to produce a connection segment path for collision avoidance. The relationship between the PH curve and constraint is analyzed, based on which PH curve is calculated simply. Afterwards, the trajectory is planned in different phases with different motion laws, i.e. polynomial motion laws and PH curve parameter-dependent motion laws, to obtain a smooth performance both in Cartesian and joint space. The relationship between the PH curve and constraint is also used to improve the efficiency of calculation, and the trajectory symmetry is used to reduce calculation time by direct symmetric transformation. Thus, real-time performance is improved. The results of simulations and experiments indicate that the approach in this paper can provide smooth motion and meet the real-time requirement under the prescribed geometrical constraint.

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.

Poly(ethylene succinate) (PES), poly(butylene succinate) (PBS), and poly(hexylene succinate) (PHS), were synthesized using succinic acid and different dihydric alcohols as materials. Enzymatic degradability by cutinase of the three kinds of polyesters was studied, as well as their solid-state properties. The biodegradation behavior relied heavily on the distance between ester groups, crystallinity, and the hydrophilicity-hydrophobicity balance of polyester surfaces. The weight loss through degradation of the three kinds of polyesters with different hydroxyl monomers took place in the order PHS > PBS > PES. The degradation behavior of the polyesters before and after degradation was analyzed by scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, gel permeation chromatography, and thermogravimetric analysis. The decrease in relative intensity at 1800–1650 estedpolyesters were degraded simultaneously. The frequencies of the crystalline and amorphous bands were almost identical before and after degradation. Thus, enzymatic degradation did not change the crystalline structure but destroyed it, and the degree of crystallinity markedly decreased. The molecular weight and polydispersity index only changed slightly. The thermal stability of the three kinds of polyesters decreased during enzymatic degradation.

The issue of synchronization for a class of hybrid coupled complex networks with mixed delays (discrete delays and distributed delays) and unknown nonstochastic external perturbations is studied. The perturbations do not disappear even after all the dynamical nodes have reached synchronization. To overcome the bad effects of such perturbations, a simple but all-powerful robust adaptive controller is designed to synchronize the complex networks even without knowing a priori the functions and bounds of the perturbations. Based on Lyapunov stability theory, integral inequality Barbalat lemma, and Schur Complement lemma, rigorous proofs are given for synchronization of the complex networks. Numerical simulations verify the effectiveness of the new robust adaptive controller.