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Abstract Cholesterol metabolism reprogramming is one of the significant characteristics of hepatocellular carcinoma (HCC). Cholesterol increases the risk of epithelial–mesenchymal transition (EMT) in cancer. Sterol O-acyltransferases 1 (SOAT1) maintains the cholesterol homeostasis. However, the exact mechanistic contribution of SOAT1 to EMT in HCC remains unclear. Here we demonstrated that SOAT1 positively related to poor prognosis of HCC, EMT markers and promoted cell migration and invasion in vitro, which was mediated by the increased cholesterol in plasmalemma and cholesterol esters accumulation. Furthermore, we reported that SOAT1 disrupted cholesterol metabolism homeostasis to accelerate tumorigenesis and development in HCC xenograft and NAFLD-HCC. Also, we detected that nootkatone, a sesquiterpene ketone, inhibited EMT by targeting SOAT1 in vitro and in vivo. Collectively, our finding indicated that SOAT1 promotes EMT and contributes to hepatocarcinogenesis by increasing cholesterol esterification, which is suppressed efficiently by nootkatone. This study demonstrated that SOAT1 is a potential biomarker and therapeutic target in NAFLD-HCC and SOAT1-targeting inhibitors are expected to be the potential new therapeutic treatment for HCC.

The Chinese hamster ovarian (CHO) cells serve as a common choice in biopharmaceutical production, traditionally cultivated in stirred tank bioreactors (STRs). Nevertheless, the pursuit of improved protein quality and production output for commercial purposes demand exploration into new bioreactor types. In this context, inverted frustoconical shaking bioreactors (IFSB) present unique physical properties distinct from STRs. This study aims to compare the production processes of an antibody-based biotherapeutic in both bioreactor types, to enhance production flexibility. The findings indicate that, when compared to STRs, IFSB demonstrates the capability to produce an antibody-based biotherapeutic with either comparable or enhanced bioprocess performance and product quality. IFSB reduces shear damage to cells, enhances viable cell density (VCD), and improves cell state at a 5-L scale. Consequently, this leads to increased protein expression (3.70 g/L vs 2.56 g/L) and improved protein quality, as evidenced by a reduction in acidic variants from 27.0% to 21.5%. Scaling up the culture utilizing the Froude constant and superficial gas velocity ensures stable operation, effective mixing, and gas transfer. The IFSB maintains a high VCD and cell viability at both 50-L and 500-L scales. Product expression levels range from 3.0 to 3.6 g/L, accompanied by an improved acidic variants attribute of 20.6%–22.7%. The IFSB exhibits superior productivity and product quality, underscoring its potential for incorporation into the manufacturing process for antibody-based biotherapeutics. These results establish the foundation for IFSB to become a viable option in producing antibody-based biotherapeutics for clinical and manufacturing applications.

Background: This study aimed to examine the differential variations in the metabolic composition of follicular fluid (FF) among normal-weight patients with polycystic ovary syndrome (PCOS) and controls and to identify potential biomarkers that may offer insights into the early identification and management of these patients. Methods: We collected FF samples from 45 normal-weight women with PCOS and 36 normal-weight controls without PCOS who were undergoing in vitro fertilization–embryo transfer. An untargeted metabolomic study of collected FF from infertile women was performed using high-performance liquid chromatography–tandem spectrometry (LC-MS). The tendency of the two groups to separate was demonstrated through multivariate analysis. Univariate analysis and variable importance in projection were used to screen out differential metabolites. Metabolic pathway analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG), and a diagnostic model was established using the random forest algorithm. Results: The metabolomics analysis revealed an increase in the expression of 23 metabolites and a decrease in that of 10 metabolites in the FF of normal-weight women with PCOS. According to the KEGG pathway analysis, these differential metabolites primarily participated in the metabolism of glycerophospholipids and the biosynthesis of steroid hormones. Based on the biomarker combination of the top 10 metabolites, the area under the curve value was 0.805. The concentrations of prostaglandin E2 in the FF of individuals with PCOS exhibited an inverse association with the proportion of high-quality embryos (p < 0.05). Conclusions: Our research identified a distinct metabolic profile of the FF from normal-weight women with PCOS. The results offer a broader comprehension of the pathogenesis and advancement of PCOS, and the detected differential metabolites could be potential biomarkers and targets for the treatment of PCOS.

BackgroundThe kangaroo-mother care method (KMC) is a skin-to-skin contact-centered care approach with numerous benefits for neonates, but its impact on the treatment of jaundiced neonates is unknown. This study aimed to investigate the efficacy of KMC combined with neonatal phototherapy (NNPT) in treating neonates with non-pathological jaundice.MethodsRelevant articles were searched in PubMed, Embase, Web of Science, and Cochrane Library databases from database establishment to April 2022. The outcomes included, without limitation, serum bilirubin levels, and duration of phototherapy.ResultsThis meta-analysis included five studies (4 randomized controlled trials and 1 observational study) involving four hundred eighty-two neonates with non-pathological jaundice. The results showed that the group receiving KMC combined with NNPT had lower serum bilirubin at 72 h after intervention [weighted mean difference (WMD) = −1.51, p = 0.03], shorter duration of phototherapy [standard mean difference (SMD) = −1.45, p

IntroductionUlcerative colitis (UC), a chronic non-specific colorectal inflammatory disease with unclear etiology, has long plagued human health. Gut microbiota dysbiosis destroy homeostasis of the colon, which is closely related to ulcerative colitis progress. Apigenin, a flavonoid widely present in celery, has been found to improve ulcerative colitis. However, the potential molecular mechanism of apigenin ameliorating ulcerative colitis through protecting intestinal barrier and regulating gut microbiota remains undefined.MethodsDextran sodium sulfate (DSS)-induced colitis mouse model was conducted to evaluate the effect of apigenin on UC. Disease activity index score of mice, colon tissue pathological, cytokines analysis, intestinal tight junction proteins expression, and colonic content short-chain fatty acids (SCFAs) and 16S rRNA gene sequencing were conducted to reflect the protection of apigenin on UC.ResultsThe results indicated that apigenin significantly relieved the intestinal pathological injury, increased goblet cells quantity and mucin secretion, promoted anti-inflammatory cytokines IL-10 expression, and inhibited the expression of proinflammatory cytokines, TNF-α, IL-1β, IL-6 and MPO activity of colon tissue. Apigenin increased ZO-1, claudin-1 and occludin expressions to restore the integrity of the intestinal barrier. Moreover, apigenin remodeled the disordered gut microbiota by regulating the abundance of Akkermansia, Turicibacter, Klebsiella, Romboutsia, etc., and its metabolites (SCFAs), attenuating DSS-induced colon injury. We also investigated the effect of apigenin supplementation on potential metabolic pathways of gut microbiota.ConclusionApigenin effectively ameliorated DSS-induced UC via balancing gut microbiome to inhibit inflammation and protect gut barrier. With low toxicity and high efficiency, apigenin might serve as a potential therapeutic strategy for the treatment of UC via regulating the interaction and mechanism between host and microorganism.

Abstract Background The effect of dairy products intake on breast cancer (BC) is highly controversial. This study aims to investigate the relationship between dairy intake and BC incidence. Methods A search was carried out in PubMed, EBSCO, Web of Science, and Cochrane Library databases before January 2021. The primary objective was the risk of BC and intake of dairy products were exposure variables. Results The meta-analysis comprised 36 articles with 1,019,232 participants. Total dairy products have a protective effect on female population (hazard ratio (HR) =0.95, 95% confidence interval (CI) =0.91–0.99, p = 0.019), especially for estrogen receptor-positive (ER+) (HR = 0.79, p = 0.002) and progesterone receptor-positive (PR+) BC (HR = 0.75, p = 0.027). For ER+/PR+ BC, there is a trend of protection, but it has not reached statistical significance (HR = 0.92, p = 0.075). Fermented dairy products can reduce BC risk in postmenopausal population (HR = 0.96, 95%CI = 0.93–0.99, p = 0.021), but have no protective effect on premenopausal population (HR = 0.98, 95%CI = 0.94–1.03, p = 0.52). Non-fermented dairy products have no significant effect on BC occurrence (p > 0.05). High-fat dairy products are harmful to women, without statistical difference (HR = 1.06, 95%CI = 1.00–1.13, p = 0.066). On the contrary, low-fat dairy products can protect the premenopausal population (HR = 0.94, 95%CI = 0.89–1.00, p = 0.048). Conclusion The intake of dairy products can overall reduce BC risk in the female population, but different dairy products have varying effects on different BC subtypes and menopausal status.

Background: This study aimed to investigate the clinical efficacy of programmed death-1 receptor and ligand-1 (PD-1/PD-L1) inhibitors in gastroesophageal cancer patients and the relationship between their clinicopathological features and curative treatment effects.Methods: A systematic search was conducted for articles published before April 2022 from online databases (PubMed, EMBASE, Web of Science and the Cochrane Library). The main outcome was overall survival (OS).Results: This meta-analysis comprised 16 studies involving 9,304 participants. The results indicated that compared with chemotherapy, patients treated with PD-1/PD-L1 inhibitors had significantly improved OS (HR = 0.80; p < 0.001) but no significant improvement in progression-free survival (PFS) (p = 0.185). Subgroup analyses demonstrated that PD-1/PD-L1 inhibitors combined with chemotherapy, esophageal squamous cell carcinoma, male, Asian patients and combined positive score (CPS) ≥1 were significantly associated with better survival outcomes. Further, subgroup analysis of gender revealed that the OS of all subgroups containing male patients was significantly improved compared with chemotherapy, unlike that of female patients. In addition, the line of therapy, Lauren classification, age and eastern cooperative oncology group (ECOG) performance status were not associated with PD-1/PD-L1 inhibitors efficacy.Conclusion: The results indicated that PD-1/PD-L1 inhibitors could prolong the OS of advanced gastroesophageal cancer patients. Clinicopathological features such as therapeutic schedules, tumor types, histological type, gender, geographical region and PD-L1 expression status (CPS) seemed to be associated with survival outcomes.

This paper argues that as poetics in the Song Dynasty developed, the thinking mode and methods of written expression in Chan Buddhism provided a theoretical reference and creative practical experience for the formation of poetic theories. This point is particularly evident in the formation of the “flexible method”, which was a key theory in poetics of the Song Dynasty. The theory comprises three layers of meaning: it advocates respecting forms, changing the meaning of those forms, and retaining the inherent grace of the forms through a natural and fluent syntax and rhetoric of “defamiliarization”. This theory was highly mature in the writing of Lv Benzhong of the Southern Song Dynasty. Xuedou Chongxian (980–1052), a sixth-generation Chan Buddhist at Xuedou Temple, made a vital contribution to its development, which is highlighted by studying the “Hundred Classic Eulogies”. Xuedou Chongxian initially constructed the connotation and system of the theory of the “flexible method” in both theoretical and practical aspects. His theory of poetics is rooted in the ways of thinking and cultivating of the Yunmen sect. He incorporated his dual identity as a senior monk of the Yunmen School and a poet. He inherited Guanxiu’s view of poetry and the Chan concept of Shitou Xiqian and Zhimen Guangzuo, which greatly impacted the literati of the Northern Song Dynasty and provided a conceptual basis for maturing and improving the “flexible method” theory. Therefore, Xuedou Chongxian’s value in the theoretical construction of the “flexible method” should not be ignored.

Abstract Despite the central role of hemocytes in crustacean immunity, the process of hemocyte differentiation and maturation remains unclear. In some decapods, it has been proposed that the two main types of hemocytes, granular cells (GCs) and semigranular cells (SGCs), differentiate along separate lineages. However, our current findings challenge this model. By tracking newly produced hemocytes and transplanted cells, we demonstrate that almost all the circulating hemocytes of crayfish belong to the GC lineage. SGCs and GCs may represent hemocytes of different developmental stages rather than two types of fully differentiated cells. Hemocyte precursors produced by progenitor cells differentiate in the hematopoietic tissue (HPT) for 3 ~ 4 days. Immature hemocytes are released from HPT in the form of SGCs and take 1 ~ 3 months to mature in the circulation. GCs represent the terminal stage of development. They can survive for as long as 2 months. The changes in the expression pattern of marker genes during GC differentiation support our conclusions. Further analysis of hemocyte phagocytosis indicates the existence of functionally different subpopulations. These findings may reshape our understanding of crustacean hematopoiesis and may lead to reconsideration of the roles and relationship of circulating hemocytes.

BackgroundThere have been several controversies about the correlation between vitamin D and depression. This study aimed to investigate the relationship between vitamin D supplementation and the incidence and prognosis of depression and to analyze the latent effects of subgroups including population and supplement strategy.MethodsA systematic search for articles before July 2021 in databases (PubMed, EMBASE, Web of Science, and the Cochrane Library) was conducted to investigate the effect of vitamin D supplementation on the incidence and prognosis of depression.ResultsThis meta-analysis included 29 studies with 4,504 participants, indicating that the use of vitamin D was beneficial to a decline in the incidence of depression (SMD: −0.23) and improvement of depression treatment (SMD: −0.92). Subgroup analysis revealed that people with low vitamin D levels (2,800 IU and intervention duration of ≥8 weeks were considered significant in both prevention and treatment analyses. Intervention duration ≤8 weeks was recognized as effective in the treatment group.ConclusionOur results demonstrate that vitamin D has a beneficial impact on both the incidence and the prognosis of depression. Whether suffering from depression or not, individuals with low vitamin D levels, dose >2,800 IU, intervention duration ≥8 weeks, and all females are most likely to benefit from vitamin D supplementation.

Mass spectrometry (MS)-based lipidomic has become a powerful tool for studying lipids in biological systems. However, lipidome analysis at the single-cell level remains a challenge. Here, we report a highly sensitive lipidomic workflow based on nanoflow liquid chromatography and trapped ion mobility spectrometry (TIMS)-MS. This approach enables the high-coverage identification of lipidome landscape at the single-oocyte level. By using the proposed method, comprehensive lipid changes in porcine oocytes during their maturation were revealed. The results provide valuable insights into the structural changes of lipid molecules during porcine oocyte maturation, highlighting the significance of sphingolipids and glycerophospholipids. This study offers a new approach to the single-cell lipidomic.

This study aimed to investigate the effect of sea cucumber hydrolysate (SCH) on immunosuppressed mice induced by cyclophosphamide (Cy). Our findings demonstrated that SCH could increase the thymus index and spleen index, decrease the serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, increase the serum IgG and small intestinal sIgA levels, reduce small intestinal and colon tissue damage, and activate the nuclear factor-κB (NF-κB) pathway by increasing TRAF6 and IRAK1 protein levels, as well as the phosphorylation levels of IκBα and p65, thereby enhancing immunity. In addition, SCH alleviated the imbalance of the gut microbiota by altering the composition of the gut microbiota in immunosuppressed mice. At the genus level, when compared with the model group, the relative abundance of Dubosiella, Lachnospiraceae, and Ligilactobacillus increased, while that of Lactobacillus, Bacteroides, and Turicibacter decreased in the SCH groups. Moreover, 26 potential bioactive peptides were identified by oligopeptide sequencing and bioactivity prediction. This study’s findings thus provide an experimental basis for further development of SCH as a nutritional supplement to alleviate immunosuppression induced by Cy as well as provides a new idea for alleviating intestinal damage induced by Cy.

Antitumor immunity is an essential component of cancer therapy and is primarily mediated by the innate immune response, which plays a critical role in initiating and shaping the adaptive immune response. Emerging evidence has identified innate immune checkpoints and pattern recognition receptors, such as CD47 and Toll-like receptor 7 (TLR7), as promising therapeutic targets for cancer treatment. Based on the fusion protein Fc-CV1, which comprises a high-affinity SIRPα variant (CV1), and the Fc fragment of the human IgG1 antibody, we exploited a preparation which coupled Fc-CV1 to imiquimod (TLR7 agonist)-loaded liposomes (CILPs) to actively target CT26. WT syngeneic colon tumor models. In vitro studies revealed that CILPs exhibited superior sustained release properties and cell uptake efficiency compared to free imiquimod. In vivo assays proved that CILPs exhibited more efficient accumulation in tumors, and a more significant tumor suppression effect than the control groups. This immunotherapy preparation possessed the advantages of low doses and low toxicity. These results demonstrated that a combination of immune checkpoint blockade (ICB) therapy and innate immunity agonists, such as the Fc-CV1 and imiquimod-loaded liposome preparation utilized in this study, could represent a highly effective strategy for tumor therapy.

BackgroundThe popularity of applying intermittent fasting (IF) has increased as more and more people are trying to avoid or alleviate obesity and metabolic disease. This study aimed to systematically explore the effects of various IF in humans.MethodsThe randomized controlled trials (RCTs) related to IF vs. non-intervention diet or caloric restriction (CR) were retrieved in PubMed, Web of Science, Cochrane Library database, and Embase. Extraction outcomes included, but were not limited to, weight, body mass index (BMI), waist circumference (WC), fasting glucose, and triglyceride (TG).ResultsThis study includes 43 RCTs with 2,483 participants. The intervention time was at least 1 month, and the median intervention time was 3 months. Contrasting results between IF and non-intervention diet showed that participants had lower weight (weighted mean difference (WMD) = 1.10, 95% CI: 0.09–2.12, p = 0.03) and BMI after IF (WMD = 0.38, 95% CI: 0.08–0.68, p = 0.01). The WC of participants after IF decreased significantly compared with the non-intervention diet (WMD = 1.02, 95% CI: 0.06–1.99, p = 0.04). IF regulated fat mass (FM) more effectively than non-intervention diet (WMD = 0.74, 95% CI: 0.17–1.31, p = 0.01). The fat-free mass of people after IF was higher (WMD = −0.73, 95% CI: (−1.45)–(−0.02), p = 0.05). There was no difference in fasting blood glucose concentrations between participants in the after IF and non-intervention diet groups. The results of insulin concentrations and HOMA-IR, though, indicated that IF was significantly more beneficial than non-intervention diet (standard mean difference (SMD) = −0.21, 95% CI: 0.02–0.40, p = 0.03, and WMD = 0.35, 95% CI: 0.04–0.65, p = 0.03, respectively). Cholesterol and TG concentrations in participants after IF were also lower than that after a nonintervention diet (SMD = 0.22, 95% CI: 0.09–0.35, p = 0.001 and SMD = 0.13, 95% CI: 0.00–0.26, p = 0.05, respectively). IF outcomes did not differ from CR except for reduced WC.ConclusionIntermittent fasting was more beneficial in reducing body weight, WC, and FM without affecting lean mass compared to the non-intervention diet. IF also effectively improved insulin resistance and blood lipid conditions compared with non-intervention diets. However, IF showed less benefit over CR.

BackgroundThis meta-analysis was conducted to explore the association between sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and ocular diseases in type 2 diabetes mellitus (T2DM) patients.MethodsPubMed, Cochrane Central Registry of Controlled Trials, Web of Science and Springer were searched for articles on randomized controlled trials (RCTs) involving T2DM patients treated with SGLT-2i versus placebo or other hypoglycemic agents published prior to August 2021. The primary outcome of this meta-analysis was incidence of ocular diseases, which was assessed using risk ratios (RR) and 95% confidence intervals (CI). We reviewed 47 papers and compared the effect of SGLT-2i with the effect of the control groups (placebo and other hypoglycemic drugs) on the incidence of ocular diseases.ResultsCompared with controls, overall SGLT-2i use in T2DM patients was not associated with incidences of cataract, glaucoma, retinal disease and vitreous disease. Ertugliflozin (RR=0.47, P=0.01) reduced the risk for retinal disease, while empagliflozin (RR=0.44, P=0.05) reduced the risk for diabetic retinopathy (DR) compared with controls. SGLT-2i (RR=0.50, P=0.02), perhaps empagliflozin (RR=0.47, P=0.06), reduced the risk of retinal disease compared with active hypoglycemic agents. Canagliflozin (RR=4.50, P=0.03) increased the risk for vitreous disease compared with placebo.ConclusionsThere was no significant correlation between overall SGLT-2i and ocular diseases (cataract, glaucoma, retinal disease, vitreous disease, corneal disease, conjunctival disease, uveal disease, eye haemorrhage and vision problems) in T2DM patients. Ertugliflozin and empagliflozin may protect against ocular diseases, but canagliflozin may promote ocular diseases.

The characterization of complex patterns arising from electroencephalogram (EEG) is an important problem with significant applications in identifying different mental states. Based on the operational EEG of drivers, a method is proposed to characterize and distinguish different EEG patterns. The EEG measurements from seven professional taxi drivers were collected under different states. The phase characterization method was used to calculate the instantaneous phase from the EEG measurements. Then, the optimization of drivers’ EEG was realized through performing common spatial pattern analysis. The structures and scaling components of the brain networks from optimized EEG measurements are sensitive to the EEG patterns. The effectiveness of the method is demonstrated, and its applicability is articulated.

BackgroundThe purpose of this meta-analysis was to compare the safety and efficacy between hypofractionated and conventional fractionation radiotherapy in patients with early-stage breast cancer after breast-conserving surgery.MethodsWe conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library to identify relevant randomized controlled trials (RCTs) published before February 2021. At the same time, the hazard ratio (HR), risk ratio (RR), and 95% confidence interval (CI) were calculated to evaluate local recurrence (LR), relapse-free survival (RFS), overall survival (OS), adverse events, and cosmetic outcomes.ResultsA total of 14 articles were included in this meta-analysis. Four thousand eight hundred and sixty-nine patients were randomly assigned to the control group to receive conventional radiotherapy (CFRT); 6,072 patients were randomly assigned to the experimental group and treated with hypofractionated radiotherapy (HFRT). The results showed that there was no statistical difference between HFRT and CFRT in LR (HR = 0.99, 95%CI = 0.97–1.02, p = 0.476), RFS (HR = 0.99, 95%CI = 0.97–1.02, p = 0.485), OS (HR = 1.00, 95%CI = 0.97–1.03, p = 0.879), and cosmetic outcomes (RR = 1.03, 95%CI = 0.95–1.12, p = 0.53). In addition, HFRT showed fewer severe adverse reactions such as acute skin toxicity, induration, breast atrophy, and pain.ConclusionOur results suggest that there is no statistical difference between HFRT and CFRT in terms of LR, RFS, OS, and cosmetic outcomes. HFRT reduces the risk of developing toxicity reactions compared to CFRT. HFRT may be a better option for patients with early breast cancer after breast-conserving surgery.

Background and Aim: Although most chronic hepatitis B (CHB) patients achieve effective virological suppression after receiving long-term nucleos(t)ide analogs (Nucs) therapy, the safety of off-therapy is controversial under the monitor.Methods: We identified studies through searching PubMed, Embase, Cochrane Library, and Web of Science from January 1990 to February 2021. The eligible studies compare the long outcomes between discontinued and continued Nucs treatments groups among CHB patients. This study was conducted to investigate long-term outcomes, including biochemical, serological, and virological outcomes, as well as hepatocellular carcinoma (HCC) development rate between discontinued and maintained Nucs therapy groups among CHB patients.Results: Five eligible studies covering 1,425 patients were selected for meta-analysis. Our result exhibits that patients with Nucs off-treatment have a higher risk of alanine aminotransferase (ALT) flares-up than those who continued Nucs therapy under the monitor (OR = 9.39, 95%CI = 3.87–22.78). Nucs off-therapy patients have a higher virological bound incidence (OR = 617.96, 95%CI = 112.48–3,395.14) and a higher HBV DNA level (OR = 9.39, 95%CI = 3.87–22.78) than those who continued Nucs therapy. There was no statistically significant difference in the risk of hyperbilirubinaemia, hepatic decompensation, and HCC development between both two groups. Patients in Nucs off-therapy group demonstrate a higher HBsAg loss rate than those in the continued group (OR = 7.10, 95%CI = 6.68–13.69).Conclusions: Nucs off-therapy patients may exhibit a higher chance of achieving HBsAg loss than those who continue Nucs therapy. It requires close monitoring after Nucs off-therapy and timely restarting of Nucs therapy when ALT concentrations increase.

Driving fatigue refers to a phenomenon in which a driver’s physiological and psychological functions become unbalanced after a long period of continuous driving, and their driving skills decline objectively. The hidden dangers of driving fatigue to traffic safety should not be underestimated. In this work, we propose a judgment excitation mode (JEM), which adds secondary cognitive tasks to driving behavior through dual-channel human–computer interaction, so as to delay the occurrence of driving fatigue. We used multifractal detrended fluctuation analysis (MF-DFA) to study the dynamic properties of subjects’ EEG, and analyzed the effect of JEM on fatigue retardation by Hurst exponent value and multifractal spectrum width value. The results show that the multifractal properties of the two driving modes (normal driving mode and JEM) are significantly different. The JEM we propose can effectively delay the occurrence of driving fatigue, and has good prospects for future practical applications.

A home-auxiliary robot system based on characteristics of the electrooculogram (EOG) and tongue signal is developed in the current study, which can provide daily life assistance for people with physical mobility disabilities. It relies on five simple actions (blinking twice in a row, tongue extension, upward tongue rolling, and left and right eye movements) of the human head itself to complete the motions (moving up/down/left/right and double-click) of a mouse in the system screen. In this paper, the brain network and BP neural network algorithms are used to identify these five types of actions. The result shows that, for all subjects, their average recognition rates of eye blinks and tongue movements (tongue extension and upward tongue rolling) were 90.17%, 88.00%, and 89.83%, respectively, and after training, the subjects can complete the five types of movements in sequence within 12 seconds. It means that people with physical disabilities can use the system to quickly and accurately complete life self-help, which brings great convenience to their lives.

Context: Hypoxic-ischemic encephalopathy (HIE) has a high morbidity and mortality rate. Resveratrol possesses numerous biological properties including antioxidant, anti-inflammatory and neuroprotective activities. Objective: The current experiment investigates the neuroprotective efficacy of resveratrol (RESV) against HIE by modulating Nrf2/HO-1 pathway in neonatal rats. Materials and methods: Seven-day-old pups (n = 48) were divided into four groups. Group-I rats receiving 2% DMSO saline (sham), group-II rats underwent unilateral carotid artery ligation and hypoxia (92% N2 and 8% O2) for 2.5 h (hypoxia-ischemia; HI), group-III and IV rats received 20 (RESV 20 + HI) or 40 mg/kg (RESV 40 + HI; group-IV) of RESV via intraperitoneal injection (ip), respectively, for 7 days prior to HI induction. Results: Pre-treatment with RESV (20 or 40) markedly reduced (p

The accurate detection and alleviation of driving fatigue are of great significance to traffic safety. In this study, we tried to apply the modified multi-scale entropy (MMSE) approach, based on variational mode decomposition (VMD), to driving fatigue detection. Firstly, the VMD was used to decompose EEG into multiple intrinsic mode functions (IMFs), then the best IMFs and scale factors were selected using the least square method (LSM). Finally, the MMSE features were extracted. Compared with the traditional sample entropy (SampEn), the VMD-MMSE method can identify the characteristics of driving fatigue more effectively. The VMD-MMSE characteristics combined with a subjective questionnaire (SQ) were used to analyze the change trends of driving fatigue under two driving modes: normal driving mode and interesting auditory stimulation mode. The results show that the interesting auditory stimulation method adopted in this paper can effectively relieve driving fatigue. In addition, the interesting auditory stimulation method, which simply involves playing interesting auditory information on the vehicle-mounted player, can effectively relieve driving fatigue. Compared with traditional driving fatigue-relieving methods, such as sleeping and drinking coffee, this interesting auditory stimulation method can relieve fatigue in real-time when the driver is driving normally.

The purpose of this paper was to develop a real-time alarm monitoring system that can detect the fatigue driving state through wireless communication. The drivers’ electroencephalogram (EEG) signals were recorded from occipital electrodes. Seven EEG rhythms with different frequency bands as gamma, hbeta, beta, sigma, alpha, theta and delta waves were extracted. They were simultaneously assessed using relative operating characteristic (ROC) curves and grey relational analysis to select one as the fatigue feature. The research results showed that the performance of theta wave was the best one. Therefore, theta wave was used as fatigue feature in the following alarm device. The real-time alarm monitoring system based on the result has been developed, once the threshold was settled by using the data of the first ten minutes driving period. The developed system can detect driver fatigue and give alarm to indicate the onset of fatigue automatically.

Rapid and accurate detection of driver fatigue is of great significance to improve traffic safety. In the present work, we propose the man-machine response mode (MRM) to relieve driver fatigue caused by long-term driving. In this paper, the characteristics of the complex brain network, which can effectively reflect brain activity information, were used to detect the change of driving fatigue over time. Combined with the traditional eye movement characteristics and a subjective questionnaire (SQ), the changes in driving fatigue characteristics were comprehensively analyzed. The results show that driving fatigue can be effectively delayed using the MRM. Additionally, the response equipment is low in cost and practical, so it will be practical to use in actual driving situations in the future.

A home-auxiliary robot platform is developed in the current study which could assist patients with physical disabilities and older persons with mobility impairments. The robot, mainly controlled by brain computer interface (BCI) technology, can not only perform actions in a person’s field of vision, but also work outside the field of vision. The wavelet decomposition (WD) is used in this study to extract the δ (0~4 Hz) and θ (4~8 Hz) sub-bands of subjects’ electroencephalogram (EEG) signals. The correlation between pairs of 14 EEG channels is determined with synchronization likelihood (SL), and the brain network structure is generated. Then, the motion characteristics are analyzed using the brain network parameters clustering coefficient (C) and global efficiency (G). Meanwhile, the eye movement characteristics in the F3 and F4 channels are identified. Finally, the motion characteristics identified by brain networks and eye movement characteristics can be used to control the home-auxiliary robot platform. The experimental result shows that the accuracy rate of left and right motion recognition using this method is more than 93%. Additionally, the similarity between that autonomous return path and the real path of the home-auxiliary robot reaches up to 0.89.

In present work, the heart rate variability (HRV) characteristics, calculated by sample entropy (SampEn), were used to analyze the driving fatigue state at successive driving stages. Combined with the relative power spectrum ratio β/(θ + α), subjective questionnaire, and brain network parameters of electroencephalogram (EEG) signals, the relationships between the different characteristics for driving fatigue were discussed. Thus, it can conclude that the HRV characteristics (RR SampEn and R peaks SampEn), as well as the relative power spectrum ratio β/(θ + α) of the channels (C3, C4, P3, P4), the subjective questionnaire, and the brain network parameters, can effectively detect driving fatigue at various driving stages. In addition, the method for collecting ECG signals from the palm part does not need patch electrodes, is convenient, and will be practical to use in actual driving situations in the future.

ABSTRACT Heteroresistance refers to phenotypic heterogeneity of microbial clonal populations under antibiotic stress, and it has been thought to be an allocation of a subset of “resistant” cells for surviving in higher concentrations of antibiotic. The assumption fits the so-called bet-hedging strategy, where a bacterial population “hedges” its “bet” on different phenotypes to be selected by unpredicted environment stresses. To test this hypothesis, we constructed a heteroresistance model by introducing a blaCTX-M-14 gene (coding for a cephalosporin hydrolase) into a sensitive Escherichia coli strain. We confirmed heteroresistance in this clone and that a subset of the cells expressed more hydrolase and formed more colonies in the presence of ceftriaxone (exhibited stronger “resistance”). However, subsequent single-cell-level investigation by using a microfluidic device showed that a subset of cells with a distinguishable phenotype of slowed growth and intensified hydrolase expression emerged, and they were not positively selected but increased their proportion in the population with ascending antibiotic concentrations. Therefore, heteroresistance—the gradually decreased colony-forming capability in the presence of antibiotic—was a result of a decreased growth rate rather than of selection for resistant cells. Using a mock strain without the resistance gene, we further demonstrated the existence of two nested growth-centric feedback loops that control the expression of the hydrolase and maximize population growth in various antibiotic concentrations. In conclusion, phenotypic heterogeneity is a population-based strategy beneficial for bacterial survival and propagation through task allocation and interphenotypic collaboration, and the growth rate provides a critical control for the expression of stress-related genes and an essential mechanism in responding to environmental stresses. IMPORTANCE Heteroresistance is essentially phenotypic heterogeneity, where a population-based strategy is thought to be at work, being assumed to be variable cell-to-cell resistance to be selected under antibiotic stress. Exact mechanisms of heteroresistance and its roles in adaptation to antibiotic stress have yet to be fully understood at the molecular and single-cell levels. In our study, we have not been able to detect any apparent subset of “resistant” cells selected by antibiotics; on the contrary, cell populations differentiate into phenotypic subsets with variable growth statuses and hydrolase expression. The growth rate appears to be sensitive to stress intensity and plays a key role in controlling hydrolase expression at both the bulk population and single-cell levels. We have shown here, for the first time, that phenotypic heterogeneity can be beneficial to a growing bacterial population through task allocation and interphenotypic collaboration other than partitioning cells into different categories of selective advantage.