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Given the growing research interest in students' school-to-work transition, we examine the positive effects of undergraduates' future orientation on their employability confidence. Specifically, building on social cognitive career theory which suggests that career choices are influenced by a person's experiences, beliefs, interests, and values, we explore the mediator of vocational identity clarity and the positive moderator of internship effectiveness in this association above. Two studies were conducted to test our model. Study 1 included a laboratory experiment (N = 136) and tested the positive association between undergraduates' future orientation and their employability confidence through vocational identity clarity. Study 2 used a time-lagged research design from undergraduates (N = 315) to replicate the results and to additionally test a mediating role of internship effectiveness. We find that undergraduates' future orientation has a strong positive relationship with employability confidence, and this relation is mediated by vocational identity clarity. Additionally, the results show a positive moderation effect, that is, when undergraduates' internship effectiveness is high, the above indirect relation becomes stronger. The current research enriches the existing understanding of how and when the students' future orientation can contribute to employability confidence theoretically and empirically. Meanwhile, these findings indicated valuable practical applications by encouraging universities to promote undergraduates' future orientation and provide effective internships for them towards enhancing their vocational identity clarity and ultimately boosting their employability confidence.

Abstract Background Adenomatous polyps (APs) with inflammation are risk factors for colorectal cancer. However, the role of inflammation-related gut microbiota in promoting the progression of APs is unknown. Methods Sequencing of the 16S rRNA gene was conducted to identify characteristic bacteria in AP tissues and normal mucosa. Then, the roles of inflammation-related bacteria were clarified by Spearman correlation analysis. Furthermore, colorectal HT-29 cells, normal colon NCM460 cells, and azoxymethane-treated mice were used to investigate the effects of the characteristic bacteria on progression of APs. Results The expression levels of inflammation-related markers (diamine oxidase, d-lactate, C-reactive protein, tumor necrosis factor-α, interleukin-6 and interleukin-1β) were increased, whereas the expression levels of anti-inflammatory factors (interleukin-4 and interleukin-10) were significantly decreased in AP patients as compared to healthy controls. Solobacterium moorei (S. moorei) was enriched in AP tissues and fecal samples, and significantly positively correlated with serum inflammation-related markers. In vitro, S. moorei preferentially attached to HT-29 cells and stimulated cell proliferation and production of pro-inflammatory factors. In vivo, the incidence of intestinal dysplasia was significantly increased in the S. moorei group. Gavage of mice with S. moorei upregulated production of pro-inflammatory factors, suppressed proliferation of CD4+ and CD8+cells, and disrupted the integrity of the intestinal barrier, thereby accelerating progression of APs. Conclusions S. moorei accelerated the progression of AP in mice via activation of the NF-κB signaling pathway, chronic low-grade inflammation, and intestinal barrier disruption. Targeted reduction of S. moorei presents a potential strategy to prevent the progression of APs.

Type 3 resistant starch from Canna edulis (Ce-RS3) is an insoluble dietary fiber which could improve blood lipids in animals, but clinically robust evidence is still lacking. We performed a double-blind randomized controlled trial to assess the effects of Ce-RS3 on lipids in mild hyperlipidemia. One hundred and fifteen patients were included followed the recruitment criteria, and were randomly allocated to receive Ce-RS3 or placebo (native starch from Canna edulis) for 12 weeks (20 g/day). In addition to serum lipids, complete blood counts, serum inflammatory factors, antioxidant indexes, and dietary survey, 16 S rRNA sequencing technique was utilized to analyze the gut microbiota alterations. Targeted quantitative metabolomics (TQM) was used to detect metabolite changes. Compared with the placebo, Ce- RS3 significantly decreased levels of total cholesterol, lowdensity lipoprotein cholesterol, and non-high-density lipoprotein cholesterol, and increased the glutathione peroxidase. Based on the 16 S rRNA sequencing, TQM, the correlation analysis, as well as the Kyoto Encyclopedia of Genes (KEGG) and Genomes and Human Metabolome Database (HMDB) analysis, we found that Ce-RS3 could increase the abundances of genera Faecalibacterium and Agathobacter, while reduce the abundances of genera norank_f_Ruminococcaceae and Christensenellaceae_R-7_ group to regulate phenylalanine metabolism, which could reduce the fatty acid biosynthesis and fatty acid elongation in the mitochondria to lower blood lipids. Conclusively, we firstly confirmed the feasibility of Ce-RS3 for clinical application, which presents a novel, effective therapy for the mild hyperlipidemia. (Chictr. org. cn. Clinical study on anti-mild hyperlipidemia of Canna edulis RS3 resistant starch, ID Number: ChiCTR2200062871).

Abstract Current treatment for functional dyspepsia (FD) has limited and unsustainable efficacy. Probiotics have the sustainable potential to alleviate FD. This randomized controlled clinical trial (Chinese Clinical Trial Registry, ChiCTR2000041430) assigned 200 FD patients to receive placebo, positive-drug (rabeprazole), or Bifidobacterium animalis subsp. lactis BL-99 (BL-99; low, high doses) for 8-week. The primary outcome was the clinical response rate (CRR) of FD score after 8-week treatment. The secondary outcomes were CRR of FD score at other periods, and PDS, EPS, serum indicators, fecal microbiota and metabolites. The CRR in FD score for the BL-99_high group [45 (90.0%)] was significantly higher than that for placebo [29 (58.0%), p = 0.001], BL-99_low [37 (74.0%), p = 0.044] and positive_control [35 (70.0%), p = 0.017] groups after 8-week treatment. This effect was sustained until 2-week after treatment but disappeared 8-week after treatment. Further metagenomic and metabolomics revealed that BL-99 promoted the accumulation of SCFA-producing microbiota and the increase of SCFA levels in stool and serum, which may account for the increase of serum gastrin level. This study supports the potential use of BL-99 for the treatment of FD.

AbstractIntroduction There is a dearth of comprehensive studies on the association between serum electrolyte and adverse short-term prognosis of Chinese patients with acute decompensated heart failure (ADHF).Patients and methods A total of 5166 patients with ADHF were divided into four serum electrolyte-related study populations (potassium (n = 5145), sodium (n = 5135), chloride (n = 4966), serum total calcium (STC) (n = 4143)) under corresponding exclusions. Different logistic regression models were utilized to gauge the association between these electrolytes or the number of electrolyte abnormalities and the risk of a composite of all-cause mortality or 30-day heart failure (HF) readmission.Results In multivariable adjusted analysis, patients with potassium below 3.5 mmol/L (odds ratios (ORs) 1.45; 95% confidence interval (CI):1.07–1.95), 4.01–4.50 mmol/L (OR: 1.29, CI: 1.02–1.62), 4.51–5.00 mmol/L (OR: 1.43, CI: 1.08–1.90) and above 5.00 mmol/L (OR: 1.74, CI: 1.21–2.51) had an increased risk of outcome when compared with potassium at 3.50–4.00 mmol/L. Sodium levels were inversely related to the risk of a composite outcome (

A two-dimensional axisymmetric fluid model is used to simulate the dynamics behavior of an atmospheric-pressure helium plasma jet in the presence of a parallel magnetic field. The plasma jet is generated in a coaxial dielectric barrier discharge (DBD) driven by pulsed direct-current voltage. Comparative analysis of the plasma jet with and without the parallel magnetic field indicates that a slightly thinner plasma sheath inside the tube is present with the parallel magnetic field as a result of the decreased accumulated electrons on the inner surface of dielectric tube. After the streamer propagates outside the tube, a little more concentrated electron distribution in the annular wall is observed by applying the magnetic field because of the reduced electron diffusion in the radial direction and the confinement effect of the magnetic field on the electrons in the avalanche heads. The tiny reduction in the length of plasma jet is attributed to the E × B drift of charged particles. These results demonstrate that the parallel magnetic field has no apparent effect on the propagation of the plasma jet, and it contributes little to the performance improvement of the coaxial DBD, which agrees well with the previous experimental observations. This little impact of the parallel magnetic field on the coaxial DBD plasma jet may result from negligible contribution of the memory effect to the sole discharge pulse as well as the weak confinement effect of the applied magnetic field on the surface electrons that moves along the magnetic field lines under electrostatic repulsion.

This study aimed to evaluate the preventive efficacy of tocotrienol in inhibiting the nuclear factor-kappa B (NF-κB) mediated inflammation pathways in colorectal cancer. We utilized the azoxymethane (AOM) and dextran sulfate sodium salt (DSS) to induce colitis-associated colorectal cancer (CAC) mice model. In generating a CAC model, mice were intraperitoneally injected with AOM at a concentration of 10 mg/kg body weight. Seven days after the AOM injection, mice drinking water containing 3 % DSS for 1 week, followed by a 2-week period of regular water. This cycle of DSS treatment (1-week 3 % DSS+2-week water) was repeated for two additional cycles. Mice were randomly divided into five groups (n = 20/group), including Blank group, Model group, three different dosages tocotrienol groups (Low dose group [50 mg/kg], Medium dose group [75 mg/kg], and High dose group [100 mg/kg]). The protective effects of tocotrienol were assessed using histological, flow cytometry, western blot and mouse Luminex assay. Compared with the blank group, expressions of toll-like receptor 4 (TLR4), myeloid differentiation protein 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF-6), NF-κB, Interleukin (IL)-6 and tumor necrosis factor (TNF) −α were increased in model group, while IL-4 and IL-10 were decreased in model group (P

An increasing body of research suggests cancer-induced cardiovascular diseases, leading to the appearance of an interdisciplinary study known as onco-cardiology. Lung cancer has the highest incidence and mortality. Cardiac dysfunction constitutes a major cause of death in lung cancer patients. However, its mechanism has not been elucidated because suitable animal models that adequately mimic clinical features are lacking. Here, we established a novel chemically induced lung cancer mouse model using benzo[a]pyrene and urethane to recapitulate the general characteristics of cardiac dysfunction caused by lung cancer, the cardiac disorders in the context of the progression of lung cancer were evaluated using echocardiographic and histological approaches. The pathological changes included myocardial ischaemia, pericarditis, cardiac pre-cachexia, and pulmonary artery hypertension. We performed sequencing to detect the tRNA-derived fragments and tRNA-derived stress-induced RNAs (tRFs/tiRNAs) expressions in mouse heart tissue. 22 upregulated and 16 downregulated tRFs/tiRNAs were identified. Subsequently, the top 10 significant results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were presented. The in vitro model was established by exposing neonatal rat cardiomyocytes and myocardial fibroblasts to lung tumour cell-conditioned medium, respectively. Western blotting revealed significant changes in cardiac failure markers (atrial natriuretic peptide and α-myosin heavy chain) and cardiac fibrosis markers (Collagen-1 and Collagen-3). Our model adequately reflects the pathological features of lung cancer-induced cardiac dysfunction. Furthermore, the altered tRF/tiRNA profiles showed great promise as novel targets for therapies. These results might pave the way for research on therapeutic targets in onco-cardiology.

Abstract Precise detection of early osteolytic metastases is crucial for their treatment but remains challenging in the clinic because of the limited sensitivity and specificity of traditional imaging techniques. Although fluorescence imaging offers attractive features for the diagnosis of osteolytic metastases, it is hampered by limited penetration depth. To address this issue, a fluoro‐photoacoustic dual‐modality imaging probe comprising a near‐infrared dye caged by a cathepsin K (CTSK)‐cleavable peptide sequence on one side and functionalized with osteophilic alendronate through a polyethylene glycol linker on the other side is reported. Through systematic in vitro and in vivo experiments, it is demonstrated that in response to CTSK, the probe generated both near‐infrared fluorescent and photoacoustic signals from bone metastatic regions, thus offering a potential strategy for detecting deep‐seated early osteolytic metastases.

BackgroundSome eating habits may be related to the development of gastrointestinal diseases, obesity, and related metabolic dysfunctions. Because of long working hours, and shift schedules, physicians are more likely to form such eating habits and have a high risk of developing these diseases.ObjectivesWe aimed to investigate the association between physicians’ eating habits and their health perception and diseases.MethodsBetween 24 June and 5 August 2020, we performed convenience sampling of in-service physicians in hospitals in mainland China. A questionnaire was administered to collect data pertaining to basic sociodemographic characteristics, eating habits, health-related information such as body mass index classification, and prevalence of common diseases. The associations among eating habits and perceived suboptimal health status, micronutrient deficiency-related diseases, obesity, and related metabolic diseases were analysed.ResultsThe prevalence of unhealthy eating habits was high: more eating out-of-home (53.4% in hospital canteens, 23.0% in restaurants and takeaways), fewer meals at home, irregular meals (30.5%), and eating too fast (the duration

Aging is the most important factor contributing to cardiovascular diseases (CVDs), and the incidence and severity of cardiovascular events tend to increase with age. Currently, CVD is the leading cause of death in the global population. In-depth analysis of the mechanisms and interventions of cardiovascular aging and related diseases is an important basis for achieving healthy aging. Tea polyphenols (TPs) are the general term for the polyhydroxy compounds contained in tea leaves, whose main components are catechins, flavonoids, flavonols, anthocyanins, phenolic acids, condensed phenolic acids and polymeric phenols. Among them, catechins are the main components of TPs. In this article, we provide a detailed review of the classification and composition of teas, as well as an overview of the causes of aging-related CVDs. Then, we focus on ten aspects of the effects of TPs, including anti-hypertension, lipid-lowering effects, anti-oxidation, anti-inflammation, anti-proliferation, anti-angiogenesis, anti-atherosclerosis, recovery of endothelial function, anti-thrombosis, myocardial protective effect, to improve CVDs and the detailed molecular mechanisms.

Branched-chain amino acids (BCAAs; a mixture of leucine, valine and isoleucine) have important regulatory effects on glucose and lipid metabolism, protein synthesis and longevity. Many studies have reported that circulating BCAA levels or dietary intake of BCAAs is associated with longevity, sarcopenia, obesity, and diabetes. Among them, the influence of BCAAs on aging and insulin resistance often present different benefits or harmful effects in the elderly and in animals. Considering the nonobvious correlation between circulating BCAA levels and BCAA uptake, as well as the influence of diseases, diet and aging on the body, some of the contradictory conclusions have been drawn. The regulatory mechanism of the remaining contradictory role may be related to endogenous branched-chain amino acid levels, branched-chain amino acid metabolism and mTOR-related autophagy. Furthermore, the recent discovery that insulin resistance may be independent of longevity has expanded the research thinking related to the regulatory mechanism among the three. However, the negative effects of BCAAs on longevity and insulin resistance were mostly observed in high-fat diet-fed subjects or obese individuals, while the effects in other diseases still need to be studied further. In conclusion, there is still no definite conclusion on the specific conditions under which BCAAs and insulin resistance extend life, shorten life, or do not change lifespan, and there is still no credible and comprehensive explanation for the different effects of BCAAs and insulin resistance on lifespan.

Objective: Cervical artery dissection (CAD) is considered one of these complications in the treatment of cervical spine manipulation (CSM), which can lead to severe complications such as stroke or death. This study aimed to explore the common manifestations and probable mechanisms of CAD caused by CSM according to the imaging findings. Methods: We retrospectively analyzed the clinical and imaging data of all patients diagnosed with CAD in the PACs system during the past 2 years in our hospital. All patients with cervical massage-induced CAD were included in this study. The imaging data was analyzed to determine the location and extent of the dissection and whether there were intracranial complications. Results: A total of 7 patients and 8 dissected vessels participated in the final cohort study, including 4 internal carotid artery dissections (ICADs) and 4 vertebral artery dissections (VADs). All patients had corresponding stroke manifestations. Through imaging analysis of each patient, we found that the C1 segment of the internal carotid artery was involved in all patients with ICAD and the V3 segment of the vertebral artery dissection was involved in all patients with VAD. Conclusions: The C1 segment of the internal carotid artery and the V3 segment of the vertebral artery may be the sites most frequently involved in CAD caused by CSM, and more evidence is needed to support the results of this study in the future.

In this study, four cylindrical cavities with diameters of more than 10 mm are utilized to confine aluminum plasmas to improve the signal intensities of laser-induced breakdown spectroscopy (LIBS). Primary and secondary enhancements of spectra are observed. This phenomenon is attributed to the fact that plasmas are compressed into a smaller core area with denser population of excited atoms by reflected shockwaves more than one time. The delay time for both primary and secondary signal enhancements is postponed with decreasing the laser energy or increasing the cavity diameter. Relative standard deviations (RSDs) of spectra signal in different experimental conditions are discussed to illustrate the uncertainties of measurement. In addition, enhancement factor, signal-to-background ratio (SBR) and signal-to-noise ratio (SNR) are also examined in the two cases. The fast images of plasma plume further prove the enhancements of emission intensity, as well as its RSD.

Allergy has become a public health problem worldwide, but effective diagnostic and therapeutic approaches are limited currently. Amino acids are essential macronutrients that potentially participated in the allergy process. This work aimed to investigate whether amino acids can be applied as a mediator for allergy diagnosis and therapy. Two cohort studies were performed to investigate the correlation between fecal amino acids and allergy responses, and a spleen cell model was used to validate the role of amino acids in regulating allergy. In a cohort study with 193 volunteers, fecal proline was found to be negatively correlated with serum IgE, and detailed data analysis revealed that people with high-IgE-mediated allergy had decreased odds of high intestinal proline. In another cohort study with distinct allergic and non-allergic individuals, proline concentration was significantly lower in the allergic group. Daily diet and metagenomics analysis showed that the proline intake and microbiota amino acid metabolism were not significantly different, implying that the body’s proline metabolism might be different between allergic and non-allergic individuals. Furthermore, the spleen cell model demonstrated that proline specifically targeted Th2 and Treg activity. Overall, this work revealed a tight correlation between gut proline and serum IgE, indicating proline as a promising biomarker and a potential therapeutic method for allergic diseases.

IntroductionUsing wrist-wearable sensors to ecological transient assessment may provide a more valid assessment of physical activity, sedentary time, sleep and circadian rhythm than self-reported questionnaires, but has not been used widely to study the association with mild cognitive impairment and their characteristics.Methods31 normal cognitive ability participants and 68 MCI participants were monitored with tri-axial accelerometer and nocturnal photo volumetric pulse wave signals for 14 days. Two machine learning algorithms: gradient boosting decision tree and eXtreme gradient boosting were constructed using data on daytime physical activity, sedentary time and nighttime physiological functions, including heart rate, heart rate variability, respiratory rate and oxygen saturation, combined with subjective scale features. The accuracy, precision, recall, F1 value, and AUC of the different models are compared, and the training and model effectiveness are validated by the subject-based leave-one-out method.ResultsThe low physical activity state was higher in the MCI group than in the cognitively normal group between 8:00 and 11:00 (P < 0.05), the daily rhythm trend of the high physical activity state was generally lower in the MCI group than in the cognitively normal group (P < 0.05). The peak rhythms in the sedentary state appeared at 12:00–15:00 and 20:00. The peak rhythms of rMSSD, HRV high frequency output power, and HRV low frequency output power in the 6h HRV parameters at night in the MCI group disappeared at 3:00 a.m., and the amplitude of fluctuations decreased; the amplitude of fluctuations of LHratio nocturnal rhythm increased and the phase was disturbed; the oxygen saturation was between 90 and 95% and less than 90% were increased in all time periods (P < 0.05). The F1 value of the two machine learning algorithms for MCI classification of multi-feature data combined with subjective scales were XGBoost (78.02) and GBDT (84.04).ConclusionBy collecting PSQI Scale data combined with circadian rhythm characteristics monitored by wrist-wearable sensors, we are able to construct XGBoost and GBDT machine learning models with good discrimination, thus providing an early warning solution for identifying family and community members with high risk of MCI.

The relationship between vitamin B levels and the development and progression of lung cancer remains inconclusive. We aimed to investigate the relationship between B vitamins and intrapulmonary lymph nodes as well as localized pleural metastases in patients with non-small cell lung cancer (NSCLC). This was a retrospective study including patients who underwent lung surgery for suspected NSCLC at our institution from January 2016 to December 2018. Logistic regression models were used to evaluate the associations between serum B vitamin levels and intrapulmonary lymph node and/or localized pleural metastases. Stratified analysis was performed according to different clinical characteristics and tumor types. A total of 1498 patients were included in the analyses. Serum vitamin B6 levels showed a positive association with intrapulmonary metastasis in a multivariate logistic regression (odds ratio (OR) of 1.016, 95% confidence interval (CI) of 1.002–1.031, p = 0.021). After multivariable adjustment, we found a high risk of intrapulmonary metastasis in patients with high serum vitamin B6 levels (fourth quartile (Q4) vs. Q1, OR of 1.676, 95%CI of 1.092 to 2.574, p = 0.018, p for trend of 0.030). Stratified analyses showed that the positive association between serum vitamin B6 and lymph node metastasis appeared to be stronger in females, current smokers, current drinkers, and those with a family history of cancer, squamous cell carcinoma, a tumor of 1–3 cm in diameter, or a solitary tumor. Even though serum vitamin B6 levels were associated with preoperative NSCLC upstaging, B6 did not qualify as a useful biomarker due to weak association and wide confidence intervals. Thus, it would be appropriate to prospectively investigate the relationship between serum vitamin B6 levels and lung cancer further.

As one of the most important enteric viruses, sapovirus (SaV) can infect humans and a variety of animals. Until now, 19 SaV genogroups have been identified, among which 4 from human (GI, GII, GIV, and GV) and 8 from swine (GIII, GV–GXI). Porcine sapovirus (PoSaV) GIII has been prevalent in China; however, the status of PoSaV infection in Yunnan province remains unknown. In this study, 202 fecal samples were collected from piglets associated with outbreaks of acute diarrhea in Yunnan between January and May 2020. PoSaV detection revealed that the total PoSaV infection rate in Yunnan was 35.2%, with 21 PoSaV strains determined and phylogenetically analyzed. The phylogenetic tree analyses demonstrated that twenty PoSaV strains belonged to GIII and fell into five genotypes, whereas one PoSaV strain (YNQB) belonged to GV. Sequence alignments revealed deletions in VP2 region in 10 of the 20 GIII strains, as well as deletions and insertions in VP1 region of the GV strain (YNQB). Furthermore, genomic recombination analyses showed that two GIII strains (YNAN and YNJD) were recombinants, closely related to reference sequences MK965898 and LC215880, MK965898 and FJ387164, respectively. In summary, PoSaV-GIII strains were identified in Yunnan in 2020, and for the first time, a PoSaV-GV strain was identified from China, whereas the comprehensive analyses illustrated high genetic diversity of Yunnan PoSaV strains. This study may shed new light on the current PoSaV infections in Yunnan and pave the way toward further control of the PoSaV infections in China.

Our previous studies have found that caprylic acid (C8:0) can improve blood lipids and reduce inflammation levels and may be related to the upregulation of the p-JAK2/p-STAT3 pathway by ABCA1. This study aims to investigate the effects of C8:0 and eicosapentaenoic acid (EPA) on lipids, inflammatory levels, and the JAK2/STAT3 pathway in ABCA1-deficient mice (ABCA1−/−) and ABCA1 knock-down (ABCA1-KD) RAW 264.7 cells. Twenty 6-week ABCA1−/− mice were randomly divided into four groups and fed a high-fat diet, or a diet of 2% C8:0, 2% palmitic acid (C16:0) or 2% EPA for 8 weeks, respectively. The RAW 264.7 cells were divided into the control or control + LPS group, and the ABCA1-KD RAW 264.7 cells were divided into ABCA1-KD with LPS (LPS group), ABCA1-KD with LPS + C8:0 (C8:0 group), and ABCA1-KD with LPS + EPA (EPA group). Serum lipid profiles and inflammatory levels were measured, and ABCA1 and JAK2/STAT3 mRNA and protein expressions were determined by RT-PCR and Western blot analyses, respectively. Our results showed that serum lipid and inflammatory levels increased in ABCA1−/− mice (p < 0.05). After the intervention of different fatty acids in ABCA1−/− mice, TG and TNF-α were significantly lower, while MCP-1 increased significantly in the C8:0 group (p < 0.05); however, LDL-C, TC, TNF-α, IL-6, and MCP-1 levels decreased significantly and IL-10 increased significantly in the EPA group (p < 0.05). In the aorta of ABCA1−/− mice, C8:0 significantly decreased p-STAT3 and p-JAK2 mRNA, while EPA significantly reduced TLR4 and NF-κBp65 mRNA. In the ABCA1-KD RAW 264.7 cells, TNF-α and MCP-1 were increased significantly and IL-10 and IL-1β were significantly decreased in the C8:0 group (p < 0.05). The protein expressions of ABCA1 and p-JAK2 were significantly higher, and the NF-κBp65 was significantly lower in the C8:0 and EPA groups (p < 0.05). Meanwhile, compared to the C8:0 group, the NF-κBp65 protein expression was significantly lower in the EPA group (p < 0.05). Our study showed that EPA had better effects than C8:0 on inhibiting inflammation and improving blood lipids in the absence of ABCA1. C8:0 may be involved mainly in inhibiting inflammation through upregulation of the ABCA1 and p-JAK2/p-STAT3 pathways, while EPA may be involved mainly in inhibiting inflammation through the TLR4/NF-κBp65 signaling pathway. The upregulation of the ABCA1 expression pathway by functional nutrients may provide research targets for the prevention and treatment of atherosclerosis.

Abstract Background Epidemiological studies have shown that young women often suffer from primary dysmenorrhea (PD) which is a common cause that affects their routine work and quality of life. Chinese herbal medicine has been widely used for PD in China. A systematic review found that Xuefu Zhuyu (XFZY) has a promising effect on PD management, yet there is a dearth of high-quality evidence in support of this claim. We want to conduct a randomized controlled trial to evaluate the efficacy and safety of XFZY for PD patients. Methods This is a protocol for a multicenter, randomized, placebo-controlled trial. A total of 248 participants with PD will be recruited at 6 centers and randomized into two groups—a herbal treatment group and a placebo group. The participants will receive either XFZY or placebo, three times per day, for 3 menstrual cycles, with a 12-week follow-up. The primary outcome will be the mean change in pain intensity as measured by VAS, while the change in menstrual pain duration, the change in peak pain intensity as measured by VAS, the Cox Menstrual Symptom Scale (CMSS), quality of life EQ-5D-5L, cumulative painkiller consumption, and health economics will be included as secondary outcomes. Adverse events will also be reported. Discussion This protocol describes a multicenter, double-blind, randomized, placebo-controlled trial that investigates the efficacy and safety of XFZY for primary dysmenorrhea. Validated evaluation tools will assess dysmenorrhea severity. We believe that this research will provide important evidence regarding the use of XFZY to treat dysmenorrhea. Trial registration Chinese Clinical Trial Registry ChiCTR1900026819 . Registered on 23 October 2019

Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative disorder of middle-aged to old individuals. The pathophysiological process of AD is believed to begin many years before the emergence of clinical symptoms. The important influence of congenital genetic aberrations on the development of AD provides a novel opportunity to initiate prenatal to early postnatal pharmacological treatment to address the role of this critical period of brain development in the disease. Methods We investigated for the first time the effect of oral treatment during prenatal to early postnatal development with a neurotrophic compound, P021 (Ac-DGGLAG-NH2), on neurobehavior and AD-like pathology in 3xTg-AD, a transgenic mouse model of AD. The transgenic and control wild-type female mice were treated from prenatal day 8 to postnatal day 21 with a custom-made diet containing P021 or a vehicle diet, followed by a standard diet. AD-type cognitive function and pathological features were studied during adulthood and old age. Results The P021 treatment rescued cognitive deficits at 4 months, reduced abnormal hyperphosphorylation and accumulation of tau at known major AD neurofibrillary pathology–associated sites, and decreased Aβ plaque load at 22 months in 3xTg-AD mice. Prenatal to early postnatal treatment with P021 also ameliorated certain markers of postsynaptic deficits, including PSD-95 levels and CREB activity, and decreased one measure of neuroinflammation, GFAP level in the brain at 4 and 22 months in 3xTg mice. Conclusions These findings suggest that neurotrophic impairment during early development can be one of the etiopathogenic factors of AD and that the neurotrophic peptide mimetic is a potential early prevention strategy for this disease.

Background: Segmental duplication (SD) regions are distinct targets for aneuploidy detection owing to the virtual elimination of amplification bias. The difficulty of searching SD sequences for assay design has hampered their applications. Methods: We developed a computational program, ChAPDes, which integrates SD searching, refinement, and design of specific PCR primer/probe sets in a pipeline to remove most of the manual work. The generated primer/probe sets were first tested in a multiplex multicolour melting curve analysis for the detection of five common aneuploidies. The primer/probe sets were then tested in a digital PCR assay for the detection of trisomy 21. Finally, a digital PCR protocol was established to quantify maternal plasma DNA sequences for the non-invasive prenatal detection of fetal trisomy 21. Findings: ChAPDes could output 21,772 candidate primer/probe sets for trisomy 13, 18, 21 and sex chromosome aneuploidies within 2 working days. Clinical evaluation of the multiplex multicolour melting curve analysis involving 463 fetal genomic DNA samples revealed a sensitivity of 100% and specificity of 99.64% in comparison with the reference methods. Using the established digital PCR protocol, we correctly identified two trisomy 21 fetuses and thirteen euploid foetuses from the maternal plasma samples. Interpretation: The combination of ChAPDes with digital PCR detection could facilitate the use of SD as potential biomarkers for the non-invasive prenatal testing of fetal chromosomal aneuploidies.

Abstract Background As reported previously by our group, medium-chain triglycerides can ameliorate atherosclerosis. Given that TLR4 is closely related to atherosclerosis, we hypothesized herein that caprylic acid (C8:0) would suppress inflammation via TLR4/NF-κB signaling and further promote the amelioration of atherosclerosis in apoE- deficient (apoE−/−) mice. Methods Fifty 6-week male apoE−/− mice were randomly allocated into five diet groups: a high-fat diet (HFD) without or with 2% caprylic acid (C8:0), capric acid (C10:0), stearic acid (C18:0), or linolenic acid (C18:3). RAW246.7 cells were treated with caprylic acid (C8:0), docosahexenoic acid (DHA), palmitic acid (C16:0), and lipopolysaccharide (LPS) with or without TLR4 knock-down (TLR4-KD). The serum lipid profiles, inflammatory biomolecules, and mRNA and protein expression levels were measured. Atherosclerotic lesions that occurred in the aorta and aortic sinuses were evaluated and quantified. Results Our results indicated that C8:0 reduced body fat, improved the lipid profiles, suppressed inflammatory cytokine production, downregulated aortic TLR4, MyD88, NF-κB, TNF-α, IKKα, and IKKβ mRNA expression, and alleviated atherosclerosis in the apoE−/− mice (P

Scope:Sonchus Oleraceus, named bitter vegetable (BV), has been known to have multiple health benefits such as anti-aging and anti-inflammation. However, the role of BV in the prevention of obesity is unclear. The aim of this study was to examine the effect of BV lipid extracts (BVL) on obesity development.Methods and Results: Following treatments of high fat diet-induced obese mice (C57BL/6J) with BVL (0.3 mg/g of BW per mouse) for a month, mice exhibited a significant reduction in weight gain, blood triglyceride, and fasting blood glucose compared to control mice. Intriguingly, phosphorylated AMPK, a key regulator of nutrient metabolism, was markedly increased in inguinal fat of BVL group. In 3T3-L1 cells, BVL-7 (100 μg/ml), an omega-3 fatty acid-rich fraction from BVL, lowered lipid accumulation, and down-regulated the gene expression of adipocyte markers. The inhibitory effect of BVL occurred at the early stage of adipocyte differentiation, leading to the delay of mitotic clonal expansion. AMPK knockdown by siRNA abolished the inhibitory effect of BVL-7 on adipogenesis, suggesting that AMPK is essential for BVL-regulated adipocyte differentiation.Conclusion: BVL can effectively inhibit adipogenesis through, at least in part, stimulating AMPK pathway and attenuate HFD-induced obesity. Our findings suggest that BVL can be a promising dietary supplement for protection against obesity, and the effective component of BVL can be potentially developed as anti-obesity drugs.

BackgroundSingle nucleotide polymorphism array (SNP-array) has been introduced for prenatal diagnosis. We aimed to evaluate the clinical value of SNP-array in the diagnosis of fetal chromosomal anomalies.MethodsA retrospective study was conducted on 5000 cases tested by SNP-array, and the results of 4022 cases analyzed by both karyotyping and SNP-array were compared.ResultsSNP-array analysis of 5000 samples revealed that the overall abnormality detection rate by SNP-array was 12.3%, and the overall detection rate of clinically significant copy number variations (CNVs) by SNP-array was 2.6%. SNP-array identified clinically significant submicroscopic CNVs in 4.5% fetuses with anomaly on ultrasonography, in 1.6% of fetuses with advanced maternal age (AMA), in 2.5% of fetuses with abnormal result on maternal serum screening, in 2.9% of fetuses with abnormal non-invasive prenatal testing (NIPT) results and in 3.0% of fetuses with other indications. Of the 4022 samples analyzed by both karyotyping and SNP-array, SNP-array could identify all the aneuploidy and triploidy detected by karyotyping but did not identify balanced structural chromosomal abnormalities and low-level mosaicism detected by karyotyping.ConclusionSNP-array could additionally identify clinically significant submicroscopic CNVs, and we recommend the combination of SNP-array analysis and karyotyping in prenatal diagnosis.

Objective To confirm diagnosis and explore the genetic aetiology in a Chinese patient suspected to have Cockayne syndrome (CS). Methods The patient was clinically examined, and the patient and her biological parents underwent genetic analysis using whole exome sequencing (WES) and Sanger sequencing. The foetus of the patient’s mother underwent prenatal diagnostic Sanger sequencing using amniotic fluid obtained at 19 weeks’ gestation. Results Clinical examination of the patient showed developmental delay, progressive neurologic dysfunction and premature aging. Two compound, heterozygous ERCC excision repair 6, chromatin remodelling factor ( ERCC6 ) gene mutations were detected in the proband by WES and confirmed by Sanger sequencing, comprising a known paternal nonsense mutation (c.643G > T, p.E215X) and a novel maternal short insertion and deletion mutation (c.1614_c.1616delGACinsAAACGTCTT, p.K538_T539delinsKNVF). The patient was consequently diagnosed with CS type I. The foetus of the patient’s mother was found to carry only the maternally-derived c.1614_c.1616delGACinsAAACGTCTT variant. Conclusion This study emphasized the value of WES in clinical diagnosis, and enriched the known spectrum of ERCC6 gene mutations.

Objective To diagnose and explore the genetic aetiology of Simpson–Golabi–Behmel syndrome type 1 (SGBS1) in two male fetuses. Methods Prenatal ultrasound scans and further genetic analysis using karyotype analysis, chromosomal microarray analysis, whole exome sequencing (WES) and Sanger sequencing were conducted. Results Prenatal ultrasound scans of two fetuses showed multiple congenital anomalies and hydramnios. Subsequent to termination of the pregnancies, a novel nonsense variant (c.892G>T, p.E298*) in the glypican 3 ( GPC3 ) gene of the two fetuses was identified by WES and further confirmed by Sanger sequencing. The two fetuses were diagnosed with SGBS1. The mother was heterozygous for the c.892G>T variant. Conclusion This study describes the prenatal sonographic features of SGBS1, emphasizes the role of WES in the diagnosis of SGBS1 and expands the known mutation spectrum of the GPC3 gene.

Age-associated macular degeneration (AMD), which leads to loss of vision at its end stage, is one of the most common neurodegenerative diseases among the elderly. However, to date, no effective drug therapy is available for the prevention of AMD. Here, we report the occurrence of AMD pathology and its prevention by chronic treatment with the neurotrophic peptidergic compound P021, in aged rats and 3xTg-AD mice. We found photoreceptor degeneration, lipofuscin granules, vacuoles, and atrophy in retinal pigment epithelium (RPE) as well as Bruch’s membrane (BM) thickening; in aged rats, we even found rosette-like structure formation. Microgliosis and astrogliosis were observed in different retinal layers. In addition, we also found that total tau, phosphorylated tau, Aβ/APP, and VEGF were widely distributed in the sub-retina of aged rats and 3xTg mice. Importantly, chronic treatment with P021 for 3 months in rats and for 18 months in 3xTg mice ameliorated the pathological changes above. These findings indicate the therapeutic potential of P021 for prevention and treatment of AMD and retinal changes associated with aging and Alzheimer’s disease.

Abstract Background Chromosomal abnormalities are one of the genetic mechanisms associated with abortion. However, the roles of submicroscopic chromosomal imbalances in early abortion are still unclear. This study aims to find out whether submicroscopic chromosomal imbalances contribute to early abortion. Methods A total of 78 chorionic villus specimens from early spontaneous abortion patients with no obvious abnormality are collected after miccroassay analysis (the case group). At the same time, 60 chorionic villus specimens from induced abortion patients with no obvious abnormality are selected as the control group. The submicroscopic structures of chromosomes from two groups are analyzed using an array-based comparative genomic hybridization (aCGH). Results In the case group, 15 specimens show submicroscopic chromosomal abnormalities including 14 micro-deletion/micro-duplication in chromosomes 2, 4, 5, 6, 7, 8, 9, 12, 15, 16, 18, and 22, and 1 uniparental disomy (UPD) in chromosome 19. Moreover, no pathogenic copy number variations are found in the control group. The results between these two groups exhibit significantly statistical difference. Conclusion Submicroscopic chromosomal imbalances may be one of the main reasons for early abortion.

Abstract Background Bile acids play a pivotal role in cholesterol metabolism via the enterohepatic circulation. This study investigated the effects of medium-chain triglycerides (MCTs)/medium-chain fatty acids (MCFAs) on the reduction of bile acid absorption in the small intestine and the mechanisms of action in vivo and partially verified in vitro. Methods Thirty-six C57BL/6 J mice with hypercholesterolaemia were randomly divided into 3 groups: fed a cholesterol-rich diet (CR group), fed a cholesterol-rich and medium-chain triglyceride diet (CR-MCT group) and fed a cholesterol-rich and long-chain triglyceride diet (CR-LCT group). Body weights and blood lipid profiles were measured in all groups after 16 weeks of treatment. The concentrations of bile acids in bile and faeces were analysed using HPLC-MS (high-performance liquid chromatography-mass spectrometry). Gene transcription and the expression levels associated with bile acid absorption in the small intestines were determined using real-time PCR and Western blot. Ileal bile acid binding protein (I-BABP) was analysed using immunofluorescence. The effects of MCFAs on the permeability of bile acid (cholic acid, CA) in Caco-2 cell monolayers and I-BABP expression levels in Caco-2 cells treated with caprylic acid (C8:0), capric acid (C10:0), stearic acid (C18:0) and oleic acid (C18:1) were determined. Results Mice in the CR-MCT group exhibited lower body weights and serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and a higher HDL-C/LDL-C ratio than the CR-LCT group (P

Models of human pancreatic intraepithelial neoplasia (PanIN) development do not exist. Here, the authors induce oncogenicKRAS and mutations in CDKN2A, SMAD4 and TP53in primary human pancreatic cells to generate a PanIN model that recapitulates molecular and pathologic features of native PanINs.

Objectives. Triphala is a herbal medicine that has been widely used for treating a variety of ailments. This study aims to systematically analyze the antitumor effects of Triphala on gynecological cancers. Methods. The antineoplastic activities of Triphala on gynecological cancers were analyzed using network pharmacology-based strategies. Afterward, the human ovarian cancer cell line SK-OV-3, cervical cancer cell line HeLa, and endometrial cancer cell line HEC-1-B were selected for experimetal valification. Results. Network pharmacology analysis suggested that Triphala could comprehensively intervene in proliferation and apoptosis through diverse signaling pathways, mainly including MAPK/ERK, PI3K/Akt/mTOR, and NF-κB/p53. The Cell Counting Kit 8 (CCK-8) assay illustrated that Triphala was able to inhibit cell proliferation with half inhibition concentration (IC 50 ) values of 98.28 ± 13.71, 95.56 ± 8.94, and 101.23 ± 7.76 µg/mL against SK-OV-3, HeLa, and HEC-1-B cells, respectively. The ELISA experiment demonstrated that Triphala was capable of promoting programmed cell death, with dosage correlations. The antiproliferative and proapoptotic activities were confirmed by flow cytometric analysis using Ki67 antibody and Annexin V/propidium iodide (PI) dual staining. Western blotting revealed a decrease in expression levels of phospho-Akt, phospho-p44/42, and phospho-NF-κB p56 in cells administered Triphala, which indicated that the possible mechanism could involve downregulation of MAPK/ERK, PI3K/Akt/mTOR, and NF-κB/p53 signaling pathways, as was predicted. Conclusion . Triphala holds great promise for treating gynecological cancers. Although the favorable pharmacological properties have been preliminarily investigated in this study, further studies are still needed to uncover the sophisticated mechanism of Triphala in cancer therapy.

Prevalence of malnutrition is a common and serious issue responsible for the morbidity and mortality rate among hospitalized patients. We aimed to provide an actual and comprehensive situation of the nutritional characteristics, nutritional support and the risk factors for malnutrition among hospitalized patients in China.We analyzed the data from nutritionDay audit 2016 in China. The international daylong cross-sectional survey was performed on November 10th, 2016 via filling out several questionnaires regarding information on patients' illness, food intake history, weight change and nutritional care. Re-assessment of patients' outcome questionnaire was performed 30 days later.Total of 781 patients from 9 hospitals and 8 kinds of departments were enrolled in this report. Of these, malnutrition rate was 29.6%. Parenteral nutrition (251/344, 73.0%) was the primary nutrition support form in Chinese hospitals. However, 41.8% (136/325) of patients at nutritional risk or already diagnosed with malnutrition did not received any form of nutritional support, whereas 34.0% (155/456) well-nourished patients did. Patients with malnutrition had extended length of hospital stay and poor 30-day outcomes compared to well-nourished patients. Nutritional support could benefit nutritional risk or malnutrition patients, rather than well-nourished patients. Moreover, major lesion types, self-related health, food intake last week were independent risk factors of malnutrition (all p

This study investigated the effect of ammoniation pretreatment of corn stalk (CS) with different temperatures, ammonia proportions, and processing times on lignocellulolytic enzyme production in solid-state fermentation (SSF) by Lentinus edodes L-8. The total N content and lignocellulose contents of ammoniated corn stalk were determined for analysis of the effect of ammoniation pretreatment on lignocellulose structure. The variation patterns of enzyme activity were analyzed according to the enzyme data determined every 2 days during the fermentation. A 4% w/w high-temperature ammoniation pretreatment had a significant effect on cellulase production, and the highest enzyme activity reached almost triple that of the control group. The results also showed that ammoniation pretreatment inhibited the generation of ligninases, such that ligninases appeared later and at lower activities in experimental groups compared to the control group.

A numerical method is proposed to determine the heat transfer capability of the high-temperature heat pipe and the stagnation temperature with supersonic vehicle leading edge applications. The finite element method is employed here to perform the temperature field simulation. Without considering the heat transfer limitations of the heat pipe, such as capillary limit and sonic limit, both numerical and experimental results indicate that equivalent high thermal conductivity method is a reasonable way to simulate the heat transfer capability of the high-temperature heat pipe in preliminary design of a heat-pipe-cooled leading edge. Several important parameters’ effects on the thermal protection performance are also numerically investigated.

PURPOSE: The purpose of this study was to evaluate the accuracy of multidetector computed tomography (MDCT) in the preoperative staging of renal cell carcinoma (RCC). MATERIALS AND METHODS: We retrospectively reviewed the clinical and pathological records of 312 patients with RCC who underwent staging MDCT before surgery. Radiographic findings were compared to the findings at surgery and pathological examination. All staging used 2009 updated TNM classification. RESULTS: The difference in tumor size between radiographic and pathological findings was 0.21cm. In T1a group, the difference was 0.33cm. Agreement between MDCT and histopathological findings was moderate for T staging (Kappa = 0.469), fair for N staging (Kappa = 0.322), and excellent for M staging (Kappa = 0.932). The sensitivity and specificity of MDCT in detecting perinephric fat invasion were 32.26% and 85.87%, in detecting tumor thrombosis were 84% and 100%, in detecting adrenal gland invasion were 60% and 95.79%, in detecting lymph node involvement were 50% and 96.36%, in detecting distant metastasis were 100% and 99.67%, respectively. In regard to stage grouping, 237 of 314 patients were correctly staged by MDCT, with an overall accuracy of 75.48%. CONCLUSIONS: MDCT with a dynamic contrast protocol is able to delineate RCC with high accuracy. However, a great portion of tumors were overstaged by MDCT because of overestimation of tumor size and poor visualization of infiltration of the perinephric fat. In addition, nodal metastatic lesion evaluation relies on node size only and remains a difficult task.

The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus.

Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes.