Search

Objectives: This study aimed to explore the dignity and related factors among older adults in long-term care facilities. Methods: Cross-sectional data were obtained from a sample of 253 Chinese older adults dwelling in long-term care facilities. Dignity among older adults was measured using the Dignity Scale, and its potential correlates were explored using multiple linear regressions. Results: Results showed that the total score of the Dignity Scale is 151.95 ± 11.75. From high to low, the different factors of dignity among older adults in long-term care facilities were as follows: caring factors (4.83 ± 0.33), social factors (4.73 ± 0.41), psychological factors (4.66 ± 0.71), value factors (4.56 ± 0.53), autonomous factors (4.50 ± 0.57), and physical factors (4.38 ± 0.55). A higher score of the Dignity Scale was associated with higher economic status, fewer chronic diseases, less medication, better daily living ability and long-time lived in cities. Conclusion: Older adults with low economic status, more chronic diseases, and poor daily living ability, taking more medications, or the previous residence in rural areas seem to be most at low-level dignity in long-term care facilities and thus require more attention than their peers.

ObjectivesThis study aimed to evaluate the willingness of patients with HIV/AIDS in Henan province to accept mobile information follow-up, to find the key factors that affect behavioral willingness to accept such follow-up, to explore the internal mechanism of the mobile service, and to provide a theoretical rationale for the further promotion of mobile follow-up.MethodsThis study used the technology acceptance model (TAM) as its main theoretical tool, which adopted a stratified random sampling method, and investigated 284 patients with HIV/AIDS in area six of Sanmenxia City. An on-site questionnaire survey method was adopted for this study. Confirmatory factor analysis was used for structural validity, with Cronbach's coefficient used for reliability. Data analysis mainly used SPSS23.0 and AMOS23.0 software.ResultsThe acceptance rate of the HIV/AIDS mobile follow-up service was 68.53%. In the study, product factors (PFs) were considered important in the indirect path of the TAM. Our TAM model suggested that high perceived usefulness (PU), perceived ease of use (PEU), and perceived innovativeness (PI) of the service were significant in improving mobile health (mHealth) acceptance among patients with HIV/AIDS in China. Subjective norms (SNs) also contributed to popularizing the service in the HIV/AIDS community. The model fitting was considered acceptable (root mean square error of approximation, RMSEA = 0.074; goodness of fit index, GFI = 0.905; comparative fit index, CFI = 0.963, and Tucker-Lewis index, TLI = 0.593).ConclusionPFs and SNs exerted an important influence on the behavioral intentions of the patients with HIV/AIDS who accepted mobile health. PU was another important factor affecting behavioral intention. The practicality of mHealth services was crucial. Convenience and the innovativeness of the experience with the service will be conducive to the promotion and use of mHealth follow-up services.

Background: One of the most common types of neurodegenerative diseases (NDDs) is Lewy body disease (LBD), which is characterized by excessive accumulation of α-synuclein (α-syn) in the neurons and affects around 6 million individuals globally. In recent years, due to the environmental factors that can affect the development of this condition, such as exposure to herbicides and pesticides, so it has become a younger disease. Currently, the vast majority of studies on the neurotoxic effects of paraquat (PQ) focus on the late mechanisms of neuronal-glial network regulation, and little is known about the early origins of this environmental factor leading to LBD. Objective: To observe the effect of PQ exposure on intestinal function and to explore the key components of communicating the gut-brain axis by establishing a mouse model. Methods and results: In this study, C57BL/6J mice were treated by intraperitoneal injection of 15 mg/kg PQ to construct an LBD time-series model, and confirmed by neurobehavioral testing and pathological examination. After PQ exposure, on the one hand, we found that fecal particle counts and moisture content were abnormal. on the other hand, we found that the expression levels of colonic tight junction proteins decreased, the expression levels of inflammatory markers increased, and the diversity and abundance of gut microbiota altered. In addition, pathological aggregation of α-syn was consistent in the colon and midbrain, and the metabolism and utilization of short-chain fatty acids (SCFAs) were also markedly altered. This suggests that pathological α-syn and SCFAs form the gut may be key components of the communicating gut-brain axis. Conclusion: In this PQ-induced mouse model, gut microbiota disruption, intestinal epithelial barrier damage, and inflammatory responses may be the main causes of gut dysfunction, and pathological α-syn and SCFAs in the gut may be key components of the communicating gut-brain axis.

Introduction Unexpected premature delivery and separation from preterm infants are common problems that parents of preterm infants must handle with. Parents of preterm infants may suffer from severe psychological distress. Family-centred care (FCC) can effectively ease parents’ psychological distress and strengthen connections between parents and their preterm infants. The purpose of this systematic review will be to systematically review and evaluate the impacts of FCC interventions on the mental health of parents of preterm infants and the parent–infant relationship.Methods and analysis This protocol for this systematic review will be conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol. We will search databases including PubMed, Embase, The Cochrane Library, CINAHL, Web of Science, PsycINFO, Scopus and ProQuest, CNKI, SinoMed and Wanfang Data from 1 July 2012 to 1 July 2022. An additional search of OpenGrey will be conducted to identify grey literature. Randomised controlled trials related to FCC inventions for preterm infants≤37 weeks’ gestational age and their parents will be included, and the outcome measures will be parental mental health and parent–infant interaction. Two reviewers will independently conduct title and abstract screening, full-text screening, data extraction and study quality assessment. Risk of bias for the studies will be evaluated using the Cochrane Collaboration Risk of Bias V.2.0. Any disagreements will be solved by a third reviewer to reach a consensus. If appropriate, a meta-analysis will be conducted to assess the effect of FCC on parental mental health and parent–infant relationship.Ethics and dissemination Research ethics approval will not be required for this review since it will not involve the collection of primary data and will only use published literature. The results will be disseminated in a peer-reviewed journal through publication or by presentation at relevant academic conference.PROSPERO registration number CRD42022299203.

Body image (BI) is a multidimensional construct that refers to one’s perceptions of and attitudes toward one’s own physical characteristics. Adolescence is a critical developmental stage in which concerns about BI increase. Therefore, the present cross-sectional study aimed to evaluate body image and aesthetic body shape standards in a sample of middle school students living in China. The researchers gathered demographic information, as well as height and weight data, for their study. They used a body silhouette to assess body image perception and body shape aesthetics and calculated two indexes: BIP, which measures the accuracy of self-perception and the estimation of bodily dimensions, and BIS, which indicates the difference between an individual’s perceived and ideal body images. A total of 1585 students in three grades at two middle schools were included in the study (759 = female, mean age = 13.67 ± 0.90; 839 = male, mean age = 13.70 ± 0.90). The results showed that the BIP bias rate of middle school students was 55.7%, and the BI dissatisfaction rate was 81.0%. Females tended to overestimate their body shape and desire to be thinner compared to males. Students with a higher BMI grading were more prone to underestimating their body shape and aspiring to be thinner. Furthermore, 8.6% of students chose underweight as the ideal body type for boys, while 22.6% chose underweight as the ideal body type for girls. In conclusion, there are significant gender differences in the aesthetic standards of body shape, and adolescents believe that for women, a thin body shape is beautiful.

Objective:To observe the effect of sling exercise therapy on adolescent patients with idiopathic non-double-curved scoliosis.Methods:A total of 42 adolescent patients with idiopathic non-double-curved scoliosis who were treated in the department of rehabilitation medicine of Zhongda Hospital Southeast University from June to December 2019, which were randomly divided into the control group and the observation group according to the random number table method, with 21 cases in each group. The both groups were given conventional rehabilitation therapy, which including muscle and fascia relaxation in the concave spine(five minutes a time), respiratory therapy(six times per group, three groups a day, rest for 40 second between two groups), traction therapy(30 minutes a time). The control group was given mat training on the basis of conventional rehabilitation therapy, including double bridge, tummy roll, left or right plank movement, each movement training 8-10 times, continous training 4-6 groups, rest for 40-60 s between two groups. The observation group was given sling exercise therapy on the basis of conventional rehabilitation therapy, which including neutral position control training in supine position, lateral position and prone position(record the training time and terminate the exercise if patients experience pain or fatigue, each movement training 8-10 times, continous training 4-6 groups, rest for 40-60 s between two groups). The above training was conducted once every other day, three times a week, continous training for six months. Before treatment and after treatment for six months, Cobb angle was used to evaluate the severity of scoliosis; clavicular angle(CA)was used to evaluate the degree of shoulder imbalance; pelvic obliquity(PO)was used to evaluate the degree of pelvic imbalance; scoliosis research association-22 item questionnaire(SRS-22)was used to evaluate the patients'self-image satisfaction.Results:Before treatment, there were no significant differences in Cobb angle, CA, PO and SRS-22 scores between the two groups(P>0.05).Compared with before treatment, Cobb angle, CA and PO in both groups were significantly decreased, and SRS-22 score was significantly increased, with statistical significance(PP

BackgroundAbnormal glycolipid metabolism plays a crucial role in hypertension. While an elevated triglyceride-glucose (TyG) index has been recognized as a risk factor for developing hypertension, the associations between the TyG index and different hypertension subtypes, namely, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH), remain unclear. This study was designed to investigate the associations between the TyG index and hypertension subtypes in a general Chinese population.Materials and methodsIn a sample of 16,793 participants from Shandong Province, China, multivariate logistic regression analyses were performed to examine the associations between the TyG index and different hypertension subtypes. Loess smooth curves were fitted to visualize the trends. Stratified analyses were conducted to further assess the potential interactions in the associations between the TyG index and different hypertension subtypes.ResultsA higher TyG index was associated with an increased odds of having IDH (OR = 2.94, 95% CI: 1.66–5.23) and SDH (OR = 1.82, 95% CI: 1.33–2.49), whereas no apparent relationship was observed between TyG index and ISH. With respect to sex, the effect of TyG index on having IDH and SDH was significant in women, but not in men. Participants with lower lipid profiles and glucose levels demonstrated a stronger strength of association between the TyG index and IDH as compared with the TyG index-SDH association. Stratified analysis showed that participants with a higher TyG index were more than 3 times more likely to have IDH and SDH among persons aged 18–42 years. Significant interactions were observed between TyG index and sex, age, and high-density lipoprotein cholesterol (HDL-C) in the SDH group, and a significant interaction was also found between TyG index and body mass index (BMI) in the ISH group.ConclusionTriglyceride-glucose index may potentially serve as a novel indicator for IDH and SDH. Our findings could also inform the development and implementation of targeted screening for hypertension.

The human programmed cell death 4 (PDCD4) gene was mapped at chromosome 10q24 and encodes the PDCD4 protein comprised of 469 amino acids. PDCD4 inhibits protein translation PDCD4 inhibits protein translation to suppress tumor progression, and its expression is frequently decreased in breast cancer. PDCD4 blocks translation initiation complex by binding eIF4A via MA-3 domains or by directly binding 5’ mRNA internal ribosome entry sites with an RNA binding domain to suppress breast cancer progression and proliferation. Numerous regulators and biological processes including non-coding RNAs, proteasomes, estrogen, natural compounds and inflammation control PDCD4 expression in breast cancer. Loss of PDCD4 expression is also responsible for drug resistance in breast cancer. HER2 activation downregulates PDCD4 expression by activating MAPK, AKT, and miR-21 in aromatase inhibitor-resistant breast cancer cells. Moreover, modulating the microRNA/PDCD4 axis maybe an effective strategy for overcoming chemoresistance in breast cancer. Down-regulation of PDCD4 is significantly associated with short overall survival of patients, which suggests that PDCD4 may be an independent prognostic marker for breast cancer.

The paper established the evaluation index system of training quality of high-level tennis team, which comprising five first-class indexes: work planning evaluation index (i = 4) includes realistic state diagnosis, training goal establishment, specific training content, and training plan formulation; work implementation evaluation index (i = 4) includes training guarantee conditions, training plan implementation, training process monitoring, and training plan adjustment; work monitoring evaluation index (i = 5) includes physical function, physical fitness, sports technique, sports tactics, and sport psychology; the evaluation index of team work management (i = 2) is the team training management and team organization management; and the competition performance index (i = 2) includes the results of large-scale events and the trend of sports talents. Each index of the system was obtained by sorting analysis of radar chart. The weight table of evaluation index was calculated by analytic hierarchy process. Therefore, the evaluation index system of training quality of high-level tennis team constructed in this study aims to provide reference for real-time monitoring, comprehensive evaluation, and diagnostic evaluation of each link of high-level tennis team training.

Abstract Background Airway management, including noninvasive endotracheal intubation or invasive tracheostomy, is an essential treatment strategy for patients with deep neck space abscess (DNSA) to reverse acute hypoxia, which aids in avoiding acute cerebral hypoxia and cardiac arrest. This study aimed to develop and validate a novel risk score to predict the need for airway management in patients with DNSA. Methods Patients with DNSA admitted to 9 hospitals in Guangdong Province between January 1, 2015, and December 31, 2020, were included. The cohort was divided into the training and validation cohorts. The risk score was developed using the least absolute shrinkage and selection operator (LASSO) and logistic regression models in the training cohort. The external validity and diagnostic ability were assessed in the validation cohort. Results A total of 440 DNSA patients were included, of which 363 (60 required airway management) entered into the training cohort and 77 (13 required airway management) entered into the validation cohort. The risk score included 7 independent predictors (p < 0.05): multispace involvement (odd ratio [OR] 6.42, 95% confidence interval [CI] 1.79–23.07, p < 0.001), gas formation (OR 4.95, 95% CI 2.04–12.00, p < 0.001), dyspnea (OR 10.35, 95% CI 3.47–30.89, p < 0.001), primary region of infection, neutrophil percentage (OR 1.10, 95% CI 1.02–1.18, p = 0.015), platelet count to lymphocyte count ratio (OR 1.01, 95% CI 1.00–1.01, p = 0.010), and albumin level (OR 0.86, 95% CI 0.80–0.92, p < 0.001). Internal validation showed good discrimination, with an area under the curve (AUC) of 0.951 (95% CI 0.924–0.971), and good calibration (Hosmer–Lemeshow [HL] test, p = 0.821). Application of the clinical risk score in the validation cohort also revealed good discrimination (AUC 0.947, 95% CI 0.871–0.985) and calibration (HL test, p = 0.618). Decision curve analyses in both cohorts demonstrated that patients could benefit from this risk score. The score has been transformed into an online calculator that is freely available to the public. Conclusions The risk score may help predict a patient’s risk of requiring airway management, thus advancing patient safety and supporting appropriate treatment.

A semi-active wavelength division multiplexing (WDM) system based on pilot-tone relay detection is proposed and experimentally demonstrated for 5G centralized front-haul network, which is composed of a passive WDM multiplexer at active antenna unit (AAU) side, an active WDM equipment at distributed unit (DU) side, and several WDM optical modules in AAU and DU, respectively. In this semi-active WDM scheme, WDM technology is applied as an optical transport layer to save fibers and the semi-active architecture based on pilot-tone modulation is capable of flexible deployment with lite operation, administration and maintenance (OAM) functions. The experimental results show that the sensitivity penalty is lower than 0.3 dB and the extinction ratio is still higher than 4.2 dB by using 4 % amplitude depth of pilot-tone modulation. The bit rate of the OAM signal is 1024 bps to reuse the existing micro-controller unit in the optical modules for generating and detecting OAM signals. The robustness of the pilot-tone signals is further demonstrated as the sensitivities of the 25-Gbps eCPRI signals and the 1024-bps OAM signals are −16 dBm and −23 dBm, respectively. Compared with the OAM demodulation both in upstream and downstream direction for the active WDM equipment, the number of OAM demodulation unit can be reduced by 50% and the sensitivity requirement of OAM demodulation can be improved by 11.5 dB by using only downstream OAM demodulation unit. Error-free 24-hour transmission of real-time 12-channel 25-Gbps eCPRI signals combined with 1024-bps pilot-tone OAM signals over 10-km single mode fiber is obtained.

Background:Although coronavirus disease 2019 (COVID-19) is considered to be a disease that mainly involves the respiratory system, an increasing number of studies have reported that COVID-19 patients had pancreatic enzymes (PE) elevation and even pancreatic injury. The study aims to determine the prevalence of PE elevation, and the relationship between elevated PE and prognosis in COVID-19 patients.MethodsA comprehensive literature search was conducted according to the PRISMA guideline in PubMed, Embase, Scopus, Web of Science, and Google Scholar for studies reporting PE elevation in patients with COVID-19 from 1st January 2020 to 24th November 2021.ResultsA total of 13 studies (24,353 participants) were included in our review. The pooled prevalence of PE elevation in COVID-19 patients was 24% (18%–31%), the pooled odds ratio (OR) of mortality was 2.5 (1.7–3.6), the pooled OR of ICU admission was 4.4 (2.8–6.8), and the pooled OR of kidney injury, respiratory failure and liver injury were 3.5 (1.6–7.4), 2.0 (0.5–8.7), and 2.3 (1.4–3.9) respectively. In addition, the subgroup analysis revealed that although PE elevated to > 3 × upper normal limit (ULN) was significantly related to the mortality (OR = 4.4, 2.1–9.4), it seemed that mild elevation of PE to 1–3 ULN also had a considerable risk of mortality (OR = 2.3, 1.5–3.5).ConclusionsPE elevation was a common phenomenon in patients with COVID-19, and was associated with poor clinical outcomes. However, due to the limited numbers of included studies, the result of our study still needed to be validated.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=295630, identifier: CRD42021295630.

C-RAN may be a promising way for 5G fronthaul network associated with significant changes in 5G fronthaul architecture.Based on the analysis of existing schemes such as optical fiber direct connection,passive WDM and active WDM/OTN,open wavelength division multiplexing (open-WDM) system was proposed to satisfy the new requirements of 5G fronthaul network.In the open-WDM system,WDM technology is used to save optical fiber resource and the semi-active architecture can achieve flexible deployment.The low-cost management and control technology was further applied to perform efficiently network operation.

Abstract Background Interleukin-6 (IL-6) was proposed to be associated with the severity of coronavirus disease 2019 (COVID-19). The present study aimed to explore the kinetics of IL-6 levels, validate this association in COVID-19 patients, and report preliminary data on the efficacy of IL-6 receptor blockade. Methods We conducted a retrospective single-institutional study of 901 consecutive confirmed cases. Serum IL-6 concentrations were tested on admission and/or during hospital stay. Tocilizumab was given to 16 patients with elevated IL-6 concentration. Results 366 patients were defined as common cases, 411 patients as severe, and 124 patients as critical according to the Chinese guideline on diagnosis and treatment of COVID-19. The median concentration of IL-6 was

The large-scale deployment of 5G brings bandwidth and lower delay requirements to transport network.As a 5G oriented multi-service transport platform,SPN will transport wireless service,home broadband service,enterprise service and private line service.SPN distribution layer and core layer network will need huge bandwidth and support long range transport.The SPN optical layer key technology and network scheme were studied,also implemented to verify the function and performance of SPN optical layer.

ABSTRACTThe ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.

Neurons are highly polarized and post-mitotic cells with the specific requirements of neurotransmission accompanied by high metabolic demands that create a unique challenge for the maintenance of cellular homeostasis. Thus, neurons rely heavily on autophagy that constitutes a key quality control system by which dysfunctional cytoplasmic components, protein aggregates, and damaged organelles are sequestered within autophagosomes and then delivered to the lysosome for degradation. While mature lysosomes are predominantly located in the soma of neurons, the robust, constitutive biogenesis of autophagosomes occurs in the synaptic terminal via a conserved pathway that is required to maintain synaptic integrity and function. Following formation, autophagosomes fuse with late endosomes and then are rapidly and efficiently transported by the microtubule-based cytoplasmic dynein motor along the axon toward the soma for lysosomal clearance. In this review, we highlight the recent knowledge of the roles of autophagy in neuronal health and disease. We summarize the available evidence about the normal functions of autophagy as a protective factor against neurodegeneration and discuss the mechanism underlying neuronal autophagy regulation. Finally, we describe how autophagy function is affected in major neurodegenerative diseases with a special focus on Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis.

Desmoplasia is a hallmark of intrahepatic cholangiocarcinoma (ICC), which constitutes a barrier to infiltration of lymphocyte, but not myeloid cells. Given that dense desmoplastic stroma has been reported to be a barrier to infiltration of lymphocyte, but not myeloid cells. We here investigated whether fibroblastic FAP influenced ICC progression via non-T cell-related immune mechanisms. We demonstrated fibroblastic FAP expression was critical for STAT3 activation and CCL2 production, and ICC-CAFs were the primary source of CCL2 in human ICC microenvironment by using ICC-Fbs from six ICC patients. Fibroblastic knockdown of FAP significantly impaired the ability of ICC-CAFs to promote ICC growth, MDSCs infiltration and angiogenesis, which was restored by adding exogenous CCL2. Furthermore, interestingly, the tumor-promoting effect of fibroblastic FAP is dependent on MDSCs via secretion of CCL2, as depletion of Gr-1+ cells reversed the restoring effects of exogenous CCL2 on tumor growth and angiogenesis. In vitro migration assay confirmed that exogenous CCL2 could rescue the impaired ability of ICC-Fbs to attract Gr-1+ cells caused by fibroblastic FAP knockdown. In contrast, fibroblastic FAP knockdown had no effect on ICC cell proliferation and apoptotic resistance. Depletion MDSCs by anti-Gr-1 monoclonal antibody in subcutaneous transplanted tumor model abrogated tumor promotion by ICC-CAFs suggested that the pro-tumor function of Fibroblastic FAP relied on MDSCs. Mechanical, flow cytometry and chamber migration assay were conducted to find Fibroblastic FAP was required by the ability of ICC-CAFs to promote MDSC migration directly. Moreover, fibroblastic FAP knockdown had no effect on cell proliferation and apoptotic resistance. Here, we revealed the T-cell independent mechanisms underlying the ICC-promoting effect of fibroblastic FAP by attracting MDSCs via CCL2, which was mainly attributed to the ability of FAP to attract MDSCs and suggests that specific targeting fibroblastic FAP may represent a promising therapeutic strategy against ICC.

The immune checkpoint molecule, B7-H3, which belongs to the B7 family, has been shown to be overexpressed in various cancers. Its role in tumors is not well defined, and many studies suggest that it is associated with poor clinical outcomes. The effect of B7-H3 on laryngeal cancer has not been reported. This study investigated the expression of B7-H3 in laryngeal squamous cell carcinoma (LSCC), and its relationship with clinicopathological factors and prognosis of LSCC patients. The gene expression quantification data and clinical data of LSCC retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were analyzed to determine the diagnostic and prognostic roles of B7-H3. Quantitative real-time polymerase chain reaction (qRT-PCR) was then performed to determine the gene expression level of B7-H3 between LSCC tissues and paired normal adjacent tissues. In addition, TCGA RNA-seq data was analyzed to evaluate the expression level of B7 family genes. Next, the protein expression of B7-H3 and CD8 in LSCC was determined using immunohistochemistry and immunofluorescence. qRT-PCR results showed that the expression level of B7-H3 mRNA was significantly higher in LSCC tissues than in adjacent normal tissues. Similar results were obtained from the TCGA analysis. The expression of B7-H3 was significantly associated with T stage, lymph node metastasis, and pathological tumor node metastasis (TNM) stage, and it was also an independent factor influencing the overall survival time (OS) of patients with LSCC. In addition, B7-H3 was negatively correlated with CD8+T cells. These results show that B7-H3 is upregulated in LSCC. Therefore, B7-H3 may serve as a biomarker of poor prognosis and a promising therapeutic target in LSCC.

Introduction Macrophages are capable of exerting both proinflammatory and anti-inflammatory functions in response to distinct environmental stimuli, by polarizing into classically inflammatory state (M1) and anti-inflammatory phenotype (M2), respectively. The Wnt/β-catenin signaling plays an important role in the tissue homeostasis and immune regulations, including the macrophage polarizations. However, the molecular mechanism of Wnt/β-catenin signaling in regulating alveolar macrophage polarization in an inflammatory state remains unclear. Methods The Wnt/β-catenin signaling-altered phenotypes of murine macrophage-like RAW264.7 cells in vitro and alveolar macrophage in vivo in both of naïve and lipopolysaccharide-induced inflammation states were accessed by immunoblotting and immunostaining assays. Results The activation of Wnt/β-catenin signaling inhibited macrophage M1 polarization, but promoted alternative M2 polarization in murine RAW264.7 cells under a naïve state. Interestingly, in an LPS-induced inflammation condition, the enhanced Wnt/β-catenin activity suppressed both M1 and M2 polarizations in RAW264.7 cells in vitro, and primary alveolar macrophages of LPS-challenged mice in vivo . Molecular analysis further demonstrated an involvement of Stat signing in regulating Wnt/β-catenin signaling-altered polarizations in mouse alveolar macrophages. Conclusion These results suggest a mechanism by which Wnt/β-catenin signaling modulates macrophage polarization in an inflammation state by regulating the Stat signaling pathway.

Background: Improvement in depression screening and treatment has emerged as a national priority in the US. This study examined temporal trends in prevalence of sub-populations of individuals with past-year major depressive episode (MDE), including those with suicidal ideation (SI), a suicide plan or attempt (SP/SA), and treatment-resistant depression (TRD). Methods: Using the National Survey on Drug Use and Health (NSDUH; 2009–2017), yearly prevalence and trends over time of sub-populations among US adults overall and among those with MDE were determined; prevalence estimates were stratified by sociodemographic characteristics. Results: Over the 9-year period, prevalence of MDE+SI increased significantly by 29.3%, from 1.7% to 2.2% (adjusted odds ratio [aOR]=1.38, 95% CI=1.20–1.59); the increase was most prominent among young adults, women, Caucasians, and Native Americans/Alaskan Natives. Among those with MDE, prevalence of SI increased by 21.2%, from 25.6% to 31.1% (aOR=1.25, 95% CI=1.06–1.48). Among those with an MDE in 2017, 31.1% reported SI, 11.5% reported a SP/SA, 9.1% had TRD, and 4.3% experienced TRD+SI. Limitations: The NSDUH is based on self-report data; rates of diagnoses and SI from objective assessments and clinical evaluations may be different. Additionally, the survey is cross-sectional rather than longitudinal. Conclusions: Substantial increases in the prevalence of SI among adults and among those with MDE were observed from 2009 to 2017; disproportionate trends were observed among some sociodemographic groups. These findings underscore the importance of understanding the reasons for these concerning trends, as well as the need for improvements in identification and treatment for at-risk individuals.

The activation of drugs within cellular systems may provide targeted therapies for cancer. Here, the authors make a drug delivery system that is activated within the cell and exploits XIAP expression to cleave a linker region, resulting in the self-assembly of the system and drug release within cancer cells.

Abstract Background To investigate whether the relative computed tomography (CT) value (rCT) of adjacent pancreatic parenchyma can distinguish focal‐type autoimmune pancreatitis (fAIP) from pancreatic ductal adenocarcinoma (PDAC). Methods A total of 13 patients with fAIP and 20 patients with PDAC were included in this study. The rCT was calculated as the ratio of the CT value of adjacent pancreatic parenchyma to that of muscle. The diagnostic performance of rCT for discriminating fAIP from PDAC was evaluated using receiver operating characteristic (ROC) analysis. Results Both fAIP and PDAC presented hyper‐fibrosis histologically and delayed enhancement on CT examination. Moreover, the pancreatic parenchyma of fAIP presented serious inflammation. The mean rCT of the parenchyma was significantly lower in fAIP than in PDAC in all phases. The best diagnostic performance of the rCT value was found in the pancreatic phase, with an area under the ROC curve of 0.912, while the areas under the ROC curve of the portal and delayed phases were 0.812 and 0.754, respectively. The optimal cut‐off value for distinguishing fAIP from PDAC was 1.62 in the pancreatic phase. Conclusions The rCT of the pancreatic parenchyma during the pancreatic phase may be a feasible CT feature for differentiating fAIP from PDAC.

Atractylodes DC. mainly includes Atractylodis Rhizoma and Atractylodis macrocephalae Rhizoma. According to Chinese Pharmacopoeia, Atractylodis Rhizoma is the rhizome of Atractylodes lancea (Thunb.) DC. (A. lancea) and Atractylodes chinensis (DC.) Koidz. (A. chinensis), while Atractylodis macrocephalae Rhizoma is the rhizome of Atractylodes macrocephala Koidz. (A. macrocephala). Although Atractylodes japonica Koidz. ex Kitam. (A. japonica) and Atractylodes coreana (Nakai) Kitam. (A. coreana) are not included in the Pharmacopoeia, they are often used as Atractylodis Rhizoma in northern China. But in Japan, A. japonica is used as Atractylodis macrocephalae Rhizoma. In order to compare the efficacy of A. japonica and A. coreana with that of Atractylodis Rhizoma and Atractylodis macrocephalae Rhizomain in Pharmacopoeia, this paper studies the anti rheumatism of the five medicinal species in Atractylodes DC., and provides the basis for the rational application of A. japonica and A. coreana. With this purpose, the rheumatoid model of rats was established by Freund's complete adjuvant. Then, Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF - α), arthritis factor (RF), anti cyclic citrullinated peptide (anti-CCP), interleukin-1β (IL-1β), Nuclear factor-κB (NF - κB), interleukin-10 (IL-10) and Prostaglandin E2 (PGE2) in rats of each group. Ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was used to analyze the plasma of each group. After that, multivariate statistical analysis method was used to analyze the data. The results showed that the five medicinal species in Atractylodes DC. can reduce the levels of IL-6, IL-1 β, PGE2 and NF - κB in the plasma of rheumatoid arthritis (RA) rats in varying degrees, among which the regulation of A. macrocephala is relatively weak. A. chinensis, A. lancea, A. coreana and A. japonica can significantly reduce the content of TNF - α, in which A. japonica and A. lancea have better and similar regulatory effects. A. chinensis and A. coreana can significantly reduce the content of RF in arthritis rats. A. coreana, A. lancea and A. japonica can significantly reduce the anti-CCP level, that is, the regulatory effect of A. coreana and A. chinensis is similar. The metabolic disorder of 11-deoxycortisol, taurocholate and other small molecules in the body of rats with RA directly affects the metabolic pathways of primary bile acid biosynthesis and steroid hormone biosynthesis, leading to the decline of immune function and other symptoms. Most of the metabolic pathways tend to be normal after oral administration of five medicinal species in Atractylodes DC. Among them, the regulating effect of A. coreana and A. chinensis is similar, while that of A. japonica and A. lancea are similar. A. macrocephala had little effect of intervention.

The sudden pandemic of SARS-Cov-2 (also known as novel coronavirus disease 2019, COVID-19) poses a severe threat to hundreds of millions of lives in the world. The complete cure of the virus largely relies on the immune system, which becomes particularly a challenge for the cancer subjects, whose immunity is generally compromised. However, in a constant evolving situation, the clinical data on the prevalence of SARS-Cov-2 for cancer patients is still limited. On top of a wide range of medical references and interim guidelines including CDC, NCI, ASCO, ESMO, NCCN, AACR, ESMO, and the National Health Commission of China, etc., we formed into a guideline based on our experience in our specialized cancer hospital in Wuhan, the originally endemic center of the virus. Furthermore, we formulated an expert consensus which was developed by all contributors from different disciplines after fully discussion based on our understanding and analysis of limited information of COVID-19. The consensus highlighted a multidisciplinary team diagnostic model with assessment of the balance between risks and benefits prior to treatment, individualizing satisfaction of patients’ medical needs, and acceptability in ethics and patients’ socio-economic conditions.

Abstract Background Mitochondrial dysfunction has been implicated in the pathogenesis of ischemic heart disease, exacerbating cardiomyocytes injury in myocardial infarction (MI). Peroxisome proliferator-activated receptor gamma co-activator (PGC-1α) has been recognized as the key regulator of mitochondrial biogenesis and energy metabolism. Yiqihuoxue decoction (YQHX), a Traditional Chinese Medicine (TCM) prescription, can prevent and treat ischemic heart disease. However, the mechanisms of YQHX on PGC-1α expression in the ischemic heart have remained unclear. Methods Myocardial ischemia rat model and ischemia/hypoxia injury model in the cardiomyocytes were used to minic human cardiovascular disease. Rats were randomly assigned into 4 groups: Sham, Model, YQHX (8.2 g/kg) and Trimetazidine (10 mg/kg) group. 28 days after MI, cardiac functions and morphology were detected by echocardiography and HE staining, respectively. In vitro, the effects of YQHX on H9c2 cell viability, LDH and ROS were detected, respectively. PGC-1α relevant proteins were evaluated by Western blotting. Results In vivo, echocardiography and HE staining results showed that YQHX improved cardiac functions and modified pathological changes. YQHX enhanced PGC-1α expression and improved the mitochondrial ultrastructure and functions in rats MI model for 4 weeks. Further, we explored its potential mechanisms in cardiomyocytes. In vitro, YQHX significantly enhanced cell viability and reduced LDH release and ROS production induced by hypoxia in cardiomyocytes. Interestingly, exposure of cardiomyocytes to hypoxic conditions for 12 h induced the downregulation of PGC-1α expression, but the expression levels nearly returned to the normal state after hypoxia for 24 h. YQHX significantly enhanced PGC-1α expression between 12 h and 24 h induced by hypoxia through a mechanism associated with the activation of AMPK phosphorylation in H9c2 cells. In addition, YQHX upregulated the expression of Tfam and NRF-1, while NRF-1 expression was completely blocked by an AMPK inhibitor. YQHX largely restored the mitochondrial morphology and increased mitochondrial membrane potential in hypoxia-induced injury. Furthermore, the UHPLC-LTQ-Orbitrap-MSn analysis found that there were 87 chemical constituents in YQHX. Conclusions These results suggest that the protective effect of YQHX on cardiomyocytes against hypoxia-induced injury may be attributed to activation of PGC-1α and maintenance of mitochondrial functions through a mechanism involving the activation of AMPK phosphorylation.

Objective: Yiqi Huoxue Decoction (YQHX) has been widely used for clinical treatment of ischemic heart disease. While oxidative stress plays a key role in the pathogenesis of ischemic heart disease, the function and molecular mechanism underlying antioxidative protective effects of YQHX on H9c2 cardiomyocytes against ischemia/hypoxia (I/H) have yet to be well clarified. Methods: H9c2 cells were subjected to 12 h of hypoxia with serum-free conditions and then treated with or without YQHX (100–400 μg/mL). Cell viability was examined using a CCK-8 assay. Maleic dialdehyde (MDA) and superoxide dismutase (SOD) activity were detected using commercial kits. Intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential were measured using fluorescence microscopy and confocal laser-scanning microscopy, respectively. Ultrastructural details of mitochondria in H9c2 cells were observed using transmission electron microscopy. The antioxidative protective pathway was assessed by measuring mRNA and protein expression of Nrf2 and HO-1, as well as AMPK activation. Results: I/H injury gradually induced oxidative stress. Treatment with YQHX significantly increased cell viability and reversed I/H-induced oxidative stress, including reducing the production of oxidative stress products (ROS and MDA), increasing SOD levels, improving mitochondrial morphology, and increasing mitochondrial membrane potential. YQHX was also observed to increase I/H-induced expression of Nrf2 and HO-1, and the activation effects of YQHX were blocked by an AMPK inhibitor. In addition, HPLC analysis showed that YQHX contained two active antioxidative constituents (calycosin and ferulic acid). Conclusion: The results suggest that anti-oxidative effects exerted by YQHX in H9c2 cardiomyocytes may be linked to upregulation of the AMPK-mediated Nrf2/HO-1 pathway. Keywords: Hypoxia, Yiqi Huoxue Decoction, Chinese medicine, Cardiomyocytes, Oxidative stress

Abstract Background Brain metastasis (BM) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). Recent studies demonstrated that microRNA-330-3p (miR-330-3p) was involved in NSCLC brain metastasis (BM). However, the exact parts played by miR-330-3p in BM of NSCLC remain unknown. Discovery and development of biomarkers and elucidation of the mechanism underlying BM in NSCLC is critical for effective prophylactic interventions. Here, we evaluated the expression and biological effects of miR-330-3p in NSCLC cells and explored the underlying mechanism of miR-330-3p in promoting cell migration and invasion in NSCLC. Methods Stable over-expression and knockdown of miR-330-3p in NSCLC cells was constructed with lentivirus. Expression levels of miR-330-3p in NSCLC cells were quantified by quantitive real-time PCR (qRT-PCR). The effects of miR-330-3p on NSCLC cells were investigated using assays of cell viability, migration, invasion, cell cycle, apoptosis, western blotting, immunohistochemical, and immunofluorescence staining. A xenograft nude mouse model and in situ brain metastasis model were used to observe tumor growth and brain metastasis. The potential target of miR-330-3p in NSCLC cells was explored using the luciferase reporter assay, qRT-PCR, and western blotting. The miR-330-3p targets were identified using bioinformatics analysis and verified by luciferase reporter assay. The correlation between GRIA3 and DNA methyltransferase (DNMT) 1 and DNMT3A was tested by RT-PCR, western blotting, and co-immunoprecipitation (IP). Results miR-330-3p was significantly up-regulated in NSCLC cell lines. MTT assay, transwell migration, and invasion assays showed that miR-330-3p promoted the growth, migration, and invasion of NSCLC cells in vitro and induced tumor growth and metastasis in vivo. Luciferase reporter assays showed that GRIA3 was a target of miR-330-3p. qRT-PCR and western blotting exhibited that miR-330-3p promoted the growth, invasion, and migration of NSCLC cells by activating mitogen-activated protein kinase (MAPK)/extracellular-regulated protein kinases (ERK) signaling pathway. Furthermore, miR-330-3p up-regulated the total DNA methylation in NSCLC cells, and co-IP-demonstrated GRIA3 was directly related with DNMT1 and DNMT3A. Conclusions miR-330-3p promoted the progression of NSCLC and might be a potential target for the further research of NSCLC brain metastasis.

BackgroundMany patients with major depressive disorder (MDD) fail to respond to antidepressant (AD) pharmacotherapy. The objectives of this study were to characterize MDD and treatment-resistant depression (TRD) at the level of pharmacologically treated episodes and to describe the sequential treatment patterns by lines of therapy (LOT) in the first two episodes.MethodsAdults (≥18 years of age) with continuous enrollment ≥12 months before and after the first MDD diagnosis and treated with an AD, with or without an MDD-indicated antipsychotic (AP), were identified (1/1/2010-12/31/2015). The MDD episode started on the date of MDD diagnosis that was preceded by a clean period without any MDD diagnosis. The MDD episode ended on the last MDD diagnosis or the end of the days' supply of AD/AP medication, whichever came last. TRD was defined as an MDD episode with ≥3 AD/AP regimens. Measured outcomes included episode duration, number of LOT, relapse hospitalization, and sequential treatment patterns of MDD episode stratified by TRD and non-TRD episodes.ResultsOf 48,440 patients who received AD/AP in the 1st MDD episode, 3,317 (6.8%) of episodes were considered TRD. Mean duration of 1st TRD episodes was 571 days, mean number of AD/AP LOTs was 3.47, and 13.7% involved relapse hospitalization. Mean duration of 1st non-TRD episodes was 200 days, mean number of AD/AP LOTs was 1.21, and 9.6% involved relapse hospitalization. Among 1st MDD episodes, 25.5% had a second LOT; 7.3% had a third LOT. Most patients received selective serotonin reuptake inhibitors (SSRIs) as the first LOT (63.0%), and the plurality of regimens were SSRIs in second (44.9%) and third LOT (41.1%).ConclusionsCompared to non-TRD episodes, TRD episodes were longer and more often involved relapse hospitalizations. SSRIs were the most common treatment; treatment changes and potential treatment unresponsiveness were frequent among MDD patients.

Copper-catalyzed (or -mediated) asymmetric coupling reactions have received significant attention over the past few years. Especially the coupling reactions of aryl or alkyl halides with nucleophiles became a very powerful tool for the formation of C–C, C–N, C–O and other carbon–heteroatom bonds as well as for the construction of heteroatom-containing ring systems. This review summarizes the recent progress in copper-catalyzed asymmetric coupling reactions for the formation of C–C and carbon–heteroatom bonds.

An amendment to this paper has been published and can be accessed via the original article.

Mitochondrial dysfunction is a central aspect of aging and neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. Mitochondria are the main cellular energy powerhouses, supplying most of ATP by oxidative phosphorylation, which is required to fuel essential neuronal functions. Efficient removal of aged and dysfunctional mitochondria through mitophagy, a cargo-selective autophagy, is crucial for mitochondrial maintenance and neuronal health. Mechanistic studies into mitophagy have highlighted an integrated and elaborate cellular network that can regulate mitochondrial turnover. In this review, we provide an updated overview of the recent discoveries and advancements on the mitophagy pathways and discuss the molecular mechanisms underlying mitophagy defects in Alzheimer’s disease and other age-related neurodegenerative diseases, as well as the therapeutic potential of mitophagy-enhancing strategies to combat these disorders.

Although the infectious diseases tuberculosis (TB) and cryptococcosis both cause formation of single or multiple nodules in immunodeficient hosts, cases of co-infection of these diseases are rarely seen. We report a patient who was co-infected with TB and cryptococcosis. A male patient with no clinical evidence of immunodeficiency presented with a 3-week history of abdominal distension accompanied by oedema of recurring lower extremities. The patient was diagnosed with tuberculous peritonitis and tuberculous pleurisy by an abdominal puncture biopsy. Several months after being treated for TB, the patient was diagnosed with Cryptococcus infection and received antifungal treatment. Computed tomographic and magnetic resonance imaging findings suggested that treatment was effective. This case illustrates the challenges encountered during assessment of neoplasms associated with TB and cryptococcosis. Differential diagnosis requires an abdominal puncture biopsy. Diagnosis of Cryptococcus infection also requires a positive cryptococcal culture and positive India ink staining analysis. Notably, our patient also showed no obvious symptoms of cryptococcosis after receiving anti-TB treatment. Accordingly, in this report, we discuss the possible pathogenic mechanisms that underlie the coincidence of both types of inflammatory lesions. We emphasize the need for a greater awareness of atypical presentations of TB accompanied by Cryptococcus infection.

This study documents information on significant ethnomedicinal plants, which was collected from the traditional healers of three indigenous communities of Bangladesh. The documented data were quantitatively analyzed for the first time in this area. The information was obtained through open-ended, semi-structured questionnaires. The benefits, importance and coverage of ethnomedicine were expressed through several quantitative indices including Informant Consensus Factor (ICF), Use Value (UV), Frequency of Citation (FC), Relative Frequency of Citation (RFC) and Relative Importance Index (RI). The agreement of homogeneity between the present and previous studies and among the indigenous communities was evaluated using the Jaccard Index (JI). A total of 159 ethnomedicinal plant species, which were distributed in 132 genera under 62 families, were documented from 174 informants. Of these, 128 plants were native and 31 were exotic. Of a majority of documented species, herbs and leaves were the most utilized plant parts for the preparation of ethnomedicines (45.28%) whereas pastes (63.03%) were the most popular formulations. Among the documented species, the dominant families were the Asteraceae (14 species) and the Lamiaceae (12 species). The highest ICF value was 0.77 for digestive system disorders. Based on UVs, the five most commonly used ethnomedicinal plant species in the study area were Duabanga grandiflora (0.43), Zingiber officinale (0.41), Congea tomentosa (0.40), Matricaria chamomilla (0.33) and Engelhardtia spicata (0.28). The highest RFC was recorded for Rauvolfia serpentina (0.25). The highest RI value was calculated for both Scoparia dulcis and Leucas aspera (0.83). Importantly, 16 species were reported with new therapeutic uses and to our knowledge, 7 species described herein have never been ethnobotanically and pharmacologically studied, viz: Agastache urticifolia, Asarum cordifolium, C. tomentosa, E. spicata, Hypserpa nitida, Merremia vitifolia and Smilax odoratissima. The present study showed that traditional treatment using medicinal plants is still widespread in the study area. Documentation of new ethnomedicinal species with their therapeutic uses shall promote further phytochemical and pharmacological investigations and possibly, lead to the development of new drugs.

Taraxacum officinale (Asteraceae) is widely distributed weedy plant used as a traditional medicinal herb. The population genetics and historical biogeography of this plant have remained relatively unexplored. This study explores phylogeny, population genetics and ancestral reconstructions adopting multi locus sequence typing (MLST) approach. MLST sequences dataset was generated from genomics and chloroplast DNA sequences obtained from 31 T. officinale haplotypes located in 16 different countries. Phylogenetic analysis distributed these haplotypes in well differentiated geographic clades. The study suggested a close relationship between Europe and adjacent Asian countries. Populations of these regions predominantly formed common haplogroups, showed considerable level of gene flow and evidence for recombination events across European and Asian population. Biogeographical inferences obtained by applying statistical dispersal-vicariance analysis (S-DIVA) and Bayesian binary MCMC (BBM) analysis showed that T. officinale was putatively originated in Europe. Molecular clock analysis based on ITS dataset suggested that the divergence between Europe and East Asian populations can be dated to 1.07 Mya with subsequent dispersal and vicariance events. Among different spatial process long distance seed dispersal mediated by wind had potentially assisted the population expansion of T. officinale.

BACKGROUND:Despite the increasing number of Crohn's disease patients self-administering nasogastric feeding as enteral nutrition support therapy, no studies have reported the experiences of self-administering nasogastric feeding from the perspective of these patients. OBJECTIVES:To explore the initial trigger factors for the self-administration of nasogastric feeding by Crohn's disease patients and to understand the experiences of self-administration of nasogastric feeding, its effects on various aspects of life and work, and relevant challenges and coping mechanisms encountered during this therapy in order to improve the understanding of this group of patients among medical staff and the public. DESIGN:This study adopted a descriptive qualitative method. Crohn's disease patients from several tertiary hospitals in Hangzhou, Zhejiang, were recruited to participate through purposive sampling combined with maximum variation and the snowballing technique. Data were collected using semi-structured interviews and analyzed using the conventional content analysis method. RESULTS:A total of 11 Crohn's disease patients were interviewed. Four themes and eight subthemes emerged from the analysis: rejecting the self-administration of nasogastric feeding (being afraid of inserting the nasogastric tube, having concerns about nasogastric feeding), accepting the reality of nasogastric feeding (health being the most important, followed by having sources of support), nasogastric feeding as a double-edged sword (the disturbances and efficacies of nasogastric feeding), and nasogastric feeding as a part of life (becoming accustomed to tube insertion and taking nasogastric feeding for granted). CONCLUSIONS:Apart from suffering from physical discomfort, diet and body image disturbances, and inconveniences in daily life, Crohn's disease patients who self-administered nasogastric feeding faced many psychological challenges. Many of these patients eventually adjusted to a life with nasogastric feeding, but not everyone achieved this state. Therefore, health care providers, including physicians and nurses, and the general public should collaborate to help these patients adapt to their "new lives" as soon as possible.

The protein stability and chromatin functions of UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) are regulated in a cell-cycle-dependent manner. We report a structural characterization of the complex between UHRF1 and the deubiquitinase USP7. The first two UBL domains of USP7 bind to the polybasic region (PBR) of UHRF1, and this interaction is required for the USP7-mediated deubiquitination of UHRF1. Importantly, we find that the USP7-binding site of the UHRF1 PBR overlaps with the region engaging in an intramolecular interaction with the N-terminal tandem Tudor domain (TTD). We show that the USP7-UHRF1 interaction perturbs the TTD-PBR interaction of UHRF1, thereby shifting the conformation of UHRF1 from a TTD-“occluded” state to a state open for multivalent histone binding. Consistently, introduction of a USP7-interaction-defective mutation to UHRF1 significantly reduces its chromatin association. Together, these results link USP7 interaction to the dynamic deubiquitination and chromatin association of UHRF1.

The increasing of multidrug resistance in bacterial associated infections has impaired the current antimicrobial therapy and it forces the search for other alternatives. In this study, we aimed to find the in vitro antibacterial activity of seed coat of Trachycarpus fortunei against a panel of clinically important bacterial species. Ethanolic extracts of target tissues were fractionated through macro porous resin by column chromatography, using ethanol as an organic solvent with a concentration gradient of 0–100%, each along with 20% concentration increment. The minimum inhibitory (MIC) concentrations of all fractions were measured. It is found that 20% ethanolic fraction showed the most significant inhibition against tested bacterial species. All fractions were analyzed by Ultra-Performance Liquid Chromatography/mass spectrometry (UPLC/MS) and compounds were identified by comparing mass spectra with standard libraries. By pairing the identified compounds from different fractions with the antibacterial activity of each fraction, it was shown that compounds stearamide (7), 1-(4-Fluorophenyl)-2-(methylthio)-1H-imidazole-5-carboxylic acid (9) and 2,4,5 triacetoxybiphenyl (10) topped in the list for anti-bacterial activity. Further experiment with pure chemicals verified that compounds 9 and 10 have antibacterial activity against Gram-negative bacteria. Whereas, the lowest MIC value (39.06 μg/mL) was obtained by compound 10 against Staphylococcus epidermidis. Hence, the seed coat of T. fortunei with its antimicrobial spectrum could be a good candidate for further bactericidal research.

Objectives. The aim of the present study was to analyze the association between pretreatment body mass index (BMI) and the aggressiveness of papillary thyroid carcinoma (PTC) along with its clinical outcomes in a Chinese population with BMI classification for Asians. Methods. A retrospective, observational study was conducted on patients from two teaching hospitals in China. 1622 classical PTC patients were categorized into four groups according to BMI. Results. We found that increased BMI was associated with extrathyroidal extension, multifocality, the presence of lymph node (LN) metastasis, and advancing TNM stage in PTC patients. Furthermore, compared to patients with normal weight, those in the overweight and obese group exhibited a significantly increased risk of extrathyroidal extension, multifocality, cervical LN metastasis, and advanced TNM stage. 40 and 37 patients experienced persistent and recurrent disease, respectively. No differences regarding persistent disease or recurrence were observed among the BMI groups. Conclusion. A higher pretreatment BMI has been strongly associated with aggressive features of PTC according to the BMI classification for Asians. Obesity was not found to be associated with a greater risk of recurrence.

Neurons face unique challenges of transporting nascent autophagic vacuoles (AVs) from distal axons toward the soma, where mature lysosomes are mainly located. Autophagy defects have been linked to Alzheimer’s disease (AD). However, the mechanisms underlying altered autophagy remain unknown. Here, we demonstrate that defective retrograde transport contributes to autophagic stress in AD axons. Amphisomes predominantly accumulate at axonal terminals of mutant hAPP mice and AD patient brains. Amyloid-β (Aβ) oligomers associate with AVs in AD axons and interact with dynein motors. This interaction impairs dynein recruitment to amphisomes through competitive interruption of dynein-Snapin motor-adaptor coupling, thus immobilizing them in distal axons. Consistently, deletion of Snapin in mice causes AD-like axonal autophagic stress, whereas overexpressing Snapin in hAPP neurons reduces autophagic accumulation at presynaptic terminals by enhancing AV retrograde transport. Altogether, our study provides new mechanistic insight into AD-associated autophagic stress, thus establishing a foundation for ameliorating axonal pathology in AD.

β site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is the major β secretase for generating β-amyloid (Aβ) peptides. The acidic environment of endosomes is optimal for β secretase activity. However, the mechanisms regulating BACE1 traffic from endosomes to lysosomes for degradation are largely unknown. Here, using snapin-deficient mice combined with gene rescue experiments, we reveal that Snapin, as a dynein motor adaptor for late endosomes, mediates BACE1 retrograde transport. hAPP mutant live neurons and mouse brains exhibited BACE1 accumulation within the altered late endocytic organelles and defective lysosomal targeting due to reduced Snapin-dynein coupling. Deleting snapin or disrupting Snapin-dynein coupling reduces BACE1 transport to lysosomes for degradation, thus enhancing APP processing. Overexpressing Snapin in hAPP neurons reduces β site cleavage of APP by enhancing BACE1 turnover. Altogether, our study provides mechanistic insights into the complex regulation of BACE1 level and activity and turnover through retrograde transport, thus controlling Aβ generation in neurons.

Tagetespatula L. is a widely cultivated herbal medicinal plant in China and other countries. In this study, two new 2, 3-dihydrobenzofuran glucosides (1, 2) and fourteen known metabolites (3−16) were isolated from the stems and leaves of T. patula (SLT). The chemical structures of the isolated compounds were characterized comprehensively based on one- and two-dimensional NMR spectroscopy and high resolution mass spectrometry. Absolute configurations of compounds 1 and 2 were determined by ECD calculations. Compounds 1 and 2 exhibited moderate in vitro inhibitory activities against human gastric cancer cell lines (AGS) with IC50 values of 41.20 μmol/L and 30.43 μmol/L, respectively. The fingerprint profiles of stems and leaves of T. patula with three color types of flowers (Janie Yellow Bright, Jinmen Orange, Shouyao Red and Yellow color) were established by high-performance liquid chromatography (HPLC). Ten different batches of stems and leaves were examined as follow: Shouyao Red and Yellow color (1, 2, 3), Janie Yellow Bright (4, 5, 6, 7) and Jinmen Orange (8, 9, 10). Twenty-two common peaks were identified with similarity values ranging from 0.910 to 0.977. Meanwhile, the average peak area of SLT in the three types of flowers was different and it was the highest in Janie Yellow Bright.

Gentiana radix is used in traditional Chinese medicine and has functions of clearing heat and drying dampness, as well as purging liver and gallbladder fire. A highly sensitive and effective strategy for rapid screening and identification of target constituents has been developed by using ultra high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap) in crude and wine-processed Gentiana radix. Based on the accurate mass measurement (Gentiana radix, including 21 iridoids, 11 flavonoids, 19 xanthones, and a triterpenoid. This study demonstrated that the established method could be a rapid, effective analytical tool for screening and characterization of compounds in the complex systems of Gentiana radix. By comparing the structure and peak areas of chemical constituents in crude and wine-processed Gentiana radix, we found that some compounds in crude and wine-processed Gentiana radix were significantly different.

Atractylodis Rhizoma is the dried rhizome of Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz and is often processed by stir-frying with wheat bran to reduce its dryness and increase its spleen tonifying activity. However, the mechanism by which the processing has this effect remains unknown. To explain the mechanism based on the pharmacokinetics of the active compounds, a rapid, sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was developed to analyze atractylenolides I, II, and III, and atractyloside A simultaneously in rat plasma after oral administration of raw and processed Atractylodis Rhizoma. Acetaminophen was used as the internal standard and the plasma samples were pretreated with methanol. Positive ionization mode coupled with multiple reaction monitoring mode was used to analyze the four compounds. The method validation revealed that all the calibration curves displayed good linear regression over the concentration ranges of 3.2⁻350, 4⁻500, 4⁻500, and 3.44⁻430 ng/mL for atractylenolides I, II, and III, and atractyloside A, respectively. The relative standard deviations of the intra- and inter-day precisions of the four compounds were less than 6% with accuracies (relative error) below 2.38%, and the extraction recoveries were more than 71.90 ± 4.97%. The main pharmacokinetic parameters of the four compounds were estimated with Drug and Statistics 3.0 and the integral pharmacokinetics were determined based on an area under the curve weighting method. The results showed that the integral maximum plasma concentration and area under the curve increased after oral administration of processed Atractylodis Rhizoma.

Neurotrophin signaling is crucial for neuron growth. While the “signaling endosomes” hypothesis is one of the accepted models, the molecular machinery that drives retrograde axonal transport of TrkB signaling endosomes is largely unknown. In particular, mechanisms recruiting dynein to TrkB signaling endosomes have not been elucidated. Here, using snapin deficient mice and gene rescue experiments combined with compartmentalized cultures of live cortical neurons, we reveal that Snapin, as a dynein adaptor, mediates retrograde axonal transport of TrkB signaling endosomes. Such a role is essential for dendritic growth of cortical neurons. Deleting snapin or disrupting Snapin-dynein interaction abolishes TrkB retrograde transport, impairs BDNF-induced retrograde signaling from axonal terminals to the nucleus, and decreases dendritic growth. Such defects were rescued by reintroducing the snapin gene. Our study indicates that Snapin-dynein coupling is one of the primary mechanisms driving BDNF-TrkB retrograde transport, thus providing mechanistic insights into the regulation of neuronal growth and survival.

Abstract The original article [1] contained incorrect affiliations for the authors.

Lycium barbarum L. polysaccharide (LBP) is prepared from Lycium barbarum L. (L. barbarum), which is a traditional Chinese medicine. LPB has been shown to have hypoglycemic effects. In order to gain some mechanistic insights on the hypoglycemic effects of LBP, we investigated the uptake of LBP and its effect on glucose absorption in the human intestinal epithelial cell line Caco2 cell. The uptake of LBP through Caco2 cell monolayer was time-dependent and was inhibited by phloridzin, a competitive inhibitor of SGLT-1. LPB decreased the absorption of glucose in Caco2 cell, and down-regulated the expression of SGLT-1. These results suggest that LBP might be transported across the human intestinal epithelium through SGLT-1 and it inhibits glucose uptake via down-regulating SGLT-1.