Donor-acceptor moiety functionalized covalent organic frameworks for boosting charge separation and H2 photogeneration.

Covalent organic frameworks (COFs) have a broad prospect to be used as a photocatalytic platform to convert solar energy into valuable chemicals due to their tunable structures and rich active catalytic sites. However, constructing COFs with tuned sp2-carbon donor-acceptor moiety remains an enormous challenge. Herein, we synthesized two new fully π-conjugated cyano-ethylene-linked COFs containing benzotrithiophene as functional group by Knoevenagel polycondensation reaction. The accetpor 2,2'-bipyridine unit in BTT-BpyDAN-COF skeleton favored the formation of a intermolecular specific electron transport pathway with the donor benzotrithiophene, and thereby promoted charge separation and transfer efficiency. Specifically, a donor-acceptor (D-A) type BTT-BpyDAN-COF exhibited high hydrogen evolution rate of 10.1 mmol g-1h-1 and an excellent apparent quantum efficiency of 4.83 % under visible light irradiation.

T cells, NK cells, and tumor-associated macrophages in cancer immunotherapy and the current state of the art of drug delivery systems.

The immune system provides full protection for the body by specifically identifying 'self' and removing 'others'; thus protecting the body from diseases. The immune system includes innate immunity and adaptive immunity, which jointly coordinate the antitumor immune response. T cells, natural killer (NK) cells and tumor-associated macrophages (TAMs) are the main tumor-killing immune cells active in three antitumor immune cycle. Cancer immunotherapy focusses on activating and strengthening immune response or eliminating suppression from tumor cells in each step of the cancer-immunity cycle; thus, it strengthens the body's immunity against tumors. In this review, the antitumor immune cycles of T cells, natural killer (NK) cells and tumor-associated macrophages (TAMs) are discussed. Co-stimulatory and co-inhibitory molecules in the three activity cycles and the development of drugs and delivery systems targeting these molecules are emphasized, and the current state of the art of drug delivery systems for cancer immunotherapy are summarized.

The molecular mechanism of three novel peptides from C-phycocyanin alleviates MPTP-induced Parkinson's disease-like pathology in zebrafish.

Previous studies have shown that peptides isolated from C-phycocyanin (C-PC) possess various functions including antioxidant and anticancer activities. However, there is little research on C-PC peptides applied for the neuroprotective effect against a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) model. In this study, twelve novel peptides from C-PC were isolated, purified and identified, and the anti-PD effect of the synthesized peptides was evaluated in a zebrafish PD model. As a result, three of these peptides (MAAAHR, MPQPPAK, and MTAAAR) significantly reversed the loss of dopamine neurons and cerebral vessels, and reduced the locomotor impairment in PD zebrafish. In addition, three novel peptides could inhibit the MPTP-induced decrease of antioxidant enzymes (SOD, CAT, and GSH-Px) and increase the ROS and protein carbonylation content. In addition, they can also alleviate apoptosis of brain regions and acetylcholinesterase (AChE) activity in zebrafish. Further studies elucidated the potential molecular mechanism of peptides' anti-PD effects in the larvae. The results showed that C-PC peptides could modulate multiple genes associated with oxidative stress, autophagy and apoptosis signaling pathways, and thereby alleviate the occurrence of PD symptoms. Overall, our results highlight the neuroprotective effects of three novel peptides and provide valuable mechanistic insights and a promising drug target for the treatment of PD.

Recent advances on covalent organic frameworks (COFs) as photocatalysts: different strategies for enhancing hydrogen generation.

The excessive use of traditional fossil fuels has led to energy and environmental pollution problems. Solar-driven hydrogen generation has attracted much attention in recent years owing to its environmental friendliness and economic feasibility. So far, a series of photocatalysts have been advanced. Unfortunately, these photocatalysts face some issues including poor sunlight harvesting ability, weak photo-corrosion resistance, broad band gap, bad stability, inferior hydrogen evolution rate and so on. It just so happens that COFs have emerged to provide an opportunity for settling these issues. Covalent organic frameworks (COFs), a novel family of porous materials with regular porosity and tunable physicochemical structures, have been extensively explored as photocatalysts for hydrogen production. Moreover, their photocatalytic activities are highly structurally dependent. In this review, we mainly focus on the linkage chemistry and disparate strategies for boosting COF-based photocatalytic hydrogen generation performance in detail. The prospects and obstacles confronted in the development of COF-based photocatalysts and proposals to settle dilemmas are also discussed.

Identification and analysis of Rap-Phr system in Bacillus cereus 0-9.

In this study, eight rap-related genes were found in the Bacillus cereus 0-9 genome; five rap genes were located on chromosomes and three on large plasmids. A total of five Rap proteins in B. cereus 0-9 were annotated as 'tetratricopeptide repeat proteins'. SMART Server analysis showed that the eight Rap proteins had typical tetrapeptide repeat sequence (TPR) domains. Biofilm assays and crystal violet staining showed that overexpression of the rapp1 and rap5 genes affected the biofilm formation of B. cereus 0-9, and the activities of Rapp1 and Rap5 proteins were inhibited by their corresponding cognate Phr, suggesting that the Rap-Phr quorum sensing (QS) system might also exist in the B. cereus 0-9 strain. In addition, overexpression of rap1 genes inhibited in the extracellular amylase decomposition capacity of B. cereus 0-9. The results of the sporulation assay indicated that overexpression of the eight rap genes inhibited the spore formation of B. cereus 0-9 to varying degrees. These results provide a reference for research on the regulation of the Rap-Phr QS system in B. cereus.

The protective effect of C-phycocyanin in male mouse reproductive system.

C-phycocyanin from Spirulina platensis has pharmacological effects such as anti-oxidation, anti-cancer, anti-inflammatory and anti-atherosclerosis activities as well as liver and kidney protection. However, there is little research on C-phycocyanin applied in the field of reproductive medicine, and it is therefore the focus of the current study. In this study, a GC-1 spg cell model and male mouse reproductive injury model were constructed by TNF α + Smac mimetic + zVAD-fmk (TSZ) and cyclophosphamide (Cy), respectively. It has been proved that C-phycocyanin can increase cell viability and reduce cell death in GC-1 spg cells induced by TSZ. C-phycocyanin could protect the reproductive system of male mice from cyclophosphamide, improve spermatogenesis, sperm quality and fertility, increase the release of testosterone, stabilize the feedback regulation mechanism, and ensure the spermatogenic ability of mice. It could also improve the ability of anti-oxidation. In addition, C-phycocyanin could play a protective role by down-regulating RIPK1, RIPK3, and p-MLKL to inhibit the necroptotic signaling pathway. These results suggest that C-phycocyanin could protect GC-1 spg cells and the reproductive system of male mice from TSZ and cyclophosphamide, and the protective mechanism may be achieved by inhibiting the signal pathway of necroptosis. Therefore, C-phycocyanin could serve as a promising reproductive system protective agent. C-phycocyanin may enter public life as a health product in the future.

Plexiform angiomyxoid myofibroblastic tumor treated by endoscopic submucosal dissection: A case report and review of the literature.

BACKGROUND: Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a rare mesenchymal tumor characterized by multiple nodular plexiform growth patterns and an immunophenotype with myofibroblasts. The pathological characteristics, immunohistochemistry, diagnostic criteria, differential diagnosis, and gene-level changes of PAMT have been reported in many studies. At present, the main treatment for PAMT in the reported cases is surgery; only eight cases were treated via endoscopy (excluding 1 thoracoscopic resection), and the lesions were all smaller than 5 cm. There are no reports on the prognosis and follow-up of young patients with lesion sizes reaching 5 cm who undergo endoscopic submucosal dissection (ESD). Herein, we present the first case of a young patient with a lesion size reaching 5 cm who was diagnosed with PAMT via endoscopic submucosal dissection. CASE SUMMARY: A 15-year-old young man with upper abdominal pain for 2 years presented to the Gastroenterology Department of our hospital. Painless gastroscopy showed a semicircular bulge approximately 5 cm in size in the lesser curvature near the cardia of the fundus; the surface was eroded, and shallow ulcers had formed. The pathological manifestations of the biopsy were spindle cell proliferative lesions with interstitial mucinous changes, and the surface mucosa showed chronic inflammatory changes with active lesions; immunohistochemistry showed smooth muscle actin (SMA) (+), CD117 (-), CD34 (-), DOG-1 (-), S-100 (-), and Ki67 (LI: < 1%). We performed ESD on the patient. The lesion that we removed was 5 cm × 4 cm × 2 cm in size. Pathologically, the resected tissue displayed typical manifestations, such as fat spindle-shaped fibroblasts and myofibroblast-like cells showing irregular nodular hyperplasia. Immunohistochemistry staining of the tumor cells revealed the following: CD34 (partially +), SMA (weakly +), CD117 (-), DOG-1 (-), S-100 (-), SDHB (+), PCK (-), and Ki67 (labelling index: 2%). There was no recurrence or metastasis during the 3-mo follow-up after the operation, and the treatment effect was good. We also performed a review of the literature on the clinical manifestations, pathological features, immunohistochemistry, and differential diagnosis of PAMT. CONCLUSION: At present, the diagnostic criteria for PAMT are relatively clear, but the pathogenesis and genetic changes require further study. PAMT is benign in nature, and these patients are less likely to experience local or metastatic recurrence. The main treatment is still surgery if the lesion is in the stomach. Partial gastrectomy and distal gastrectomy are the most frequently performed surgical treatments for PAMT, followed by local resection, subtotal gastrectomy, and wedge resection. But for comprehensive evaluation of the disease, ESD can be considered a suitable method to avoid excessive treatment.

Association Between Environmental Factors and Oral Epstein-Barr Virus DNA Loads: A Multicenter Cross-sectional Study in China.

Background: Oral Epstein-Barr virus (EBV) status reflects host EBV activity and potentially links to EBV-associated diseases, however, factors influencing oral EBV loads or reactivation, such as environmental exposures or host factors, are not fully understood. Methods: A 2-stage, multicenter, cross-sectional study of 6558 subjects from 21 administrative cities of southern China and 3 populations from representative geographical areas in China (referred to as the south, north, and northeastern populations) was performed. The relationships between demographical factors and environmental exposures to EBV loads were analyzed by logistic regression models. Results: Current smoking, with a dose-response effect, was found to be strongly associated with higher oral EBV loads in the pooled data, with an odds ratio of 1.58 (95% confidence interval, 1.39-1.79), as well as in each of the separate populations. The odds ratio increased to 3.06 when current smokers in southern China were compared to never smokers in northern China. Additionally, higher oral EBV loads tended to be detected in older participants, male participants, and participants in southern China. Conclusions: This study provided evidence linking the effect of host-environmental factors, particularly smoking, to oral EBV activity. It could strengthen our understanding of the possible causal roles of EBV-related diseases, which may help to prevent or mitigate EBV-associated diseases.

Comprehensive Survey of Clinical Trials Registration for Melanoma Immunotherapy in the ClinicalTrials.gov.

Objective: Comprehensively evaluate the immunotherapeutic clinical trials and provide reference for melanoma treatment and research. Methods: The website of ClinicalTrials.gov was searched to retrieve and download all registered clinical trials for melanoma immunotherapy on August 1 (updated on August 25), 2019. All registration trials met the inclusion criteria were collected regardless of the type of study, the status of recruitment, and the results of the study. The general characteristics, methodological characteristics, and the types of immunotherapeutic drugs included of these trials were analyzed. Results: Finally, 242 eligible trials were included and evaluated. Of them, 30.6% were completed, 16.9% were terminated, and two were withdrawn; 77.7% recruited less than 100 participants; 30.5% were randomized; 45.5% was single group assignment; 88.8% were not masked; the primary purpose was treatment; 44.2% had data on monitoring committees; 27.7% used US FDA-regulated immunization drugs; 78.5% without results posted; 43.0% were sponsored by the industry. Immunological checkpoint inhibitors were most often studied, with 53.6% of the trials involving PD-1, the most commonly studied was Nivolumab. Conclusions: Currently, most of the registered clinical trials for melanoma immunotherapy were interventional open-label trials. Most immunotherapy research hotspots were in the FDA-regulated drug product, and a few trials reported available test results. It is necessary to strengthen the supervision of results and explore and disseminate more effective and safe immunotherapy methods.

Decreased oral Epstein-Barr virus DNA loads in patients with nasopharyngeal carcinoma in Southern China: A case-control and a family-based study.

The link of nasopharyngeal carcinoma (NPC) with Epstein-Barr virus (EBV) has been established for decades. Although an abnormal high level of EBV sero-antibody spectrum and cell-free circulating EBV DNA loads were exhibited in NPC patients, oral EBV DNA loads, which are primarily responsible for the EBV transmission, has not been previously studied in NPC patients. We conducted an epidemiological study to measure the oral EBV loads, viral components, and the relationship with the serum antibody titers in a large case-control population (968 cases and 1656 controls) and a family-based population (91 cases and 165 unaffected family members). EBV DNA loads were detected by quantitative PCR approach targeting the BamHI-W region. Although a large individualized variation existed, we still observed a decreased oral EBV DNA loads in the population of NPC patients compared to that of healthy controls (ORs were 1.00, 0.69, 0.62, 0.33 classified by the quartiles of viral loads, Ptrend  < .001) and family members. In contrast, the elevated levels of oral EBV loads were present in asymptomatic males and elders, suggesting a different important source for EBV transmission. Notably, oral EBV loads were inversely associated with serum antibody titers of VCA-IgA, EA-IgA (All Ptrend  < .001) in the cases but not in the controls. Our study provides the first epidemiological data of oral EBV loads and viral components in NPC patients and controls in the highest risk area of Southern China, indicating that NPC status is unlikely to be an important determinant of EBV transmission.

The Relationship Between Environmental Factors and the Profile of Epstein-Barr Virus Antibodies in the Lytic and Latent Infection Periods in Healthy Populations from Endemic and Non-Endemic Nasopharyngeal Carcinoma Areas in China.

Our previous study found that smoking was associated with an elevated level of the antibody against VCA in the Epstein-Barr virus (EBV) lytic phase, which was an important predictive marker of the risk of nasopharyngeal carcinoma (NPC). It remained unknown whether environmental factors were associated with the levels of other EBV antibodies, such as Zta-IgA, EA-IgA, EBNA1-IgA, and LMP1-IgA, in the lytic and latent infection periods. We aimed to investigate the possible environmental inducers that could affect EBV antibody levels in two independent healthy male populations from endemic NPC areas in South China (N=1498) and non-endemic NPC areas in North China (N=1961). We performed ELISA and immunoenzymatic assays to test the levels of antibodies specific to the EBV antigens. The seropositive rates of antibodies against the antigens expressed in both the EBV latent and lytic infection periods, namely, LMP1-IgA, EBNA1-IgA, and Zta-IgA, in endemic areas (28.65%, 5.43% and 14.49%, respectively) were significantly higher than those in non-endemic areas (14.43%, 1.07% and 6.32%, respectively). Smoking was associated with higher seropositivity for EBNA1-IgA (OR=1.47, 95% CI=1.12-1.93) and Zta-IgA (OR=1.28, 95% CI=0.99-1.66), with dose-response effects, while not associated with the levels of LMP1-IgA. In conclusion, smoking was an important environmental factor, which associated with increased levels of EBNA1-IgA, and Zta-IgA.

An epidemiological and molecular study of the relationship between smoking, risk of nasopharyngeal carcinoma, and Epstein-Barr virus activation.

BACKGROUND: Elevated levels of antibodies against antigens in the Epstein-Barr virus (EBV) lytic phase are important predictive markers for nasopharyngeal carcinoma (NPC) risk. Several lifestyle factors, including smoking, have also been associated with NPC risk. We hypothesized that some specific lifestyle factors induce transformation of EBV from the latent to the lytic stage and contribute to NPC occurrence. METHODS: We conducted a case-control study using data from male case patients (n = 1316) and control subjects (n = 1571) living in Guangdong Province, an area in China at high risk for NPC, to study potential NPC risk factors and EBV inducers. Two independent healthy male populations from a second high-risk area (n = 1657) and a low-risk area (n = 1961) were also included in the analysis of potential EBV inducers using logistic regression models. In vitro assays were performed to investigate the effect of cigarette smoke extract on EBV activation in two EBV-positive cell lines. All statistical tests were two-sided. RESULTS: Smoking was associated with an increased risk of NPC among the Guangdong participants with 20-40 and 40 or more pack-years vs never smokers (OR = 1.52, 95% CI = 1.22 to 1.88 and OR = 1.76, 95% CI = 1.34 to 2.32, respectively; P (trend) < .001). Smoking was the only factor linked to EBV seropositivity among the expanded control group and the independent low-risk population. In vitro experiments showed that cigarette smoke extract promoted EBV replication, induced the expression of the immediate-early transcriptional activators Zta and Rta, and increased transcriptional expression levels of BFRF3 and gp350 in the lytic phase. CONCLUSION: Smoking is not only associated with NPC risk in individuals from China but is also associated with EBV seropositivity in healthy males and is involved in EBV activation.

Pretreatment lifestyle behaviors as survival predictors for patients with nasopharyngeal carcinoma.

BACKGROUND: Lifestyle behaviors have been widely reported to influence the survival of patients with head and neck cancer. However, the relationship between pretreatment lifestyle behaviors and survival among patients with nasopharyngeal carcinoma (NPC) is unclear. METHODS: A prospective cohort study was designed to determine the relationship between lifestyle behaviors and survival in 1,533 NPC patients recruited from October 2005 to October 2007. Pretreatment lifestyle behaviors (such as body-mass index [BMI], smoking, alcohol, diet) of the patients were investigated. Univariate and multivariate proportional-hazards models were used to assess the impact of lifestyle behaviors on patient survival. RESULTS: Smoking was a predictor of survival; both current smokers (hazard ratio [HR] = 1.88; 95% CI, 1.33 to 2.65) and heavy smokers (≥ 25 Pack-years; HR = 1.84; 95% CI, 1.30 to 2.60) showed associations with poor survival. Higher BMI was significantly associated with a lower risk of death (P(trend) = 0.002). Compared with under/normal-weight patients (BMI less than 22.99 kg/m(2)), the multivariate HR for survival was 0.66 (95% CI, 0.48 to 0.90) and 0.47 (95% CI, 0.23 to 0.97) for overweight and obese patients, respectively. No alcohol intake and high fruit intake were associated with favorable survival in the univariate analysis but lost significance in the multivariate model. CONCLUSION: Our findings indicate that pretreatment lifestyle behaviors, especially smoking status and BMI, as easily available data, provide prognostic value for survival in NPC patients.

3-Nitro-naphthalimide and nitrogen mustard conjugate NNM-25 induces hepatocellular carcinoma apoptosis via PARP-1/p53 pathway.

Hepatocellular carcinoma (HCC) is one of the main causes of death in cancer. Some naphthalimide derivatives exert high anti-proliferative effects on HCC. In this study, it is confirmed that 3-nitro-naphthalimide and nitrogen mustard conjugate (NNM-25), a novel compound conjugated by NNM-25, displayed more potent therapeutic action on HCC, both in vivo and in vitro, than amonafide, a naphthalimide drug in clinical trials. More importantly, preliminary toxicological evaluation also supported that NNM-25 exhibited less systemic toxicity than amonafide at the therapeutic dose. The antitumor mechanism of conjugates of naphthalimides with nitrogen mustard remains poorly understood up to now. Here, we first reported that apoptosis might be the terminal fate of cancer cells treated with NNM-25. Inhibition of p53 by siRNA resulted in a significant decrease of NNM-25-induced apoptosis, which corroborated that p53 played a vital role in the cell apoptosis triggered by NNM-25. NNM-25 inhibited the PARP-1 activity, AKT phosphorylation, up-regulated the protein expression of p53, Bad, and mTOR as well as down-regulating the protein expression of Bcl-2 and decreasing mitochondrial membrane potential. It also facilitated cytochrome c release from mitochondria to cytoplasm, activated caspase 8, caspase 9, and caspase 3 in HepG2 cells in vitro, as also authenticated in H22 tumor-bearing mice in vivo. Collectively, the conjugation of naphthalimides with nitrogen mustard provides favorable biological activity and thus is a valuable strategy for future drug design in HCC therapy.

Alcohol and tea consumption in relation to the risk of nasopharyngeal carcinoma in Guangdong, China.

To investigate whether alcohol and tea consumption has an etiological association with nasopharyngeal carcinoma (NPC) in a high-incident population, a large scale case-control study was conducted. The study included 2846 individuals in Guangdong Province, China, with 1387 newly diagnosed cases of NPC and 1459 frequency-matched controls. Exposure histories of alcohol and tea consumption were obtained via personal interviews. Information regarding socio-demographic characteristics (age, sex, education, dialect and household type), family history of NPC, Epstein-Barr virus (EBV) infection, dietary habits and other potential confounding factors was also studied. An analysis was performed using unconditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). The risk of NPC was found to be associated with habitual alcohol consumption and tea consumption. Tea consumption has been associated with a decreased occurrence of NPC (OR = 0.62), while consumption of alcohol was associated with a complex effect. Specifically, moderate consumption of alcohol was associated with decreased risk of NPC, while overuse, especially strong distillate spirits, appeared to be a risk factor.

Recent advances in the preparation progress of protein/peptide drug loaded PLA/PLGA microspheres.

Sustained release drug delivery from microparticles is an excellent alternative for daily protein/peptide drug administration protocol. Poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) are the most commonly used polymer carriers in the development of protein/peptide microspheres. Basically there are three preparation methods for PLA/PLGA microspheres: the solvent extraction/evaporation based multiple emulsion (W/O/W emulsion) method, the phase separation method and the spray drying method. The stability of the protein/pipetide loaded, encapsulation efficiency, and the burst effect of the microspheres are key problems usually met in the preparation of microspheres. In this review the preparation techniques and progress in the development of protein/pipetide microspheres which aimed to stabilize protein/peptide structural integrity, keep the bioactivity of drugs, increase the encapsulation efficiency and improve the release profile were summarized and evaluated.

[Clinical observation on acupuncture combined with medication for intractable angina pectoris].

OBJECTIVE: To compare clinical effects of acupuncture combined with medication and simple medication on intractable angina pectoris (IAP). METHODS: Seventy cases of IAP were randomly divided into two groups, a control group and a treatment group, 35 cases in each group. The control group were treated with nitric acid ester, beta-receptor blocking agent, calcium antagonist, aspirin and hypo-molecular heparin, and the treatment group were treated with acupuncture at Danzhong (CV 17) and Neiguan (PC 6) and others, once daily for 10 consecutive days on the basis of the above treatment. RESULTS: The total effective rates for symptoms and electrocardiogram were 88.6% and 62.9% in the treatment group and 60.0% and 31.4% in the control group, respectively, with a significant difference between the two groups; the incidence of acute heart attack and sudden death of 5.7% in the treatment group was lower than 20.0% in the control group, with no serious adverse effect. CONCLUSION: Acupuncture combined with medication is safe and effective for intractable angina pectoris and it can improve short-term prognosis.