Nanoparticles Encapsulated in Red Blood Cell Membranes for Near-Infrared Second Window Imaging-Guided Photothermal-Enhanced Immunotherapy on Tumors.

Photothermal therapy (PTT), which uses the high thermal conversion ability of photothermal agents to ablate tumor cells at high temperatures, has gained significant attention because it has the advantages of high selectivity and specificity, precise targeting of tumor sites, and low invasiveness and trauma. However, PTT guided by the NIR-I has limitations in tissue penetration depth, resulting in limited imaging monitoring and therapeutic effects on deep-seated tumor tissues. Moreover, nanoparticles are easily cleared by the immune system and difficult to passively target tumor sites during the process of treatment. To address these issues, we prepared nanoparticles using NIR-II dyes IR1048 and DSPE-PEG-OH and further encapsulated them in red blood cell membranes derived from mice. These biomimetic nanoparticles, called RDIR1048, showed reduced clearance by the immune system and had long circulation characteristics. They effectively accumulated at tumor sites, and strong fluorescence could still be observed at the tumor site 96 h after administration. Furthermore, through mouse thermal imaging experiments, we found that RDIR1048 exhibited good PTT ability. When used in combination with an immune checkpoint inhibitor, anti-PD-L1 antibodies, it enhanced the immunogenic cell death of tumor cells caused by PTT and improved the therapeutic effect of immunotherapy, which demonstrated good therapeutic efficacy in the treatment of tumor-bearing mice. This study provides a feasible basis for the future development of NIR-II nanoparticles with long circulation properties.

A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results.

Therapeutic vaccines that elicit cytotoxic T cell responses targeting tumor-specific neoantigens hold promise for providing long-term clinical benefit to patients with cancer. Here we evaluated safety and tolerability of a therapeutic vaccine encoding 20 shared neoantigens derived from selected common oncogenic driver mutations as primary endpoints in an ongoing phase 1/2 study in patients with advanced/metastatic solid tumors. Secondary endpoints included immunogenicity, overall response rate, progression-free survival and overall survival. Eligible patients were selected if their tumors expressed one of the human leukocyte antigen-matched tumor mutations included in the vaccine, with the majority of patients (18/19) harboring a mutation in KRAS. The vaccine regimen, consisting of a chimp adenovirus (ChAd68) and self-amplifying mRNA (samRNA) in combination with the immune checkpoint inhibitors ipilimumab and nivolumab, was shown to be well tolerated, with observed treatment-related adverse events consistent with acute inflammation expected with viral vector-based vaccines and immune checkpoint blockade, the majority grade 1/2. Two patients experienced grade 3/4 serious treatment-related adverse events that were also dose-limiting toxicities. The overall response rate was 0%, and median progression-free survival and overall survival were 1.9 months and 7.9 months, respectively. T cell responses were biased toward human leukocyte antigen-matched TP53 neoantigens encoded in the vaccine relative to KRAS neoantigens expressed by the patients' tumors, indicating a previously unknown hierarchy of neoantigen immunodominance that may impact the therapeutic efficacy of multiepitope shared neoantigen vaccines. These data led to the development of an optimized vaccine exclusively targeting KRAS-derived neoantigens that is being evaluated in a subset of patients in phase 2 of the clinical study. ClinicalTrials.gov registration: NCT03953235 .

Multiple disadvantages: class, social capital, and well-being of ethnic minority groups in the UK during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has caused untold damage to the socio-economic lives of people all over the world. Research has also demonstrated great inequality in the pandemic experience. In the UK as in many other countries, people from ethnic minority backgrounds and in working-class positions have suffered disproportionately more than the majority group and those in salariat positions in terms of income loss, financial difficulty, and vulnerability to infection. Yet little is known about how people coped in the daily lives and tried to maintain their well-being during the most difficult days of the pandemic through social capital. Methods: In this paper, we draw data from the COVID-19 Survey in Five National Longitudinal Studies to address these questions. The survey covered the period from May 2020 to February 2021, the height of the pandemic in the UK. It contains numerous questions on contact, help and support among family, friends, community members, socio-political trust, and physical and mental health. We conceptualise three types of social capital and one type of overall well-being and we construct latent variables from categorical indicator variables. We analyse the ethnic and socio-economic determinants of the three types of social capital and their impacts on well-being. Results: Our analysis shows that social capital plays very important roles on well-being, and that ethnic minority groups, particularly those of Pakistani/Bangladeshi and Black heritages, faced multiple disadvantages: their poorer socio-economic positions prevented them from gaining similar levels of social capital to those of the white group. However, for people with the same levels of social capital, the effects on well-being are generally similar. Discussion: Socio-economic (class) inequality is the root cause for ethnic differences in social capital which in turn affects people's well-being.

Who Gains Mental Health Benefits from Work Autonomy? The Roles of Gender and Occupational Class.

In recent years, improving work autonomy as an important priority in the UK labour market has been shown to enhance employee mental health and well-being. However, previous theories and empirical studies have paid little attention to the intersectional inequalities in the mental health benefits of work autonomy, preventing us from gaining a comprehensive understanding of the mental consequences of work autonomy. By integrating literature from occupational psychology, gender and social class, this study develops theoretical hypotheses regarding whether and how the mental health benefits of work autonomy vary alongside the intersectional axes of gender and occupational class and tests these hypotheses using long-term panel data in the UK (2010-2021). Overall, we find that those from higher occupational class and male employees acquire significantly more mental health benefits from high work autonomy compared with those from lower occupational class and female employees. Moreover, further analyses show significant intersectional inequalities of gender and occupational class. While male employees from all occupational classes gain significant mental health benefits from work autonomy, only female employees from higher (but not lower) occupational classes benefit from work autonomy. These findings contribute to the literature in the sociology of work by demonstrating the intersectional inequalities in mental health consequences of work autonomy, especially for women in the lower occupational class, highlighting the need for a more gender- and occupation-sensitive design in future labour market policies.

Plasma metabolomics and network pharmacology identified glutamate, glutamine, and arginine as biomarkers of depression under Shuganjieyu capsule treatment.

Depression is a psychiatric disorder and confers an enormous burden on society. Mild to moderate forms of depression (MMD) are particularly common. Our previous studies showed that the Shuganjieyu (SGJY) capsule might improve depressive and cognitive symptoms in patients with MMD. However, biomarkers evaluating the efficacy of SGJY and the underlying mechanism remains unclear. The aim of the present study was to discover efficacy biomarkers and explore the underlying mechanisms of SGJY as antidepression treatment. Twenty-three patients with MMD were recruited and administered with SGJY for 8 weeks. Results showed that the content of 19 metabolites changed significantly in the plasma of patients with MMD, among which 8 metabolites improved significantly after SGJY treatment. Network pharmacology analysis showed that 19 active compounds, 102 potential targets, and 73 enzymes were related to the mechanistic action of SGJY. Through a comprehensive analysis, we identified four hub enzymes (GLS2, GLS, GLUL, and ADC), three key differential metabolites (glutamine, glutamate, and arginine), and two shared pathways (alanine, aspartate, and glutamate metabolism; and arginine biosynthesis). Receiver operating characteristic curve (ROC) analysis showed that the three metabolites had a high diagnostic ability. The expression of hub enzymes was validated using RT-qPCR in animal models. Overall, glutamate, glutamine, and arginine may be potential biomarkers for evaluating the efficacy of SGJY. The present study provides a new strategy for pharmacodynamic evaluation and mechanistic study of SGJY, and offers new information for clinical practice and treatment research.

Self-Assembled Aza-BODIPY and Iron(III) Nanoparticles for Photothermal-Enhanced Chemodynamic Therapy in the NIR-II Window.

Despite its promising potential in cancer treatment, synergistic photothermal/chemodynamic therapy remains underdeveloped with regard to the utilization of metal-organic materials under second near-infrared (NIR-II) laser excitation. Herein, we report a three-dimensional network constructed via the metal coordination between catechol-functionalized aza-boron dipyrromethenes and iron ions (ABFe), which was further encapsulated by F127 to obtain ABFe nanoparticles (NPs) for combined photothermal/chemodynamic therapy. ABFe NPs exhibited intense absorption in the NIR-II range and negligible fluorescence. Upon 1064 nm laser irradiation, ABFe NPs showed high photothermal conversion efficiency (PCE = 55.0%) and excellent photothermal stability. The results of electron spin resonance spectra and o-phenylenediamine chromaticity spectrophotometry proved that ABFe NPs were capable of generating harmful reactive oxygen species from hydrogen peroxide for chemodynamic therapy, which was promoted by photothermal performance. Notably, in vitro and in vivo experiments demonstrated the great potential of ABFe NPs in photoacoustic imaging and photothermal-enhanced chemodynamic therapy under NIR-II laser irradiation. Therefore, the current work presents a prospective NIR-II excitation therapeutic nanomedicine for combination therapy, offering a novel strategy for simultaneously achieving extended NIR absorption of aza-BODIPY and enhanced chemodynamic therapy with metal-organic materials.

LncRNA XIST promotes carboplatin resistance of ovarian cancer through activating autophagy via targeting miR-506-3p/FOXP1 axis.

OBJECTIVE: Resistance to chemotherapy drugs makes ovarian cancer (OC) difficult to treat and ultimately kills patients. Long non-coding RNAs are closely related to carboplatin resistance in OC. In present study, we explored the role of lncRNA X-inactive specific transcript (XIST) on carboplatin resistance in OC. METHODS: Cell viability, proliferation, and apoptosis were assessed through 2,5-diphenyl-2H-tetrazolium bromide, colony formation, and flow cytometry assays, respectively. Microtubule-associated protein 1A/1B-light chain 3 expression was evaluated by immunofluorescence assay to analyze the cell autophagy. The interaction of XIST/miR-506-3p or miR-506-3p/forkhead box protein P1 (FOXP1) was analyzed using RNA immunoprecipitation (RIP) and dual-luciferases reporter assays. The function of XIST/miR-506-3p/FOXP1 axis in vivo was further confirmed by tumor xenograft study and immunohistochemistry. RESULTS: The expression of XIST and FOXP1 increased while miR-506-3p decreased in OC and carboplatin resistance cells. XIST silencing repressed the proliferative and autophagic capacities of carboplatin resistance cells while promoted the apoptosis. XIST overexpression led to the opposite results. XIST targeted miR-506-3p and downregulated its expression. MiR-506-3p inhibition facilitated the proliferative and autophagic capacities while suppressed the apoptosis of cells, XIST knockdown reversed these effects. MiR-506-3p bound to FOXP1. XIST knockdown or miR-506-3p overexpression reversed the increase of cell proliferative and autophagic abilities and the decrease of apoptosis rate induced by FOXP1 overexpression. XIST affected autophagy and carboplatin resistance in vivo via regulating the miR-506-3p/FOXP1 axis. CONCLUSION: XIST knockdown inhibited autophagy and carboplatin resistance of OC through FOXP1/protein kinase B (AKT)/mammalian target of rapamycin pathway by targeting miR-506-3p.

A new species of Validifemur Ma, Song & Zhu, 2007 (Lithobiomorpha, Lithobiidae) from northwest China.

Background: The myriapod fauna of China is still poorly known and very little attention has been paid to the study of Lithobiomorpha, with only more 100 species/subspecies hitherto known from the country, amongst which are only three species of Validifemur. Here we are describing a new species from northwest China. New information: A new lithobiid species, Validifemurradispinipes sp. n., is described and illustrated from Wolong Mountain Park, Jingyuan County, Guyuan City, Ningxia Hui Autonomous Region, northwest China. The new species is compared with V.pedodontus Ma, Song & Zhu, 2007 from Shaanxi Province, China. Type specimens are deposited in the Institute of Myriapodology, School of Life Sciences, Hengshui University, Hengshui, China.

Femtosecond Pumping of Nuclear Isomeric States by the Coulomb Collision of Ions with Quivering Electrons.

Efficient production of nuclear isomers is critical for pioneering applications, like nuclear clocks, nuclear batteries, clean nuclear energy, and nuclear γ-ray lasers. However, due to small production cross sections and quick decays, it is extremely difficult to acquire a significant amount of isomers with short lifetimes via traditional accelerators or reactors because of low beam intensity. Here, for the first time, we experimentally present femtosecond pumping of nuclear isomeric states by the Coulomb excitation of ions with the quivering electrons induced by laser fields. Nuclei populated on the third excited state of ^{83}Kr are generated with a peak efficiency of 2.34×10^{15} particles/s from a tabletop hundred-TW laser system. It can be explained by the Coulomb excitation of ions with the quivering electrons during the interaction between laser pulses and clusters at nearly solid densities. This efficient and universal production method can be widely used for pumping isotopes with excited state lifetimes down to picoseconds, and could be a benefit for fields like nuclear transition mechanisms and nuclear γ-ray lasers.

Analysis of prediction and early warning indexes of patients with COVID-19.

BACKGROUND: The aim was to compare the laboratory data of patients with suspected and confirmed new coronavirus pneumonia (COVID-19) and look for diagnostic predictive and early warning indicators, which will help to better manage the disease. METHODS: A total of 36 confirmed COVID-19 patients were divided into the general (n = 17) and critical group (n = 19). The suspected group enrolled 23 suspected COVID-19 patients with the negative nucleic acid test result. We collected all patients' clinical characteristics and some laboratory indicators at the time of admission and conducted Logistic regression analysis after comparing the differences between groups. RESULTS: There were no significant differences in age, gender, disease duration, fever history, and comorbidities between the suspected and general group (P > 0.05); however, fibrinogen was statistically different (P < 0.05). Compared with the general group, the oxygenation index and lymphocytes were significantly reduced and the Neutrophil-to-lymphocyte Ratio (NLR) and total bilirubin were increased in the critical group (P < 0.05). The fibrinogen OR value was 2.52 (95% CI 1.18-5.36, P = 0.017) and the NLR OR value was 2.91 (95% CI 1.36-6.21, P = 0.006). CONCLUSIONS: Fibrinogen is a valuable diagnostic predictor for patients with suspected COVID-19. For confirmed COVID-19 patients, the NLR is a valuable early warning indicator.

Improve cognition of depressive patients through the regulation of basal ganglia connectivity: Combined medication using Shuganjieyu capsule.

Shuganjieyu capsule (Shugan) is a combined extract of Hypericum perforatum (HP) and Eleutherococcus senticosus (ES). Both HP and ES have been proven effective in the treatment of depression and impaired cognition. However, for mild to moderate depression (MMD), the treatment effect and underlying mechanism by combining both HP and ES are largely unknown. Here, we aim to evaluate the therapeutic effects on impaired cognition using Shugan, a combined medication of HP and ES. Resting-state magnetic resonance imaging (MRI) data and cognitive assessment have been collected from 54 healthy controls and 55 MMD patients that have been undergoing 8-week Shugan-treatment. The functional connectivity (FC) and brain region volume changes of the basal ganglia seeded circuit have been measured, and their relation with the cognitive assessment score was calculated. After that, a literature-based pathway analysis has been conducted to explore the biological relations among Shugan, brain regions, and depression. Compared to healthy controls, MMD patients demonstrated a significantly higher FC (P= 0.0025) between right ventral caudate (vCa) and left orbitofrontal cortex (OFC), which was decreased after the treatment (P < 0.001). A volume of the right caudate, which is increased in MMD, has also been reduced by Shugan treatment (P= 0.017). Importantly, the cognitive scores were strongly correlated with both Shugan treatment and the FC between vCa and OFC (r= 0.321, P= 0.02). Besides, we identified multiple signaling pathways, through which Shugan might improve the cognition of MMD patients. Our results support the therapeutic effects of Shugan on cognition in MMD, which may be realized partly through the regulation within two brain regions, vCa and OFC.

Siglec1 enhances inflammation through miR-1260-dependent degradation of IκBα in COPD.

It has been documented that sialic acid-binding Ig-like lectin 1 (Siglec1) is a cell surface protein with a variety of functions in the immune system. In the present study, we evaluated whether Siglec1 plays a role in chronic obstructive pulmonary disease (COPD). Results show that the expression of Siglec1 was increased in the lung of COPD rats, and that Siglec1 overexpression greatly enhanced the expression of inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and IL-6 in cigarette smoke extract (CSE)-treated NR8383 cells, a rat lung-derived macrophage cell line. Notably, the proinflammatory effect of Siglec1 was totally inhibited by overexpression of nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor α (IκBα). Importantly, Siglec1 overexpression increased miR-1260, which then degraded IκBα through its 3' untranslated region (3'UTR). Further study demonstrated that miR-1260 inhibitor attenuated inflammation in CSE-induced rat COPD lung and in CSE-treated NR8383 cells. Finally, the inhibitory effect of miR-1260 on inflammation was totally lost when IκBα was inhibited. In summary, the present study demonstrated that Siglec1 exerts its proinflammatory effects through increasing miR-1260, leading to decreased expression of IκBα.

Entrenched Inequalities? Class, Gender and Ethnic Differences in Educational and Occupational Attainment in England.

Research in social stratification tends to focus on class differences in educational and occupational attainment, with particular attention to primary and secondary effects in the former, and class reproduction in the latter, domain. Research in ethnic studies tends to focus, however, on ethnic penalty or premium. Many studies have been conducted in each tradition on specific issues but little research is available that examines class, gender and ethnic effects simultaneously or in tandem with contextual effects, let alone on the whole trajectory from compulsory schooling, through further and higher education, to labor market position. Using data from the Longitudinal Study of Young People in England, this paper shows pronounced class differences but remarkable gender progress in each of the educational domains. With regard to ethnicity, people from minority ethnic heritages had lower GCSE scores due to poorer family conditions but achieved higher transition rates to A-Level study, higher university enrollment and, for some groups, greater attendance at elite universities, resulting in an overall higher rate of degree-level attainment than did whites. One might expect members of ethnic minority backgrounds to fare equally well in their earlier careers in the labor market, but only to find them more vulnerable to unemployment, less likely to have earnings, and more disadvantaged in terms of disposable incomes.

RRM2 Regulated By LINC00667/miR-143-3p Signal Is Responsible For Non-Small Cell Lung Cancer Cell Progression.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a common and fatal cancer worldwide with a very low 5-year overall survival rate. Ribonucleotide reductase M2 subunit (RRM2), a small subunit of the ribonucleotide reductase complex, has been found to be an oncogenic role in a variety of tumors including NSCLC. However, the regulatory mechanism of RRM2 in NSCLC is not clear. Increasing evidence suggests that non-coding RNAs (ncRNAs) including miRNAs and lincRNAs may promote or inhibit tumor initiation and development through regulating the expression of oncogenic genes. It is interesting to find ncRNAs which play important role in regulating RRM2 expression. MATERIALS AND METHODS: The expression levels of RRM2, LINC0066 and miR-143-3p in NSCLC tumor tissues and cell lines were detected using qRT-PCR. The regulatory relationships among RRM2, LINC0066 and miR-143-3p were predicted using database analysis and verified by luciferase reporter assay and RIP analysis. The proliferation ability of NSCLC cells was assessed using CCK8 and colony formation assays. The expression of related proteins was determined by Western blot. In vivo effect of RRM2, LINC0066 and miR-143-3p to NSCLC were detected through xenograft experiments. RESULTS: In this study, we found RRM2 was upregulated in NSCLC tumor and cell lines, and the aberrant upregulation predicted a poor prognosis. Then, we predicted and confirmed that RRM2 was negatively regulated by miR-143-3p. Further study implied that LINC00667 acted as a ceRNA by sponging miR-143-3p and regulated RRM2 expression indirectly. Moreover, we found that the growth of NSCLC was regulated by LINC00667/miR-143-3p/RRM2 signal pathway both in vitro and in vivo. LINC00667 and RRM2 promoted the tumor growth while miR-143-3p inhibited it. CONCLUSION: Our study revealed a LINC00667/miR-143-3p/RRM2 signal pathway that played an important role in the progress of NSCLC, which might be potential therapeutic targets for NSCLC.

Family fortunes: The persisting grandparents' effects in contemporary British society.

This study examines grandparents' effects on grandchildren in contemporary British society. We begin with grandchildren's occupational aspiration in their adolescent years and move on to assess their educational and class attainment in adulthood. Using the British Household Panel Survey and the UK Household Longitudinal Study, we find persisting grandparental effects in all three domains even after controlling for parents' socio-economic-cultural resources and other demographic and contextual factors. In addition, we find that self-employed grandparents have a strong impact on grandsons' (albeit not on granddaughters') likelihood of engagement in self-employment, a pattern that holds true even when parents are not self-employed. Our study shows that grandparents' class still affects grandchildren's life chances in contemporary UK society just as earlier research showed for mid-20th century Britain and that the effects are manifested at different stages of the life course, from occupational aspiration as teenagers to educational attainment as young adults to occupational destination as adults.

Purified Phlorizin from DocynIa Indica (Wall.) Decne by HSCCC, Compared with Whole Extract, Phlorizin and Non-Phlorizin Fragment Ameliorate Obesity, Insulin Resistance, and Improves Intestinal Barrier Function in High-Fat-Diet-Fed Mice.

Natural products generally contain complex and multiple bioactive compounds that are responsible for the effects on health through complicated synergistic and/or suppressive actions. As an important raw material of local ethnic minority tea, ethnomedicines and food supplements in southwestern areas of China, Docynia indica (Wall.) Decne (DID) mainly consists of phlorizin (PHZ), which is the main active component. In this study, the holistic activities and the interactions of components of PHZ, non-phlorizin (NP) in the DID extract (DIDE) were evaluated. A rapid and effective high-speed counter-current chromatography (HSCCC) was performed to knock out PHZ from DIDE and the purity of PHZ was 96.01% determined by HPLC, with a recovery rate of 96.76%. After 13 weeks of treatment course in a high-fat diet (HFD)-induced obese mice model, the results revealed that the DIDE and PHZ significantly decreased weight gain, blood lipid levels, hyperplasia of adipocytes and alleviated inflammation (p < 0.05). Both DIDE and PHZ improves insulin resistance (p < 0.001). Meanwhile, the intestinal barrier function was improved compared to HFD group, through the determination of serum lipopolysaccharides (LPS), glucagon-likepeptide-2 (GLP-2) and hematoxylin-eosin staining of jejunum. Interestingly, after NP treatment, the metabolic syndrome of the HFD-induced obesity appeared to have a similar improvement. All the experiments showed that there is a synergistic weakening phenomenon when PHZ and NP interact with each other in the mixed state. In conclusion, for the PHZ and NP showing a good effect on anti-obesity, anti-inflammation, and intestinal barrier function, DIDE could be a good source of functional food to prevent obesity.

Acellular Cauda Equina Allograft as Main Material Combined with Biodegradable Chitin Conduit for Regeneration of Long-Distance Sciatic Nerve Defect in Rats.

Autologous nerve grafting (ANG), the gold standard treatment for peripheral nerve defects, still has many restrictions. In this study, the acellular cauda equina allograft (ACEA), which consists of biodegradable chitin conduit and acellular cauda equina, is developed. The cauda equina is able to complete decellularization more quickly and efficiently than sciatic nerves under the same conditions, and it is able to reserve more basal lamina tube. In vitro, ACEA shows superior guidance capacity for the regeneration of axons and migration of Schwann cells compared to acellular sciatic nerve allograft (ASNA) in dorsal root ganglion culture. In vivo, ACEA is used to bridge 15 mm long-distance defects in rat sciatic nerves. On day 21 after transplantation, the regenerative distance of neurofilaments in the grafting segment is not significantly different between the ACEA and ANG groups. At week 12, ACEA group shows better sciatic nerve repair than chitin conduit only and ASNA groups, and the effect is similar to that in the ANG group as determined by gait analysis, neural electrophysiological, and histological analyses. The above results suggest that the ACEA has the potential to become a new biological material as a replacement for autografting in the treatment of long-distance nerve defects.

Downregulation of microRNA-301a inhibited proliferation, migration and invasion of non-small cell lung cancer by directly targeting DLC1.

Increasing evidence has indicated that the abnormal expression of microRNAs contributes to tumorigenesis and tumor development. Understanding the roles of microRNAs in non-small cell lung cancer (NSCLC) might provide valuable information for therapeutic strategies in the therapy for patients with NSCLC. In the present study, significant upregulation of microRNA (miR)-301a was observed in NSCLC tissues and cell lines compared with normal adjacent tissues and a normal human bronchial epithelial cell line. The inhibition of miR-301a suppressed proliferation, migration and invasion of NSCLC cells. Functional analyses indicated that DLC1 was a direct target of miR-301a in NSCLC. Inhibiting miR-301a expression decreased DLC1 expression at mRNA and protein levels. Moreover, DLC1 knockdown partially reversed the inhibition of proliferation, migration and invasion induced by miR-301a knockdown in NSCLC cells. Therefore, these findings may provide novel insights into the molecular mechanisms of miR-301a in proliferation, migration and invasion of NSCLC cells. The findings also indicated that miR-301a may act as a novel potential therapeutic target for patients with NSCLC.

Carrot intake and incidence of urothelial cancer: a systematic review and meta-analysis.

Previous studies regarding the relationship between carrot intake and risk of urothelial cancer have reported conflicting results. Hence we performed a meta-analysis of eligible studies to summarize evidence on this association. A comprehensive search up to January 2017 was performed in PubMed, Web of Science, Scopus, EMBASE, Cochrane register, and Chinese National Knowledge Infrastructure (CNKI) databases. The combined odds ratio (OR) with 95% confidence interval (CI) for the highest versus the lowest intake of carrot was calculated. A total of six epidemiological studies consisting of four case-control and two cohort studies were included. Overall analysis indicated a significantly reduced risk of urothelial cancer for high intake of carrot (OR = 0.63, 95% CI 0.44-0.90). Obvious significant heterogeneity was observed among included studies (P < 0.001 for heterogeneity; I2 = 79.6%). There was no significant publication bias by Begg's test (P = 0.348) or Egger's test (P = 0.130). In conclusion, this meta-analysis indicates that high intake of carrot is associated with a low incidence of urothelial cancer. Considering the limited included studies and huge heterogeneity, further large well-designed prospective cohort studies are warranted to confirm the findings from our meta-analysis.

Predictive value of serum bradykinin and desArg9-bradykinin levels for chemotherapeutic responses in active tuberculosis patients: A retrospective case series.

BACKGROUND: There is an urgent need for methods that can rapidly and accurately assess therapeutic responses in patients with active tuberculosis (TB) in order to predict treatment outcomes. Exposure to bacterial pathogens can rapidly activate the plasma contact system, triggering the release of bradykinin (BK) and its metabolite desArg9-bradykinin (DABK) to induce inflammation and innate immune responses. We hypothesized that serum BK and DABK levels might act as sensitive immune response signatures for changes in Mycobacterium tuberculosis (Mtb) burden, and therefore examined how serum levels of these markers corresponded with anti-TB therapy in a small cohort of active TB cases. METHODS: Nanotrap Mass-Spectrometry (MS) was used to analyze serial blood specimens from 13 HIV-negative adults with microbiologically confirmed active TB who were treated with first-line anti-TB chemotherapy. MS signal for BK (m/z 1060.5) and DABK (m/z 904.5) serum peptides were evaluated at multiple time-points (before, during, and after treatment) to evaluate how BK and DABK levels corresponded with disease status. RESULTS: Serum BK levels declined from pretreatment baseline levels during the early stage anti-TB therapy (induction phase) and tended to remain below baseline levels during extended treatment (consolidation phase) and after therapy completion. BK levels were consistent with induction phase sputum culture conversions indicative of decreased Mtb burden reflecting good treatment responses. Serum DABK levels tended to increase during the induction phase and decrease at consolidation and post-therapy time points, which may indicate a shift from active disease to chronic inflammation to a disease free state. Elevated BK and DABK levels after treatment completion in one patient may be related to the subsequent recurrent TB disease. CONCLUSIONS: Our pilot data suggests that changes in the circulating BK and DABK levels in adult TB patients can be used as potential surrogate markers of the host response both early and late in anti-TB treatment for both pulmonary and extrapulmonary TB patients. We will further exploit these host-response signatures in the future as biomarkers in combination with other clinical and microbiologic tools which may improve treatment efficacy and facilitate the development of host-directed therapy.