Causal relationship between psoriasis vulgaris and dementia: Insights from Mendelian randomization analysis.

Many clinical studies have demonstrated a correlation between psoriasis vulgaris and dementia, yet this correlation remains controversial. Our study employed the Mendelian randomization (MR) method to investigate the causal relationship between psoriasis vulgaris and dementia. Data were obtained from the summary statistics of the genome-wide association studies from IEU-OpenGWAS project database. In univariate Mendelian randomization (UVMR) analysis, psoriasis vulgaris was used as exposure. Alzheimer disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD) and frontotemporal dementia (FTD) served as the outcomes. In multivariate Mendelian randomization (MVMR) analysis, VaD served as the outcome. The first MVMR analysis used psoriasis vulgaris, mean platelet volume (MPV), platelet distribution width (PDW) and platelet count (PLT) as exposures. The second MVMR analysis used psoriasis vulgaris, vitamin D level and 25 hydroxyvitamin D level as exposures. The main analysis employed the inverse variance weighted method, and the outcomes were evaluated by odds ratio (OR) and 95% confidence interval (95% CI). In UVMR analysis, the results depicted that psoriasis vulgaris was associated with VaD (OR: 0.903, 95% CI: 0.818-0.996, p = 0.041). The results revealed insignificant associations between psoriasis vulgaris and other dementia types. After adjusting the effects of MPV, PDW and PLT in MVMR analysis, the association between psoriasis vulgaris and VaD was no longer significant (p = 0.164). Similarly, after adjusting the effects of vitamin D level and 25 hydroxyvitamin D level in MVMR analysis, the association between psoriasis vulgaris and VaD was also no longer significant (p = 0.533). Our study suggests that psoriasis vulgaris may potentially decrease VaD incidence. However, the causal association between psoriasis vulgaris and VaD may be impeded by platelet-related indices, vitamin D level and 25 hydroxyvitamin D level.

Evaluation of the diagnostic performance of colposcopy in the detection of cervical high-grade squamous intraepithelial lesions among women with transformation zone type 3.

BACKGROUND: Inaccurate colposcopy diagnosis may lead to inappropriate management and increase the incidence of cervical cancer. This study aimed to evaluate the diagnostic accuracy of colposcopy in the detection of histologic cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with transformation zone type 3 (TZ3). METHODS: Records from 764 patients with TZ3 who underwent colposcopy-directed biopsy and/or endocervical curettage in Putuo Hospital China between February 2020 and March 2023 were retrospectively collected. Colposcopy was carried out based on 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) and Colposcopy nomenclature. The diagnostic performance of colposcopy for identifying CIN2 + was evaluated compared with biopsies. The Kappa and McNemar tests were used to perform statistical analyses. RESULTS: Among the study population, 11.0% had pathologic CIN2+. The relative sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of colposcopy for histologic CIN2 + were 51.2%, 96.5%, 64.2% and 94.1%, respectively. The senior colposcopists (80.6%) had a higher colposcopic accuracy to diagnose histologic CIN2 + than junior colposcopists (68.6%). In subgroup analyses, age group ≥ 60 years (70.3%) showed lowest diagnostic accuracy when compared with age groups of < 45 years (84.4%) and 45-59 years (74.9%). CONCLUSION: Our findings suggest an increased risk of diagnostic inaccuracy of colposcopy in identifying CIN2 + in those ≥ 60 years of age with TZ3, and the accuracy of colposcopy is required to be further improved.

Hypercholesterolemia and the Increased Risk of Vascular Dementia: a Cholesterol Perspective.

PURPOSE OF REVIEW: Vascular dementia (VaD) is the second most prevalent type of dementia after Alzheimer's disease.Hypercholesterolemia may increase the risk of dementia, but the association between cholesterol and cognitive function is very complex. From the perspective of peripheral and brain cholesterol, we review the relationship between hypercholesterolemia and increased risk of VaD and how the use of lipid-lowering therapies affects cognition. RECENT FINDINGS: Epidemiologic studies show since 1980, non-HDL-C levels of individuals has increased rapidly in Asian countries.The study has suggested that vascular risk factors increase the risk of VaD, such as disordered lipid metabolism. Dyslipidemia has been found to interact with chronic cerebral hypoperfusion to promote inflammation resulting in cognitive dysfunction in the brain.Hypercholesterolemia may be a risk factor for VaD. Inflammation could potentially serve as a link between hypercholesterolemia and VaD. Additionally, the potential impact of lipid-lowering therapy on cognitive function is also worth considering. Finding strategies to prevent and treat VaD is critical given the aging of the population to lessen the load on society. Currently, controlling underlying vascular risk factors is considered one of the most effective methods of preventing VaD. Understanding the relationship between abnormal cholesterol levels and VaD, as well as discovering potential serum biomarkers, is important for the early prevention and treatment of VaD.

Mechanistic study on ursolic acid inhibiting the growth of colorectal cancer cells through the downregulation of TGF-ß3 by miR-140-5p.

Colorectal cancer (CRC) is a common digestive tract tumor with a high incidence and a poor prognosis. Traditional chemotherapy drugs are usually accompanied by unpleasant side effects, highlighting the importance of exploring new adjunctive drugs. In this study, we aimed to explore the role of ursolic acid (UA) in CRC cells. Specifically, HT-29 cells were treated with UA at different concentrations (10, 20, 30, and 40 µM), and the expression of miR-140-5p, tumor growth factor-ß3 (TGF-ß3), ß-catenin, and cyclin D1 was determined by real-time quantitative PCR. The cell cycle and apoptosis were checked by flow cytometry, and cell proliferation was detected by Cell Counting Kit-8 assay. The HT-29 cell model was established through overexpression (miR-140-5p mimics) and interference (miR-140-5p inhibitor) of miR-140-5p. Western blot was used to detect the protein expression of TGF-ß3. We found that UA could inhibit the proliferation of HT-29 cells, block cells in the G1 phase, and promote cell apoptosis. After UA treatment, the expression of miR-140-5p increased and TGF-ß3 decreased. Notably, miR-140-5p downregulated the expression of TGF-ß3, while the overexpression of miR-140-5p exerted a similar function to UA in HT-29 cells. Additionally, the messenger RNA expression of TGF-ß3, ß-catenin, and cyclin D1 was decreased in HT-29 cells after UA treatment. In conclusion, UA inhibited CRC cell proliferation and cell cycle and promoted apoptosis by regulating the miR-140-5p/TGF-ß3 axis, which may be related to the inhibition of Wnt/ß-catenin signaling pathway.

Detection of cervical high-grade squamous intraepithelial lesions and assessing diagnostic performance of colposcopy among women with oncogenic HPV.

BACKGROUND: HPV screening tests may improve cervical cancer risk stratification and better guide decisions about follow-up with colposcopy/biopsy. This study aimed to estimate the risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with oncogenic HPV types and evaluate the performance of colposcopy in the diagnosis of histologic CIN2 + at Putuo Hospital, Shanghai, China. METHODS: This cross-sectional survey was conducted from February 2020 to December 2022 among women who were referred to colposcopy. Women with high-risk (HR) HPV-positive, cytology testing and colposcopy-directed biopsy were included. RESULTS: Univariate and multivariate analysis indicated that high-grade colposcopic impression ((OR, 17.61%, 95%CI: 11.54-26.85%) was associated with the highest risk for detecting CIN2+, followed by HSIL + cytology (OR, 6.90%, 95%CI: 3.56-13.37%) and HPV16/18 positive (OR, 2.91%, 95%CI: 2.12-3.99%). Overall, CIN2 + was detected in 14.6% of 2007 women. HPV16/18 had higher CIN2 + risks than other HR-HPV genotypes (30.1% vs. 10.2%, P<0.001). Among women with low-grade cytology, 24.1% had CIN2+, and the risks for HPV16/18 (58.2%) were higher than for other HR-HPV(16.8%). For those with high-grade cytology, there was no significant difference between HPV groups ( 75.0% vs. 72.9%, P > 0.05). The diagnostic performance of colposcopy in diagnosis of CIN2 + by senior and junior colposcopists was comparable. CONCLUSIONS: The results indicated that referral to colposcopy is recommended in managing women with HR-HPV positive, and colposcopic impressions provide key clues for identification CIN2+.

Prevalence of cervicovaginal human papillomavirus infection and genotype distribution in Shanghai, China.

BACKGROUND: The evaluation of human papillomavirus (HPV) prevalence rate dynamics and genotype distribution could support the adoption of more targeted prevention and treatment of cervical cancer. We aimed to assess the infection status and genotype characteristics of HPV among gynecological outpatients in Shanghai, China. METHODS: Clinical specimens were collected from patients attending gynaecological department of the Putuo Hospital, Shanghai University of Traditional Chinese Medicine, between January 2015 and December 2019. The cervicovaginal infection of 17 high-risk genotypes and 10 low-risk genotypes were analyzed by Luminex-based multiple assays. RESULTS: The overall HPV infection rate was 18.81% (95% CI 18.31-19.30%) in Shanghai city, with high-risk, low-risk and mixed high- and low-risk HPV prevalence being 11.65% (95% CI 11.24-12.06%), 4.19% (95% CI 3.94-4.44%) and 2.96% (95% CI 2.74-3.17%), respectively. The five most prevalent high-risk genotypes were HPV-52 (2.95%), HPV-16 (2.34%), HPV-58 (2.07%), HPV-53 (1.67%) and HPV-39 (1.36%). The most common low-risk genotype was HPV-61 (1.52%), followed by HPV-6 (1.29%) and HPV-81 (1.19%). Moreover, the coverage of HPV genotype by nonavalent vaccine was 10.42%, and non-vaccine-covered high-risk genotype was 7.70%. The 15-24 years age group demonstrated the highest HPV prevalence (43.14%), and significant differences were observed among different age groups (P < 0.001). CONCLUSIONS: This study revealed the HPV prevalence and genotype distribution among women in Shanghai city, which could serve as guidance for HPV vaccination and preventative strategies against cervical cancer in this area.

Genital Human Papillomavirus Prevalence and Genotyping Among Males in Putuo District of Shanghai, China 2015-2019.

BACKGROUND Reports of human papillomavirus (HPV) infection and genotype distribution in Chinese men are limited, and HPV vaccination has not yet been recommended for men in China. MATERIAL AND METHODS We retrospectively reviewed the prevalence and genotyping of male genital HPV. A total of 1227 male patients (aged 17 to 81 years) attending the dermatology and sexually transmitted disease clinics at Putuo District Center Hospital in Shanghai from 2015 to 2019 were included. Genital exfoliated specimens were obtained for detection and genotyping of 27 HPV types by Luminex-based multiplex assay. RESULTS The prevalence of any HPV was 65.5% (804/1227). The rate of multiple infection was 25.8% (317/1227). The 5 main HPV types were 6 (32.0%), 11 (23.2%), 16 (5.6%), 43 (4.3%), and 59 (4.0%). Among all detected HPV genotypes, 65.5% (875/1336) were 9-valent HPV genotypes. No significant differences were observed in the detection rate of HPV infection over 5 years (P>0.05). Age groups ≤24 years (70.7%) and ≥55 years (72.9%) showed higher infection rates, and significant differences were detected in rates of low-risk HPV infection in different age-stratified groups (P<0.05). Prevalence of HPV infection among patients with warts (74.4%) was significantly higher than that of patients with other clinical characteristics (40.4%) and physical examination (63.6%). CONCLUSIONS Our study suggested that more than half of Chinese male patients have detectable HPV infections, and penis-genital and anogenital warts were the most common clinical manifestations. Moreover, the available 9-valent HPV vaccine covers the most frequently observed HPV types among men.

Toll-like receptor 4 contributes to uterine activation by upregulating pro-inflammatory cytokine and CAP expression via the NF-κB/P38MAPK signaling pathway during pregnancy.

Evidence indicates that inflammatory response is significant during the physiological process of human parturition; however, the specific signaling pathway that triggers inflammation is undefined. Toll-like receptors (TLRs) are key upstream gatekeepers that control inflammatory activation before preterm delivery. Our previous study showed that TLR4 expression was significantly increased in human pregnancy tissue during preterm and term labor. Therefore, we explore whether TLR4 plays a role in term labor by initiating inflammatory responses, therefore promoting uterine activation. The results showed that expression of TLR4, interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), CC chemokine ligand 2 (CCL-2), and uterine contraction-associated proteins (CAPs) was upregulated in the human and mice term labor (TL) group compared with the not-in-labor (TNL) group, and the TLR4 level positively correlated with CAP expression. In pregnant TLR4-knockout (TLR4-/- ) mice, gestation length was extended by 8 hr compared with the wild-type group, and the expression of IL-1ß, IL-6, TNF-α, CCL-2, and CAPs was decreased in TLR4-/- mice. Furthermore, nuclear factor-κB (NF-κB) and P38MAPK activation is involved in the initiation of labor but was inhibited in TLR4-/- mice. In uterine smooth muscle cells, the expression of inflammatory cytokines and CAPs decreased when the NF-κB and P38MAPK pathway was inhibited. Our data suggest that TLR4 is a key factor in regulating the inflammatory response that drives uterine activation and delivery initiation via activating the NF-κB/P38MAPK pathway.

Association of 758 G/A polymorphism of 3'untranslated region of prohibitin with risk of gastric cancer.

BACKGROUND: A polymorphic variant allele (T-allele) in the 3'-UTR of prohibitin (C-to-T at nucleotide 729) was reported to be associated with an increased risk of breast cancer. However, the association between the 3'-UTR polymorphism of prohibitin and the susceptibility to gastric cancer remains unknown. Thus, we investigated the distribution of prohibitin genotypes in Chinese patients with gastric cancer and subsequently analyzed the association between the 3'-UTR polymorphism of prohibitin and the risk of gastric cancer in that population. METHODS: The distribution of 3'-UTR polymorphism of prohibitin in 82 gastric cancer patients was determined by sequencing and compared with that of 171 healthy controls. Luciferase reporter assay was used to investigate the effect of 3'-UTRs variant on PHB expression. RESULTS: Our study discovered two major polymorphic sites in the 3'-UTR of prohibitin (C-to-T at nucleotide 729 and G to A at nucleotide 758). The C/T polymorphism at 729 site was not associated with the increased risk of gastric cancer (P=.961, OR=1.044, 95%CI: 0.187-5.818); however, G/A polymorphism at nucleotide 758 increased the risk of gastric cancer (P=.017, OR=1.923, 95%CI: 1.119-3.305). Luciferase reporter constructs containing the 758A allele showed higher luciferase activity compared with the wild-type allele, which indicated that 758 G>A in 3'-UTR increased PHB expression. CONCLUSIONS: The G to A transition but not the C-to-T transition in the 3'-UTR of prohibitin was associated with an increased risk of gastric cancer in Chinese population.

Diagnostic Value of Serum hsa-mir-92a in Patients with Cervical Cancer.

BACKGROUND: Hsa-mir-92a acts as an onco-miRNA and may contribute to the progression and invasion of cervical cancer, which is a common malignant tumor in women worldwide. The objective of the present study was to evaluate whether serum hsa-mir-92a could serve as a diagnostic biomarker for cervical cancer patients. METHODS: The expression levels of hsa-mir-92a were analyzed in the serum of patients with CIN I, CIN II, CIN III, cervical cancer Ia - IIa and compared with those of the control group samples. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic significance of cervical cancer. RESULTS: It was found that the expression of hsa-miR-92a in the serum of individuals with CIN or cervical cancer was significantly higher than that in healthy volunteers (p < 0.01). The expression of hsa-miR-92a was higher in the serum of patients with advanced stage and cervical cancer than those with early stage. ROC analysis revealed that the cutoff value of hsa-mir-92a was 1.52 for the diagnosis of CIN and cervical cancer. The sensitivity and specificity were 69.6% and 80.4%, respectively, and an area under the curve (AUC) was 0.83. CONCLUSIONS: hsa-mir-92a up-regulation was associated with cervical cancer and the serum level of hsa-mir-92a could be used as an independent marker for the diagnosis of cervical cancer.

Increased expression of MyD88 and association with paclitaxel resistance in breast cancer.

MyD88 was reported to be associated with paclitaxel sensitivity in lung cancer; however, its roles in breast cancer remain unclear. The objective of this study is to investigate the expression and function of MyD88 in breast cancer. Immunohistochemistry (IHC) was used to analyze the expression of MyD88 in both breast cancer tissues and adjacent normal tissues. Real-time PCR and Western blots were further used to measure the messenger RNA (mRNA) and protein expression. The proliferation was assessed by WST-1. Flow cytometry was used to measure the cell cycle and apoptosis. The transwell assay was used to observe the change of migration and invasion of transfected cells. In breast cancer tissues, the expression of MyD88 was significantly higher than that in tumor-adjacent normal tissues (P < 0.001). MyD88 expression was found to be associated with the differentiation stages (P = 0.019). Kaplan-Meier survival curves showed statistically significant difference on survival in patients with high expression of MyD88 compared with those with normal expression of MyD88 (P = 0.018). Knockdown of MyD88 reduced the proliferation, migration, and invasion of MCF-7 cells and increased the sensitivity of MCF-7 cells to paclitaxel treatment through the inhibition of activation of NF-κB via PI3K/Akt. Our data indicate that MyD88 may be a potential target molecule to be used in diagnosis and treatment of breast cancer.

Diversified phenotype of antigen specific CD8+ T cells responding to the immunodominant epitopes of IE and pp65 antigens of human cytomegalovirus.

To study the cytomegalovirus (CMV)-specific CD8+ T cells in individuals with HLA A*1101, A*0201 and A*2402, our findings showed that peptide SK-10-2, KI-10 and KV-10 of CMV IE and pp65 antigens were immunodominant in 198 individuals with HLA A*1101, A*0201 and A*2402, the most frequent genotypes in Chinese. Interestingly, SK-10-2 induced the strongest T cell response to produce IFN-γ whereas the others did not induce prominent IFN-γ production despite they all induced remarkable T cell proliferation. The peptides induced different phenotypes including IFN-γ(high)TNF-α(low) and TNF-α(low)Foxp3(low). It suggests that only some of CMV-reactive CD8+ T cells are real protective IFN-γ(high) cytotoxic T cells.

Effective nitrogen doping of TiO2 polymorphs at mild temperatures for visible-light-responsive hydrogen evolution.

Herein, a mild-temperature nitrogen doping route with the urea-derived gaseous species as the active doping agent is proposed to realize visible-light-responsive photocatalytic hydrogen evolution both for the anatase and rutile TiO2. DFT simulations reveal that the cyanic acid (HOCN), derived from the decomposition of urea, plays a curial role in the effective doping of nitrogen in TiO2 at mild temperatures. Photocatalytic performance demonstrates that both the anatase and rutile TiO2 doped at mild temperatures exhibit the highest hydrogen evolution rates, although the ones prepared at high temperatures possess higher absorbance in the visible range. Steady-state and transient surface photovoltage characterizations of these doped TiO2 polymorphs prepared at different temperatures reveal that harsh conditions (high temperature reaction) typically result in the formation of intrinsic defects that are detrimental to the transport of the low-energy visible-light-induced electrons, while the mild-temperature nitrogen-doping could flatten the pristine upward band bending without triggering the formation of Ti3+, thus achieving enhanced visible-light-responsive hydrogen evolution rates. We anticipate that our findings will provide inspiring information for shrinking the gap between the visible-light-absorbance and the visible-light-responsiveness in the band engineering of wide-bandgap metal-oxide photocatalysts.

Leveraging existing 16S rRNA gene surveys to decipher microbial signatures and dysbiosis in cervical carcinogenesis.

The presence of dysbiotic cervicovaginal microbiota has been observed to be linked to the persistent development of cervical carcinogenesis mediated by the human papillomavirus (HPV). Nevertheless, the characteristics of the cervical microbiome in individuals diagnosed with cervical cancer (CC) are still not well understood. Comprehensive analysis was conducted by re-analyzing the cervical 16S rRNA sequencing datasets of a total of 507 samples from six previously published studies. We observed significant alpha and beta diversity differences in between CC, cervical intraepithelial neoplasia (CIN) and normal controls (NC), but not between HPV and NC in the combined dataset. Meta-analysis revealed that opportunistic pernicious microbes Streptococcus, Fusobacterium, Pseudomonas and Anaerococcus were enriched in CC, while Lactobacillus was depleted compared to NC. Members of Gardnerella, Sneathia, Pseudomonas, and Fannyhessea have significantly increased relative abundance compared to other bacteria in the CIN group. Five newly identified bacterial genera were found to differentiate CC from NC, with an area under the curve (AUC) of 0.8947. Moreover, co-occurrence network analysis showed that the most commonly encountered Lactobacillus was strongly negatively correlated with Prevotella. Overall, our study identified a set of potential biomarkers for CC from samples across different geographic regions. Our meta-analysis provided significant insights into the characteristics of dysbiotic cervicovaginal microbiota undergoing CC, which may lead to the development of noninvasive CC diagnostic tools and therapeutic interventions.

Characteristics of lymphocyte subsets and inflammatory factors in patients with COVID-19.

Objective: This research aims to examine the involvement of lymphocyte subsets and inflammatory cytokines in the development and progression of COVID-19. Methods: 164 COVID-19 patients were admitted to hospital between December 2022 and January 2023. Based on lung CT scans and whether it is necessary for intensive care unit (ICU) admission, they were categorized into: severe groups (84) and mild disease groups (80). Peripheral blood were also collected from 101 healthy examinees and 164 patients. Flow cytometry (FCM) was used to measure the absolute and relative counts of lymphocyte subsets, while chemiluminescence was used to detect the level of inflammatory cytokines. Results: The COVID-19 patient group exhibited lower count of lymphocytes subsets than healthy control group. Moreover, COVID-19 patient case presented higher content of cytokines (IL-6, IL-4, IL-8, IL-10, and TNF-α) expression compared to healthy control case. Within the COVID-19 patient group, individuals with severe disease showed lower counts of lymphocytes subsets than the mild disease case. Furthermore, IL-6 levels in severe case were higher than the mild disease patients case. Multi-variate logistic regression analysis confirmed IL-6 (odds ratio: 0.985 [0.977-0.993]), CD3+ T cells (odds ratio:1.007 [1.004-1.010]), CD8+ T cells (odds ratio:1.016 [1.009-1.023]), and CD19+ B cells (odds ratio:1.011 [1.002-1.020]) independently predicted severe progression. ROC curve results indicated AUC for lymphocytes in patients with severe COVID-19 was 0.8686 (0.8112-0.9260), CD3+ T cells was 0.8762 (0.8237-0.9287), CD8+ T cells was 0.7963 (0.7287-0.8638), CD4+ T cells was 0.8600 (0.8036-0.9164), CD19+ B cells was 0.7217 (0.6434-0.8001), NK cells was 0.6492 (0.5627-0.7357), age was 0.6699 (0.5877-0.7521), diabetes was 0.5991 (0.5125-0.6857), and IL-6 was 0.7241 (0.6479-0.8003). Furthermore, the ROC curves for different factors (CD3+ T cells, age, IL-6) yielded an AUC of 0.9031 (0.8580-0.9483). Conclusions: The research indicated that COVID-19 patients experience a decrease in lymphocytes subset and an increase in the inflammatory factor IL-6, particularly in the severe case group. As a result, the count of lymphocyte subset (CD3+ T cells) and the content of inflammatory cytokine (IL-6) can serve as predictive markers for assessing the severity of COVID-19 and developing treatment plans efficacy.

Ursolic acid inhibits the metastasis of colon cancer by downregulating ARL4C expression.

Ursolic acid (UA), a natural pentacyclic triterpenoid, is known to exhibit various biological activities and anticancer effects. However, the underlying anticancer mechanism is not fully understood to date. The present study aimed to investigate the antimetastatic effect of UA through ADP­ribosylation factor like GTPase 4C (ARL4C) in colon cancer. A lung metastasis model of colon cancer in nude mice was established through tail vein injection. A Cell Counting Kit­8 assay was used to investigate the proliferation of colon cancer cells. Transwell assays were used to detect cell migration and invasion. The expression levels of proteins including ARL4C, matrix metallopeptidase 2 (MMP2), phosphorylated (p)­AKT and p­mTOR were measured using western blot analysis. Immunohistochemistry was used to determine the protein expression level in tissues. ARL4C ubiquitination levels were analysed using immunoprecipitation and western blotting. The results indicated that UA inhibits the metastasis of colon cancer in vivo and in vitro. The expression of ARL4C in human colon cancer tissue was significantly higher than that in adjacent tissues and its high expression level was associated with lymph node metastases and tumour stage. UA treatment significantly decreased ARL4C and MMP2 protein levels and inhibited the AKT/mTOR signalling pathway. Overexpression of ARL4C reversed the inhibitory effect of UA on the invasion and migration of HCT­116 and SW480 cells, as well as the expression and secretion of MMP2 protein. In addition, UA and an AKT signalling pathway inhibitor (LY294002) induced the ubiquitination of the ARL4C protein, which was reversed by a proteasome inhibitor (MG­132). Collectively, it was revealed in the present study that UA served as a novel solution to relieve colon cancer metastasis by inducing the ubiquitination­mediated degradation of ARL4C by modulating the AKT signalling pathway. Thus, UA may be a promising treatment option to prolong the survival of patients with colon cancer metastasis.

Study of miRNA and lymphocyte subsets as potential biomarkers for the diagnosis and prognosis of gastric cancer.

Objective: The aim of this study was to identify the expression of miRNA and lymphocyte subsets in the blood of gastric cancer (GC) patients, elucidate their clinical significance in GC, and establish novel biomarkers for the early diagnosis and prognosis of GC. Methods: The expression of miRNAs in the serum of GC patients was screened using second-generation sequencing and detected using qRT-PCR. The correlation between miRNA expression and clinicopathological characteristics of GC patients was analyzed, and molecular markers for predicting cancer were identified. Additionally, flow cytometry was used to detect the proportion of lymphocyte subsets in GC patients compared to healthy individuals. The correlations between differential lymphocyte subsets, clinicopathological features of GC patients, and their prognosis were analyzed statistically. Results: The study revealed that hsa-miR-1306-5p, hsa-miR-3173-5p, and hsa-miR-296-5p were expressed at lower levels in the blood of GC patients, which is consistent with miRNA-seq findings. The AUC values of hsa-miR-1306-5p, hsa-miR-3173-5p, and hsa-miR-296-5p were found to be effective predictors of GC occurrence. Additionally, hsa-miR-296-5p was found to be negatively correlated with CA724. Furthermore, hsa-miR-1306-5p, hsa-miR-3173-5p, and hsa-miR-296-5p were found to be associated with the stage of the disease and were closely linked to the clinical pathology of GC. The lower the levels of these miRNAs, the greater the clinical stage of the tumor and the worse the prognosis of gastric cancer patients. Finally, the study found that patients with GC had lower absolute numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and lymphocytes compared to healthy individuals. The quantity of CD4+ T lymphocytes and the level of the tumor marker CEA were shown to be negatively correlated. The ROC curve and multivariate logistic regression analysis demonstrated that lymphocyte subsets can effectively predict gastric carcinogenesis and prognosis. Conclusion: These miRNAs such as hsa-miR-1306-5p, hsa-miR-3173-5p, hsa-miR-296-5p and lymphocyte subsets such as the absolute numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, lymphocytes are down-regulated in GC and are closely related to the clinicopathological characteristics and prognosis of GC patients. They may serve as new molecular markers for predicting the early diagnosis and prognosis of GC patients.

A novel three-step method for preparation of a TiB2-promoted LiBH4-MgH2 composite for reversible hydrogen storage.

The reversible dehydrogenation properties of the 2LiBH(4)-MgH(2) composite can be effectively improved by incorporating heterogeneous nucleation agents, typically transition metal borides. A careful study of the 2LiBH(4)-MgH(2) composite with a titanium trifluoride (TiF(3)) additive finds that using the conventional one-step milling method renders only a partial conversion from TiF(3) to titanium boride (TiB(2)) through an intermediate of titanium hydride (TiH(2)). Based on a fundamental understanding of the reaction processes of the system, we developed a three-step preparation method, which involves pre-milling the LiBH(4)-TiF(3) mixture, isothermal treatment and milling together with MgH(2). A combination of phase/chemical state/microstructural analyses using X-ray diffraction, X-ray photoelectron spectroscopy and transmission electron microscopy techniques shows that the newly developed method can effectively promote the formation of TiB(2) and meanwhile, ensure a homogeneous dispersion of TiB(2) nanoparticles in the composite matrix. As a consequence, the composite sample prepared by the new method exhibits a favorable combination of high hydrogen capacity, fast reaction kinetics and satisfactory cyclic stability.

Skin B/N-doped anatase TiO2 {001} nanoflakes for visible-light photocatalytic water oxidation.

The limited visible-light-responsive photoactivities of most doped wide-bandgap photocatalysts with widened absorption range have long been the obstacles for the efficient conversion of solar energy to chemical energy by photocatalysis. The weak transport ability of visible-light-induced low-energy charge carriers, and numerous recombination centers arising from the energy-band modifiers along the transport path are two major factors responsible for such a mismatch. A potential solution is to shorten the transport path of photo-induced charges in well-modulated light absorbers with low-dimensional structure and the spatially concentrated dopants underneath their surfaces. As a proof of concept, skin B/N-doped red anatase TiO2 {001} nanoflakes with the absorption edge up to 675 nm were synthesized in this study. Experimental results revealed that boron dopants in the TiO2 nanoflakes from the hydrolysis of nanosized TiB2 played a crucial role in controlling nitrogen doping in the surface layer of the nanoflakes. As visible light excitation occurs at the surface layer, the photons can be sufficiently absorbed by the formed energy levels at the surface layers, and the photogenerated charge carriers can effectively migrate to the surface, thus leading to efficient visible-light-responsive photocatalytic oxygen evolution activity from water oxidation.

Elevated expression of Toll-like receptor 4 and cytokines in both serum and myometrium at term may serve as promising biomarkers for uterine activation preceding labor.

Objective: Increased inflammation and cytokine levels are considered risk factors and promoters of preterm birth (PTB). However, the regulatory mechanism of pregnancy-related inflammation remains unclear. Toll-like receptor 4 (TLR4) plays a critical role in inflammatory responses in various diseases. Therefore, our study aimed to investigate whether TLR4 is involved in the inflammatory responses during uterine activation for labor, with the goal of identifying potential biomarkers for uterine activation at term. Materials and methods: We used flow cytometry to detect TLR4 expression on CD14+ maternal blood monocytes in the first, second, and third trimesters. ELISA was employed to measure TLR4 and cytokines levels in the maternal serum of term non-labor (TNL), term labor (TL) women and LPS induced preterm labor and PBS injected controls. TLR4siRNA was transfected into the human myometrial smooth muscle cells (HMSMCs), which were subsequently treated with IL-1ß. The mRNA and protein levels of TLR4, uterine contraction-related protein connexin 43 (CX43), oxytocin receptor (OTR), MAPK/NF-κB signaling pathway, and cytokines were analyzed using qRT-PCR, western blotting, and immunohistochemistry. Results: The study revealed TLR4 expression on CD14+ maternal blood monocytes was higher in the third trimester group compared to the first and second trimester groups (p<0.001). Maternal serum concentrations of TLR4 and cytokines were significantly higher in the TL group than the TNL group (p<0.001). TLR4, OTR, CX43, activated MAPK/NF-κB expression, and cytokines levels were upregulated in TL group, and similarly significantly higher in the LPS-induced preterm group than in the control group. Using the HMSMCs we demonstrated that TLR4siRNA transfection suppressed contractility. Interfering with TLR4 expression reduced the expression of OTR, CX43, cytokines, and MAPK/NF-κB activation. There was a significant positive relationship between TLR4 expression and the inflammatory status in the myometrium. ROC analysis indicated that TLR4 and cytokines may serve as potential biomarkers for predicting uterine activation for labor. Conclusion: Our data suggest that TLR4 and cytokines can act as stimulators of uterine activation for labor at term. Furthermore, the MAPK/NF-κB pathway appears to be one of the potential signaling pathways mediating TLR4's regulation of parturition initiation.