Urinary schistosomiasis, caused by Schistosoma haematobium, remains a significant public health problem worldwide, despite years of efforts to control it. Haematuria is one of the notable indirect indicators of S. haematobium infection and is commonly assessed along with other routine screens using a urinary dipstick test. A portable "field friendly" electronic analyser would offer an automated and thus more objective read-out compared to visual-read dipstick methods.

Hematopoietic stem cell (HSC) transplantation has been widely applied to the treatment of malignant blood diseases. However, limited number of functional HSCs hinders successful transplantation. The purpose of our current study is to develop a new and cost-efficient medium formulation that could greatly enhance the expansion of HSCs while retaining their long-term repopulation and hematopoietic properties for effective clinical transplantation.

LncRNA PTCSC3 is a known tumor suppressor, while its roles in other human diseases are unclear.

Laryngeal squamous cell carcinoma (LSCC) is among the most common malignant tumors with poor prognosis. Accumulating evidences have identified the important roles of long noncoding RNAs (lncRNAs) in the initiation and progression of various cancer types; however, the global lncRNAs expression profile for metastatic LSCC is limited.

Our previous study proved that nanofat could enhance fat graft survival by promoting neovascularization. Fat extract (FE), a cell-free component derived from nanofat, also possesses proangiogenic activity.

Hepatic alveolar echinococcosis (HAE) is caused by the growth of Echinococcus multilocularis larvae in the liver. It is a chronic and potentially lethal parasitic disease. Early stage diagnosis for this disease is currently not available due to its long asymptomatic incubation period. In this study, a proton nuclear magnetic resonance (1H NMR)-based metabolomics approach was applied in conjunction with multivariate statistical analysis to investigate the altered metabolic profiles in blood serum and urine samples obtained from HAE patients. The aim of the study was to identify the metabolic signatures associated with HAE.

T-cell mediated immunotherapy brought clinical success for many cancer patients. Nonetheless, downregulation of MHC class I antigen presentation, frequently occurring in solid cancers, limits the efficacy of these therapies. Unraveling the mechanisms underlying this type of immune escape is therefore of great importance. We here investigated the immunological effects of metabolic stress in cancer cells as a result of nutrient deprivation.

Although abnormal expression of eukaryotic initiation factor 6 (eIF6) has been found in several human solid tumors, the functions and underlying mechanisms of eIF6 in the progression of colorectal cancer (CRC) still needs further elucidation. In the present study, large-scale gene analysis based on Oncomine and The Cancer Genome Atlas (TCGA) database revealed significantly higher baseline expression of eIF6 in colorectal cancer than in normal tissues. Furthermore, our Chinese cohort study revealed that high expression of eIF6 was correlated with aggressive characteristics and poor survival in CRC patients. Functional studies using magnetic nanoparticle extraction indicated that eIF6 was an oncogene in CRC cells. Regarding its mechanism, through Gene ontology (GO) and KEGG pathway analysis based on TCGA RNAseq database, we found that eIF6 can activate multiple AKT-related cancer signaling pathways, such as p-AKT\MMP1\cyclinD1\Bcl2-related signaling, to regulate cell proliferation, invasion, cell cycle and apoptosis in CRC. Collectively, these findings suggested that eIF6 can positively regulate AKT-related cancer signaling and enhance tumorigenicity in CRC, and may serve as a potential prognostic indicator and therapeutic target in CRC.

Compartmentalization is vital for biological systems at multiple levels, including biochemical reactions in metabolism. Organelle-based compartments such as mitochondria and peroxisomes sequester the responsible enzymes and increase the efficiency of metabolism while simultaneously protecting the cell from dangerous intermediates, such as radical oxygen species. Recent studies show intracellular nucleotides, such as ATP and GTP, are heterogeneously distributed in cells with high concentrations at the lamellipodial and filopodial projections, or leading edge. However, the intracellular distribution of purine nucleotide enzymes remains unclear. Here, we report the enhanced localization of GTP-biosynthetic enzymes, including inosine monophosphate dehydrogenase (IMPDH isotype 1 and 2), GMP synthase (GMPS), guanylate kinase (GUK1) and nucleoside diphosphate kinase-A (NDPK-A) at the leading edge in renal cell carcinoma cells. They show significant co-localization at the membrane subdomain, and their co-localization pattern at the membrane is distinct from that of the cell body. While other purine nucleotide biosynthetic enzymes also show significant localization at the leading edge, their co-localization pattern with IMPDH is divergent. In contrast, a key glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), predominantly localized in the cytoplasm. Mechanistically, we found that plasma membrane localization of IMPDH isozymes requires active actin polymerization. Our results demonstrate the formation of a discrete metabolic compartment for localized purine biosynthesis at the leading edge, which may promote localized nucleotide metabolism for cell migration and metastasis in cancers.

Evidence indicates that 1α, 25-dihydroxy vitamin D3 (1, 25-(OH)2D3) markedly reduces intraocular pressure (IOP) in nonhuman primates, while the biochemical mechanisms are unclear. To investigate the influence of oxidative stress on human trabecular meshwork cells (HTMCs) and the effect and regulatory mechanism of 1, 25-(OH)2D3 in HTMCs under oxidative stress, we established an oxidative stress model in HTMCs using hydrogen peroxide (H2O2) and showed that 1, 25-(OH)2D3 could inhibit oxidative stress-induced apoptosis and reduce extracellular matrix (ECM) composition of HTMCs. Moreover, 1, 25-(OH)2D3 could attenuate H2O2-induced inflammation in HTMCs. Mechanistically, our findings revealed that H2O2-induced damage was mediated by the transforming growth factor-β (TGF-β)-SMAD3 pathway in HTMCs, and 1, 25-(OH)2D3 could protect HTMCs against oxidative stress through vitamin D receptor (VDR), which antagonises the effects of SMAD3. Overall, these findings define a mechanism by which 1, 25-(OH)2D3 reduces ECM accumulation and suppresses the TGF-β-SMAD3-VDR pathway in HTMCs, thus protecting the cells from oxidative stress, suggesting 1, 25-(OH)2D3 might be a potential therapeutic for glaucoma.

Brain computations involve multiple processes by which sensory information is encoded and transformed to drive behavior. These computations are thought to be mediated by dynamic interactions between populations of neurons. Here, we demonstrate that human brains exhibit a reliable sequence of neural interactions during speech production. We use an autoregressive Hidden Markov Model (ARHMM) to identify dynamical network states exhibited by electrocorticographic signals recorded from human neurosurgical patients. Our method resolves dynamic latent network states on a trial-by-trial basis. We characterize individual network states according to the patterns of directional information flow between cortical regions of interest. These network states occur consistently and in a specific, interpretable sequence across trials and subjects: the data support the hypothesis of a fixed-length visual processing state, followed by a variable-length language state, and then by a terminal articulation state. This empirical evidence validates classical psycholinguistic theories that have posited such intermediate states during speaking. It further reveals these state dynamics are not localized to one brain area or one sequence of areas, but are instead a network phenomenon.

Altered glutamine metabolism is a hallmark of cancer growth, forming the theoretical basis for development of metabolic therapies as cancer treatments. Glutaminase (GLS), a crucial enzyme involved in the regulation of glutamine metabolism, has been reported to play crucial roles in cancer development. However, the precise function of GLS in prostate cancer (PCa) remains unclear. The purpose of the present study was to assess the GLS expression and its clinical significance in PCa. We found that GLS was significantly up-regulated in PCa tissues and cell lines. High expression of GLS was significantly associated with Gleason score (P=0.001) and Tumor stage (P=0.015). Functionally, we silenced GLS in PCa cell lines and revealed that GLS knockdown largely blunted the proliferation of DU145 and PC-3 cells. Mechanistically, we demonstrated that knockdown of GLS induced apoptosis and cell cycle arrest. Moreover, we observed that the expressions of Bax were increased while the levels of cyclinD1 and Bcl-2 were decreased after knockdown of GLS in PCa cells. Importantly, through Western blot analysis, we identified that GLS knockdown dramatically suppressed Wnt/β-catenin pathway. Taken together, GLS is a novel oncogene in PCa and may be a potential treatment target for PCa patients.

Background: Sensitive skin affects an increasingly large proportion of the population and is less tolerant to frequent and prolonged use of cosmetics. This study investigates the antiaging effects of a skin care system developed for use on sensitive skin. Methods: A total of 30 healthy Caucasian females, aged 32-72, were enrolled in this double-blind randomized placebo-controlled split-face study. A routine consisting of twice daily topical applications of the test cleanser and test moisturizer or placebo or positive control products was followed for 28 days, with parameters measured at baseline and at 7-day intervals. Objective skin assessments for hydration, transepidermal water loss (TEWL), skin surface topography, elasticity and safety assessment were conducted. Results: Wrinkle surface, length and depth significantly improved by 34.8±4.7% (P<0.001), 19.0±3.2% (P<0.05) and 24.3±3.5% (P<0.05), respectively, after 28 days of skin care treatment with the test cleanser and test moisturizer. R2 (gross elasticity), R5 (net elasticity) and R7 (biological elasticity) significantly increased by 32.8±6.5% (P<0.001), 47.3±8.6% (P<0.001) and 50.6±5.1% (P<0.001), respectively, while R6 (viscoelastic portion) significantly decreased by 33.4±4.6% (P<0.001) after 28 days. Skin hydration was also found to increase significantly after 28 days by 42.2±8.5% (P<0.01), but there was no change in TEWL. No adverse events were reported. Conclusions: A novel skin care routine developed for use on sensitive skin significantly improves the signs of aging including hydration, wrinkle size and elasticity without significant adverse effects.

Background: Early recurrence of distal cholangiocarcinoma (DCC) may result in a poorer prognosis. This study aimed to evaluate the clinicopathological factors that predict survival and recurrence in patients with DCC. Methods: Fifty-five patients with DCC who underwent pancreaticoduodenectomy between 2005 and 2015 were studied retrospectively. The following clinicopathological parameters were analyzed as predictors of disease-free survival (DFS) and overall survival (OS): sex, age, body mass index, presence of biliary tract decompression, macroscopic type, histological type, tumor size, TNM classification, lymph node metastasis ratio, number of positive lymph nodes (PLNs), lymphatic invasion, venous invasion, perineural invasion, proximal bile duct margin, dissected margin, portal system invasion, arterial system invasion, stage, and residual tumor. Results: Univariate analysis showed that contiguous extension of the primary tumor, PLN, lymphatic invasion, venous invasion, perineural invasion, and stage were significant prognostic factors for DFS and OS. Multivariate analysis revealed that PLN and lymphatic invasion were prognostic for DFS and OS (P<0.001). Significant differences in OS and DFS were found in analyses stratified by PLN (0, 1, 2 vs ≥3) and lymphatic invasion (0 vs 1, 2, 3). Conclusion: Among the clinicopathological parameters analyzed, PLN and lymphatic invasion were confirmed as prognostic factors for DCC.

Background: Great progress has been achieved lately in the therapy for chronic lymphocytic leukemia (CLL), one of the most frequently diagnosed adult leukemias. New classes of drugs, such as kinase inhibitors and BCL-2 protein antagonists, have been approved for treatment of CLL patients. Despite the abovementioned therapies the disease can still be effectively treated with purine nucleoside analogs (PNA). However, some patients, for example, those with TP53 gene abnormalities, become resistant, and the other factors involved in the therapy resistance are still being investigated. This study was aimed at analyzing the possible role of microRNAs as markers predicting the outcome of chemotherapy based on PNA - fludarabine and cladribine in CLL patients. Methods: The expression of miR-21, miR-34a, miR-181a and miR-221 in previously separated leukemic cells was assessed with the use of qRQ-PCR technique at the moment of diagnosis in 40 CLL patients. In turn, apoptosis induced by fludarabine and cladribine in 24-hour cell culture was evaluated by determining the increase in the percentage of apoptotic cells of CD5+/CD19+/Cas3+ phenotype, using a flow cytometry method. Nine of the 40 studied subjects were treated with fludarabine-based regimens and were analyzed with regards to in vivo response to PNA. Results: We detected a significantly higher PNA-induced apoptosis rate in patients with high miR-34a expression in comparison to low expression ones. Interestingly, such differences were detected particularly in standard cytogenetic patients. Conclusions: These results may prove an important role of miR-34a expression as a predictor of apoptosis, even in cases when other risk factors like cytogenetic abnormalities are absent. An assessment of microRNAs expression seems to be useful as an indicator of sensitivity to PNA and may help to predict PNA-based therapy outcome.

Purpose: The biological functions of neuropilin and tolloid-like 2 (NETO2) in the progression of pancreatic cancer remained unexplored. We aimed to investigate the biological roles and underlying molecular mechanisms of NETO2 in pancreatic cancer. Materials and methods: Thirty paired pancreatic tumor tissue samples and corresponding nontumor tissues were obtained from 30 pancreatic cancer patients who did not receive preoperative chemotherapy or radiotherapy. The changes in multiple cellular functions associated with tumor progression were assessed after NETO2 knockdown/overexpression in pancreatic cancer cell lines. Additionally, a mouse-xenograft model was developed to verify the in vitro results. Results: NETO2 was upregulated in pancreatic tumor tissues. Elevated expression of NETO2 was not only associated with an advanced tumor stage, but was also a prediction of poor prognosis for pancreatic cancer patients. Knockdown of NETO2 in pancreatic cancer cell lines arrested the cell cycle and inhibited cell proliferation, colony formation, invasion, and migration; in contrast, overexpression of NETO2 had an opposite effect on all of these parameters. A STAT3 specific inhibitor, cryptotanshinone, reversed the tumor-promoting effects induced by NETO2 overexpression in pancreatic cancer. Western blot analysis showed that invasion and migration were closely related to epithelial-mesenchymal transition, and that the STAT3 signaling pathway was involved in NETO2-mediated oncogenic transformation in pancreatic cancer cells. Furthermore, NETO2 knockdown significantly inhibited the growth of pancreatic tumor xenografts in nude mice. Conclusion: NETO2 has an important role in the progression and metastasis of pancreatic cancer and could serve as a novel candidate for targeted therapy of pancreatic cancer.

Background: The mTOR pathway is altered in a multitude of cancers, including lung cancer; however, abnormal activation in this pathway is less common in lung adenocarcinoma (LUAD) than in lung squamous cell carcinoma (LUSC). Gephyrin is a highly conserved and widely expressed ancient protein in vertebrate tissues. Its role and molecular mechanism in lung cancer development are largely unknown. Method: We analyzed the expression profile of gephyrin and overall survival rates in LUAD and LUSC. The LUSC cells (H520 and SK-MES-1) were transfected with pLV-gephyrin to establish gephyrin stable overexpression cell lines. Real-time quantitative PCR and Western blot were performed to detect the mRNA and protein levels. The cell growth and cell cycle were detected by the MTT assay and flow cytometry. Finally, a xenograft tumor model was established to determine cell tumorigenesis in vivo. Results: Our results show that gephyrin was reduced in LUAD and LUSC, and its low expression in LUSC patients indicated poor prognosis. Gephyrin overexpression suppressed LUSC cell proliferation, arrested cell cycle progression, and decreased the expression of cell-cycle related proteins such as cyclin D1, cyclin-dependent kinase-2 (CDK2), and proliferation-related protein proliferating cell nuclear antigen (PCNA). Conversely, knockdown of gephyrin promoted LUSC cell growth. Moreover, gephyrin reduced mTOR pathway activation to inhibit cyclin D1 and CDK2 translation. Mechanistically, gephyrin suppressed mTOR pathway activation by promoting mTOR degradation. Furthermore, gephyrin overexpression suppressed LUSC tumorigenesis. Conclusion: Gephyrin suppressed LUSC development by reducing mTOR pathway activation, implicating gephyrin as a potential molecular target for LUSC management.

Purpose: The present study was conducted to find the preferred mode of learning among first-year preclinical students and compare the preferred mode of learning with sex, faculty of students, and academic performance of the students using the VARK questionnaire. Methods: A cross-sectional study was done among 142 first-year Bachelor of Medicine-Bachelor of Surgery and Bachelor of Dental Surgery students from February to May 2018. Demographic data and various academic performance marks were recorded for each individual. VARK (visual, aural, read/write and kinesthetic) questionnaire version 7.8 was administered to calculate the score of each component. Mean VARK scores were calculated and each student classified by their preferred mode of learning. The preferred mode of learning was compared with sex, nationality, faculty of students, and academic performance using χ 2, unpaired t-tests, and the Mann-Whitney U test. P<0.05 was taken as statistically significant for comparison. Results: A majority of the students (53.52%) were multimodal. The most common multimodal mode of preference was bimodal (26.06%), while the most common unimodal preference was kinesthetic (29.06%). Total V score, K score, and VARK score were higher among males, while A and R scores were higher among females. The K score (7.96±2.35 in males and 6.96±2.43 in females) differed significantly (P=0.019) between male and female subjects. More subjects with higher scores in the theory exam of anatomy were unimodal learners (53.8%) compared to multimodal learners (46.2%). Conclusion: From this study, it can be concluded that undergraduate students were diverse in their learning styles, but most were multimodal. Though learning styles were found to vary by sex, nationality, and academic performance, differences were not statistically significant.

A new species of Rhopalias Stiles & Hassall, 1898 is described from the small intestine of the Common opossum, Didelphismarsupialis Linnaeus from the Yucatán Peninsula, Mexico. Rhopaliasoochi sp. nov. is morphologically very similar to the type species of the genus, Rhopaliascoronatus (Rudolphi, 1819) Stiles & Hassall 1898, a species widely distributed in opossums across Mexico. A molecular phylogenetic analysis using a mitochondrial gene (cox1), and the nuclear ribosomal internal transcribed spacer region (ITS1-5.8S-ITS2), of specimens of R.coronatus collected in several localities of Mexico revealed that those from the Yucatán Peninsula, originally recorded on morphological grounds as R.coronatus actually represented an independent genetic lineage. Maximum Likelihood and Bayesian Inference analyses were performed for each data set independently, and for the concatenated data set (ITS1-5.8S-ITS2 + cox1). All phylogenetic analyses showed that the specimens from Yucatán represented a monophyletic lineage, with high bootstrap support and Bayesian posterior probabilities. In addition, the genetic divergence estimated between R.oochi sp. nov. and two species of Rhopalias, R.coronatus, and R.macracanthus Chandler, 1932 that also occur in Mexican marsupials ranged between 7-8% and 16-17%, for cox1, and between 0.1-0.2% and 7% for the ITS region, respectively. The molecular evidence gathered in this study (reciprocal monophyly in both phylogenetic analyses, and estimated genetic divergence) suggested that the specimens found in the intestine of D.marsupialis originally reported as R.coronatus from Yucatán, actually represent a new species. Morphological evidence was found through light and scanning electron microscopy to support the species distinction based on molecular data.

Trials on assessing the benefits of EGFR inhibitors in head and neck squamous cell carcinoma (HNSCC) patients have gradually been published. Nevertheless, the benefits of gefitinib in advanced HNSCC are still unknown.