IL-6 Mutation Attenuates Liver Injury Caused by Aeromonas hydrophila Infection by Reducing Oxidative Stress in Zebrafish.

Interleukin-6 (IL-6), a pleiotropic cytokine, plays a crucial role in acute stress induced by bacterial infection and is strongly associated with reactive oxygen species (ROS) production. However, the role of IL-6 in the liver of fish after Aeromonas hydrophila infection remains unclear. Therefore, this study constructed a zebrafish (Danio rerio) il-6 knockout line by CRISPR/Cas9 to investigate the function of IL-6 in the liver post bacterial infection. After infection with A. hydrophila, pathological observation showed that il-6-/- zebrafish exhibited milder liver damage than wild-type (WT) zebrafish. Moreover, liver transcriptome sequencing revealed that 2432 genes were significantly up-regulated and 1706 genes were significantly down-regulated in il-6-/- fish compared with WT fish after A. hydrophila infection. Further, gene ontology (GO) analysis showed that differentially expressed genes (DEGs) were significantly enriched in redox-related terms, including oxidoreductase activity, copper ion transport, etc. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were significantly enriched in pathways such as the PPAR signaling pathway, suggesting that il-6 mutation has a significant effect on redox processes in the liver after A. hydrophila infection. Additionally, il-6-/- zebrafish exhibited lower malondialdehyde (MDA) levels and higher superoxide dismutase (SOD) activities in the liver compared with WT zebrafish following A. hydrophila infection, indicating that IL-6 deficiency mitigates oxidative stress induced by A. hydrophila infection in the liver. These findings provide a basis for further studies on the role of IL-6 in regulating oxidative stress in response to bacterial infections.

A fluorescence-based assay for Trichomonas vaginalis drug screening.

BACKGROUND: The emergence and spread of drug resistance in Trichomonas vaginalis parasites has become an important concern in trichomoniasis treatment. Fast and reliable growth assessment is critical for validating in vitro drug susceptibility and high-throughput screening of newly developed drugs. METHODS: Modified media without yeast extract were evaluated for their ability to support the growth of T. vaginalis parasites. The potential of the nucleic acid-binding dye SYBR Green I for detecting T. vaginalis drug resistance was characterized, and seeding parasite concentration and incubation time were optimized. The fluorescence assay based on SYBR Green I was further validated in four T. vaginalis isolates with different susceptibilities to the antibiotics metronidazole, tinidazole, ornidazole and secnidazole, and compared with the traditional method that detects minimum lethal concentrations (MLCs). RESULTS: A modified medium consisting of RPMI 1640 and Tryptone Plus as replacements for yeast extract and tryptone, respectively, in traditional trypticase-yeast extract-maltose (TYM) medium exhibited similar performance as TYM medium in maintaining T. vaginalis growth, while it showed much lower background fluorescent signals. The T. vaginalis SYBR Green I-based fluorescence (TSF) drug assay was found to have to satisfy one of two conditions to demonstrate the 50% inhibitory concentration of metronidazole for the sensitive isolate TV-334: (i) a seeding density of 3 × 104 parasites/ml and an incubation time of 48 h; or (ii) a seeding density of 1 × 104 parasites/ml and an incubation time of 72 h. Subsequent validation experiments revealed that the 48-h incubation/3 × 104 parasites/ml seeding density condition had a greater sensitivity to detect drug resistance than the 72-h condition. The TSF assay also exhibited high efficiency in identifying parasite drug resistance, as evidenced by its strong correlation with the standard MLC assay results (P = 0.003). CONCLUSIONS: This study presents a robust TSF assay that has the potential to facilitate high-throughput, automated in vitro anti-trichomoniasis susceptibility testing for drug resistance monitoring and drug development. In comparison to the standard MLC method, this assay offers the advantages of reduced labor and elimination of subjective examination.

Chronic Mucocutaneous Candidiasis: A Case Report.

Chronic mucocutaneous candidiasis (CMC) is a rare infectious skin disease. This study reported a case of CMC in a child with clinical manifestations of oral mucosal leukoplakia and erythema and crust-like thick scabs on the skin of the face and upper limbs. Microscopic fungal examination revealed a large amount of pseudohyphae, and the fungal culture indicated Candida albicans. A drug sensitivity test indicated that it was sensitive to itraconazole and nystatin. Laboratory tests did not show significant immunodeficiency or endocrine abnormalities, and gene sequencing did not identify DNA gene mutations in the coiled-coil domain (CCD) or the DNA-binding domain (DBD) of signal transducer and activator of transcription 1 (STAT1). The skin lesions subsided after oral administration of itraconazole but relapsed 6 months later, and hypoparathyroidism occurred 1 year later. Patients with repeated superficial fungal infection should be alert to the possibility of CMC. CMC has numerous complications and a poor prognosis that requires the attention of clinicians. In this case, STAT1 mutation was not found, and parathyroid dysfunction was rare, providing reference for clinical diagnosis and treatment of CMC.

Long noncoding RNA HAND2-AS1: A crucial regulator of malignancy.

Long non-coding RNAs (LncRNAs) are single-stranded RNAs over 200 nucleotides in length that have no protein-coding function and have long been considered non-functional by-products of transcription. Recent studies have shown that dysregulation of lncRNAs may be involved in the malignant biological behavior of tumors. Targeted regulation of lncRNAs has become a research focus of anti-tumor treatment. LncRNAs heart and neural crest derivatives expressed 2 antisense RNA 1 (HAND2-AS1) was down-regulated in various tumors and can be used as a critical tumor regulator to modulate tumor cells proliferation, apoptosis, metastasis, invasion, metabolism and drug resistance. Additionally, aberrantly expressed HAND2-AS1 was closely related to the clinical pathological characteristics of cancer patients and serve as a promising tumor diagnostic and prognostic biomarker. This article aims to review the roles of HAND2-AS1 in tumorigenesis and development, as well as the underlying molecular mechanisms and clinical significance.

Accretion of the cratonic mantle lithosphere via massive regional relamination.

Continental, orogenic, and oceanic lithospheric mantle embeds sizeable parcels of exotic cratonic lithospheric mantle (CLM) derived from distant, unrelated sources. This hints that CLM recycling into the mantle and its eventual upwelling and relamination at the base of younger plates contribute to the complex structure of the growing lithosphere. Here, we use numerical modeling to investigate the fate and survival of recycled CLM in the ambient mantle and test the viability of CLM relamination under Hadean to present-day mantle temperature conditions and its role in early lithosphere evolution. We show that the foundered CLM is partially mixed and homogenized in the ambient mantle; then, as thermal negative buoyancy vanishes, its long-lasting compositional buoyancy drives upwelling, relaminating unrelated growing lithospheric plates and contributing to differentiation under cratonic, orogenic, and oceanic regions. Parts of the CLM remain in the mantle as diffused depleted heterogeneities at multiple scales, which can survive for billions of years. Relamination is maximized for high depletion degrees and mantle temperatures compatible with the early Earth, leading to the upwelling and underplating of large volumes of foundered CLM, a process we name massive regional relamination (MRR). MRR explains the complex source, age, and depletion heterogeneities found in ancient cratonic lithospheric mantle, suggesting this may have been a key component of the construction of continents in the early Earth.

Glucometabolic reprogramming: From trigger to therapeutic target in hepatocellular carcinoma.

Glucose, the central macronutrient, releases energy as ATP through carbon bond oxidation and supports various physiological functions of living organisms. Hepatocarcinogenesis relies on the bioenergetic advantage conferred by glucometabolic reprogramming. The exploitation of reformed metabolism induces a uniquely inert environment conducive to survival and renders the hepatocellular carcinoma (HCC) cells the extraordinary ability to thrive even in the nutrient-poor tumor microenvironment. The rewired metabolism also confers a defensive barrier which protects the HCC cells from environmental stress and immune surveillance. Additionally, targeted interventions against key players of HCC metabolic and signaling pathways provide promising prospects for tumor therapy. The active search for novel drugs based on innovative mutation targets is warranted in the future for effectively treating advanced HCC and the preoperative downstage. This article aims to review the regulatory mechanisms and therapeutic value of glucometabolic reprogramming on the disease progression of HCC, to gain insights into basic and clinical research.

Dietary supplementation with nanoparticle CMCS-20a enhances the resistance to GCRV infection in grass carp (Ctenopharyngodon idella).

Combination of antimicrobial proteins and nanomaterials provides a platform for the development of immunopotentiators. Oral administration of immunopotentiators can significantly enhance the immunity of organisms, which provides ideas for disease prevention. In this study, we confirmed that nanoparticles CMCS-20a can efficiently prevent grass carp reovirus (GCRV) infection. Firstly, we verified that CiCXCL20a is involved in the immune responses post GCRV challenge in vivo and alleviates the cell death post GCRV challenge in CIK cells. Then, we prepared nanoparticles CMCS-20a using carboxymethyl chitosan (CMCS) loaded with grass carp (Ctenopharyngodon idella) CXCL20a (CiCXCL20a). Meanwhile, we confirmed nanoparticles CMCS-20a can alleviate the degradation in intestine. Subsequently, we added it to the feed by low temperature vacuum drying method and high temperature spray drying method, respectively. Grass carp were oral administration for 28 days and challenged by GCRV. Low temperature vacuum drying group (LD-CMCS-20a) significantly improve grass carp survival rate, but not high temperature spray drying group (HD-CMCS-20a). To reveal the mechanisms, we investigated the serum biochemical indexes, intestinal mucus barrier, immune gene regulation and tissue damage. The complement component 3 content, lysozyme and total superoxide dismutase activities are highest in LD-CMCS-20a group. LD-CMCS-20a effectively attenuates the damage of GCRV to the number of intestinal villous goblet cells and mucin thickness. LD-CMCS-20a effectively regulates mRNA expressions of immune genes (IFN1, Mx2, Gig1 and IgM) in spleen and head kidney tissues. In addition, LD-CMCS-20a obviously alleviate tissue lesions and viral load in spleen. These results indicated that the nanoparticles CMCS-20a can enhance the disease resistance of fish by improving their immunity, which provides a new perspective for fish to prevent viral infections.

Nonlinear forces in urban thermal environment using Bayesian optimization-based ensemble learning.

Urbanization witnessed unprecedented development globally, which causes citizens and urban temperature to become increasingly intertwined. Although researchers were interested in the field, most studies focused on holistic linear links between the characteristics of the urban built-up environment and temperature. The study used Bayesian optimization ensemble learning and Shapley value to decouple the urban thermal environment by Landsat satellite data. This work's novelties reveal the specific driving effect of different value ranges of urban features in the overall process on the urban thermal environment and advancing an optimum observation buffer zone of the urban surface temperature. The study's results were only for daytime and Beijing scope. The following are the main findings: (1) The 2 km observation buffer zone is best to analyze the urban thermal environment for this dataset. (2) The ecological environment factors have a more significant effect on the urban temperature than the urban morphology factors. (3) In summer, when the vegetation coverage exceeds 58.1%, every 10% increase could reduce the temperature by 0.84 °C. In contrast to summer, when vegetation coverage exceeds 64.7% and 73.2%, respectively, in spring and fall, there will be a significant marginal utility. (4) The effect of the building height has seasonal variations. It has the greatest cooling effect in the spring when the height is between 18 m and 75 m, and the daytime surface temperature at the time of Landsat overpass will drop by 1.25 °C. These findings will aid in understanding how building construction influences urban surface temperature and provide statistical support for planners.

In Silico and In Vitro Antimalarial Screening and Validation Targeting Plasmodium falciparum Plasmepsin V.

Malaria chemotherapy is greatly threatened by the recent emergence and spread of resistance in the Plasmodium falciparum parasite against artemisinins and their partner drugs. Therefore, it is an urgent priority to develop new antimalarials. Plasmepsin V (PMV) is regarded as a superior drug target for its essential role in protein export. In this study, we performed virtual screening based on homology modeling of PMV structure, molecular docking and pharmacophore model analysis against a library with 1,535,478 compounds, which yielded 233 hits. Their antimalarial activities were assessed amongst four non-peptidomimetic compounds that demonstrated the promising inhibition of parasite growth, with mean IC50 values of 6.67 µM, 5.10 µM, 12.55 µM and 8.31 µM. No significant affection to the viability of L929 cells was detected in these candidates. These four compounds displayed strong binding activities with the PfPMV model through H-bond, hydrophobic, halogen bond or π-π interactions in molecular docking, with binding scores under -9.0 kcal/mol. The experimental validation of molecule-protein interaction identified the binding of four compounds with multiple plasmepsins; however, only compound 47 showed interaction with plasmepsin V, which exhibited the potential to be developed as an active PfPMV inhibitor.

Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China-Myanmar border during 2008‒2017.

BACKGROUND: Plasmodium vivax remains the predominant species at the China-Myanmar border, imposing a major challenge to the recent gains in regional malaria elimination. To closely supervise the emerging of drug resistance in this area, we surveyed the variations in genes potentially correlated with drug resistance in P. vivax parasite and the possible drug selection with time. METHODS: A total of 235 P. vivax samples were collected from patients suffering uncomplicated malaria at Yingjiang, Tengchong, and Longling counties, and Nabang port in China, Yunnan province, and Laiza sub-township in Myanmar, from 2008 to 2017. Five potential drug resistance genes were amplified utilizing nested-PCR and analyzed, including pvdhfr, pvdhps, pvmdr1, pvcrt-o, and pvk12. The Pearson's Chi-squared test or Fisher's exact test were applied to determine the statistical frequency differences of mutations between categorical data. RESULTS: The pvdhfr F57I/L, S58R, T61M and S117T/N presented in 40.6%, 56.7%, 40.1%, and 56.0% of the sequenced P. vivax isolates, and these mutations significantly decreased with years. The haplotype formed by these quadruple mutations predominated in Yingjiang, Tengchong, Longling and Nabang. While a mutation H99S/R (56.6%) dominated in Laiza and increased with time. In pvdhps, the A383G prevailed in 69.2% of the samples, which remained the most prevalent haplotype. However, a significant decrease of its occurrence was also noticed over the time. The S382A/C and A553G existed in 8.4% and 30.8% of the isolates, respectively. In pvmdr1, the mutation Y976F occurred at a low frequency in 5/232 (2.2%), while T958M was fixed and F1076L was approaching fixed (72.4%). The K10 insertion was detected at an occurrence of 33.2% in pvcrt-o, whereas there was no significant difference among the sites or over the time. No mutation was identified in pvk12. CONCLUSIONS: Mutations related with resistance to antifolate drugs are prevalent in this area, while their frequencies decrease significantly with time, suggestive of increased susceptibility of P. vivax parasite to antifolate drugs. Resistance to chloroquine (CQ) is possibly emerging. However, since the molecular mechanisms underneath CQ resistance is yet to be better understood, close supervision of clinical drug efficiency and continuous function investigation is urgently needed to alarm drug resistance.

The Potential Impact of Food Insecurity in an Urban Trauma Population.

BACKGROUND: Food insecurity (FI) has been defined as a lack of consistent access to enough food for a healthy active lifestyle. As of 12.7% of the United States are suffering from FI, which has been correlated with increased hospital costs and poorer health outcomes. Currently, limited data exists examining the relationship between trauma populations and FI despite both having similar root causes. We sought to determine this and validate a screening tool for FI in this population. METHODS: A cross-sectional survey study of trauma patients was conducted at a level 1 trauma center in Atlanta, Georgia. Survey questions included the first two items of the Core Food Security Module. Zip codes were used to determine FI, defined by the USDA Food Access Research and compared to individual participant survey responses. Binary classification test metrics were calculated to validate the two items as a screening tool in this population. RESULTS: The cohort included 136 patients, of which the majority were black (60.3%) and male (60.3%). Thirty-one respondents affirmed food security (22.8%) despite over half (51.5%) living in a food insecure community. The sensitivity and specificity for this screening to predict FI were 25 and 80%, respectively. CONCLUSION: Although the specificity is high, this screening tool has a low sensitivity, accuracy, NPV, and PPV to determine food insecurity in this population. Community-level statistics suggests that food insecurity is a significant public problem amongst trauma patients. Prevention efforts should, therefore, aim to address both issues simultaneously.

Racial and Ethnic Differences and Clinical Outcomes of Patients With Coronavirus Disease 2019 (COVID-19) Presenting to the Emergency Department.

BACKGROUND: Since the introduction of remdesivir and dexamethasone for severe COVID-19 treatment, few large multi-hospital-system US studies have described clinical characteristics and outcomes of minority COVID-19 patients who present to the emergency department (ED). METHODS: This cohort study from the Cerner Real World Database (87 US health systems) from 1 December 2019 to 30 September 2020 included PCR-confirmed COVID-19 patients who self-identified as non-Hispanic Black (Black), Hispanic White (Hispanic), or non-Hispanic White (White). The main outcome was hospitalization among ED patients. Secondary outcomes included mechanical ventilation, intensive care unit care, and in-hospital mortality. Descriptive statistics and Poisson regression compared sociodemographics, comorbidities, receipt of remdesivir or dexamethasone, and outcomes by racial/ethnic groups and geographic region. RESULTS: 94 683 COVID-19 patients presented to the ED. Blacks comprised 26.7% and Hispanics 33.6%. Nearly half (45.1%) of ED patients presented to hospitals in the South. 31.4% (n = 29 687) were hospitalized. Lower proportions of Blacks were prescribed dexamethasone (29.4%; n = 7426) compared with Hispanics (40.9%; n = 13 021) and Whites (37.5%; n = 14 088). Hospitalization risks, compared with Whites, were similar in Blacks (RR: .94; 95% CI: .82-1.08; P = .4) and Hispanics (.99; .81-1.21; P = .91), but risk of in-hospital mortality was higher in Blacks (1.18; 1.06-1.31; P = .002) and Hispanics (1.28; 1.13-1.44; P < .001). CONCLUSIONS: Minority patients were overrepresented among COVID-19 ED patients, and while their risks of hospitalization were similar to Whites, in-hospital mortality risk was higher. Interventions targeting upstream social determinants of health are needed to reduce racial/ethnic disparities in COVID-19.

Dialysis Facility Profit Status and Early Steps in Kidney Transplantation in the Southeastern United States.

BACKGROUND AND OBJECTIVES: Dialysis facilities in the United States play a key role in access to kidney transplantation. Previous studies reported that patients treated at for-profit facilities are less likely to be waitlisted and receive a transplant, but their effect on early steps in the transplant process is unknown. The study's objective was to determine the association between dialysis facility profit status and critical steps in the transplantation process in Georgia, North Carolina, and South Carolina. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective cohort study, we linked referral and evaluation data from all nine transplant centers in the Southeast with United States Renal Data System surveillance data. The cohort study included 33,651 patients with kidney failure initiating dialysis from January 1, 2012 to August 31, 2016. Patients were censored for event (date of referral, evaluation, or waitlisting), death, or end of study (August 31, 2017 for referral and March 1, 2018 for evaluation and waitlisting). The primary exposure was dialysis facility profit status: for profit versus nonprofit. The primary outcome was referral for evaluation at a transplant center after dialysis initiation. Secondary outcomes were start of evaluation at a transplant center after referral and waitlisting. RESULTS: Of the 33,651 patients with incident kidney failure, most received dialysis treatment at a for-profit facility (85%). For-profit (versus nonprofit) facilities had a lower cumulative incidence difference for referral within 1 year of dialysis (-4.5%; 95% confidence interval, -6.0% to -3.2%). In adjusted analyses, for-profit versus nonprofit facilities had lower referral (hazard ratio, 0.84; 95% confidence interval, 0.80 to 0.88). Start of evaluation within 6 months of referral (-1.0%; 95% confidence interval, -3.1% to 1.3%) and waitlisting within 6 months of evaluation (1.0%; 95% confidence interval, -1.2 to 3.3) did not meaningfully differ between groups. CONCLUSIONS: Findings suggest lower access to referral among patients dialyzing in for-profit facilities in the Southeast United States, but no difference in starting the evaluation and waitlisting by facility profit status.

Long-term mortality among kidney transplant recipients with and without diabetes: a nationwide cohort study in the USA.

INTRODUCTION: Little is known about the role diabetes (type 1 (T1D) and type 2 (T2D)) plays in modifying prognosis among kidney transplant recipients. Here, we compare mortality among transplant recipients with T1D, T2D and non-diabetes-related end-stage kidney disease (ESKD). RESEARCH DESIGN AND METHODS: We included 254 188 first-time single kidney transplant recipients aged ≥18 years from the US Renal Data System (2000-2018). Diabetes status, as primary cause of ESKD, was defined using International Classification of Disease 9th and 10th Clinical Modification codes. Multivariable-adjusted Cox regression models (right-censored) computed risk of death associated with T1D and T2D relative to non-diabetes. Trends in standardized mortality ratios (SMRs) (2000-2017), relative to the general US population, were assessed using Joinpoint regression. RESULTS: A total of 72 175 (28.4%) deaths occurred over a median survival time of 14.6 years. 5-year survival probabilities were 88%, 85% and 77% for non-diabetes, T1D and T2D, respectively. In adjusted models, mortality was highest for T1D (HR=1.95, (95% CI: 1.88 to 2.03)) and then T2D (1.65 (1.62 to 1.69)), as compared with non-diabetes. SMRs declined for non-diabetes, T1D, and T2D. However, in 2017, SMRs were 2.38 (2.31 to 2.45), 6.55 (6.07 to 7.06), and 3.82 (3.68 to 3.98), for non-diabetes, T1D and T2D, respectively. CONCLUSIONS: In the USA, diabetes type is an important modifier in mortality risk among kidney transplant recipients with highest rates among people with T1D-related ESKD. Development of effective interventions that reduce excess mortality in transplant recipients with diabetes is needed, especially for T1D.

Differences in Outpatient Dermatology Encounter Work Relative Value Units and Net Payments by Patient Race, Sex, and Age.

Importance: Clinical productivity measures may be factors in financial incentives for providing care to specific patient populations and thus may perpetuate inequitable health care. Objective: To identify the association of patient race, age, and sex with work relative value units (wRVUs) generated by outpatient dermatology encounters. Design, Setting, and Participants: This cross-sectional study obtained demographic and billing data for outpatient dermatology encounters (ie, an encounter performed within a department of dermatology) from September 1, 2016, to March 31, 2020, at the Emory Clinic, an academic dermatologic practice in Atlanta, Georgia. Participants included adults aged 18 years or older with available age, race, and sex data in the electronic health record system. Main Outcomes and Measures: The primary outcome was wRVUs generated per encounter. Results: A total of 66 463 encounters among 30 036 unique patients were included. Patients had a mean (SD) age of 55.9 (18.5) years and were predominantly White (46 575 [70.1%]) and female (39 598 [59.6%]) individuals. In the general dermatologic practice, the mean (SD) wRVUs per encounter was 1.40 (0.71). In adjusted analysis, Black, Asian, and other races (eg, American Indian or Native American, Native Hawaiian or Other Pacific Islander, and multiple races); female sex; and younger age were associated with fewer wRVUs per outpatient dermatology encounter. Compared with general dermatologic visits with White patients, visits with Black patients generated 0.27 (95% CI, 0.25-0.28) fewer wRVUs per encounter, visits with Asian patients generated 0.22 (95% CI, 0.20-0.25) fewer wRVUs per encounter, and visits with patients of other race generated 0.19 (95% CI, 0.14-0.24) fewer wRVUs per encounter. Female sex was also associated with 0.11 (95% CI, 0.10-0.12) fewer wRVUs per encounter, and wRVUs per encounter increased by 0.006 (95% CI, 0.006-0.006) with each 1-year increase in age. In the general dermatologic practice excluding Mohs surgeons, destruction of premalignant lesions and biopsies were mediators for the observed differences in race (56.2% [95% CI, 53.1%-59.3%] for Black race, 53.2% [95% CI, 45.6%-63.8%] for Asian race, and 53.6% [95% CI, 40.4%-77.4%] for other races), age (65.6%; 95% CI, 60.5%-71.4%), and sex (82.3%; 95% CI, 72.7%-93.1%). In a data set including encounters with Mohs surgeons, the race, age, and sex differences in wRVUs per encounter were greater than in the general dermatologic data set. Mohs surgery for basal cell and squamous cell carcinomas was a mediator for the observed differences in race (46.0% [95% CI, 42.6%-49.4%] for Black race, 41.9% [95% CI, 35.5%-49.2%] for Asian race, and 34.6% [95% CI, 13.8%-51.5%] for other races), age (49.2%; 95% CI, 44.9%-53.7%), and sex (47.9%; 95% CI, 42.0%-54.6%). Conclusions and Relevance: This cross-sectional study found that dermatology encounters with racial minority groups, women, and younger patients generated fewer wRVUs than encounters with older White male patients. This finding suggests that physician compensation based on wRVUs may encourage the provision of services that exacerbate disparities in access to dermatologic care.

Global survey of miRNAs and tRNA-derived small RNAs from the human parasitic protist Trichomonas vaginalis.

BACKGROUND: Small non-coding RNAs play critical regulatory roles in post-transcription. However, their characteristics in Trichomonas vaginalis, the causative agent of human sexually transmitted trichomoniasis, still remain to be determined. METHODS: Small RNA transcriptomes from Trichomonas trophozoites were deep sequenced using the Illumina NextSeq 500 system and comprehensively analyzed to identify Trichomonas microRNAs (miRNAs) and transfer RNA (tRNA)-derived small RNAs (tsRNAs). The tsRNA candidates were confirmed by stem-loop quantitative reverse transcription-PCR, and motifs to guide the cleavage of tsRNAs were predicted using the GLAM2 algorithm. RESULTS: The miRNAs were found to be present in T. vaginalis but at an extremely low abundance (0.0046%). Three categories of endogenous Trichomonas tsRNAs were identified, namely 5'tritsRNAs, mid-tritsRNAs and 3'tritsRNAs, with the 5'tritsRNAs constituting the dominant category (67.63%) of tsRNAs. Interestingly, the cleavage site analysis verified both conventional classes of tRNA-derived fragments (tRFs) and tRNA-halves in tritsRNAs, indicating the expression of tRNA-halves in the non-stress condition. A total of 25 tritsRNAs were experimentally confirmed, accounting for 78.1% of all tested candidates. Three motifs were predicted to guide the production of tritsRNAs. The results prove the expression of tRFs and tRNA-halves in the T. vaginalis transcriptome. CONCLUSIONS: This is the first report of genome-wide investigation of small RNAs, particularly tsRNAs and miRNAs, from Trichomonas parasites. Our findings demonstrate the expression profile of tsRNAs in T. vaginalis, while miRNA was barely detected. These results may promote further research aimed at gaining a better understanding of the evolution of small non-coding RNA in T. vaginalis and their functions in the pathogenesis of trichomoniasis.

Increasing Incidence of Advanced Non-cardia Gastric Cancers Among Younger Hispanics in the USA.

BACKGROUND: Recent findings indicate a shift in the epidemiology of non-cardia gastric cancer in the USA. In particular, an uprising trend in incidence rates among non-Hispanic whites aged < 50 years. AIM: To examine secular trends in the incidence of non-cardia gastric cancer among adults aged < 50 years in the USA by race/ethnicity and stage at diagnosis. METHODS: Age-adjusted incidence rates and trends in adults aged < 50 years and ≥ 50 years were calculated using data from all 50 states in the National Program of Cancer Registries and the SEER program. We used joinpoint regression to compute average annual percent change (AAPC) in cancer incidence rates. RESULTS: Overall, we found an increasing trend of non-cardia gastric cancer among non-Hispanic whites aged < 50 years between 2001 and 2014 (AAPC = 1.24, 95% CI 0.49, 1.99). However, among non-Hispanic whites aged < 50 years, the rates of localized disease increased (AAPC = 5.28, 95% CI 3.94, 6.64), whereas the rates of distant stage non-cardia gastric cancer remained unchanged (AAPC = 0.68, 95% CI - 0.63, 2.00). Conversely, we found a significant increase in rates of distant stage non-cardia gastric cancer among Hispanics aged < 50 years (AAPC = 1.78, 95% CI 0.66, 2.91). Non-cardia gastric cancer incidence rates decreased over the study period among non-Hispanic whites and Hispanics aged ≥ 50 years. CONCLUSION: Given the rapid growth of the young Hispanic population in the USA, preventative strategies for non-cardia gastric cancer cannot neglect this population.

Oral Administration of Bacillus subtilis Subunit Vaccine Significantly Enhances the Immune Protection of Grass Carp against GCRV-II Infection.

Grass carp reovirus (GCRV) is a severe virus that causes great losses to grass carp culture every year, and GCRV-II is the current popular and fatal strain. VP56, fibrin on the outer surface of GCRV-II, mediates cell attachment. In this study, we firstly divided the VP56 gene into four fragments to screen the optimal antigen by enzyme-linked immunosorbent assay and neutralizing antibody methods. The second fragment VP56-2 demonstrates the optimal efficiency and was employed as an antigen in the following experiments. Bacillus subtilis were used as a carrier, and VP56-2 was expressed on the surface of the spores. Then, we performed the oral immunization for grass carp and the challenge with GCRV-II. The survival rate was remarkably raised, and mRNA expressions of IgM were significantly up-regulated in spleen and head kidney tissues in the B. s-CotC-VP56-2 group. Three crucial immune indexes (complement C3, lysozyme and total superoxide dismutase) in the sera were also significantly enhanced. mRNA expressions of four important genes (TNF-α, IL-1ß, IFN1 and MHC-II) were significantly strengthened. Tissue lesions were obviously attenuated by histopathological slide examination in trunk kidney and spleen tissues. Tissue viral burdens were significantly reduced post-viral challenge. These results indicated that the oral recombinant B. subtilis VP56-2 subunit vaccine is effective for controlling GCRV infection and provides a feasible strategy for the control of fish virus diseases.