Comprehensive fundamental somatic variant calling and quality management strategies for human cancer genomes.

Next-generation sequencing (NGS) technology has revolutionised human cancer research, particularly via detection of genomic variants with its ultra-high-throughput sequencing and increasing affordability. However, the inundation of rich cancer genomics data has resulted in significant challenges in its exploration and translation into biological insights. One of the difficulties in cancer genome sequencing is software selection. Currently, multiple tools are widely used to process NGS data in four stages: raw sequence data pre-processing and quality control (QC), sequence alignment, variant calling and annotation and visualisation. However, the differences between these NGS tools, including their installation, merits, drawbacks and application, have not been fully appreciated. Therefore, a systematic review of the functionality and performance of NGS tools is required to provide cancer researchers with guidance on software and strategy selection. Another challenge is the multidimensional QC of sequencing data because QC can not only report varied sequence data characteristics but also reveal deviations in diverse features and is essential for a meaningful and successful study. However, monitoring of QC metrics in specific steps including alignment and variant calling is neglected in certain pipelines such as the 'Best Practices Workflows' in GATK. In this review, we investigated the most widely used software for the fundamental analysis and QC of cancer genome sequencing data and provided instructions for selecting the most appropriate software and pipelines to ensure precise and efficient conclusions. We further discussed the prospects and new research directions for cancer genomics.

Prognostic value of fibroblast activation protein expressing tumor volume calculated from [68 Ga]Ga-FAPI PET/CT in patients with esophageal squamous cell carcinoma.

BACKGROUND: This study aimed to investigate the prognostic value of semiquantitative parameters derived from [68 Ga]Ga-fibroblast activation protein inhibitor (FAPI) PET/CT for patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy. METHODS: We conducted a retrospective analysis on patients from a prospective parent study (NCT04416165). A total of 45 patients with locally advanced ESCC who underwent [68 Ga]Ga-FAPI from December 2019 to March 2021 were included. The maximum standard uptake value (SUVmax), gross tumor volume (GTV), and total lesion-FAPI (TL-FAPI) of the primary tumor were calculated from the corresponding PET/CT image. Unpaired parameters were compared using Student's t test or the Mann-Whitney U test. Paired parameters were compared using the paired t test or the Wilcoxon matched-pairs signed-rank test. Kaplan-Meier curves were generated to calculate progression-free survival (PFS) and overall survival (OS) rates, and Cox regression analysis was performed to determine which PET/CT parameters were prognostic factors for PFS and/or OS. RESULTS: Thirty-four of the 45 patients met the criteria, and the median follow-up time was 24 months (16-29 months). SUVmax-FAPI, GTVFAPI, and TL-FAPI in patients with stage T4 tumors were significantly higher than those in patients with stage T2/T3 tumors (all P < 0.01). In the univariate Cox regression analysis, T stage, N stage, GTVFAPI, and TL-FAPI were associated with PFS, and T stage, GTVFAPI, and TL-FAPI were associated with OS. Upon multivariable analysis, GTVFAPI was an independent prognostic factor for both PFS (hazard ratio (HR), 5.76; 95% confidence interval (CI), 2.13-15.57, P = 0.001) and OS (HR, 4.96; 95% CI, 2.55-18.79, P = 0.001). CONCLUSION: This pilot study revealed that [68 Ga]Ga-FAPI PET/CT may have prognostic value for patients with ESCC treated with definitive chemoradiotherapy. It may aid in personalized patient management by steering treatment modifications before therapy. Prospective studies with larger samples and longer observation periods are needed.

Flexible Seven-in-One Microsensor Embedded in High-Pressure Proton Exchange Membrane Water Electrolyzer for Real-Time Microscopic Monitoring.

The voltage, current, temperature, humidity, pressure, flow, and hydrogen in the high-pressure proton exchange membrane water electrolyzer (PEMWE) can influence its performance and life. For example, if the temperature is too low to reach the working temperature of the membrane electrode assembly (MEA), the performance of the high-pressure PEMWE cannot be enhanced. However, if the temperature is too high, the MEA may be damaged. In this study, the micro-electro-mechanical systems (MEMS) technology was used to innovate and develop a high-pressure-resistant flexible seven-in-one (voltage, current, temperature, humidity, pressure, flow, and hydrogen) microsensor. It was embedded in the upstream, midstream, and downstream of the anode and cathode of the high-pressure PEMWE and the MEA for the real-time microscopic monitoring of internal data. The aging or damage of the high-pressure PEMWE was observed through the changes in the voltage, current, humidity, and flow data. The over-etching phenomenon was likely to occur when this research team used wet etching to make microsensors. The back-end circuit integration was unlikely to be normalized. Therefore, this study used lift-off process to further stabilize the quality of the microsensor. In addition, the PEMWE is more prone to aging and damage under high pressure, so its material selection is very important.

HotSpot3D web server: an integrated resource for mutation analysis in protein 3D structures.

MOTIVATION: HotSpot3D is a widely used software for identifying mutation hotspots on the 3D structures of proteins. To further assist users, we developed a new HotSpot3D web server to make this software more versatile, convenient and interactive. RESULTS: The HotSpot3D web server performs data pre-processing, clustering, visualization and log-viewing on one stop. Users can interactively explore each cluster and easily re-visualize the mutational clusters within browsers. We also provide a database that allows users to search and visualize proximal mutations from 33 cancers in the Cancer Genome Atlas. AVAILABILITY AND IMPLEMENTATION: http://niulab.scgrid.cn/HotSpot3D/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Glucosamine regulation of fibroblast growth factor 21 expression in liver and adipose tissues.

Obesity is associated with metabolic disorders. Fibroblast growth factor 21 (FGF21) has been recognized as important in metabolism. Glucosamine (GLN) has been demonstrated to perform diverse beneficial functions. This study aimed to reveal whether and how GLN would modulate FGF21 production in relation to metabolism. With in vivo model of normal diet (ND) and high-fat diet (HFD) mice receiving GLN injection and in vitro model of mouse AML12 liver cells and differentiated 3T3L1 adipocytes challenged with GLN, GLN appeared to improve the glucose metabolism in HFD and ND mice and to elevate FGF21 protein expression in HFD liver and to increase both FGF21 protein and mRNA levels in WAT from HFD and ND mice and it also upregulated FGF21 expression in both AML12 and differentiated 3T3L1 cells. By using inhibitors against various signaling pathways, p38, Akt, NF-κB, and PKA appeared potentially involved in GLN-mediated FGF21 production in AML12 cells; GLN was able to mediate activation of NF-κB, p38 or PKA/CREB signaling. Our accumulated findings suggest that GLN may potentially improve the metabolic performance by inducing FGF21 production in liver and adipose tissues and such induction in liver cells may act in part due to GLN induction of the NF-κB, p38 and PKA pathways.

Association between VDR polymorphisms and multiple sclerosis: systematic review and updated meta-analysis of case-control studies.

Vitamin D receptor (VDR) polymorphisms have been inconsistently investigated in multiple sclerosis (MS). However, published studies demonstrated differences concerning design and effect size. A meta-analysis is necessary to determine the magnitude of the association between VDR polymorphisms and MS risk. The aim of the current study was to quantify the magnitude of the association between BsmI, FokI, ApaI, and TaqI VDR polymorphisms and MS risk. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic search and meta-analysis of the VDR gene polymorphisms and the risk of MS. The pooled odds ratios (OR) and 95% confidence interval (CI) were calculated by using Stata Version 11.0 with dominant and recessive models and allele analyses. A total of 4013 cases and 4218 controls in 24 case-control studies were included in the meta-analyses. The results did not indicate an association between any of the VDR polymorphisms and the risk of MS among overall populations, Asians, and Caucasians. However, our subgroup analysis suggests that the A allele was associated with MS risk in Asian populations (P = 0.005, OR = 1.267, 95% CI 1.074-1.496). Interestingly, the sensitivity analysis excluding studies with controls not in HWE showed insignificant association between the A allele and MS risk (P = 0.211), which was different from those in the non-sensitivity analysis. Our preliminary results indicate the VDR gene ApaI, BsmI, FokI, and TaqI polymorphisms may not be associated with elevated MS risk among overall populations. But ApaI polymorphism may confer different susceptibility to MS among different populations, and more well-designed studies with a large sample size are still needed to validate our results.

Serum adipokines levels in patients with systemic sclerosis: A meta-analysis.

BACKGROUND: Systemic sclerosis is an chronic inflammatory autoimmune diseases. Adipokine has been reported to play an important role in modulating immune responses. Recent studies suggest that adipokine also plays some roles in the pathogenesis of systemic sclerosis (SSc). However, published data regarding the relationship between plasma/serum adipokine levels and SSc are contradictory. The aim of this study was at performing a meta-analysis to derive a more accurate estimation and further investigate the association of plasma/serum leptin and adiponectin levels with SSc patients. METHODS: PubMed, and Web of Science databases (up to Feb 20, 2016) were used to obtain all relative published literatures. The study quality was assessed by the Newcastle-Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. RESULTS: A total of fourteen studies were finally included in this meta-analysis. Among them, six of which were studied for the serum adiponectin levels in SSc patients, six of which were studied for the serum leptin levels in SSc patients, and two of them were studied both for serum adiponectin levels and serum leptin levels in SSc patients. The meta-analysis results showed that the serum adiponectin levels in SSc patients were significantly lower than that in normal controls (SMD = -0.608 ng/ml, 95% CI = -1.029 to -0.186, p = 0.005). However, there were no significant differences in serum leptin levels between SSc patients and healthy controls (SMD = -0.990 ng/ml, 95% CI = -2.340 to 0.359, p = 0.150). The subgroup analysis showed that Asia SSc patients with age less than 50 years old had lower plasma/serum adiponectin levels when compared with controls. CONCLUSION: The serum adiponectin levels, but not serum leptin levels, in SSc patients were significantly lower than that in normal controls.

[A preliminary study of the significance of autoantibodies against light chain of myeloperoxidase on pulmonary damages in myeloperoxidase-antineutrophil cytoplasmic antibody associated vasculitis].

OBJECTIVE: To investigate the clinical characteristics of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (MPO-AAV) with pulmonary injury and the relationship between pulmonary injury and ANCA against light chain of MPO (LCMPO-ANCA). METHODS: A total of 195 patients with newly diagnosed primary active MPO-AAV were recruited in this prospective study. Indirect immunofluorescence assay was used to detect peri-nuclear ANCA (p-ANCA). Immunoblotting and ELISA were used to detect myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). Clinical features of patients with both positive p-ANCA and MPO-ANCA were collected. Disease activity was evaluated by Birmingham Vasculitis Activity Score- version 3 (BVAS-V3) Recombinant light chain of MPO was used to coat substrate of LCMPO-ANCA by ELISA. The clinical characteristics of pulmonary injury and its correlation with serum levels of p-ANCA, MPO-ANCA and LCMPO-ANCA were explored. RESULTS: All 195 patients (64 male and 131 female), consisted of 191 patients (98.0%) with microscopic polyangiitis, 3 patients (1.5%) with granulomatosis with polyangiitis, and 1(0.5%) with eosinophilic granulomatosis with polyangiitis including 64 men and 131 women. Their mean age was (63.2 ± 13.5) years old. The level of MPO-ANCA had a positive correlation with general BVAS-V3 (r=0.193, P=0.007) in all patients, and the level of LCMPO-ANCA was positively related with the pulmonary BVAS-V3 (r=0.228, P=0.001). As for multiple systemic damages, the incidence of lung involvement was 60.51% (118/195), which ranked second to renal involvement (71.80%, 140/195). The most common pulmonary injuries represented as pulmonary infiltration of 80.51% (95/118), pleural effusion / pleurisy of 41.53% (49/118), pulmonary nodule or cavity of 22.03% (26/118). Compared with those without lung involvement, the patients with pulmonary injuries were older [(66.39 ± 10.70) years old vs (58.30 ± 15.72) years old; t=4.277, P=0.001], had a shorter course of disease [2.00(1.00,10.50) months vs 3.00(1.00,3.50) months; t=-2.283, P=0.024], and higher scores of general BVAS-V3 (18.21 ± 6.08 vs 15.18 ± 5.64; t=3.501, P=0.001). Also, in the patients with pulmonary lesions, the positive rate of LCMPO-ANCA was significantly higher (35.59% vs 6.49%; χ² =21.569, P<0.001), and the level of LCMPO-ANCA was significantly higher (0.377 ± 0.229 vs 0.285 ± 0.079; t=3.399, P=0.001) than those without lung involvement. The pulmonary BVAS-V3 in the patients with LCMPO-ANCA was significantly higher than that in the patients without LCMPO-ANCA (4.34 ± 2.10 vs 2.59 ± 2.52; t=4.301, P<0.001), whereas the pulmonary BVAS-V3 was not correlated with LCMPO-ANCA (r=0.035, P=0.708) in patients with lung injuries. CONCLUSION: Pulmonary injury was relatively common and insidious in patients with MPO-AAV. To monitor ANCA level is necessary in patients with pulmonary injury. LCMPO-ANCA might play an important role in the pathogenesis of pulmonary lesions in AAV.

Isolation, characterization, and pathogenicity assessment of Corynebacterium pseudotuberculosis biovar equi strains from alpacas (Vicugna pacos) in China.

Corynebacterium pseudotuberculosis is a zoonotic pathogen that causes lymphadenitis in humans, livestock, and wildlife. In this study, C. pseudotuberculosis biovar equi strains were isolated from three alpacas. Antibiotic susceptibility tests and pathogenicity tests were also conducted. Moreover, one strain was sequenced using DNBSEQ and Oxford Nanopore technology. The three strains exhibited resistance to aztreonam, fosfomycin, and nitrofurantoin. The median lethal doses (LD50) of strains G1, S2 and BA3 in experimentally infected mice was 1.66 × 105 CFU, 3.78 × 105 CFU and 3.78 × 105 CFU, respectively. The sequencing of strain G1 resulted in the assembly of a chromosomal scaffold comprising 2,379,166 bp with a G + C content of 52.06%. Genome analysis of strain G1 revealed the presence of 48 virulence genes and 5 antibiotic resistance genes (ARGs). Comparative genomic analysis demonstrates a high degree of genetic similarity among C. pseudotuberculosis strains, in contrast to other Corynebacterium species, with a clear delineation between strains belonging to the two biovars (ovis and equi). The data of the present study contribute to a better understanding of the properties of C. pseudotuberculosis biovar equi strains and the potential risk they pose to alpacas and other livestock, as well as the necessity of ongoing surveillance and monitoring of infectious diseases in animals.

Development and validation of a Systemic Sclerosis Health Literacy Scale.

Background and aim: Health literacy levels are strongly associated with clinical outcomes and quality of life in patients with chronic diseases, and patients with limited health literacy often require more medical care and achieve poorer clinical outcomes. Among the large number of studies on health literacy, few studies have focused on the health literacy of people with systemic sclerosis (SSc), and there is no specific tool to measure health literacy in this group. Therefore, this study plans to develop a health literacy scale for patients with SSc. Methods: This study included 428 SSc patients from the outpatient and inpatient departments of the Department of Rheumatology and Immunology, the first affiliated Hospital of Anhui Medical University and the first affiliated Hospital of University of Science and Technology of China. The formulation of the scale was completed by forming the concept of health literacy of SSc patients, establishing the item pool, screening items, and evaluating reliability and validity. Classical measurement theory was used to screen items, factor analysis was used to explore the construct validity of the scale, and Cronbach's alpha coefficient was used to assess the internal consistency. Results: Our study population was predominantly middle-aged women, with a male to female ratio of 1:5.7 and a mean age of 51.57 ± 10.99. A SSc Health Literacy scale with 6 dimensions and 30 items was developed. The six dimensions are clinic ability, judgment/evaluation information ability, access to information ability, social support, treatment compliance and application information ability. The Cronbach's alpha coefficient of the scale is 0.960, retest reliability is 0.898, split-half reliability is 0.953, content validity is 0.983, which has good reliability and validity. Conclusion: The Systemic Sclerosis Health Literacy Scale may become a valid tool to evaluate the health literacy level of patients with SSc.

Virulence-related factors and antimicrobial resistance in Proteus mirabilis isolated from domestic and stray dogs.

Introduction: Proteus mirabilis is a multi-host pathogen that causes diseases of varying severity in a wide range of mammals, including humans. Proteus mirabilis is resistant to multiple antibiotics and has acquired the ability to produce expanded spectrum of ß-lactamases, leading to serious public health problems. However, the available information on P. mirabilis isolated from feces of dogs, is still poorly understood, as is the correlation between its virulence-associated genes (VAGs) and antibiotic resistance genes (ARGs). Method: In this study, we isolated 75 strains of P. mirabilis from 241 samples, and investigated the swarming motility, biofilm formation, antimicrobial resistance (AMR), distribution of VAGs and ARGs, as well as the presence of class 1, 2, and 3 integrons in these isolates. Results: Our findings suggest a high prevalence of intensive swarming motility and strong biofilm formation ability among P. mirabilis isolates. Isolates were primarily resistant to cefazolin (70.67%) and imipenem (70.67%). These isolates were found to carry ureC, FliL, ireA, zapA, ptA, hpmA, hpmB, pmfA, rsbA, mrpA, and ucaA with varying prevalence levels of 100.00, 100.00, 100.00, 98.67, 98.67, 90.67, 90.67, 90.67, 90.67, 89.33, and 70.67%, respectively. Additionally, the isolates were found to carry aac(6')-Ib, qnrD, floR, blaCTX-M, blaCTX-M-2, blaOXA-1, blaTEM, tetA, tetB and tetM with varying prevalence levels of 38.67, 32.00, 25.33, 17.33, 16.00, 10.67, 5.33, 2.67, 1.33, and 1.33%, respectively. Among 40 MDR strains, 14 (35.00%) were found to carry class 1 integrons, 12 (30.00%) strains carried class 2 integrons, while no class 3 integrons was detected. There was a significant positive correlation between the class 1 integrons and three ARGs: blaTEM, blaCTX-M, and blaCTX-M-2. This study revealed that P. mirabilis strains isolated from domestic dogs exhibited a higher prevalence of MDR, and carried fewer VAGs but more ARGs compared to those isolated from stay dogs. Furthermore, a negative correlation was observed between VAGs and ARGs. Discussion: Given the increasing antimicrobial resistance of P. mirabilis, veterinarians should adopt a prudent approach towards antibiotics administration in dogs to mitigate the emergence and dissemination of MDR strains that pose a potential threat to public health.

Biological response of nasopharyngeal carcinoma to radiation therapy: a pilot study using serial 18F-FDG PET/CT scans.

We used serial (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) to evaluate tumors' maximum standardized uptake value (SUV(max)) before, during, and after radiotherapy to explore the biological behavior of and response to radiation therapy in various subtypes of nasopharyngeal carcinoma (NPC). Sixty-one patients with pathologically diagnosed NPC were prospectively enrolled into the study. WHO type II(B) disease had a higher initial SUV(max) and more significant biological response at the primary site as compared with type II(A) subtype. The two subtypes of WHO type II NPC may significantly differ in their biological behavior and response to radiotherapy.

Isolation of an ectoine-producing Sinobaca sp. and identification of genes that are involved in ectoine biosynthesis.

A moderate halophilic bacterium that could accumulate ectoine and hydroxyectoine was isolated from soil near a salt mine and was identified as a Sinobaca sp. (designed strain H24) according to 16S rRNA gene sequence analysis. The bacterium grew well in the presence of 1-2 M NaCl, while growth in a medium that contained 2 M NaCl led to higher accumulation of ectoines. The yields of ectoine and hydroxyectoine by Sinobaca sp. H24 reached 11.27 mg/l and 1.34 mg/l, respectively, when cultured in the following medium: NaCl (2 M), peptone (5 g/l), yeast extract (1 g/l), NH4Cl (0.02 M), KH2PO4 (1 M), K2HPO4 (0.1 M), and glycerol (1% w/v). Genes that are involved in ectoine biosynthesis of Sinobaca sp. H24 were also identified, and their sequences were determined by a metagenomics approach. The results demonstrated that Sinobaca sp. H24 possesses ectoine metabolism genes for both ectoine biosynthesis (ectA, ectB, ectC, and ectD) and ectoine degradation (doeA). Genes that are related to ectoine biosynthesis, such as lysC and asd, were also characterized. The identification and characterization results for ectoine/hydroxyectoine biosynthesis genes are in agreement with the physiology of Sinobaca sp. H24 as a potential candidate for ectoine production for industrial applications. This report established for the first time the accumulation of ectoine/hydroxyectoine in Sinobaca sp. and characterized the genes that are involved in ectoine/hydroxyectoine biosynthesis in Sinobaca sp. H24.

High-Pressure-Resistant Flexible Seven-in-One Microsensor Embedded in High-Pressure Proton Exchange Membrane Water Electrolyzer for Real-Time Microscopic Measurement.

The high-pressure proton exchange membrane water electrolyzer (PEMWE) used for hydrogen production requires a high-operating voltage, which easily accelerates the decomposition of hydrogen molecules, resulting in the aging or failure of the high-pressure PEMWE. As the high-pressure PEMWE ages internally, uneven flow distribution can lead to large temperature differences, reduced current density, flow plate corrosion, and carbon paper cracking. In this study, a new type of micro hydrogen sensor is developed with integrated flexible seven-in-one (voltage; current; temperature; humidity; flow; pressure; and hydrogen) microsensors.

Changes in Gut Microbiota Composition Associated with the Presence of Enteric Protist Blastocystis in Captive Forest Musk Deer (Moschus Berezovskii).

Blastocystis is a common protistan parasite inhabiting the gastrointestinal tract of a wide range of hosts including humans and domestic and wild animals. Many studies have revealed the associations between Blastocystis and gut microbiome in humans. However, only a few studies have focused on the associations between Blastocystis and gut microbiome of animals, especially in forest musk deer (Moschus berezovskii). We investigated the effects of the Blastocystis colonization on the intestinal bacterial community compositions using amplicon sequencing targeting the V4 variable region of the 16S rRNA. Two subtypes of Blastocystis (ST5 and ST10) and Blastocystis-free (control) were included in this study. We found that compared with the forest musk deer without Blastocystis, ST10-colonized forest musk deer had higher bacterial richness and diversity, while ST5-colonized forest musk deer showed a comparable bacterial diversity. Likewise, beta diversity revealed significant differences in bacterial community structure between ST10-colonized and Blastocystis-free forest musk deer. The proportion of Bacteroidetes were significantly enriched in ST10-colonized forest musk deer. Bacterial community structure between ST5-colonized and Blastocystis-free forest musk deer did not differ significantly. The present study explored the associations between Blastocystis and gut microbial community of forest musk deer for the first time, and revealed ST10 colonization, instead of ST5, is associated with higher bacterial diversity and shifted microbial structure. Our data provides valuable insights into the associations between gut microbiomes and parasites. IMPORTANCE Forest musk deer is listed as an endangered species by International Union for Conservation of Nature Red List, and the Chinese government has introduced captivity breeding measures to curb the rapid decline of the musk deer population since the 1950s. It has been suggested that Blastocystis colonization can modulate the composition of the host's intestinal microbiota, thereby affecting the host health. The present study investigated the effects of the Blastocystis colonization on the gut microbiota in the feces of forest musk deer in Sichuan Province, China. Two subtypes (ST5 and ST10) have differential effects on the bacterial diversity and community composition, suggesting that the study of Blastocystis should be distinguished at the subtype level. Because the pathogenicity of Blastocystis is controversial, pathogenic, or commensal, continuous monitoring of the impact of Blastocystis colonization on the intestinal microbiota is of great significance to assess its health effects on forest musk deer.

Occurrence, genetic diversity and zoonotic potential of Blastocystis sp. in forest musk deer (Moschus berezovskii) in Southwest China.

Blastocystis sp. is a common anaerobic protist with controversial pathogenicity that can infect various animals and humans. However, there are no reports of Blastocystis sp. infections in forest musk deer (Moschus berezovskii). The present study was designed to examine the occurrence, subtype distribution and genetic characterization of Blastocystis sp. in forest musk deer in southwestern China, and to assess the potential for zoonotic transmission. A total of 504 fresh stool samples were collected from captive forest musk deer in four distinct areas of southwestern China. Overall, 14.7% of the forest musk deer (74/504) were found to be infected with Blastocystis sp. The highest occurrence of Blastocystis sp. was observed in Dujiangyan (27.5%), followed by Maerkang (23.3%). The occurrence of Blastocystis sp. was 7.9% and 4.1% in Shimian and Hanyuan, respectively. Significant differences in the occurrence of Blastocystis sp. among different areas were observed (p < 0.05), while we did not observe significant differences among animals of different age and sex (p > 0.05). Two known zoonotic subtypes (ST1 and ST5) and three animal-predominant subtypes (ST10, ST13, and ST14) were identified, of which ST10 was the most common (36/74, 48.6%). Our findings highlight that forest musk deer may be potential reservoirs of zoonotic human Blastocystis sp. infections.

Title: Présence, diversité génétique et potentiel zoonotique de Blastocystis sp. chez le cerf porte-musc (Moschus berezovskii) dans le sud-ouest de la Chine. Abstract: Blastocystis sp. est un protiste anaérobie commun, de pathogénicité controversée, et qui peut infecter divers animaux et les humains. Cependant, aucun cas d'infection par Blastocystis sp. n'a été rapporté chez le cerf porte-musc (Moschus berezovskii). La présente étude a été conçue pour examiner la présence, la distribution des sous-types et la caractérisation génétique de Blastocystis sp. chez le cerf porte-musc du sud-ouest de la Chine et pour évaluer son potentiel de transmission zoonotique. Au total, 504 échantillons de selles fraîches ont été prélevés sur des cerfs porte-musc captifs dans quatre régions distinctes du sud-ouest de la Chine. Dans l'ensemble, 14,7 % (74/504) des cerfs porte-musc se sont avérés infectés par Blastocystis sp. La plus forte occurrence de Blastocystis sp. a été observée à Dujiangyan (27,5 %), suivi de Maerkang (23,3 %). La présence de Blastocystis sp. était respectivement de 7,9 % et 4,1 % à Shimian et Hanyuan. Des différences significatives dans la présence de Blastocystis sp. entre les différentes zones ont été observées (p < 0,05), alors que nous n'avons pas observé de différences significatives entre les animaux d'âge et de sexe différents (p > 0,05). Deux sous-types zoonotiques connus (ST1 et ST5) et trois sous-types à prédominance animale (ST10, ST13 et ST14) ont été identifiés, dont ST10 était le sous-type le plus courant (36/74, 48,6 %). Nos découvertes mettent en évidence que le cerf porte-musc forestier peut être un réservoir potentiel d'infections à Blastocystis sp.

Engineering of Escherichia coli for targeted delivery of transgenes to HER2/neu-positive tumor cells.

Targeting of non-phagocytic tumor cells and prompt release of gene cargos upon entry into tumors are two limiting steps in the bacterial gene delivery path. To tackle these problems, the non-pathogenic Escherichia coli strain BL21(DE3) was engineered to display the anti-HER2/neu affibody on the surface. After co-incubation with tumor cells for 3 h, the anti-HER2/neu affibody-presenting E. coli strain was selectively internalized into HER2/neu-positive SKBR-3 cells. The invasion efficiency reached as high as 30%. Furthermore, the bacteria were equipped with the phage ϕX174 lysin gene E-mediated autolysis system. Carrying the transgene (e.g., eukaryotic green fluorescent protein, GFP), the tumor-targeting bacteria were subjected to the thermal shock to trigger the autolysis system upon entry into HER2/neu-positive cells. Flow cytometric analysis revealed that 3% of infected cells expressed GFP 24 h post thermal induction. Overall, the results show a promise of the proposed approach for developing bacteria as a delivery carrier.

First identification and molecular subtyping of Blastocystis sp. in zoo animals in southwestern China.

BACKGROUND: Blastocystis sp. is an anaerobic protozoan that parasitizes many animal hosts and the human gastrointestinal tract, and its pathogenicity is controversial. Captive wildlife may be potential reservoirs for human infection with Blastocystis sp. The present study was performed to investigate the prevalence and subtype distribution of Blastocystis sp. in zoo animals in Sichuan Province, southwestern China. METHODS: A total of 420 fresh fecal samples were collected from 54 captive wildlife species in four zoos in southwestern China between June 2017 and September 2019. The prevalence and subtype (ST) genetic characteristics of Blastocystis sp. were determined by PCR amplification of the barcode region of the SSU rRNA gene and phylogenetic analysis. RESULTS: Overall, 15.7% (66/420) of the animal samples and 20.7% (14/54) of the species tested were shown to be infected with Blastocystis sp. The highest prevalence of Blastocystis sp. was found in Panzhihua Zoo (24.3%), which was significantly higher than that in Chengdu Zoo (6.9%), and Xichang Zoo (2.9%) (P < 0.05). There are also significant differences in the prevalence of Blastocystis sp. among different species (P < 0.05), and the highest of Blastocystis sp. prevalence was observed in white-cheeked gibbon, black great squirrel, and red giant flying squirrel (100%). Subtype analysis of Blastocystis sp. revealed nine subtypes, including six zoonotic STs (ST1-5, and ST8) and three animal-specific STs (ST10, ST14, and ST17), with ST17 as the predominant subtype (26/66) in Blastocystis sp.-positive isolates. CONCLUSIONS: To our knowledge, this is the first report on the prevalence and subtype distribution of Blastocystis sp. among captive wildlife in zoos in southwestern China. This study highlights that these animals may serve as reservoirs for human Blastocystis sp. infections.

A Method to Realize Efficient Deep-Red Phosphorescent OLEDs with a Broad Spectral Profile and Low Operating Voltages.

Organic light-emitting diodes (OLEDs) used as phototherapy light sources require sufficient spectral distribution in the effective wavelength ranges and low operating voltages. Herein, a double emitting layer structure consisting of a red-emitting Ir(piq)2acac and a deep-red Ir(fliq)2acac was designed to generate a broad electroluminescence spectrum. An efficient TCTA:CN-T2T exciplex system was used as the host of the emitting layer, facilitating effective energy transfer from the exciplex host to the red and deep-red phosphors. The materials used in the exciplex host were also used as the carrier transport layers to eliminate the energy barriers and thus increase the current density. The hole injection layer structures were varied to examine the hole injection capabilities and the carrier balance. The resulting optimized phosphorescent OLEDs with a broad spectral profile exhibit a 90% coverage ratio in the target ranges from 630 to 690 nm, together with a high peak efficiency of 19.1% (10.2 cd/A and 13.8 lm/W). The proposed device only needs 5.2 V to achieve a power density of 5 mW/cm2, implying that the device could be driven via two series-connected button cell batteries. These results illustrate the feasibility of our design concepts and demonstrate the realization of a portable and lightweight OLED phototherapy light source.