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Emerging evidence has suggested that circular RNAs (circRNAs) have vital functions during the initiation and progression of various diseases. However, circRNA potential mechanisms in colorectal cancer (CRC) are largely unknown. Here, we sought to investigate the role and underlying regulatory mechanism of circ0104103 in CRC. circ0104103 was validated by quantitative real-time polymerase chain reaction (qRT-PCR) and Sanger sequencing. Gain- and loss-of-function assays in cell lines and mouse xenograft models were utilized to investigate the effects of circ0104103 in CRC. RNA pull-down assays, RNA immunoprecipitation assays, bioinformatics analyses, RNA fluorescence in situ hybridization (FISH) and luciferase reporter assays were used to elucidate the potential mechanism of circ0104103 in CRC. We identified circ0104103, which is strongly downregulated in CRC tissues and cell lines. Functional studies revealed that circ0104103 inhibited CRC cell growth, migration and invasion both in vitro and in vivo. Mechanistically, circ0104103 binds to HuR, a functional RNA-binding protein (RBP) commonly expressed in CRC. HuR binds to the 3'UTR of LACTB mRNA to facilitate stabilization and increase its expression. Moreover, circ0104103 was verified as a competing endogenous RNA (ceRNA) via negative regulation of miR-373-5p to increase LACTB expression, resulting in inhibiting the occurrence and progression of CRC. Taken together, our study revealed that circ0104103 acts as a tumour suppressor and may be a novel biomarker and therapeutic target in CRC.

Apple polyphenols are abundantly present in apple pomace, and their applications are limited by the low efficiency of traditional extraction methods and the tendency to pollute the environment. Starch nanoparticles (SNPs) have received much attention due to their renewable, low cost and biocompatibility. The aim of this study was to prepare SNPs of different sizes from corn starch using ultrasonic-assisted chemical precipitation with adsorption of apple polyphenols, investigate the relationship between particle size and adsorption, while experiments were performed to assess antioxidant activity, simulate in vivo digestion and polyphenol release. The results showed that the smaller the particle size of SNPs the higher the adsorption of polyphenols, and the combination of characterization and adsorption kinetics showed that this adsorption was a physicochemical binding process. DPPH radical scavenging activity showed that polyphenols bound to SNPs were more stable than free polyphenols. In vitro simulation of digestion and release processes, SNPs loaded with polyphenols showed better anti-digestive properties, polyphenols are released in small amounts in gastric juices and continuously in intestinal juices. Our results provide a theoretical basis for the direct separation of polyphenols from fruit pomace polyphenol extracts using nanomaterials and the industrial utilization of polyphenol products.

Background: Diabetes is a common chronic disease which has caused a great burden on families and society. The treatment of diabetes has always been a hotspot. This study aimed to explore the effect and mechanism of miR-30d-5pon inflammation of high glucose-impaired human keloid fibroblasts (HKF). Methods: Differently-expressed miRNAs were predicted by bioinformatics methods. Exosomes were observed by transmission electron microscope. Exosome particle sizes were measured by NanoSight. Western Blot was used to detect the expression of CD81, CD63, CD9, and Calnexin. QRT-PCR was used to detect the expression of miR-30d-5p, IL-1β, TNF-α, VEGF, FGF21, NRF2, and HO-1. The levels of IL-1β, TNF-α, IL-6, IL-10, and TGF-β were determined by ELISA. Cell apoptosis and CD86, CD206 positive cells were detected by flow cytometry. Results: Tori formula could promote the secretion of endothelial progenitor cell (EPCs) exosomes. EPCs exosomes and miR-30d-5p could stimulate the proliferation of HKF impaired by high glucose and the expression of IL-10 and TGF-β. MiR-30d-5p inhibited the proliferation of M1 macrophages and the expression of IL-1β and TNF-α. It could also promote the proliferation of M2 macrophages and the expression of CCL17 and CCL22. Moreover, miR-30d-5p stimulated the expression of VEGF, FGF21, NRF2, and HO-1, as well as suppressed the expression of IL-1β, TNF-α, and IL-6. MiR-30d-5p also restrained the apoptosis of impaired HKF. Conclusion: This study confirmed that miR-30d-5p could promote the M1/M2 polarization and inhibit the inflammatory response of impaired HKF, which provided a certain idea and direction for treating diabetes.

Filial piety is a Confucian concept that guides how children treat and take care of their parents. The Filial Behaviour Scale (FBS) is a 25-item instrument developed in the Chinese context measuring behavioural manifestations of filial piety. Although the components of filial piety have been found to be relevant across cultures, little research has investigated the psychometric properties of the FBS in other cultural contexts. The present study evaluated the factor structure, internal consistency, measurement invariance and construct validity of the FBS across three cultural groups: the United States, Italy and Malaysia. Participants were 1090 emerging adults (67% females; Mage =21.29 years, SD=1.97; White Americans: n=455, White Italians: n=428, Malays: n=328). A two-factor structure emerged across groups: Obedience/Obligation (behaviours showing obedience and obligation towards parents) and Relationship (behaviours expressing affection and promoting positive parent-child relationships). The two factors demonstrated adequate internal consistency, full configural, partial metric and partial scalar invariance, as well as unique associations with depressive symptoms and parent-child relationships across groups. These findings yielded a more nuanced understanding of filial behaviour and supported the utility of a two-factor FBS among emerging adults in various cultural contexts.

Thioredoxin reductase (TXNRD1) acts as part of a major enforcer of redox homeostasis in the intracellular environment. However, its prognostic value and the relationship between TXNRD1 and core ferroptosis-related genes in hepatocellular carcinoma remain unclear. Here, we systematically analyzed and described the potential function and prognostic value of TXNRD1 in hepatocellular carcinoma. TXNRD1 was aberrantly expressed in several cancer types including liver cancer, and elevated TXNRD1 expression was associated with tumor histological grade and pathologic stage, resulting in markedly shorter survival in these patients. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) results suggested that TXNRD1 is mainly involved in glucose and fat metabolism. Importantly, TXNRD1 may affect cancer prognosis partially by regulating ferroptosis. A prognostic model based on TXNRD1 and seven ferroptosis-related genes (ATG5, PCBP2, SLC7A11, ACSL6, SAT1, SLC40A1, and STEAP3) divided patients with liver cancer into the low-risk group and the high-risk group and was shown to be an independent risk factor for clinical application. We further found that patients with high-risk scores underwent an increased macrophage infiltration compared to patients with low-risk scores, which resulted in immune escape. In short, TXNRD1 is an overlooked predictor, which can be utilized as a candidate prognostic biomarker in liver cancer, and it may hold promise in drug-resistant patients.

Although parental warmth has been shown to be related to children's social competence, the mediating role of preadolescent children's emotion regulation in this context has been less explored, particularly in Asian cultures. Thus, this study examined the role of emotion regulation as a mediator in the relationship between parental warmth (i.e., paternal and maternal warmth) and social competence among preadolescent children in Malaysia. Preadolescent children (N = 720; Mage = 10.95; SD = 0.59; 58.8% female) completed self-administered questionnaires. Results of correlation analysis showed that higher levels of paternal and maternal warmth were associated with greater emotion regulation in preadolescent children and a greater level of social competence. However, analysis of structural equation modeling revealed that emotion regulation significantly mediated only the relationship between maternal warmth and social competence. These findings underscored the importance of maternal warmth in promoting Malaysian preadolescent children's social competence as well as their emotion regulation as a mediating pathway. This study also highlights the direct effect of paternal warmth on preadolescents' social competence. Theoretical and practical implications of this study are discussed. The authors show gratitude to Fundamental Research Grant Scheme (FRGS Grant number: FRGS/1/11/SS/UPM/02/7) in providing financial support to data collection process.

Downy mildew is a serious threat to corn (maize) production in the tropics and subtropics. Corn is native to Central America, and was introduced into South-East Asia by the Spanish colonisers in the 1700s. Corn is evolutionarily naïve to downy mildews of the genus Peronosclerospora. Consequently, corn monocultures are particularly susceptible to a variety of Peronosclerospora species, which spread to the crop from local grasses. Globally, corn is one of the most important crops for both humans and livestock. Several downy mildews of corn have been identified as potential threats to global food security, and trade with corn seeds is strictly regulated to avoid spreading the pathogens. Despite their importance, little is known about the biodiversity of graminicolous downy mildews, because their identification has often relied on variable morphological features, such as conidial dimensions. DNA barcodes for most species have become available only recently. During surveys for downy mildews on corn in Indonesia, a previously unrecognised species of Peronosclerospora was found and investigated using a combination of morphological characters and molecular phylogenetic analyses. The new species, introduced here as Peronosclerospora neglecta, is widely distributed in South-East Asia from Thailand to eastern Indonesia. The impact of this downy mildew can be severe, with complete crop losses in heavily affected fields. Given the aggressiveness of the species, close surveillance is warranted to restrict its further spread.

Background: Hyperglycemia is widespread in the world’s population, increasing the risk of many diseases. This study aimed to explore the regulatory effect and mechanism of astragaloside IV (ASIV)-mediated endothelial progenitor cells (EPCs) exosomal LINC01963 in endothelial cells (HUVECs) impaired by high glucose. Methods: Morphologies of exosomes were observed by light microscope and electron microscope. Immunofluorescence was used to identify EPCs and detect the expressions of caspase-1. LINC01963 was detected by quantitative reverse transcription PCR. NLRP3, ASC, and caspase-3 were detected by Western Blot. Nanoparticle tracking analysis was carried out to analyze the exosome diameter. High-throughput sequencing was applied to screen target lncRNAs. The proliferation of endothelial cells was measured by cell counting kit-8 assay. The apoptosis level of HUVECs was detected by flow cytometry and TdT-mediated dUTP Nick-End labeling. The levels of IL-1β, IL-18, ROS, SOD, MDA, and LDH were measured by enzyme-linked immunosorbent assay. Results: ASIV could promote the secretion of the EPC exosome. LINC01963 was obtained by high-throughput sequencing. It was observed that high glucose could inhibit the proliferation, reduce the level of SOD, the expression of NLRP3, ASC, and caspase-1, increase the levels of IL-1β, IL-18, ROS, MDA, and LDH, and promote apoptosis of HUVECs. Whereas LINC01963 could inhibit the apoptosis of HUVECs, the expression of NLRP3, ASC, and caspase-1 increased, and the levels of IL-1β, IL-18, ROS, MDA, and LDH decreased. Conclusion: EPCs exosomal LINC01963 play an inhibitory role in high glucose-induced pyroptosis and oxidative stress of HUVECs. This study provides new ideas and directions for treating hyperglycemia and researching exosomal lncRNAs.

Pyrethrum (Tanacetum cinerariifolium (Trevir.) Sch. Bip.) is grown to extract pyrethrins which are active ingredients for insecticides (Greenhill 2007). The Australian pyrethrum industry supplies over 50% of the world market. Surveys of Tasmanian crops in spring 2013, detected the presence of a fungus putatively identified as Itersonilia perplexans Derx. on foliage in 54 of 86 surveyed fields (Hay et al. 2015). This fungus was associated with necrotic leaf tips often spreading to encompass whole leaves. However, pathogenicity to pyrethrum was not confirmed. To isolate, tissue was excised from foliar lesions, surface sterilised using 0.4% NaClO, placed onto 2% water agar and incubated at 20°C for 5 days. Colonies were pure-cultured by hyphal-tip transfer onto potato-dextrose agar. Eleven isolates were cultured onto yeast mold agar (YMA) for 14 days at 15°C in the dark (Horita and Yasuoka 2002). Colonies were slow growing (1.9 to 2.3 mm/day) white to buff on both surfaces, with a darker center visible on lower surfaces. Mycelia were straight and hyaline with clamp connections at the septa. Squares transferred from the edge of YMA colonies onto microscope slides produced ballistoconidia that were aseptate, granular and lunate, kidney or lemon-shaped after 24 h. Ballistoconidia lengths and widths (n = 50/isolate) ranged from 14.6 to 20.4 µm and 10.0 to 13.6 µm. Chlamydospores were not observed. These observations were consistent with descriptions of I. perplexans (Koike and Tjosvold 2001; Liu et al. 2015). All 11 isolates were sequenced across the internal transcribed spacer (ITS) region of rDNA (ITS; primers V9G/ITS4; de Hoog and van den Ende 1998; White et al. 1990), and large (LSU; primers LROR/LR7; Rehner and Samuels 1995), and small (SSU; NS1/NS4; White et al. 1990) subunits of rDNA (Genbank accession nos. KU563626 to KU563658). The ITS (673 bp), SSU (1,047 bp) and LSU (1,318 bp) differed by 3, 1 and 0 bp, respectively, across isolates. Maximum parsimony and maximum likelihood analyses of a concatenated 3 loci alignment with Cystofilobasidiales representatives (Liu et al. 2015) placed all isolates and the I. perplexans ex-neotype strain CBS 363.85 within a single monophyletic clade with 100% bootstrap support. Two representative isolates are stored at the Plant Pathology Herbarium (accession nos. BRIP 57986 and 57987). Leaves of 46-day-old pyrethrum plants (n = 45), generated from surface sterilised seed, were inoculated with a 1.5 × 105 ballistoconidia/ml suspension (equal mix of eight isolates) and maintained between 10 and 22°C under a 12-h photoperiod for 14 days. Brown necrotic leaf tips, consistent with reported field symptoms were observed on 71% of plants and I. perplexans was recovered from 69% of symptomatic plants. For flower inoculations, pyrethrum plants were removed from fields as vegetative plants in spring and maintained in a greenhouse set at 20:14°C and 14:10 h day:night. Open flowers (10 per plant) were dipped into a 1.2 × 104 ballistoconidia/ml suspension mix of three isolates. Brown withered ray florets were observed on 10/12 plants 18 days post-inoculation, matching those described in petal blight of chrysanthemum (McRitchie et al. 1973). I. perplexans was re-isolated from 11/12 inoculated plants and 1 control plant (of 12) which exhibited the same symptoms. In both experiments, I. perplexans was identified based on its distinctive morphology. This confirms the pathogenicity of I. perplexans to both pyrethrum leaves and flowers.

Blood is conventionally thought to be sterile. However, emerging evidence on the blood microbiome has started to challenge this notion. Recent reports have revealed the presence of genetic materials of microbes or pathogens in the blood circulation, leading to the conceptualization of a blood microbiome that is vital for physical wellbeing. Dysbiosis of the blood microbial profile has been implicated in a wide range of health conditions. Our review aims to consolidate recent findings about the blood microbiome in human health and to highlight the existing controversies, prospects, and challenges around this topic. Current evidence does not seem to support the presence of a core healthy blood microbiome. Common microbial taxa have been identified in some diseases, for instance, Legionella and Devosia in kidney impairment, Bacteroides in cirrhosis, Escherichia/Shigella and Staphylococcus in inflammatory diseases, and Janthinobacterium in mood disorders. While the presence of culturable blood microbes remains debatable, their genetic materials in the blood could potentially be exploited to improve precision medicine for cancers, pregnancy-related complications, and asthma by augmenting patient stratification. Key controversies in blood microbiome research are the susceptibility of low-biomass samples to exogenous contamination and undetermined microbial viability from NGS-based microbial profiling, however, ongoing initiatives are attempting to mitigate these issues. We also envisage future blood microbiome research to adopt more robust and standardized approaches, to delve into the origins of these multibiome genetic materials and to focus on host-microbe interactions through the elaboration of causative and mechanistic relationships with the aid of more accurate and powerful analytical tools. Published version

This prospective study compares the diagnostic performance of strain elastography (SE) based on the elastogram to B-mode (E/B) size ratio to shear-wave elastography (SWE) incorporating assessment of boundary tissue stiffness.In this prospective study, 81 women consented to undergo ultrasound (US) elastographic assessment prior to biopsy of their mass(es). A total of 101 masses were evaluated with SE and SWE using a single machine (Siemens Acuson S2000). The histopathologic diagnosis was used as the reference standard. The sensitivity, specificity and area under curve (AUC) were obtained for SE and SWE.The sensitivity and specificity of SE using the E/B ratio was 94.7% (95% CI: 87.6 100) and 81.0% (95% CI: 71.3 90.1) respectively. For SWE the sensitivity and specificity was 73.7% (95% CI: 59.7 87.7) and 82.5% (95% CI: 73.2 91.9) respectively. The AUC for SE was higher (0.878) compared to SWE (0.697).SE elastography using the E/B ratio yields diagnostic performance which is superior to SWE incorporating assessment of peripheral stiffness.

Novel microfungi from Australia.

There are five closely related Sporobolus species, collectively known as weedy Sporobolus grasses (WSG) or the rat’s tail grasses. They are fast growing, highly competitive, unpalatable weeds of pastures, roadsides and woodlands. An effective biological control agent would be a welcomed alternative to successive herbicide application and manual removal methods. This study describes the initial exploratory phase of isolating and identifying native Australian microfungi associated with WSG, prior to evaluating their efficacy as inundative biological control agents. Accurate species-level identification of plant-pathogenic microfungi associated with WSG is an essential first step in the evaluation and prioritisation of pathogenicity bioassays. Starting with more than 79 unique fungal morphotypes isolated from diseased Sporobolus grasses in Queensland, Australia, we employed multi-locus phylogenetic analyses to classify these isolates into 54 fungal taxa. These taxa belong to 22 Ascomycete families (12 orders), of which the majority fall within the Pleosporales (>24 taxa in 7 families). In the next phase of the study, the putative species identities of these taxa will allow us to prioritise those which are likely to be pathogenic based on existing literature and their known ecological roles. This study represents the first step in a systematic, high-throughput approach to finding potential plant pathogenic biological control agents.

Mounting evidence indicates that long non-coding RNAs (lncRNAs) have critical roles in colorectal cancer (CRC) progression, providing many potential diagnostic biomarkers, prognostic biomarkers, and treatment targets. Here, we sought to investigate the role and underlying regulatory mechanism of lncRNA small nucleolar RNA host gene 16 (

Objective: To develop and validate a questionnaire which evaluates the blood donors’ satisfaction. Background: In Malaysia, blood procurement relies mainly on voluntary non- remunerated donors. Hence, it is important to ensure the satisfaction of the blood donors in order to increase retention. Methods: This study was conducted among blood donors who attended blood donation and understood the Malay language. Non-Malaysian and illiterate donors were excluded. The questionnaire was developed by the transfusion medicine team. Content validity was established by content reviewers, while face validity was examined in the cognitive debriefing stage. For the 18- item questionnaire, 90 respondents were required based on the 1:5 ratio. A retest was performed in two weeks’ time. Results: One hundred and thirty-seven participants responded in the first phase, while 103 responded after two weeks. The five domains were: technical, interpersonal, accessibility/ convenience, physical experience and overall satisfaction. The Kaiser-Meyer-Olkin (KMO) value was 0.896, with significant Bartlett’s Test of Sphericity (P < 0.001). The factor loadings ranged from 0.729 to 0.953. The Cronbach alpha values of the five domains ranged from 0.814 to 0.955 and the intraclass correlation coefficient ranged from 0.663 to 0.847. Conclusion: The Malaysian blood donor’s satisfaction (M-BDS) questionnaire is a reliable and valid tool suitable for the assessment of blood donor’s satisfaction in blood donation centres.

Worldwide, most isolates of Macrophomina (Botryosphaeriaceae) have been attributed to the generalist phytopathogen M. phaseolina. Since 2014, three cryptic species of Macrophomina have been recognised by molecular methods. This study elucidates the taxonomy of Macrophomina species associated with broadacre and horticultural crops in Australia. A five-locus phylogenetic analysis of 80 isolates of Macrophomina from 28 plant species in Australia, combined with genealogical concordance phylogenetic species recognition and coalescent-based species delimitation approaches, found M. phaseolina, M. pseudophaseolina and supported the introduction of M. tecta sp. nov. Macrophomina phaseolina was the most frequently isolated (88%). Macrophomina pseudophaseolina is reported for the first time in Australia. Macrophomina tecta was isolated from stems of Sorghum bicolor and Vigna radiata with charcoal rot symptoms in New South Wales and Queensland. The potential for two or more Macrophomina species to co-infect the same host has implications for disease epidemiology and pathogen evolution. Future investigations into the distribution, biology, host range and population diversity of the new Macrophomina records are needed.

Machine learning systems play an important role in helping and assisting engineers in their daily activities. Many jobs can now be automated, and one of them is in handling and processing customers’ complaints before they could proceed with failure investigation. In this paper, we discuss a real-life challenge faced by the manufacturing engineers in a life science multinational company. This paper presents a step by step methodology of multilingual translation and multiclassification of Repair Codes. This solution will allow manufacturing engineers to take advantage of machine learning model to reduce the time taken to manually translate row by row and verify the Repair Codes in the file.

Ascochyta koolunga (Didymellaceae, Pleosporales) was first described in 2009 (as Phoma koolunga) and identified as the causal agent of Ascochyta blight of Pisum sativum (field pea) in South Australia. Since then A. koolunga has not been reported anywhere else in the world, and its origins and occurrence on other legume (Fabaceae) species remains unknown. Blight and leaf spot diseases of Australian native, pasture and naturalised legumes were studied to investigate a possible native origin of A. koolunga. Ascochyta koolunga was not detected on native, naturalised or pasture legumes that had leaf spot symptoms, in any of the studied regions in southern Australia, and only one isolate was recovered from P. sativum. However, we isolated five novel species in the Didymellaceae from leaf spots of Australian native legumes from commercial field pea regions throughout southern Australia. The novel species were classified on the basis of morphology and phylogenetic analyses of the internal transcribed spacer region and part of the RNA polymerase II subunit B gene region. Three of these species, Nothophoma garlbiwalawardasp. nov., Nothophoma naiawusp. nov. and Nothophoma ngayawangsp. nov., were isolated from Senna artemisioides. The other species described here are Epicoccum djirangnandirisp. nov. from Swainsona galegifolia and Neodidymelliopsis tinkyukukusp. nov. from Hardenbergia violacea. In addition, we report three new host-pathogen associations in Australia, namely Didymella pinodes on S. artemisioides and Vicia cracca, and D. lethalis on Lathyrus tingitanus. This is also the first report of Didymella prosopidis in Australia.

Self-assembly reactions of Pb2+ and L2– (H2L = 4-(5,7-dioxopyrrolo[3,4-f]benzimidazol-6-yl)benzoic acid) lead to two new coordination networks: [Pb3(L)3(H2O)2]·10DMF·6.5H2O (1) is a metal–organic f...

The newly emerged Omicron variant of SARS-CoV-2 has numerous mutations that are not found in other variants of concern (VOCs). Despite acquiring extended functions in adapting to the host-cell environment, the viral genetic variation exerts a potential negative impact on a molecular test, which in turn, compromises public health and safety. The Liberty16 has been clinically validated as a flexible and accessible device system for running the affordable SalivaDirect™ real time PCR detection assay for SARS-CoV-2 especially in low resource settings. Preliminary, based on in-silico sequence analysis, we found that Omicron’s mutation at position 28,311 overlaps with the CDC 2019-nCoV_N1 probe binding region. In order to verify the performance of CDC 2019-nCoV-N1 primers-probe set in detecting the Omicron variant of SARS-CoV-2, plasmids containing Wuhan/WH01/2019 (wild-type) and B.1.1.529 (Omicron) sequences were serially diluted and subsequently directed for SalivaDirect™ RT-qPCR detection on Liberty16 using commercially procured reagents. Our findings provide analytical support for reports that the mutations in the Omicron variant have little or no impact on SalivaDirect™ assay in terms of amplification efficiency and detection sensitivity using either standard and the recently reported fast Liberty16 SalivaDirect™ thermal cycling protocols.

Phomopsis husk rot (PHR) in macadamia is a disease of economic importance in major commercial production areas in Australia and South Africa. Effective control of PHR is hindered by limited knowledge about its aetiology and epidemiology. The diversity and pathogenicity of more than 50 isolates of Diaporthe associated with PHR in macadamia orchards in Australia and South Africa was assessed. Multilocus phylogenetic analyses of DNA sequences of the ITS, tef1α, and tub2 gene loci revealed four novel clades that are described as Diaporthe australiana sp. nov., D. drenthii sp. nov., D. macadamiae sp. nov., and D. searlei sp. nov. Pathogenicity tests with representative isolates found that all four species caused PHR of varying severity between and within species, as well as between the two macadamia cultivars HAES 344 and HAES 816. The Australian species, D. australiana, was the most aggressive species compared with the three South African species. This study improves our understanding of the aetiology of PHR in macadamia and paves the way for more effective disease management.

Burkholderia pseudomallei is a selective agent that causes septic melioidosis and exhibits a broad range of lethal doses in animals. Host cellular virulence and phagocytic resistance are pathologic keys of B. pseudomallei. We first proposed Caenorhabditis elegans as the host cellular virulence model to mimic bacterial virulence against mammals and second established the resistance of B. pseudomallei to predation by Dictyostelium discoideum as the phagocytosis model. The saprophytic sepsis-causing Burkholderia sp. (B. pseudomallei, Burkholderia thailandensis, Burkholderia cenocepacia, and Burkholderia multivorans) exhibited different virulence patterns in both simple models, but B. pseudomallei was the most toxic. Using both models, attenuated isolates of B. pseudomallei were selected from a transposon-mutant library and a panel of environmental isolates and reconfirmed by in vitro mouse peritoneal exudate cell association and invasion assays. The distinct pathological patterns of melioidosis were inducted by different selected B. pseudomallei isolates. Fatal melioidosis was induced by the isolates with high virulence in both simple models within 4-5 day, whereas the low-virulence isolates resulted in prolonged survival greater than 30 day. Infection with the isolates having high resistance to D. discoideum predation but a low C. elegans killing effect led to 83% of mice with neurologic melioidosis. By contrast, infection with the isolates having low resistance to D. discoideum predation but high C. elegans killing effect led to 20% cases with inflammation in the salivary glands. Our results indicated that individual B. pseudomallei isolates selected from simple biological models contribute differently to disease progression and/or tissue tropism.

To investigate the genotypes and clinical characteristics of thalassemia on children in Wuhan region.A total of 159 patients diagnosed as thalassemia in Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology from December 2017 to December 2019. The patients were retrospectively analyzed for their types of mutations, detection rates and clinical characteristics.Among the 422 samples, 159 samples were finally diagnosed as thalassemia through genetic testing, the total detection rate was 37.68%. The detection rate of α, β and αβ-thalassemia was 17.30%, 20.14% and 0.24% respectively. Among α-thalassemia, αα/-SEA was the most common one, with a composition ratio of 68.49%(50/73), followed by αα/-α3.7 (19.18%), αα/-α4.2 (6.85%) and αα/ QS (1.37%). 9 types of β-thalassemia gene mutations were detected, and the most common three mutations were IVSII-654(C→T), with a composition ratio of 40.00%, CD41-42(-TTCT) (20.00%) and CD17(A→T)(16.47%). Two novel mutations of β-thalassemia, HBB: c.92-2A＞T and HBB:c.-23A＞G were detected. Among all the positive patients, 134 (84.28%) were 0-3 years old, 19 (11.95%) were 4-6 years old, and 6 (3.77%) were 7 years of age or older. There were 147 patients with mild anemia (92.45%), 11 patients with moderate anemia (6.92%), and 1 patients with severe anemia (0.63%). The MCV of 94(59.12%) patients was lower than 65 fL, and that of 51(32.08%) patients was between 65 fL and 80 fL, while 14(8.81%) patients was higher than 80 fL. MCV in β-thalassemia group was lower than that in α-thalassemia group, and the difference showed statistically significant (P0.05).The genotypes of thalassemia in children in Wuhan area are diverse, and most of them are mild thalassemia, and diagnosed under 3 years old. Children with β-thalassemia have smaller red blood cell volumes than those with α-thalassemia.中国武汉地区儿童地中海贫血基因类型及临床特征分析.分析武汉地区儿童地中海贫血的基因型及临床特征.回顾性选取2017年12月至2019年12月于本院儿科就诊并确诊为地中海贫血的159例患儿，分析本地区儿童地贫基因型、检出率及其临床特征.共送检422份样品，其中159例通过基因检测确诊为地中海贫血，总检出率为37.68%。其中α-地中海贫血检出率为17.30%，β-地中海贫血检出率为20.14%，αβ-复合地中海贫血检出率为0.24%。α-地中海贫血中αα/-SEA最常见，共检出50例，构成比为68.49%，其次为αα/-α3.7 14例（19.18%），αα/-α4.2 5例 (6.85%)，αα/ QS 1例 (1.37%)；检出9种β-地中海贫血基因突变类型，最常见的3种突变类型依次为IVSⅡ-654(C→T) 34例（40.00%）、CD41-42(-TTCT) 17例（20.00%）、CD17(A→T) 14例（16.47%），检测出2例新发突变：HBB：c.92-2A＞T、HBB：c.-23A＞G。送检样本年龄在0-3岁者134例（84.28 %），4-6岁者19例（11.95%），＞7岁者6例（3.77%）。轻度贫血147例（92.45%），中度贫血11例（6.92%），重度贫血1例（0.63%）。MCV＜65 fL组94例（59.12%），65-80 fL组51例（32.08%），≥80 fL组14例（8.81%）。β-地中海贫血组MCV小于α-地贫组，差异有统计学意义（P＜0.05）.武汉地区儿童地中海贫血基因型具有多样性，与其他地区存在差异，且以轻型为主，多数于3岁以内确诊；β-地中海贫血患儿红细胞体积较α-地中海贫血更小.

Talaromyce marneffei is an important thermally dimorphic pathogen causing disseminated mycoses in immunocompromised individuals in southeast Asia. Previous studies have suggested that NLRP3 inflammasome plays a critical role in antifungal immunity. However, the mechanism underlying the role of NLRP3 inflammasome activation in host defense against T. marneffei remains unclear. We show that T. marneffei yeasts but not conidia induce potent IL-1β production. The IL-1β response to T. marneffei yeasts is differently regulated in different cell types; T. marneffei yeasts alone are able to induce IL-1β production in human PBMCs and monocytes, whereas LPS priming is essential for IL-1β response to yeasts. We also find that Dectin-1/Syk signaling pathway mediates pro-IL-1β production, and NLRP3-ASC-caspase-1 inflammasome is assembled to trigger the processing of pro-IL-1β into IL-1β. In vivo, mice deficient in NLRP3 or caspase-1 exhibit higher mortality rate and fungal load compared to wild-type mice after systemic T. marneffei infection, which correlates with the diminished recruitment of CD4 T cells into granulomas in knockout mice. Thus, our study first demonstrates that NLRP3 inflammasome contributes to host defense against T. marneffei infection.