Natural variables separate the endemic areas of Clonorchis sinensis and Opisthorchis viverrini along a continuous, straight zone in Southeast Asia.

BACKGROUND: Clonorchiasis and opisthorchiasis, caused by the liver flukes Clonorchis sinensis and Opisthorchis viverrini respectively, represent significant neglected tropical diseases (NTDs) in Asia. The co-existence of these pathogens in overlapping regions complicates effective disease control strategies. This study aimed to clarify the distribution and interaction of these diseases within Southeast Asia. METHODS: We systematically collated occurrence records of human clonorchiasis (n = 1809) and opisthorchiasis (n = 731) across the Southeast Asia countries. Utilizing species distribution models incorporating environmental and climatic data, coupled machine learning algorithms with boosted regression trees, we predicted and distinguished endemic areas for each fluke species. Machine learning techniques, including geospatial analysis, were employed to delineate the boundaries between these flukes. RESULTS: Our analysis revealed that the endemic range of C. sinensis and O. viverrini in Southeast Asia primarily spans across part of China, Vietnam, Thailand, Laos, and Cambodia. During the period from 2000 to 2018, we identified C. sinensis infections in 84 distinct locations, predominantly in southern China (Guangxi Zhuang Autonomous Region) and northern Vietnam. In a stark contrast, O. viverrini was more widely distributed, with infections documented in 721 locations across Thailand, Laos, Cambodia, and Vietnam. Critical environmental determinants were quantitatively analyzed, revealing annual mean temperatures ranging between 14 and 20 °C in clonorchiasis-endemic areas and 24-30 °C in opisthorchiasis regions (P < 0.05). The machine learning model effectively mapped a distinct demarcation zone, demonstrating a clear separation between the endemic areas of these two liver flukes with AUC from 0.9 to1. The study in Vietnam delineates the coexistence and geographical boundaries of C. sinensis and O. viverrini, revealing distinct endemic zones and a transitional area where both liver fluke species overlap. CONCLUSIONS: Our findings highlight the critical role of specific climatic and environmental factors in influencing the geographical distribution of C. sinensis and O. viverrini. This spatial delineation offers valuable insights for integrated surveillance and control strategies, particularly in regions with sympatric transmission. The results underscore the need for tailored interventions, considering regional epidemiological variations. Future collaborations integrating eco-epidemiology, molecular epidemiology, and parasitology are essential to further elucidate the complex interplay of liver fluke distributions in Asia.

Undescribed matrine-type alkaloids from Sophora alopecuroides with anti-inflammatory activity.

A phytochemical investigation on the alkaloid fractions of Sophora alopecuroides L. led to the production of 11 undescribed matrine-type alkaloids, sophaloseedlines I-S (1-11), 12 known analogs (12-23), and an unexpected artificial matrine-derived Al(III) complex (24). The corresponding structures were elucidated by the interpretation of spectroscopic analyses, quantum chemical calculation, and six instances (1-4, 18, and 24), verified by X-ray crystallography. The biological activities screening demonstrated that none of the isolates exhibited cytotoxicity against four human cancer cell lines (HepG2, A549, THP-1, and MCF-7) and respiratory syncytial virus (RSV) at 50 µM, while moderate anti-inflammatory activity with IC50 value from 15.6 to 47.8 µM was observed. The key structure-activity relationships of those matrine-type alkaloids for anti-inflammatory effects have been summarized. In addition, the most potent 7-epi-sophoramine (19) and aluminum sophaloseedline T (24) could effectively inhibit the release of pro-inflammatory factors (TNF-α, IL-6, and IL-1ß), as well as the expression of iNOS and COX-2 proteins.

Lindenane sesquiterpenoid dimers from Chloranthus holostegius with anti-neuroinflammatory activities in BV-2 microglia.

Fifteen undescribed lindenane-type sesquiterpenoid dimers, designated chloranholides F-T (1-15), together with twenty-five known analogs (16-40), were isolated from the whole plants of Chloranthus holostegius. The isolate structures were elucidated by analysis of spectroscopic data and chemical methods, and their absolute configurations were determined by X-ray crystallography and electronic circular dichroism spectra. In anti-neuroinflammatory assays, all isolates were evaluated by examination of their inhibitory effect on nitric oxide (NO) in LPS-stimulated BV-2 cells, and the results showed that 21-24, 26, 30, 32 and 36 significantly inhibited the production of the inflammatory mediator NO, with IC50 values ranging from 3.18 to 11.46 µM, which was better than that of quercetin. Structure-activity relationship analysis revealed that two essential functional groups played an indispensable role in the anti-inflammatory effects. Moreover, 22 and 24 inhibited the LPS-induced upregulation of iNOS and COX-2 enzymes in BV-2 microglia at the protein level.

Soil-transmitted helminthiasis in mainland China from 2016 to 2020: a population-based study.

Background: Soil-transmitted helminthiasis is epidemic in China and many other countries of the world, and has caused substantial burdens to human health. We conducted successive national monitoring in China from 2016 to 2020 to analyze the prevalence, changing trends, and factors influencing soil-transmitted helminthiasis, which provided a reference for future control strategies. Methods: Soil-transmitted helminth monitoring was carried out in 31 provinces (autonomous regions or municipalities, herein after referred to as "provinces") throughout China. Each province determined the number and location of monitoring sites (counties), and a unified sampling method was employed. At least 1,000 subjects were investigated in each monitoring county. Stool samples were collected and the modified Kato-Katz thick smear method was employed for stool examination. Infection data and the details of factors influencing soil-transmitted helminthiasis from 2016 to 2020 were collected from national monitoring sites. Additional influencing factors such as environment, climate and human activities were obtained from authoritative websites. Prevalence of soil-transmitted helminths was presented by species, province, sex, and age group. ArcGIS software was used to conduct spatial autocorrelation and hotspot analysis on the infection data. A Poisson distribution model and SaTScan software were used to analyze the infection data with retrospective spatiotemporal scan statistics. A database was built by matching village-level infection rate data with influencing factors. Subsequently, machine learning methods, including a Linear Regression (LR), a Random Forest (RF), a Gradient Boosted Machine (GBM), and an Extreme gradient boosting (XGBOOST) model was applied to construct a model to analyze the main influencing factors of soil-transmitted helminthiasis. Findings: The infection rates of soil-transmitted helminths at national monitoring sites from 2016 to 2020 were 2.46% (6,456/262,380), 1.78% (5,293/297,078), 1.29% (4,200/326,207), 1.40% (5,959/424,766), and 0.84% (3,485/415,672), respectively. The infection rate of soil-transmitted helminths in 2020 decreased by 65.85% compared to that in 2016. From 2016 to 2020, the infection rate of soil-transmitted helminthiasis was relatively high in southern and southwestern China, including Hainan, Yunnan, Sichuan, Guizhou, and Chongqing. In general, the infection rate was higher in females than in males, with the highest rate in the population aged 60 years and above, and the lowest in children aged 0-6 years. Global autocorrelation and hotspot analyses revealed spatial aggregation in both the national and local distribution of soil-transmitted helminthiasis in China from 2016 to 2020. The hotspots were concentrated in southwestern China. The spatiotemporal scanning analysis revealed aggregation years from 2016 to 2017 located in southwestern China, including Yunnan, Sichuan, Chongqing, Guizhou and Guangxi. The RF model was the best fit model for the infection rate of soil-transmitted helminths in China. The top six influencing factors of this disease in the model were landform, barefoot farming, isothermality, temperature seasonality, year, and the coverage of sanitary toilets. Interpretation: The overall infection rate of soil-transmitted helminths in China showed a decreasing trend from 2016-2020 due to the implementation of control measures and the economic boom in China. However, there are still areas with high infection rates and the distribution of such areas exhibit spatiotemporal aggregation. As a strategic next step, control measures should be adjusted to local conditions based on the main influencing factors and the prevalence of different sites to aid in the control and elimination of soil-transmitted helminthiasis. Funding: This research was funded by the National Key Research and Development Program of China (Grant Nos. 2021YFC2300800 and 2021YFC2300804) and the National Natural Science Foundation of China (Grant No. 32161143036).

Lycopodium Alkaloids from Huperzia serrata and Their Anti-acetylcholinesterase Activities.

One new fawcettimine-type alkaloid (1), one new miscellaneous-type alkaloid (2), four new lycodine-type alkaloids (3-6), and eight known ones (7-14) were isolated from the whole plants of Huperzia serrata. Their structures and absolute configurations were elucidated based on spectroscopic data, X-ray diffraction, ECD calculation and Mosher's method. Compound 1 was a rare C18 N2 -type Lycopodium alkaloid, possessing serratinine skeleton with an amide side chain in C-5. The absolute configuration of the 18-OH of compounds 4-6 were first determined by Mosher's method. Moreover, compounds 1-14 were assayed anti-acetylcholinesterase effect in vitro, and compound 7 showed significant anti-acetylcholinesterase activity with an IC50 value of 16.18±1.64 µM.

ART1 and putrescine contribute to rice aluminum resistance via OsMYB30 in cell wall modification.

Cell wall is the first physical barrier to aluminum (Al) toxicity. Modification of cell wall properties to change its binding capacity to Al is one of the major strategies for plant Al resistance; nevertheless, how it is regulated in rice remains largely unknown. In this study, we show that exogenous application of putrescines (Put) could significantly restore the Al resistance of art1, a rice mutant lacking the central regulator Al RESISTANCE TRANSCRIPTION FACTOR 1 (ART1), and reduce its Al accumulation particularly in the cell wall of root tips. Based on RNA-sequencing, yeast-one-hybrid and electrophoresis mobility shift assays, we identified an R2R3 MYB transcription factor OsMYB30 as the novel target in both ART1-dependent and Put-promoted Al resistance. Furthermore, transient dual-luciferase assay showed that ART1 directly inhibited the expression of OsMYB30, and in turn repressed Os4CL5-dependent 4-coumaric acid accumulation, hence reducing the Al-binding capacity of cell wall and enhancing Al resistance. Additionally, Put repressed OsMYB30 expression by eliminating Al-induced H2 O2 accumulation, while exogenous H2 O2 promoted OsMYB30 expression. We concluded that ART1 confers Put-promoted Al resistance via repression of OsMYB30-regulated modification of cell wall properties in rice.

National surveillance of hookworm disease in China: A population study.

BACKGROUND: Hookworm disease is endemic in China and is widespread globally. The disease burden to humans is great. METHODS: The study described the national surveillance of hookworm implemented in 31 provinces/autonomous regions/municipalities (P/A/Ms) of China in 2019. Each P/A/M determined the number and location of surveillance spots (counties). A unified sampling method was employed, and at least 1000 subjects were investigated in each surveillance spot. The modified Kato-Katz thick smear method was employed for stool examination. Fifty samples positive with hookworm eggs were cultured in each surveillance spot to discriminate species between A. duodenale and N. americanus. Twenty-five soil samples were collected from each surveillance spot and examined for hookworm larva. The 2019 surveillance results were analyzed and compared with that of 2016-2018. RESULTS: A total of 424766 subjects were investigated in 31 P/A/Ms of China in 2019, and the overall hookworm infection rate was 0.85% (3580/424766). The weighted infection and standard infection rates were 0.66% (4288357/648063870) and 0.67% (4343844/648063870), respectively. Sichuan province had the highest standard infection rate (4.75%) in 2019, followed by Chongqing (2.54%) and Hainan (2.44%). The standard infection rates of other P/A/Ms were all below 1%, with no hookworm detected in 15 P/A/Ms. The standard hookworm infection rate in the males and the females were 0.61% (2021216/330728900) and 0.71% (2267141/317334970), respectively, with a significant difference between different genders ([Formula: see text] = 17.23, P<0.0001). The highest standard hookworm infection rate (1.97%) was among age ≥ 60 years, followed by 45~59 years (0.77%), 15~44 years (0.37%), and 7~14 years (0.20%). The lowest standard infection rate was among the 0~6 years age group (0.12%). A significant difference was observed among different age groups ([Formula: see text] = 2 305.17, P<0.0001). The constitute ratio for N. americanus, A. duodenale, and coinfection was 78.70% (1341/1704), 2.03% (346/1704), and 1.00% (17/1704), respectively. The detection rate of hookworm larva from soil was 3.45% (71/2056). CONCLUSION: The national surveillance showed that the hookworm infection rate has been decreasing annually from 2016 to 2019, and it is now below 1%. China has made significant progress in controlling hookworm. The national surveillance system is an important way to understand the endemic status and provide important information in this process and thus needs to be continually optimized.

The Tomato Transcription Factor SlNAC063 Is Required for Aluminum Tolerance by Regulating SlAAE3-1 Expression.

Aluminum (Al) toxicity constitutes one of the major limiting factors of plant growth and development on acid soils, which comprises approximately 50% of potentially arable lands worldwide. When suffering Al toxicity, plants reprogram the transcription of genes, which activates physiological and metabolic pathways to deal with the toxicity. Here, we report the role of a NAM, ATAF1, 2 and CUC2 (NAC) transcription factor (TF) in tomato Al tolerance. Among 53 NAC TFs in tomatoes, SlNAC063 was most abundantly expressed in root apex and significantly induced by Al stress. Furthermore, the expression of SlNAC063 was not induced by other metals. Meanwhile, the SlNAC063 protein was localized at the nucleus and has transcriptional activation potentials in yeast. By constructing CRISPR/Cas9 knockout mutants, we found that slnac063 mutants displayed increased sensitivity to Al compared to wild-type plants. However, the mutants accumulated even less Al than wild-type (WT) plants, suggesting that internal tolerance mechanisms but not external exclusion mechanisms are implicated in SlNAC063-mediated Al tolerance in tomatoes. Further comparative RNA-sequencing analysis revealed that only 45 Al-responsive genes were positively regulated by SlNAC063, although the expression of thousands of genes (1,557 upregulated and 636 downregulated) was found to be affected in slnac063 mutants in the absence of Al stress. The kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed that SlNAC063-mediated Al-responsive genes were enriched in "phenylpropanoid metabolism," "fatty acid metabolism," and "dicarboxylate metabolism," indicating that SlNAC063 regulates metabolisms in response to Al stress. Quantitative real-time (RT)-PCR analysis showed that the expression of SlAAE3-1 was repressed by SlNAC063 in the absence of Al. However, the expression of SlAAE3-1 was dependent on SlNAC063 in the presence of Al stress. Taken together, our results demonstrate that a NAC TF SlNAC063 is involved in tomato Al tolerance by regulating the expression of genes involved in metabolism, and SlNAC063 is required for Al-induced expression of SlAAE3-1.

Potential Role of Domains Rearranged Methyltransferase7 in Starch and Chlorophyll Metabolism to Regulate Leaf Senescence in Tomato.

Deoxyribonucleic acid (DNA) methylation is an important epigenetic mark involved in diverse biological processes. Here, we report the critical function of tomato (Solanum lycopersicum) Domains Rearranged Methyltransferase7 (SlDRM7) in plant growth and development, especially in leaf interveinal chlorosis and senescence. Using a hairpin RNA-mediated RNA interference (RNAi), we generated SlDRM7-RNAi lines and observed pleiotropic developmental defects including small and interveinal chlorosis leaves. Combined analyses of whole genome bisulfite sequence (WGBS) and RNA-seq revealed that silencing of SlDRM7 caused alterations in both methylation levels and transcript levels of 289 genes, which are involved in chlorophyll synthesis, photosynthesis, and starch degradation. Furthermore, the photosynthetic capacity decreased in SlDRM7-RNAi lines, consistent with the reduced chlorophyll content and repression of genes involved in chlorophyll biosynthesis, photosystem, and photosynthesis. In contrast, starch granules were highly accumulated in chloroplasts of SlDRM7-RNAi lines and associated with lowered expression of genes in the starch degradation pathway. In addition, SlDRM7 was activated by aging- and dark-induced senescence. Collectively, these results demonstrate that SlDRM7 acts as an epi-regulator to modulate the expression of genes related to starch and chlorophyll metabolism, thereby affecting leaf chlorosis and senescence in tomatoes.

Cost yield of different treatment strategies against Clonorchis sinensis infection.

BACKGROUND: Clonorchiasis is attributed to the ingestion of raw freshwater fish harboring Clonorchis sinensis. Morbidity control is targeted through the administration of antihelminthics. This study modelled the cost yield indicated by effectiveness and utility of different treatment strategies against clonorchiasis. METHODS: About 1000 participants were enrolled from each of 14 counties selected from four provincial-level administrative divisions namely Guangxi, Guangdong, Heilongjiang and Jilin in 2017. Fecal examination was adopted to detect C. sinensis infection, while behavior of ingesting raw freshwater fish was enquired. Counties were grouped into four categories based on prevalence, namely low prevalence group (< 1%), moderate prevalence group (1-9.9%), high prevalence group (10-19.9%) and very high prevalence group (≥ 20%), while population were divided into three subgroups, namely children aged below 14 years old, adult female and adult male both aged over 14 years old. The average of cost effectiveness indicated by the cost to treat single infected cases with C. sinensis and of cost utility indicated by the cost to avoid per disability-adjusted life years (DALYs) caused by C. sinensis infection was calculated. Comparisons were performed between three treatment schedules, namely individual treatment, massive and selective chemotherapy, in which different endemic levels and populations were considered. RESULTS: In selective chemotherapy strategy, the cost to treat single infected case in very high prevalence group was USD 10.6 in adult male, USD 11.6 in adult female, and USD 13.2 in children. The cost increased followed the decrease of endemic level. In massive chemotherapy strategy, the cost per infected case in very high prevalence group was USD 14.0 in adult male, USD 17.1 in adult female, USD 45.8 in children, which were also increased when the endemic level decreased. In individual treatment strategy, the cost was USD 12.2 in adult male, USD 15.0 in adult female and USD 41.5 in children in very high prevalence group; USD 19.2 in adult male, USD 34.0 in adult female, and USD 90.1 in children in high prevalence group; USD 30.4 in adult male, USD 50.5 in adult female and over USD 100 in children in moderate prevalence group; and over USD 400 in any population in low prevalence group. As to cost utility, the differences by treatment strategies, populations and endemic levels were similar to those in cost effectiveness. CONCLUSIONS: Both cost effectiveness and cost utility indicators are highly impacted by the prevalence and population, as well as the treatment schedules. Adults especially men in the areas with a prevalence over 10% should be prioritized, in which selective chemotherapy was best and massive chemotherapy was also cost effective. In moderate endemic areas, the yield is not ideal, but selective chemotherapy for adult male may also be adopted. In low endemic areas, all strategies were high costly and new strategies need to be developed.

Soil-transmitted helminthiasis in China: A national survey in 2014-2015.

BACKGROUND: Based on two national surveys, the prevalence of soil-transmitted helminthiasis (STH) in China had decreased from 53.58% in 1988-1992 to 19.56% in 2001-2004. To update the epidemiology and characteristics of STH in China, a third national survey was implemented in 2014-2015. METHODOLOGY/PRINCIPAL FINDINGS: This survey covered rural areas in 31 provinces in mainland of China. Multiple-stage stratified cluster sampling was employed, which included three levels (provinces, ecozones and economical levels). Stool samples were collected and the Kato-Katz method was applied for helminth eggs detection. Samples with hookworm eggs were selected and hatched to differentiate the species based on larval morphology. Between June 2014 and May 2015, a total of 484,210 participants from 604 counties were enrolled. The weighted prevalence of STH overall was 4.49% (95% confidential interval (CI): 2.45%-6.53%), including 2.62% (95% CI: 0.86%-4.38%) hookworm infections, 1.36% (95% CI: 0.49%-2.23%) ascariasis, and 1.02% (95% CI: 0.15%-1.89%) trichuriasis. The estimated population infected was 29.12 million (95% CI: 15.88 million-42.32 million) for all STH; 16.97 million (95% CI: 5.57 million-28.39 million) for hookworm infections; 8.83 million (95% CI: 3.18 million-14.45 million) for ascariasis; and 6.60 million (95% CI: 0.97 million-12.25 million) for trichuriasis. Overall, the prevalence of ascariasis and trichuriasis was relatively high in children, while hookworm infections were more common in the older population, especially those over 60. STH was highly prevalent in western China, and moderately in central areas, but low in eastern and northern regions. Out of 3,579 hookworm cases with species differentiation, 479 cases (13.38%) were infected with only Ancylostoma spp., 2,808 cases (78.46%) with only Necator americanus, and another 292 cases (8.16%) with both species. CONCLUSIONS/SIGNIFICANCE: This survey demonstrated the continuous decrease of STH in rural China. However, endemicity still prevails in the western areas of the country. Hookworm, especially N. americanus, is becoming the predominant species. Older farmers in western China should be prioritized for control due to the high prevalence of hookworm.

[Discussions on Clinical Characteristics and Diagnostic Criteria of Pertussis in Children].

OBJECTIVE: To compare the clinical manifestations of pertussis in children of different ages and different immunization statuses in Wenzhou, and to explore the limitations of diagnostic criteria for pertussis. METHODS: The clinical data of 288 children diagnosed with pertussis at Yuying Children's Hospital & the Second Affiliated Hospital of Wenzhou Medical University from October 2017 to December 2019 were retrospectively analyzed. The clinical characteristics of children of different ages and different immunization statuses were analyzed. Their clinical data were compared to relevant diagnostic criteria of pertussis in children of different ages according to the Recommendations for Diagnosis and Treatment of Chinese Children with Pertussis and the diagnosis conformity rate was analyzed. RESULTS: Among the 288 children, 124 cases (43.06%) were 3 months old or younger, and 164 cases (288, 56.94%) were >3 months old. Among patients≤3 months of age, cyanosis, three-depression sign, face redness, dyspnea and peripheral blood lymphocyte ratio were significantly higher than those of patients >3 months of age. They also had higher incidence of pneumonia, higher proportion of developing severe pertussis, and longer stay at the hospital. All these findings showed statistically significant difference ( P<0.05). 83 children were fully immunized (receiving the full course of vaccination), and 205 were not fully immunized (not receiving the full course of vaccination or being unvaccinated). The proportion of children presenting cyanosis, shortness of breath, three depression sign and face redness in the incomplete immunization group was higher than that in the complete immunization group. In the incomplete immunization group, the proportion of lymphocytes was higher, the level of C-reactive protein (CRP) was lower, and the length of hospitalization was longer than those of the complete immunization group. All the differences were statistically significant ( P<0.05). Among patients aged ≤3 months, the conformity rate of diagnosis (112/114, 90.32%) upon admission was higher than that among patients aged >3 months (119/164, 72.56%). Among patients aged ≤3 months, 41.94% (52/124, while 54.03% (67/124) of the patients aged ≤3 months had WBC count <20×10 9 L -1. CONCLUSION: Pertussis in children ≤3 months of age in Wenzhou City were more serious, showing higher rate of diagnosis conforming to the recommended clinical diagnostic criteria than that in children >3 months old. The WBC threshold in routine blood test of ≤3 months old could be lowered appropriately and the current diagnostic criteria still needed improvement.

The Epidemiology, Molecular, and Clinical of Human Adenoviruses in Children Hospitalized With Acute Respiratory Infections.

INTRODUCTION: Human adenovirus (HAdV) is a common pathogen in children with acute respiratory infections (ARIs). The aim was to describe the epidemiology, molecular, and clinical characteristics of HAdV among children hospitalized with ARIs in Wenzhou in southeastern China. METHODOLOGY: From January 2018 to December 2019, nasopharyngeal swab or sputum specimens were prospectively collected from hospitalized children with ARIs. HAdV was detected using direct immunofluorescence. We used a multiplex PCR assay combined with capillary electrophoresis targeting the hexon gene's hypervariable region to identify HAdV types 1, 2, 3, 4, 5, 7, 14, 21, 37, 40, 41, and 55. We analyzed the epidemiological, molecular, and clinical data according to the HAdV type. RESULTS: HAdVs were detected in 1,059 (3.5%) of the total of 30,543 children tested. A total of 947 cases with monotype HAdV identified by the PCR assay were included in the analysis. HAdV-3 (415/947, 43.8%), HAdV-7 (318/947, 33.6%), HAdV-2 (108/947, 11.4%), and HAdV-1 (70/947, 7.4%) were the predominant types. Of the 550 (58.1%) cases detected from December 2018 to August 2019, HAdV-3, and HAdV-7 were the main types. The main diagnoses included 358 cases of pneumonia, 232 cases of tonsillitis, 198 cases of bronchitis, and 159 cases of upper respiratory tract infection (URTI). Among children with pneumonia the main types were HAdV-7 (51.1%), HAdV-3 (36.9%), and HAdV-1 (2.2%). Among children with bronchitis, the main types were HAdV-3 (48.0%), HAdV-7 (28.3%), and HAdV-2 (10.6%). Among children with URTIs, the main types were HAdV-3 (49.7%), HAdV-7 (22.6%), and HAdV-2 (13.2%). Among children with tonsillitis, the main types were HAdV-3 (47.4%), HAdV-2 (22.4%), and HAdV-7 (18.5%). In total, 101 (55.2%) patients required supplemental oxygen, 15 (8.2%) required critical care, and 1 child (0.5%) with HAdV-7 pneumonia died. CONCLUSION: HAdV-3 -7, -2, and -1 were the predominant types identified in hospitalized children with ARIs in Wenzhou. From December 2018 to August 2019, there were outbreaks of HAdV-3 and -7. There were significant differences in HAdV types among children with pneumonia, tonsillitis, bronchitis, and URTI. HAdV-7 can cause more severe pneumonia in children than HAdV-3.

[Diversity and Function Prediction of Bacterioplankton Under Human Disturbance in the Main Stream of the Laoguan River Before and After the Flood Season].

The Laoguan River is the tributary of Danjiangkou Reservoir located nearest to the water diversion outlet, and water quality here directly affects the safety of the diverted water. To explore the community composition and functional change of bacterioplankton in the Laoguan River before and after the flood season, four representative sites were sampled in the main stream before (May) and after (October) the 2018 and 2019 flood seasons. Water quality was assessed and high-throughput sequencing of bacterioplankton was performed. Yanghe (YH) was slightly disturbed, Xixiabei (XX) was moderately disturbed, Dangziling (DZL) was heavily disturbed, and Zhangying (ZY) was moderately disturbed. In total, 599 genera from 40 phyla were collected. The diversity of bacterioplankton before the flood season was higher than afterwards, and moderate levels of disturbance increased the Shannon-Wiener diversity index. LEfSe analysis indicated that significant differences existed in some dominant phyla; Armatimonadete in Yanghe, Epsilonbacteraeota and Firmicutes in Xixiabei, and Cyanophyta in Dangziling dominated before flood season, while significant differences only occurred in Firmicutes and Cyanophyta in Dangziling after the flood season. The PCoA of the bacterioplankton community showed that the sampling points were distinct before and after the flood season, and that differences among samples were greater before the flood season. The RDA and CCA indicated that total nitrogen and ammonia nitrogen were the main environmental factors causing declines in bacterioplankton diversity. PICRUSt showed a total of ten dominant categories of COG function genes. A total of 30 KO function genes related to nitrogen metabolism group also different between the two periods, with greater differences before flood season. The genes cynt and can in Yanghe were significant different from the other three sampling points before the flood season. Overall, nitrogen and phosphorus were the main factors regulating the bacterioplankton community structure and eutrophication in the Laoguan River. Changes in nitrogen inputs will result in changes in microbial nitrogen metabolic function in different regions of the river.

Comparative Physiological and Transcriptomic Analyses Reveal Altered Fe-Deficiency Responses in Tomato Epimutant Colorless Non-ripening.

The mechanisms associated with the regulation of iron (Fe) homeostasis have been extensively examined, however, epigenetic regulation of these processes remains largely unknown. Here, we report that a naturally occurring epigenetic mutant, Colorless non-ripening (Cnr), displayed increased Fe-deficiency responses compared to its wild-type Ailsa Craig (AC). RNA-sequencing revealed that a total of 947 and 1,432 genes were up-regulated by Fe deficiency in AC and Cnr roots, respectively, while 923 and 1,432 genes were, respectively, down-regulated. Gene ontology analysis of differentially expressed genes showed that genes encoding enzymes, transporters, and transcription factors were preferentially affected by Fe deficiency. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed differential metabolic responses to Fe deficiency between AC and Cnr. Based on comparative transcriptomic analyses, 24 genes were identified as potential targets of Cnr epimutation, and many of them were found to be implicated in Fe homeostasis. By developing CRISPR/Cas9 genome editing SlSPL-CNR knockout (KO) lines, we found that some Cnr-mediated Fe-deficiency responsive genes showed similar expression patterns between SlSPL-CNR KO plants and the Cnr epimutant. Moreover, both two KO lines displayed Fe-deficiency-induced chlorosis more severe than AC plants. Additionally, the Cnr mutant displayed hypermethylation in the 286-bp epi-mutated region on the SlSPL-CNR promoter, which contributes to repressed expression of SlSPL-CNR when compared with AC plants. However, Fe-deficiency induced no change in DNA methylation both at the 286-bp epi-allele region and the entire region of SlSPL-CNR gene. Taken together, using RNA-sequencing and genetic approaches, we identified Fe-deficiency responsive genes in tomato roots, and demonstrated that SlSPL-CNR is a novel regulator of Fe-deficiency responses in tomato, thereby, paving the way for further functional characterization and regulatory network dissection.

P22077 inhibits LPS-induced inflammatory response by promoting K48-linked ubiquitination and degradation of TRAF6.

Inflammation is a biological process associated with multiple human disorders such as autoimmune diseases and metabolic diseases. Therefore, alleviation of inflammation is important for disease prevention or treatment. Recently, deubiquitinating enzymes (DUBs), especially ubiquitin specific protease-7 (USP7) attracts increasing attention as a potential drug target for inflammation. As an inhibitor of USP7, P22077 has been used to study the roles of USP7 in inflammatory response and neuroblastoma growth. However, the role and precise mechanism of P22077 in anti-inflammatory is still indistinct. In this study, we demonstrated that P22077 could attenuate the release of pro-inflammatory factors including TNF-α, IL-1ß, IL-6 and NO, suppress mRNA expression of COX-2 and iNOS, and inhibit activation of NF-κB and MAPKs signaling pathways in Raw264.7 cells and mouse peritoneal macrophages after LPS stimulation. In vivo study showed that P22077 could relieve inflammatory response and reduce the lung injury in C57BL/6 mice with LPS-induced endotoxemia. Mechanically, P22077 might play an anti-inflammatory role by promoting tumor necrosis factor receptor-associated factor 6 (TRAF6) degradation via K48-linked polyubiquitination. These findings provide a rationale for the role of the P22077 in anti-inflammatory pathway and the promising clinical application of P22077 to treat inflammatory diseases.

Engagement of the National Institute of Parasitic Diseases in control of soil-transmitted helminthiasis in China.

Soil-transmitted helminthiases (STHs) have been widely transmitted in China and the control of STHs was initiated by NIPD-CTDR since its foundation. Three national surveys on STHs have been carried out in China, and the infection rate has dropped from 53.58% in the first national survey (1988-92) to 4.49% in the third national survey (2014-16) due to strong interventions including mass drug administration, health education and environment improvement. National surveillance of STHs started in 2006 and has been implemented successively until now, which allows to understand the endemic status and trends of STHs prevalence in China. Surveillance has been expanded to 30 provinces of China since 2016. Integrated pilot programmes have been implemented between 2006 and 2009, in which an integrated strategy, with health education and control of infection sources as key components, was adopted. Since 2019, new control pilots have been started, which will be continued for five successive years to further explore appropriate control strategies in the current "new era". With the decline of infection rate of STHs, China is approaching the elimination stage for STHs. In order to achieve this final target, poverty alleviation programmes should be integrated with precise control measures, according to real situations.

From awareness to action: NIPD's engagement in the control of food-borne clonorchiasis.

Clonorchiasis is caused by ingestion of raw freshwater fish containing infective larvae of Clonorchis sinensis. China harbours the largest number of people with C. sinensis infection. During the past three decades, the National Institute of Parasitic Diseases, affiliated to the Chinese Center for Disease Control and Prevention (NIPD) conducted many studies to facilitate the control on clonorchiasis. Three national surveys have shown the updated epidemiology of clonorchiasis in China. Recently, a national surveillance system has also been established, which will enable the production of high-resolution map. The evaluation of the disease burden has enhanced the awareness on clonorchiasis. Diverse diagnosis techniques including rapid screening by questionnaire, serological tests, faecal examination and a molecular method have been developed or evaluated. The NIPD also participated in the early evaluation of praziquantel against clonorchiasis, which enhanced its application in China. Also, the NIPD has verified the efficacy of tribendimidine against clonorchiasis. A new sustainable strategy is also being explored. However, more research is expected to further facilitate control of clonorchiasis in China, as well as international cooperation in fighting human liver fluke infections in Asia.

Rapid screening of Clonorchis sinensis infection: Performance of a method based on raw-freshwater fish-eating practice.

Clonorchis sinensis infection is caused by ingestion of raw freshwater fish containing the infective larvae of Clonorchis sinensis. It is highly endemic in East Asia, especially in China. Selective chemotherapy of people who report habitual eating of raw freshwater fish is a control measure. As the performance of this screening technique has not yet been fully evaluated in China, a cross-sectional study was conducted, covering 17 counties in four major clonorchiasis-endemic provinces. About 1 000 participants were enrolled from each county. Fecal samples were collected and examined for helminth eggs and each person enrolled was asked about their practice with respect to eating raw freshwater fish. In total, 16 230 participants from 16 counties were finally included. The overall prevalence of C. sinensis infection was 10.8%, ranging from 0 to 53.7% in the 16 counties, while the percentage of inhabitants eating raw freshwater fish was 26.5%, ranging from 0 to 79.1%. The overall sensitivity and specificity of screening for C. sinensis infection in this approach was 82.3% and 80.3%, respectively, yielding a Youden's index of 0.6. The overall positive and negative likelihood ratios were 4.2 and 0.2, respectively, while the overall positive and negative predictive values were 33.5% and 97.4%, respectively. Furthermore, the sensitivity was higher with regard to high-intensity infections compared to light infections.

National surveillance on soil-transmitted helminthiasis in the People's Republic of China.

Soil-transmitted helminths (STHs) are widely distributed and remain a public health problem in the People's Republic of China. Altogether, 301 counties across 30 regions were investigated during the national surveillance on STHs carried out in 2016 based on the modified Kato-Katz thick smear method to examine faecal samples. A total of 305 081 people were investigated with 7 366 (2.4%) found to be infected. The infection rates were the following: hookworm 1.4%, Ascaris lumbricoides 0.8% and Trichuris trichiura 0.5%. Having established that the STHs infection rate is relatively low, it is time to move towards elimination. The national surveillance system is essential for providing basic data and formulation of useful control strategies towards achieving this goal.