Responses of CO2 and CH4 in the alpine wetlands of the Tibetan Plateau to warming and nitrogen and phosphorus additions.

Wetland ecosystems store large amounts of carbon, and CO2 and CH4 fluxes from this ecosystem receive the double impact of climate change and human activities. Nonetheless, research on how multi-gradient warming and nitrogen and phosphorus additions affect these wetland greenhouse gas emissions is still limited, particularly in alpine wetland ecosystems. Therefore, we conducted a field experiment on the Tibetan Plateau wetlands, investigating the effects of warming and nitrogen and phosphorus additions on the CO2 and CH4 fluxes in alpine wetlands. Results indicated that warming enhanced the CO2 absorption and CH4 emission in the alpine meadow ecosystem, possibly related to changes in plant growth and microbial activity induced by warming, while we noticed that the promotion of CO2 uptake weakened with the increase in the magnitude of warming, suggesting that there may be a temperature threshold beyond which the ecosystem's capacity for carbon sequestration may be reduced. Nitrogen addition increased CH4 emission, with the effect on CO2 absorption shifting from inhibition to enhancement as the amount of applied nitrogen or phosphorus increased. The interaction between warming and nitrogen and phosphorus additions further influenced CH4 emission, exhibiting a synergistic enhancement effect. This study deepens our understanding of the greenhouse gas responses of alpine wetland ecosystems to warming and nitrogen and phosphorus additions, which is significant for predicting and managing ecosystem carbon balance under global change.

Enhancing heat transfer efficiency in corrugated tube heat exchangers: A comprehensive approach through structural optimization and field synergy analysis.

In this paper, a precise and efficient method to optimize corrugated tube heat exchangers is proposed by combining computational fluid dynamics simulation with optimization. The optimization of tubular heat exchangers involves contradictory Colburn coefficient j, and the friction coefficient f, so it is a multi-objective optimization problem. The approximate model is obtained by an extreme learning machine, and the structure parameter of the heat exchanger is optimized by the nondominated sorting genetic algorithm-Ⅱ. Compared to the results between the original and optimized tube, the optimized structure Colburn coefficient increased by 5.1 % and the friction coefficient decreased by 9.3 %. Finally, the internal flow field is compared qualitatively from temperature, pressure, and velocity. The optimization effect is further emphasized by using the field synergy theory.

Discovery of an efficacious KDM5B PROTAC degrader GT-653 up-regulating IFN response genes in prostate cancer.

Epigenetic alterations promote cancer development by regulating the expression of various oncogenes and anti-oncogenes. Histone methylation modification represents a pivotal area in epigenetic research and numerous publications have demonstrated that aberrant histone methylation is highly correlated with tumorigenesis and development. As a key histone demethylase, lysine-specific demethylase 5B (KDM5B) demethylates lysine 4 of histone 3 (H3K4) and serves as a transcriptional repressor of certain tumor suppressor genes. Meanwhile, KDM5B inhibits STING-induced intrinsic immune response of tumor cells or recruits SETDB1 through non-enzymatic function to silence reverse transcription elements to promote immune escape. The conventional small molecule inhibitors can only inhibit the enzymatic function of KDM5B with no effect on the non-enzymatic function. In the article, we present the development of the first series of KDM5B degraders based on CPI-455 to inhibit the non-enzymatic function. Among them, GT-653 showed optimal KDM5B degradation efficiency in a ubiquitin proteasome-dependent manner. GT-653 efficiently reduced KDM5B protein levels without affecting KDM5B transcription. Interestingly, GT-653 increased H3K4me3 levels and activated the type-I interferon signaling pathway in 22RV1 cells without significant phenotypic response on cell proliferation.

Ultrasonography screening of hepatic cystic echinococcosis in sheep flocks used for evaluating control progress in a remote mountain area of Hejing County, Xinjiang.

BACKGROUND: Although ultrasonography (US) has been widely used in the diagnosis of human diseases to monitor the progress of cystic echinococcosis (CE) control, the screening method for hepatic CE in sheep flocks requires adjustment. In this study, we used a US scanner to screen sheep flocks and evaluated the efficacy of dosing dogs once a year with praziquantel for 7 years from 2014 to 2021. METHODS: All sheep in the three flocks were screened using an ultrasound scanner in 2014 and compared with the prevalence of infection in 2021 in Bayinbuluke, Xinjiang, China. Sheep age was determined using incisor teeth. Cyst activity and calcification were determined using US images. The dogs were dewormed with praziquantel once a year to control echinococcosis in the community. RESULTS: Three flocks had 968 sheep in 2014, with 13.22%, 22.62%, 18.7%, 27.27%, 11.88%, and 6.3% of sheep aged 1, 2, 3, 4, 5, and ≥ 6 years old, respectively. US scanning revealed that the overall CE prevalence was 38.43% (372/968), with active cysts and calcified cysts present in 9.40% (91/968) and 29.02% (281/968) of the sheep, respectively. For the young sheep aged 1 and 2 years, the prevalence of active and calcified cysts was: 1.56% and 0.91%, and 10.94% and 18.72%, respectively. Approximately 15.15% and 16.52% of the 4- and 5-year-old sheep, respectively, harbored active cysts. There was no significant difference in the infection rates of sheep between 2014 and 2021 (P > 0.05). CONCLUSIONS: US is a practical tool for the field screening of CE in sheep flocks. One-third of the sheep population in the flocks was 1-2 years old, and these sheep played a very limited role in CE transmission, as most of the cysts were calcified. Old sheep, especially culled aged sheep, play a key role in the transmission of CE. Dosing dogs once a year did not affect echinococcosis control.

Molecular characterization of Cryptosporidium spp., Giardia spp. and Enterocytozoon bieneusi in eleven wild rodent species in China: Common distribution, extensive genetic diversity and high zoonotic potential.

Cryptosporidium spp., Giardia spp. and Enterocytozoon bieneusi are common zoonotic pathogens in humans and animals. Although rodents are important parts of the ecosystem and common hosts for these pathogens, little is known of the distribution, genetic diversity and zoonotic potential of these pathogens in wild rodents. A total of 442 fecal samples were collected from eleven wild rodent species in three provinces of China, and analyzed for these pathogens by PCR and DNA sequencing. The infection rates of Cryptosporidium spp., Giardia spp. and E. bieneusi were 19.9% (88/442), 19.8% (75/378) and 12.2% (54/442), respectively. Altogether, 23 known Cryptosporidium species/genotypes were identified and their distribution varied among different sampling locations or rodent species. Subtyping of the zoonotic Cryptosporidium species identified two novel subtype families XVe and XVf in C. viatorum, the subtype family XIIh and a novel subtype family XIIj in C. ubiquitum, and the subtype family IId in C. parvum. Three Giardia species were identified, including G. microti (n = 57), G. muris (n = 15) and G. duodenalis (n = 3), with G. duodenalis assemblages A and G identified in brown rats in urban areas of Guangdong. In addition, 13 E. bieneusi genotypes including eight known and five novel ones were identified, belonging to Groups 1, 2, 10, 14 and 15. Within nine genotypes in the zoonotic Group 1, common human-pathogenic genotypes D, Type IV, PigEbITS7 and Peru8 were detected only in brown rats and Lesser rice-field rats in urban areas of Guangdong. Apparent host adaptation and geographical differences were observed among Cryptosporidium spp., Giardia spp. and E. bieneusi genotypes in wild rodents in the present study. Furthermore, the zoonotic Cryptosporidium species and E. bieneusi genotypes commonly found here suggest a high zoonotic potential of these pathogens in wild rodents, especially in brown rats in urban areas. Hygiene and One Health measures should be implemented in urban streets and food stores to reduce the possible direct and indirect transmission of these rodent-related pathogens.

Electrocatalytic C-H/S-H Coupling of Amino Pyrazoles and Thiophenols: Synthesis of Amino Pyrazole Thioether Derivatives.

A mild method for the C-H/S-H coupling of pyrazol-5-amines and thiophenols was developed via electrochemistry, giving diverse amino pyrazole thioether derivatives in 37-98% yields. This electrochemical reaction is sustainable and an atom-efficient approach with good functional group tolerance and scalability by avoiding metal and external chemical oxidants.

Electrochemically Enable N-Sulfenylation/Phosphinylation of Sulfoximines via Oxidative Dehydrocoupling Reaction.

An electrochemical oxidative cross-coupling strategy for the synthesis of N-sulfenylsulfoximines from sulfoximines and thiols was accomplished, giving diverse N-sulfenylsulfoximines in moderate to good yields. Moreover, this strategy can be extended to construct the N-P bond of N-phosphinylated sulfoximines. With electrons as reagents, the oxidative dehydrogenation cross-coupling reaction proceeds smoothly in the absence of traditional redox reagents.

Microencapsulation with fructooligosaccharides and whey protein enhances the antioxidant activity of anthocyanins and their ability to modulate gut microbiota in vitro.

Anthocyanins are the primary functional pigments in the diet. However, anthocyanins exhibit instability during digestion, coupled with limited bioavailability. Microencapsulation offers anthocyanins a sheltered environment, enhancing their stability and bioactivity. Fructooligosaccharides (FOS) and whey protein (WP) commonly serve as wall materials in microencapsulation and represent a significant source of probiotic functionality. Our prior research successfully established a robust microencapsulation system for anthocyanins utilizing FOS and WP. This study investigates the antioxidative capacity, stability during in vitro digestion, modulation on gut microbiota, and short-chain fatty acids (SCFAs) production of black soybean skin anthocyanins microencapsulated with FOS and WP (anthocyanin-loaded microencapsule particles, ALM). The results demonstrate that ALM exhibits a superior antioxidant capacity compared to free anthocyanins (ANCs) and cyanidin-3-glucoside (C3G). During simulated digestion, ALM exhibits enhanced anthocyanin retention compared with ANC in both gastric and intestinal phases. In comparison with ANC and even non-loaded microcapsules (NLM), in vitro fermentation demonstrates that ALM exhibits the highest gas production and lowered pH, indicating excellent fermentation activity. Furthermore, in comparison with ANC or NLM, ALM exerts a positive influence on the diversity and composition of gut microbiota, with potentially beneficial genera such as Faecalibacterium and Akkermansia exhibiting higher relative abundance. Moreover, ALM stimulates the production of SCFAs, particularly acetic and propionic acids. In conclusion, microencapsulation of anthocyanins with FOS-WP enhances their antioxidative capacity and stability during in vitro digestion. Simultaneously, this microencapsulation illustrates a positive regulatory effect on the intestinal microbiota community and SCFA production, conferring potential health benefits.

eDOTS: Improving the Treatment of Pulmonary Tuberculosis in Xinjiang, China.

Purpose: To increase pulmonary tuberculosis (PTB) treatment adherence in Xinjiang Region, an electronic DOTS (eDOTS) system developed was applied and evaluated. Methods: An eDOTS system comprised electronic medicine boxes, mobile phones and a central processing platform. Between April and June 2016, persons with active PTB (PAPTB) were recruited from villages and a city and were prescribed a six-month course of antibiotics using either DOTS or eDOTS. Treatment adherence rate and chest X-ray digital radiography (DR) score were used to evaluate usefulness of eDOTS. Results: A total 167 PAPTB were recruited with 81 participants from villages and 86 from neighbourhoods. Of the 81 village patients, 43 (53%) used eDOTS and 38 (47%) used DOTS. Among the 86 patients from neighbourhoods, 50 (58%) used eDOTS and 36 (42%) used DOTS. After 6 months of treatment, the average treatment compliance of the village patients who used eDOTS were 47.0%±20.5% compared to 26.7%±21.1% who used DOTS (t=-4.475, p<0.001). The patients using eDOTS from both the villages and city had significantly lower X-ray DR scores than the patients using DOTS by 1.81 points, 95% CI (0.72-2.90) and 1.05 points, 95% CI (0.15-1.95), respectively. Conclusion: eDOTS is an effective means of managing the treatment of active PTB patients through daily reminding and monitoring of patient compliance. Ease of contact with doctors and special education programs encouraged PAPTB to complete their treatment course as required.

Serological investigation of brucella infection using a dipstick assay among individuals with unexplained fever in farming-pastoral areas of Xinjiang, China.

OBJECTIVE: To evaluate the brucellosis detection of the dipstick assay coated with LPS antigen from Brucella melitensis vaccine strain M5 compared with Rose Bengal test (RB) and serum agglutination test (SAT), and investigate the brucella infection with the dipstick assay among people with unexplained fever in farming-pastoral areas of Xinjiang, China. METHODS: The dipstick assay was repeated to verify 130 positive and 200 negative serum samples, which had been confirmed by RB and SAT, for sensitivity and specificity analysis. Subsequently, 313 sera from people with unexplained fever in farming-pastoral areas including 6 counties in 3 regions where brucellosis is endemic and 200 sera from nonendemic city area (Urumqi City) in Xinjiang were detected with the dipstick assay for population infection rate survey. RESULTS: Sensitivity and specificity was 100% and 97% respectively with dipstick assay compared with RB and SAT. The average positive rate of sera from people with unexplained fever from farming-pastoral areas in Xinjiang was 18.5% (58/313) and the highest was 22.5% (9/40). CONCLUSIONS: The proportion of brucellosis infection among individuals with fever of unknown origin is relatively high in agricultural and pastoral areas of Xinjiang. The dipstick assay has a series of advantages such as low cost and fast speed, which make it suitable for the primary screening of high-risk populations.

Oral Delivery of Anti-Parasitic Agent-Loaded PLGA Nanoparticles: Enhanced Liver Targeting and Improved Therapeutic Effect on Hepatic Alveolar Echinococcosis.

Background: Alveolar echinococcosis (AE) is a lethal parasitic disease caused by infection with the metacestode of the dog/fox tapeworm Echinococcus multilocularis, which primarily affects the liver. Although continued efforts have been made to find new drugs against this orphan and neglected disease, the current treatment options remain limited, with drug delivery considered a likely barrier for successful treatment. Methods: Nanoparticles (NPs) have gained much attention in the field of drug delivery due to their potential to improve delivery efficiency and targetability. In this study, biocompatible PLGA nanoparticles encapsulating a novel carbazole aminoalcohol anti-AE agent (H1402) were prepared to promote the delivery of the parent drug to liver tissue for treating hepatic AE. Results: H1402-loaded nanoparticles (H1402-NPs) had a uniform spherical shape and a mean particle size of 55 nm. Compound H1402 was efficiently encapsulated into PLGA NPs with a maximal encapsulation efficiency of 82.1% and drug loading content of 8.2%. An in vitro uptake assay demonstrated that H1402-NPs rapidly penetrated the in vitro cultured pre-cyst wall and extensively accumulated in the pre-cysts of E. multilocularis within only 1 h. The biodistribution profile of H1402-NPs determined through ex vivo fluorescence imaging revealed significantly enhanced liver distribution compared to unencapsulated H1402, which translated to improved therapeutic efficacy and reduced systemic toxicity (especially hepatotoxicity and cytotoxicity) in a hepatic AE murine model. Following a 30-day oral regimen (100 mg/kg/day), H1402-NPs significantly reduced the parasitic burden in both the parasite mass (liver and metacestode total weight, 8.8%) and average metacestode size (89.9%) compared to unmedicated infected mice (both p-values < 0.05); the treatment outcome was more effective than those of albendazole- and free H1402-treated individuals. Conclusion: Our findings demonstrate the advantages of encapsulating H1402 into PLGA nanoparticles and highlight the potential of H1402-NPs as a promising liver-targeting therapeutic strategy for hepatic AE.

NIR-II fluorescence microscopic bioimaging for intrahepatic angiography and the early detection of Echinococcus multilocularis microlesions.

Hepatic alveolar echinococcosis (HAE) is caused by the metacestode of Echinococcus multilocularis, which shows characteristics of malignant tumors with high mortality. However, traditional diagnostic imaging methods are still not sufficient for the recognition of HAE microlesions in the early stages. Near-infrared-II (900-1700 nm, NIR-II) fluorescence microscopic imaging (NIR-II-FMI) has shown great potential for biomedical detection. A novel type of negative target imaging method based on NIR-II-FMI with the assistance of indocyanine green (ICG) was explored. Then, NIR-II-FMI was applied to the early detection of HAE for the first time. The negative targeting NIR-II fluorescence imaging of HAE-infected mice at different stages with the assistance of ICG under 808 nm of laser irradiation was obtained. Especially, HAE microlesions at the early stage were detected clearly. Moreover, clear intrahepatic angiography was achieved under the same NIR-II-FMI system.

A Diverse Virome Is Identified in Parasitic Flatworms of Domestic Animals in Xinjiang, China.

Parasitic flatworms infect diverse vertebrates and are major threats to animal and even human health; however, little is known about the virome of these lower life forms. Using viral metagenomic sequencing, we characterized the virome of the parasitic flatworms collected from major domestic animals, including Dicrocoelium lanceatum and Taenia hydatigena, Echinococcus granulosus sensu stricto and Echinococcus multilocularis. Seven and three different viruses were discovered from D. lanceatum and T. hydatigena, respectively, and no viral sequences were found in adult tapeworms and protoscoleces of E. granulosus sensu stricto and E. multilocularis. Two out of the five parasitic flatworm species carry viruses, showing a host specificity of these viruses. These viruses belong to the Parvoviridae, Circoviridae, unclassified circular, Rep-encoding single-stranded (CRESS) DNA virus, Rhabdoviridae, Endornaviridae, and unclassified RNA viruses. The presence of multiple highly divergent RNA viruses, especially those that cluster with viruses found in marine animals, implies a deep evolutionary history of parasite-associated viruses. In addition, we found viruses with high identity to common pathogens in dogs, including canine circovirus and canine parvovirus 2. The presence of these viruses in the parasites implies that they may infect parasitic flatworms but does not completely exclude the possibility of contamination from host intestinal contents. Furthermore, we demonstrated that certain viruses, such as CRESS DNA virus may integrate into the genome of their host. Our results expand the knowledge of viral diversity in parasites of important domestic animals, highlighting the need for further investigations of their prevalence among other parasites of key animals. IMPORTANCE Characterizing the virome of parasites is important for unveiling the viral diversity, evolution, and ecology and will help to understand the "Russian doll" pattern among viruses, parasites, and host animals. Our data indicate that diverse viruses are present in specific parasitic flatworms, including viruses that may have an ancient evolutionary history and viruses currently circulating in parasite-infected host animals. These data also raise the question of whether parasitic flatworms acquire and/or carry some viruses that may have transmission potential to animals. In addition, through the study of virus-parasite-host interactions, including the influence of viral infection on the life cycle of the parasite, as well as its fitness and pathogenicity to the host, we could find new strategies to prevent and control parasitic diseases.

Untargeted Lipidomics Revealed the Protective Effects of Cyanidin-3-O-glucoside on Bisphenol A-Induced Liver Lipid Metabolism Disorder in Rats.

Bisphenol A (BPA) is an estrogenic endocrine disruptor that induces metabolic disorders. Cyanidin-3-O-glucoside (C3G) has multiple functional activities and is the most abundant anthocyanin belonging to the flavonoid subgroup. This study aimed to investigate the protective effect of C3G on BPA-induced liver lipid metabolism disorder and explore its mechanism via lipidomics analysis. The results showed that C3G supplementation significantly ameliorated the serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, triacylglycerols (TG), and alanine and aspartate aminotransferase (ALT and AST). Furthermore, liver lipidomics indicated that C3G effectively facilitated the recovery of differential lipid metabolites, including TGs, phosphatidylethanolamines, phosphatidylcholines, lysophosphatidylcholines, phosphatidylinositol, cholesteryl esters, and phosphatidylserine, and reversed the levels of hepatic lipid synthesis-related genes. Our results suggest that C3G has an effective regulatory effect on BPA-induced disorders of lipid metabolism.

Chromosome-level genome assembly defines female-biased genes associated with sex determination and differentiation in the human blood fluke Schistosoma japonicum.

Schistosomiasis is a neglected tropical disease of humans caused by blood flukes of the genus Schistosoma, the only dioecious parasitic flatworm. Although aspects of sex determination, differentiation and reproduction have been studied in some Schistosoma species, almost nothing is known for Schistosoma japonicum, the causative agent of schistosomiasis japonica. This mainly reflects the lack of high-quality genomic and transcriptomic resources for this species. As current genomes for S. japonicum are highly fragmented, we assembled and report a chromosome-level reference genome (seven autosomes, the Z-chromosome and partial W-chromosome), achieving a substantially enhanced gene annotation. Utilizing this genome, we discovered that the sex chromosomes of S. japonicum and its congener S. mansoni independently suppressed recombination during evolution, forming five and two evolutionary strata, respectively. By exploring the W-chromosome and sex-specific transcriptomes, we identified 35 W-linked genes and 257 female-preferentially transcribed genes (FTGs) from our chromosomal assembly and uncovered a signature for sex determination and differentiation in S. japonicum. These FTGs clustering within autosomes or the Z-chromosome exhibit a highly dynamic transcription profile during the pairing of female and male schistosomula, thereby representing a critical phase for the maturation of the female worms and suggesting distinct layers of regulatory control of gene transcription at this development stage. Collectively, these data provide a valuable resource for further functional genomic characterization of S. japonicum, shed light on the evolution of sex chromosomes in this highly virulent human blood fluke, and provide a pathway to identify novel targets for development of intervention tools against schistosomiasis.

Formation of hydroxyphenyl-pyranoanthocyanins derived from cyanidin-3-O-glucoside and effects of high-pressure processing on the transformation efficiency.

Hydroxyphenyl-pyranoanthocyanins (PACNs), derived from anthocyanins (ACNs) reacted with hydroxycinnamic acids, have higher practical application value because of better physicochemical stability than their precursors. However, the slow formation rate restricted their broader applications. In the present study, cyanidin-3-O-glucoside (C3G) was chosen to react with four kinds of hydroxycinnamic acids in a model solution. Changes of color and the production of hydroxyphenyl-PACNs were monitored. The formation of derivatives was time-dependent, and the orange-yellow changing trend was correlated with the formation of PACNs and the consumption of C3G. In addition, high-pressure processing (HPP) as a widely-used non-thermal processing method in the food industry was conducted to investigate its impact on hydroxyphenyl-PACNs formation. The results showed that HPP significantly improves the yield of two types of hydroxyphenyl-PACNs (C3G-4-vinylcatechol and C3G-4-vinylphenol) and the retention of total residual pigments during 56 days of storage. Therefore, HPP contributed to color-protecting and the transformation of hydroxyphenyl-PACNs.

Serum Proteomic Analysis for New Types of Long-Term Persistent COVID-19 Patients in Wuhan.

The emergence of a new type of COVID-19 patients, who were retested positive after hospital discharge with long-term persistent SARS-CoV-2 infection but without COVID-19 clinical symptoms (hereinafter, LTPPs), poses novel challenges to COVID-19 treatment and prevention. Why was there such a contradictory phenomenon in LTPPs? To explore the mechanism underlying this phenomenon, we performed quantitative proteomic analyses using the sera of 12 LTPPs (Wuhan Pulmonary Hospital), with the longest carrying history of 132 days, and mainly focused on 7 LTPPs without hypertension (LTPPs-NH). The results showed differential serum protein profiles between LTPPs/LTPPs-NH and health controls. Further analysis identified 174 differentially-expressed-proteins (DEPs) for LTPPs, and 165 DEPs for LTPPs-NH, most of which were shared. GO and KEGG analyses for these DEPs revealed significant enrichment of "coagulation" and "immune response" in both LTPPs and LTPPs-NH. A unity of contradictory genotypes in the 2 aspects were then observed: some DEPs showed the same dysregulated expressed trend as that previously reported for patients in the acute phase of COVID-19, which might be caused by long-term stimulation of persistent SARS-CoV-2 infection in LTPPs, further preventing them from complete elimination; in contrast, some DEPs showed the opposite expression trend in expression, so as to retain control of COVID-19 clinical symptoms in LTPPs. Overall, the contrary effects of these DEPs worked together to maintain the balance of LTPPs, further endowing their contradictory steady-state with long-term persistent SARS-CoV-2 infection but without symptoms. Additionally, our study revealed some potential therapeutic targets of COVID-19. Further studies on these are warranted. IMPORTANCE This study reported a new type of COVID-19 patients and explored the underlying molecular mechanism by quantitative proteomic analyses. DEPs were significantly enriched in "coagulation" and "immune response". Importantly, we identified 7 "coagulation system"- and 9 "immune response"-related DEPs, the expression levels of which were consistent with those previously reported for patients in the acute phase of COVID-19, which appeared to play a role in avoiding the complete elimination of SARS-CoV-2 in LTPPs. On the contrary, 6 "coagulation system"- and 5 "immune response"-related DEPs showed the opposite trend in expression. The 11 inconsistent serum proteins seem to play a key role in the fight against long-term persistent SARS-CoV-2 infection, further retaining control of COVID-19 clinical symptom of LTPPs. The 26 proteins can serve as potential therapeutic targets and are thus valuable for the treatment of LTPPs; further studies on them are warranted.

Echinococcus granulosus sensu stricto and antigen B may decrease inflammatory bowel disease through regulation of M1/2 polarization.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic idiopathic disease characterized by inflammation-related epithelial barrier damage in the intestinal tract. Helminth infection reduces autoimmune disease symptoms through regulation of inflammatory responses based on hygiene theory. However, the underlying mechanisms remain unclear. METHODS: BALB/c mice were infected with microcysts of E. granulosus sensu stricto and drank water containing 3.5% dextran sodium sulfate (DSS) at the 100th day post-infection. After 7 days of drinking DSS, the mouse body weight change and disease activity index (DAI) were recorded every day, and colon length and histological score were evaluated after sacrifice. After injection with antigen B (AgB), inducible nitric oxide synthase (iNOS) and Fizz1 expression and F4/80+CD11c+ M1 and F4/80+CD206+ M2 in the peritoneal cells and colon tissues were analysed by qPCR and flow cytometry, respectively. Gut microbiota were profiled by 16S rRNA sequencing of the mouse faecal samples. For in vitro assay, RAW264.7 macrophages were cultured in medium containing AgB before induction by lipopolysaccharide (LPS). Then, NO in the supernatant was measured, and the expression of cytokine genes associated with macrophages were determined by qRT-PCR. RESULTS: Echinococcus granulosus s.s. infection and AgB significantly reduced the symptoms and histological scores of IBD induced by DSS (P < 0.05). Flow cytometry showed that AgB inoculation increased F4/80+ and CD206+ in peritoneal cells. The results of qPCR showed that AgB significantly decreased iNOS and increased Fizz1 expression in the colon of mice inoculated by DSS (P < 0.05). Furthermore, AgB injection led to significant changes in the profiles of five genera (Paraprevotella, Odoribacter, Clostridium cluster XlVa, Oscillibacter, and Flavonifractor) in faecal samples. In vitro analysis showed that AgB reduced NO levels (P < 0.01), with a significant decrease in iNOS expression (P < 0.05) in RAW264.7 cells induced by LPS. CONCLUSIONS: Echinococcus granulosus infection and AgB may improve IBD conditions by inducing an M2-predominant cellular (F4/80+ CD206+) profile and decreasing type 1 macrophages (F4/80+CD11c+) in the intestinal lamina propria. In addition, AgB intervention induced changes in the microbiota condition of the gastrointestinal duct and reversed NO expression. Thus, AgB may be a drug candidate for IBD treatment.

A bla SIM-1 and mcr-9.2 harboring Klebsiella michiganensis strain reported and genomic characteristics of Klebsiella michiganensis.

As a newly emerging Klebsiella pathogen, more and more Klebsiella michiganensis drug resistant strains have been reported in recent years, which posed serious threats to public health. Here we first reported a multidrug-resistant K. michiganensis strain 12084 with two bla SIM-1 and one mcr-9.2 genes isolated from the sputum specimen of a patient in the Second Affiliated Hospital of Zhejiang University School of Medicine and analyzed its genetic basis and drug-resistance phenotypes. Genetic analysis showed that this strain harbored three different incompatibility groups (IncHI2, IncHI5, and IncFIIpKPHS2:IncFIB-4.1) of plasmids (p12084-HI2, p12084-HI5, and p12084-FII). A total of 26 drug-resistance genes belonging to 12 classes of antibiotics were identified, most of which (24) were located on two plasmids (p12084-HI2 and p12084-HI5). Interestingly, two bla SIM-1 genes were identified to locate on p12084-HI2 and p12084-HI5, respectively, both of which were embedded in In630, indicating their genetic homogeny. It was noting that one bla SIM-1 gene was situated in a novel unit transposon (referred to as Tn6733) on the p12084-HI5 plasmid. We also discovered an mcr-9.2 gene on the p12084-HI2 plasmid. To the best of our knowledge, this is the first report of a bla SIM-1 and mcr-9.2 harboring K. michiganensis strain. We then investigated the population structure/classification, and antibiotic resistance for all 275 availably global K. michiganensis genomes. Population structure revealed that K. michiganensis could be divided into two main clades (Clade 1 and Clade 2); the most popular ST29 was located in Clade 1, while other common STs (such as ST50, ST27, and ST43) were located in Clade 2. Drug-resistance analysis showed 25.5% of the K. michiganensis strains (70/275) harboring at least one carbapenemase gene, indicating severe drug resistance of K. michiganensis beyond our imagination; this is a dangerous trend and should be closely monitored, especially for ST27 K. michiganensis with the most drug-resistant genes among all the STs. Overall, we reported a bla SIM-1 and mcr-9.2 harboring K. michiganensis strain, and further revealed the population structure/classification, and drug-resistance of K. michiganensis, which provided an important framework, reference, and improved understanding of K. michiganensis.