ABSTRACT
Plantation forests enhance carbon storage in terrestrial ecosystems in China. Larix kaempferi (Lamb.) Carrière (Lamb.) (Larix olgensis Henry) is the main species for afforestation in the eastern Liaoning Province. Therefore, it is important to understand the correlation between the site class and carbon sink potential of Larix kaempferi plantations in Liaoning Province for afforestation and carbon sink in this area. The model was fitted using three classical theoretical growth equations: the Richards model, the Korf model, and the Hossfeld model. This study used the forest resource inventory data for management in Liaoning Province in 2011 to build six dynamic height-age models for a Larix kaempferi plantation in Dandong City regardless of base-age. The optimal model derived by the generalized algebraic difference approach (GADA) method was compared with the model derived by the algebraic difference approach (ADA) method. The superiority of GADA was demonstrated by comparison. The Levenberg-Marquardt algorithm was used to fit the model. The statistical and biological characteristics were considered synthetically when comparing the models. The best model was screened out by statistical analysis and graphic analysis. The results show that the differential height-age model derived from Richards equation can well explain the growth process of Larix kaempferi in Dandong City, Liaoning Province under different conditions. The site index model based on Richards equation and derived by GADA was used to calculate the site class of a Larix kaempferi plantation in Dandong City. The net primary productivity (NPP) value from the past ten years was extracted from the MOD17A3HGF data set. Spearman correlation analysis and Kendall correlation analysis were used to show that there is a significant positive correlation between NPP value and site class of Larix kaempferi plantation in Dandong City. Among them, the highest growth occurred in 2016; NPP increased by about 3.914 gC/m2/year for every two increases in height-age grade; the lowest increase in NPP was in 2014; NPP increased by about 2.113 gC/m2/year for every two increases in height-age grade; and for every two increases in height-age grade in the recent ten years, the average NPP value increased by about 2.731 gC/m2/year.
Subject(s)
Larix , Larix/growth & development , China , Forests , Carbon Sequestration , Ecosystem , Models, Theoretical , Conservation of Natural Resources , East Asian PeopleSubject(s)
Diagnostic Errors , Humans , Fecal Impaction/diagnostic imaging , Colonoscopy/methods , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/pathology , Cecal Neoplasms/diagnosis , Cecal Neoplasms/pathology , Cecal Neoplasms/surgery , Appendiceal Neoplasms/diagnosis , Appendiceal Neoplasms/pathology , Male , Appendix/pathology , Appendix/diagnostic imaging , Female , Middle AgedABSTRACT
This paper investigates the prescribed performance control problems of strict-feedback nonlinear systems with state quantization, input quantization, unknown disturbances and unknown nonlinear functions. Since the quantized states are discontinuous, the differentiability of the stabilizing functions in the backstepping technique cannot be guaranteed. To this end, a smooth approximation of the quantized states is first obtained by introducing a class of functions. Based on this smooth approximation, a quantized control scheme is presented such that all the closed-loop signals are bounded with the prescribed performance bounds. It is shown that the unknown nonlinearities and the unknown disturbances are not estimated and the derivatives of the stabilizing functions are eliminated. Lastly, two examples are provided to illustrate the effectiveness of the presented method.
ABSTRACT
BACKGROUND: Liver metastasis (LM) stands as a primary cause of mortality in metastatic colorectal cancer (mCRC), posing a significant impediment to long-term survival benefits from targeted therapy and immunotherapy. However, there is currently a lack of comprehensive investigation into how senescent and exhausted immune cells contribute to LM. METHODS: We gathered single-cell sequencing data from primary colorectal cancer (pCRC) and their corresponding matched LM tissues from 16 mCRC patients. In this study, we identified senescent and exhausted immune cells, performed enrichment analysis, cell communication, cell trajectory, and cell-based in vitro experiments to validate the results of single-cell multi-omics. This process allowed us to construct a regulatory network explaining the occurrence of LM. Finally, we utilized weighted gene co-expression network analysis (WGCNA) and 12 machine learning algorithms to create prognostic risk model. RESULTS: We identified senescent-like myeloid cells (SMCs) and exhausted T cells (TEXs) as the primary senescent and exhausted immune cells. Our findings indicate that SMCs and TEXs can potentially activate transcription factors downstream via ANGPTL4-SDC1/SDC4, this activation plays a role in regulating the epithelial-mesenchymal transition (EMT) program and facilitates the development of LM, the results of cell-based in vitro experiments have provided confirmation of this conclusion. We also developed and validated a prognostic risk model composed of 12 machine learning algorithms. CONCLUSION: This study elucidates the potential molecular mechanisms underlying the occurrence of LM from various angles through single-cell multi-omics analysis in CRC. It also constructs a network illustrating the role of senescent or exhausted immune cells in regulating EMT.
Subject(s)
Cellular Senescence , Colorectal Neoplasms , Epithelial-Mesenchymal Transition , Liver Neoplasms , Humans , Colorectal Neoplasms/pathology , Colorectal Neoplasms/immunology , Colorectal Neoplasms/genetics , Epithelial-Mesenchymal Transition/genetics , Liver Neoplasms/secondary , Liver Neoplasms/immunology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Single-Cell Analysis , Myeloid Cells/immunology , Myeloid Cells/metabolism , Myeloid Cells/pathology , Male , Female , Prognosis , Gene Expression Regulation, Neoplastic , T-Lymphocytes/immunologyABSTRACT
The non-degradable nature of petroleum-based plastics and the dependence on petroleum-based products in daily life and production are dilemmas of human development today. We hereby developed a plastic waste upcycling process to address these challenges. A multi-stream fraction strategy was developed to process poly (ethylene terephthalate) (PET) plastics into soluble and insoluble fractions. The soluble fraction was used as a sole carbon source for microbial fermentation to produce biodiesel precursor lipids with an appreciable bioconversion yield. The insoluble fraction containing fractionated polymers was used as the asphalt binder modifiers. The downsized PET additive improved the high-temperature performance of the asphalt binder by 1 performance grade (PG) without decreasing the low-temperature PG. Subsequent SEM imaging unveiled alterations in the micromorphology induced by PET incorporation. Further FTIR and 1H NMR analysis highlighted the aromatic groups of PET polymers as a crucial factor influencing performance enhancement. The results demonstrated the multi-stream fraction as a promising approach for repurposing plastic waste to produce biodiesel and modify asphalt. This approach holds the potential to tackle challenges in fuel supply and enhance infrastructure resilience to global warming.
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Blastocystis is a protist that is distributed in the gut tract of humans and animals. However, the reports about Blastocystis infection in Tibetan antelope are scarce. We collected 173 Tibetan antelope feces samples from Xinjiang, Qinghai and Xizang, and amplified the SSU rRNA gene of 600 bp region of Blastocystis in our research. Fifty-one samples in total were positive for Blastocystis, with all subtypes being ST31. The lowest prevalence of Blastocystis was observed in Xizang (2/20, 9.1%), followed by Qinghai (18/92, 16.4%), Xinjiang (31/61, 33.7%). The highest prevalence of Blastocystis in Tibetan antelope was detected during the summer was (19/30, 38.8%). This is the first research work regarding the Blastocystis subtypes ST31 in Tibetan antelope. Our research provides information for future researches on the distribution of this Blastocystis subtype and the control of Blastocystis infection.
Subject(s)
Antelopes , Blastocystis Infections , Blastocystis , Humans , Animals , Blastocystis/genetics , Blastocystis Infections/epidemiology , Blastocystis Infections/veterinary , Tibet/epidemiology , Antelopes/genetics , Feces , Phylogeny , Prevalence , Genetic VariationABSTRACT
Aqueous zinc-ion batteries (AZIBs) have gained significant attentions for their inherent safety and cost-effectiveness. However, challenges, such as dendrite growth and anodic corrosion at the Zn anode, hinder their commercial viability. In this paper, an organic-inorganic coating layer (Nafion-TiO2) was introduced to protect the Zn anode and electrolyte interface. Briefly, Nafion effectively shields against the corrosion from water molecules through the hydrophobic wall of -CF3 and guided zinc deposition from the -SO3 functional group, while TiO2 particles with a higher Young's modulus (151 GPa vs 120 GPa from Zn metal) suppress the zinc dendrite formation. As a result, with the protection of Nafion-TiO2, the symmetrical Znâ¥Zn battery shows an improved cycle life of 1,750 h at 0.5 mA cm-2, and the full cell based on Znâ¥MnO2 shows a long cycle life over 1,500 cycles at 1 A g-1. Our research offers a novel approach for protecting zinc metal anodes, potentially applicable to other metal anodes such as those in lithium and sodium batteries.
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Background: The challenge of systemic treatment for hepatocellular carcinoma (HCC) stems from the development of drug resistance, primarily driven by the interplay between cancer stem cells (CSCs) and the tumor microenvironment (TME). However, there is a notable dearth of comprehensive research investigating the crosstalk between CSCs and stromal cells or immune cells within the TME of HCC. Methods: We procured single-cell RNA sequencing (scRNA-Seq) data from 16 patients diagnosed with HCC. Employing meticulous data quality control and cell annotation procedures, we delineated distinct CSCs subtypes and performed multi-omics analyses encompassing metabolic activity, cell communication, and cell trajectory. These analyses shed light on the potential molecular mechanisms governing the interaction between CSCs and the TME, while also identifying CSCs' developmental genes. By combining these developmental genes, we employed machine learning algorithms and RT-qPCR to construct and validate a prognostic risk model for HCC. Results: We successfully identified CSCs subtypes residing within malignant cells. Through meticulous enrichment analysis and assessment of metabolic activity, we discovered anomalous metabolic patterns within the CSCs microenvironment, including hypoxia and glucose deprivation. Moreover, CSCs exhibited aberrant activity in signaling pathways associated with lipid metabolism. Furthermore, our investigations into cell communication unveiled that CSCs possess the capacity to modulate stromal cells and immune cells through the secretion of MIF or MDK, consequently exerting regulatory control over the TME. Finally, through cell trajectory analysis, we found developmental genes of CSCs. Leveraging these genes, we successfully developed and validated a prognostic risk model (APCS, ADH4, FTH1, and HSPB1) with machine learning and RT-qPCR. Conclusions: By means of single-cell multi-omics analysis, this study offers valuable insights into the potential molecular mechanisms governing the interaction between CSCs and the TME, elucidating the pivotal role CSCs play within the TME. Additionally, we have successfully established a comprehensive clinical prognostic model through bulk RNA-Seq data.
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This study aimed to investigate the feasibility and effectiveness of left bundle branch area pacing (LBBaP) in young children. From September 2020 to May 2021, a total of 31 children (≤ 7 years) with complete atrioventricular block were included. All patients were scheduled to undergo LBBaP. Pacing parameters, and cardiac function and synchrony were evaluated during follow-up. LBBaP succeeded in 21 children (3.3 ± 2.1 years old), with a success rate of 70.9%. LBBaP failed in nine children, who eventually received right ventricular septal pacing (RVSP). The average postoperative QRS duration in patients of LBBaP group was narrower than that of RVSP group: 100.9 ± 9.1 versus 114.2 ± 11.9 ms (P = 0.002). The median follow-up duration was 12 [interquartile range (IQR) 6-15] months. At last time of follow-up, the capture threshold of ventricular electrode in patients of LBBaP group were significantly lower than that of RVSP group (0.70 ± 0.25 versus 1.39 ± 0.94 V, P = 0.011). The echo-left ventricular ejection fraction (LVEF) in patients in the LBBaP group was better than that in the RVSP group (66.1 ± 3.3 versus 63.1 ± 2.2%, P = 0.025). LBBaP can be safely and effectively administered in young children. Satisfactory pacing parameters, and narrow QRS durations were obtained.
Subject(s)
Ventricular Function, Left , Ventricular Septum , Child , Humans , Child, Preschool , Infant , Feasibility Studies , Stroke Volume , Heart Ventricles/diagnostic imagingABSTRACT
Vibrio cholerae is a waterborne bacterium that primarily infects the human intestine and causes cholera fatality. Quorum sensing (QS) negatively regulates the expression of V. cholerae virulence gene. However, the primary associated mechanisms remain undetermined. This investigation identified a new QS regulator from the TetR family, LuxT, which increases V. cholerae virulence by directly inhibiting hapR expression. HapR is a master QS regulator that suppresses virulence cascade expression. The expression of luxT increased 4.8-fold in the small intestine of infant mice than in Luria-Bertani broth. ΔluxT mutant strain revealed a substantial defect in the colonizing ability of the small intestines. At low cell densities, the expression level of hapR was upregulated by luxT deletion, suggesting that LuxT can suppress hapR transcription. The electrophoretic mobility shift analysis revealed that LuxT directly binds to the hapR promoter region. Furthermore, luxT expression was upregulated by the two-component system ArcB/ArcA, which responses to changes in oxygen levels in response to the host's small intestine's anaerobic signals. In conclusion, this research reveals a novel cell density-mediated virulence regulation pathway and contributes to understanding the complex association between V. cholerae virulence and QS signals. This evidence furnishes new insights for future studies on cholerae's pathogenic mechanisms.
Subject(s)
Cholera , Vibrio cholerae , Animals , Humans , Mice , Vibrio cholerae/genetics , Quorum Sensing/genetics , Virulence/genetics , Cholera/microbiology , Gene Expression Regulation, Bacterial , Bacterial Proteins/genetics , Bacterial Proteins/metabolismABSTRACT
Oxeiptosis is a recently discovered caspase-independent, non-inflammatory programmed cell death modality. Current studies suggest that oxeiptosis has crucial effects on biological processes in a variety of diseases. However, the mechanism of oxeiptosis in hepatocellular carcinoma (HCC) remains unclear and no relevant studies have been published. Therefore, this study is intended to investigate the mechanism and prognostic role of oxeiptosis-related genes in HCC. We explored the mechanisms and molecular phenotypes underlying the role of oxeiptosis in HCC through multi-omics analysis. Firstly, we obtained RNA-sequencing and clinical data from public database and divided the samples into trial and validation cohorts in subsequent analyses. We then screened oxeiptosis core genes (OCGs) and screened prognosis-related genes. Based on different molecular markers, we identified the molecular phenotypes of HCC, and the potential OCGs molecular mechanisms were explored. Subsequently, we construct a prognostic prediction system for HCC. Finally, we analyzed the tumor microenvironment and the immune escape phenomenon. We screened a total of 69 OCGs, most of which were prognostic risk factors for HCC. A majority of OCGs were enriched in cell cycle regulation and mitotic processes, which were related to both tumor cell proliferation and death. We identified 2 different molecular typing options with significant differences in prognosis, function, and signaling pathway enrichment between different molecular subtypes. The prognostic prediction model combined with molecular phenotypes and had a good predictive effect. Finally, we found CD4â +â T-cell exhaustion in samples with specific molecular phenotypes. Through multi-omics analysis of OCGs, we not only revealed the possible molecular mechanisms of OCGs in HCC but also provided a prognostic prediction system for clinical application through molecular typing and risk scoring model. Meanwhile, we found immune escape mechanisms in HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Multiomics , Liver Neoplasms/genetics , Apoptosis , CD4-Positive T-Lymphocytes , Prognosis , Tumor MicroenvironmentABSTRACT
The KDR (karst development rate) of rocks and their PCR(porosity of carbonate rocks) are common research topics in Jinfo Mountain. The use of traditional carbonate research methods (TCRMs) for karst studies has been shown to be costly and time-consuming. Therefore, this study attempted to find a new, reliable, low-cost, and time-saving method for karst research. The Jinfo Mountain area is a typical carbonate rock area that is suitable for karst research. In this study, many images of rock samples from the Jinfo Mountain were obtained using rock-polarizing microscopes, which provided a good basis for the karst study of Jinfo Mountain. Furthermore, in this study, image analysis technology was used to find the karst development rate of rocks and their porosity. To ensure the accuracy of these research results, we compared the research results obtained using the image analysis techniques with those obtained using TCRM. The comparison showed that the image analysis technology is a feasible research techniques for studying karst in the Jinfo Mountain area. Furthermore, it has good reference significance for other karst study outside the Jinfo Mountain area.
ABSTRACT
The pyruvate dehydrogenase complex regulator (PdhR) was originally identified as a repressor of the pdhR-aceEF-lpd operon, which encodes the pyruvate dehydrogenase complex (PDHc) and PdhR itself. According to previous reports, PdhR plays a regulatory role in the physiological and metabolic pathways of bacteria. At present, the function of PdhR in Plesiomonas shigelloides is still poorly understood. In this study, RNA sequencing (RNA-Seq) of the wild-type strain and the ΔpdhR mutant strains was performed for comparison to identify the PdhR-controlled pathways, revealing that PdhR regulates ~7.38% of the P. shigelloides transcriptome. We found that the deletion of pdhR resulted in the downregulation of practically all polar and lateral flagella genes in P. shigelloides; meanwhile, motility assay and transmission electron microscopy (TEM) confirmed that the ΔpdhR mutant was non-motile and lacked flagella. Moreover, the results of RNA-seq and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) showed that PdhR positively regulated the expression of the T3SS cluster, and the ΔpdhR mutant significantly reduced the ability of P. shigelloides to infect Caco-2 cells compared with the WT. Consistent with previous research, pyruvate-sensing PdhR directly binds to its promoter and inhibits pdhR-aceEF-lpd operon expression. In addition, we identified two additional downstream genes, metR and nuoA, that are directly negatively regulated by PdhR. Furthermore, we also demonstrated that ArcA was identified as being located upstream of pdhR and lpdA and directly negatively regulating their expression. Overall, we revealed the function and regulatory pathway of PdhR, which will allow for a more in-depth investigation into P. shigelloides pathogenicity as well as the complex regulatory network.
Subject(s)
Escherichia coli Proteins , Plesiomonas , Humans , Pyruvate Dehydrogenase Complex/metabolism , Escherichia coli Proteins/metabolism , Plesiomonas/genetics , Escherichia coli/metabolism , Repressor Proteins/genetics , Caco-2 Cells , Gene Expression ProfilingABSTRACT
Vibrio cholerae is an intestinal pathogen that can cause severe diarrheal disease. The disease has afflicted millions of people since the 19th century and has aroused global concern. The Vibrio Pathogenicity Island-2 (VPI-2) is a 57.3 kb region, VC1758-VC1809, which is present in choleragenic V. cholerae. At present, little is known about the function of VC1795 in the VPI-2 of V. cholerae. In this study, the intestinal colonization ability of the ΔVC1795 strain was significantly reduced compared to that of the wild-type strain, and the colonization ability was restored to the wild-type strain after VC1795 gene replacement. This result indicated that the VC1795 gene plays a key role in the intestinal colonization and pathogenicity of V. cholerae. Then, we explored the upstream and downstream regulation mechanisms of the VC1795 gene. Cyclic adenylate receptor protein (CRP) was identified as being located upstream of VC1795 by a DNA pull-down assay and electrophoretic mobility shift assays (EMSAs) and negatively regulating the expression of VC1795. In addition, the results of Chromatin immunoprecipitation followed by sequencing (ChIP-seq), EMSAs, and Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) indicated that VC1795 directly negatively regulates the expression of its downstream gene, VC1794. Furthermore, by using qRT-PCR, we hypothesized that VC1795 indirectly positively regulates the toxin-coregulated pilus (TCP) cluster to influence the colonization ability of V. cholerae in intestinal tracts. In short, our findings support the key regulatory role of VC1795 in bacterial pathogenesis as well as lay the groundwork for the further determination of the complex regulatory network of VC1795 in bacteria.
Subject(s)
Vibrio cholerae , Vibrio , Humans , Vibrio cholerae/genetics , Genomic Islands/genetics , Intestines , Biological AssayABSTRACT
Single-mode tunable quantum cascade lasers (QCLs) are promising for high-resolution and highly sensitive trace gases sensing across the mid-infrared (MIR) region. We report on the development of a tunable single-mode slot waveguide QCL array in the long wavelength part of the MIR regime (>12 µm). This laser array exhibits a tuning range of around 12â cm-1, from 735.3 to 747.3â cm-1. Using this developed single-mode tunable QCL, we demonstrate individual gas sensing, yielding the detection limit of 940 ppb and 470 ppb for acetylene and o-xylene, respectively. To verify the potential of the developed QCL array in multi-species gas detection, laser absorption measurements of two mixed gases of acetylene and o-xylene were conducted, showing the absorption features of the corresponding gases agree well with the theoretical predictions.
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Although the microbial ecology of integrated rice-crayfish farming systems is receiving increasing attention with the expanding application area in China, the effects of rice transplanting patterns on the microbial community of water, sediment and Procambarus clarkii intestine in rice-crayfish system has yet to be determined. This study explored the microbial community present in water, sediment and intestine samples from three transplant patterns (rice crayfish with wide-narrow row transplanting, rice-crayfish with normal transplanting and pond-crayfish, abbreviated as RC-W, RC, and PC, respectively) using high-throughput sequencing. The results showed that the dominant microbial taxa from sediment, surrounding water, and intestine at phylum level were Proteobacteria, Chloroflexi, Cyanobacteria, Actinobacteria, Bacteroidetes. The patterns of rice transplanting had significant effects on microbial biodiversity and species composition in surrounding water. The OTUs community richness of water under RC group was significantly higher than that of PC group and RC-W group. The OTU relative abundance of top 10 operational taxonomic units had significantly different (p < 0.05) in the water samples from the three groups. The intestinal OTU community richness of Procambarus clarkii in the three groups was positively correlated with the community richness of water. The proximity between intestinal and water samples in PCA diagram indicated that their species composition was more similar. The results also showed that rice transplanting patterns can affect intestinal microbial biodiversity of Procambarus clarkii and the intestinal microbial biodiversity correlated with water bodies. Although the intestinal microbial diversity of crayfish in RC-W group was lower than that in RC group, the relative abundance of potential pathogenic bacteria, such as Vibrio, Aeromonas, in intestine of the crayfish in the RC-W group was significantly decreased under rice wide-narrow row transplanting model. Redundancy analysis revealed that environmental parameters, such as pH, DO, nitrate, which regulate the composition of microbial community structures. This study provides an understanding for microbial response to different rice transplanting pattern in rice-crayfish farming system.
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Background: Orientia tsutsugamushi is a zoonotic intracellular pathogen that requires parasitism in eukaryotic cells to reproduce. In recent years, tsutsugamushi disease reported in many places nationwide has crossed the Yangtze River, continuously, spreading to the North China. Now this phenomenon has aroused people's attention. Materials and Methods: In this study, meta-analysis was used to analyze the infection of rodents (vectors) in China, to clarify the transmission rule of O. tsutsugamushi. Results: This study included literature from six databases (PubMed, Web of Science, Science Direct, Wanfang, CNKI, and VIP). A total of 55 articles were included in the study from 610 retrieved articles. The total infection rate of O. tsutsugamushi in rodents was 5.5% (1206/20,620, 95% confidence interval [CI]: 0.0553-0.0617). The prevalence of O. tsutsugamushi in rodents before 2013 (7.73%, 95% CI: 4.11-12.37) was higher than after 2013 (2.11%, 95% CI: 0.64-4.41). O. tsutsugamushi spread among a variety of rodents, among which Rattus losea (13.3%, 95% CI: 4.33-26.26), Rattus tanezumi (5.69%, 95% CI: 1.37-12.72), and Apodemus agrarius (5.32%, 95% CI: 2.26-9.58) infection rate was higher. Kawasaki (8.32%, 95% CI: 1.42-20.17), Karp (7.36%, 95% CI: 2.62-14.22), Kato (2.54%, 95% CI: 0.08-8.28), and Gilliam (2.13%, 95% CI: 0.42-5.09) were the main prevalent genotypes in China. The prevalence of O. tsutsugamushi in rodents was seasonal, increasing gradually in summer (2.39%, 95% CI: 0.46-5.77), peaking in autumn (4.59%, 95% CI: 1.15-10.16), and then declining. The positive rate of immunofluorescence assay (25.07%, 95% CI: 8.44-46.88) was the highest among the detection methods, and it was statistically significant (p < 0.05). Based on the subgroup of geographical factors and climatic factors, the probability of O. tsutsugamushi infection in rodents was the highest when the temperature >19â (8.20%, 95% CI: 1.22-20.52), the altitude <100 millimeters (7.23%, 95% CI: 3.45-12.26), the precipitation >700 millimeters (12.22%, 95% CI: 6.45-19.50), and the humidity 60-70% (7.80%, 95% CI: 4.17-12.44). Conclusions: Studies have shown that rodents carrying O. tsutsugamushi are common. People should prevent and control rodents in life and monitor rodents carrying O. tsutsugamushi for a long time.
Subject(s)
Orientia tsutsugamushi , Scrub Typhus , Trombiculidae , Animals , Humans , Orientia tsutsugamushi/genetics , Prevalence , Scrub Typhus/epidemiology , Scrub Typhus/veterinary , Murinae , China/epidemiologyABSTRACT
BACKGROUND: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease and its pathogenesis is closely related to CD4 + T cells. In recent years, gut microbiota is considered to play an important role in the pathogenesis of MG. Astragaloside IV (AS-IV) is one of the main active components extracted from Astragalus membranaceus and has immunomodulatory effects. To study the immunomodulatory effect of AS-IV and the changes of gut microbiota on experimental autoimmune myasthenia gravis (EAMG) mice, we explore the possible mechanism of AS-IV in improving MG. METHODS: In this study, network pharmacology was utilized to screen the crucial targets of AS-IV in the treatment of MG. Subsequently, a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to identify potential pathways through which AS-IV acts against MG. Furthermore, experimental investigations were conducted to validate the underlying mechanism of AS-IV in MG treatment. Before modeling, 5 mice were randomly selected as the control group (CFA group), and the other 10 were induced to EAMG model. These mice were randomly divided into EAMG group and EAMG + AS-IV group, n = 5/group. In EAMG + AS-IV group, AS-IV was administered by gavage. CFA and EAMG groups were given the same volume of PBS. Body weight, grip strength and clinical symptoms were assessed and recorded weekly. At the last administration, the feces were collected for 16S RNA microbiota analysis. The levels of Treg, Th1 and Th17 cells in spleen and Th1 and Th17 cells in thymus were detected by flow cytometry. The levels of IFN-γ, IL-17 and TGF-ß in serum were measured by ELISA. Furthermore, fecal microbial transplantation (FMT) experiments were performed for exploring the influence of changed intestinal flora on EAMG. After EAMG model was induced, the mice were treated with antibiotics daily for 4 weeks to germ-free. Then germ-free EAMG mice were randomly divided into two groups: FMT EAMG group, FMT AS-IV group, n = 3/group. Fecal extractions from EAMG and EAMG + AS-IV groups as gathered above were used to administered daily to the respective groups for 4 weeks. Body weight, grip strength and clinical symptoms were assessed and recorded weekly. The levels of Treg, Th1 and Th17 cells in spleen and Th1 and Th17 cells in thymus were detected at the last administration. The levels of IFN-γ, IL-17 and TGF-ß in serum were measured by ELISA. RESULTS: The network pharmacology and KEGG pathway analysis revealed that AS-IV regulates T cell pathways, including T cell receptor signaling pathway and Th17 cell differentiation, suggesting its potential in improving MG. Further experimental verification demonstrated that AS-IV administration improved muscle strength and body weight, reduced the level of Th1 and Th17 cells, enhanced the level of Treg cells, and resulted in alterations of the gut microbiota, including changes in beta diversity, the Firmicutes/Bacteroidetes (F/B) ratio, and the abundance of Clostridia in EAMG mice. We further conducted FMT tests and demonstrated that the EAMG Abx-treated mice which were transplanted the feces of mice treated with AS-IV significantly alleviated myasthenia symptoms, reduced Th1 and Th17 cells levels, and increased Treg cell levels. CONCLUSION: This study speculated that AS-IV ameliorates EAMG by regulating CD4 + T cells and altering the structure and species of gut microbiota of EAMG.
ABSTRACT
The synergistic effect of the initial state of the enzyme and pressure level on the denaturation of PPO has not been clear yet, but it significantly affects the application of high hydrostatic pressure (HHP) in the enzyme-containing food processing. Solid (S-) and low/high concentration liquid (LL-/HL-) polyphenol oxidase (PPO) was used as the study object, and the microscopic conformation, molecular morphology and macroscopic activity of PPO under HHP treatments (100-400 MPa, 25 °C/30 min) were investigated by spectroscopic techniques. The results show that the initial state has a significant effect on the activity, structure, active force and substrate channel of PPO under pressure. The effec can be ranked as follows: physical state > concentration > pressure, S-PPO > LL-PPO > HL-PPO. High concentration has a weakening effect on the pressure denaturation of the PPO solution. Under high pressure, the α-helix and concentration factors play a crucial role in stabilizing the structure.