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BACKGROUND: The effects of heat acclimation (HA) on the hypothalamus after exertional heatstroke (EHS) and the specific mechanism have not been fully elucidated, and this study aimed to address these questions. METHODS: In the present study, rats were randomly assigned to the control, EHS, HA, or HA + EHS groups (n = 9). Hematoxylin and eosin (H&E) staining was used to examine pathology. Tandem mass tag (TMT)-based proteomic analysis was utilized to explore the impact of HA on the protein expression profile of the hypothalamus after EHS. Bioinformatics analysis was used to predict the functions of the differentially expressed proteins. The differential proteins were validated by western blotting. An enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines in the serum. RESULTS: The H&E staining (n = 5) results revealed that there were less structural changes in hypothalamus in the HA + EHS group compared with the EHS group. Proteomic analysis (n = 4) revealed that proinflammatory proteins such as argininosuccinate synthetase (ASS1), high mobility group protein B2 (HMGB2) and vimentin were evidently downregulated in the HA + EHS group. The levels of interleukin (IL)-1ß, IL-1, and IL-8 were decreased in the serum samples (n = 3) from HA + EHS rats. CONCLUSIONS: HA may alleviate hypothalamic damage caused by heat attack by inhibiting inflammatory activities, and ASS1, HMGB2 and vimentin could be candidate factors involved in the exact mechanism.
Subject(s)
Heat Stroke , Hypothalamus , Proteomics , Rats, Sprague-Dawley , Animals , Hypothalamus/metabolism , Heat Stroke/metabolism , Rats , Male , Physical Exertion/physiology , Disease Models, AnimalABSTRACT
Purinergic receptor P2Y11, a G protein-coupled receptor that is stimulated by extracellular ATP, has been demonstrated to be related to the chemotaxis of granulocytes, apoptosis of neutrophils, and secretion of cytokines in vitro. P2Y11 mutations were associated with narcolepsy. However, little is known about the roles of P2RY11 in the occurrence of narcolepsy and inflammatory response in vivo. In this study, we generated a zebrafish P2Y11 mutant using CRISPR/Cas9 genome editing and demonstrated that the P2Y11 mutant replicated the narcolepsy-like features including reduced HCRT expression and excessive daytime sleepiness, suggesting that P2Y11 is essential for HCRT expression. Furthermore, we accessed the cytokine expression in the mutant and revealed that the P2RY11 mutation disrupted the systemic inflammatory balance by reducing il4, il10 and tgfb, and increasing il6, tnfa, and il1b. In addition, the P2RY11-deficient larvae with caudal fin injuries exhibited significantly slower migration and less recruitment of neutrophils and macrophages at damaged site, and lower expression of anti-inflammatory cytokines during tissue damage. All these findings highlight the vital roles of P2RY11 in maintaining HCRT production and secreting anti-inflammatory cytokines in the native environment, and suggested that P2RY11-deficient zebrafish can serve as a reliable and unique model to further explore narcolepsy and inflammatory-related diseases with impaired neutrophil and macrophage responses.
Subject(s)
Cytokines , Inflammation , Macrophages , Neutrophils , Zebrafish Proteins , Zebrafish , Animals , Neutrophils/metabolism , Neutrophils/immunology , Macrophages/metabolism , Inflammation/metabolism , Inflammation/pathology , Inflammation/genetics , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , Cytokines/metabolism , Mutation/genetics , Receptors, Purinergic P2/genetics , Receptors, Purinergic P2/metabolism , Receptors, Purinergic P2/deficiencyABSTRACT
OBJECTIVES: To investigate the optimal timing for initiating antiviral therapy in hepatitis B virus (HBV) carriers with low-level viremia (LLV). METHODS: We retrospectively enrolled 126 HBV carriers with LLV who underwent liver biopsy. Patients' clinical data, routine blood test results, portal vein diameter, splenic vein diameter and thickness, and measurements (LSM) within 1 week before liver biopsy were obtained. Single-factor and multifactor statistical methods were used to analyze factors that affected inflammation and fibrosis in pathological liver tissues. The receiver operating characteristic curve was used to analyze liver stiffness and HBV DNA levels to determine liver tissue inflammation and fibrosis. R -Studio software was used to draw nomograms, calibration plots, and model decision curves. RESULTS: Infection duration and HBV DNA levels affected liver tissue inflammation. Albumin(ALB), aspartate aminotransferase (AST), HBV DNA, liver stiffness, age, and splenic thickness affected liver fibrosis. The best cutoff value of the LSM for diagnosing liver inflammation and fibrosis was 7.45 (specificity, 92%). The best cutoff value of HBV DNA for diagnosing liver inflammation and fibrosis was 39.5 (specificity, 96%). HBV DNA,and splenic thickness affected the treatment decision in naive chronic hepatitis Bpatients with LLV CONCLUSIONS: HBV carriers with LLV have high incidences of liver tissue inflammation and fibrosis. The infection duration and HBV DNA levels affected liver inflammation whereas the ALB, AST levels, HBV DNA, LSM, age, and splenic thickness affected liver fibrosis. Eligible expansion of antiviral treatment indications is necessary, however, a universal treatment approach may be inefficient. HBV DNA can be a reference for initiating antiviral therapy.
Subject(s)
Carrier State , Hepatitis B, Chronic , Liver , Viremia , Humans , Male , Female , Retrospective Studies , Adult , Liver/pathology , Middle Aged , Hepatitis B, Chronic/pathology , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/virology , DNA, Viral/analysis , Liver Cirrhosis/virology , Liver Cirrhosis/pathology , Hepatitis B virus/genetics , Hepatitis B virus/isolation & purification , Antiviral Agents/therapeutic useABSTRACT
BACKGROUND: Percutaneous endoscopic transforaminal discectomy (PETD) is an effective method for treating lumbar disc herniation, and is typically performed under local anesthesia. However, inadequate analgesia during the procedure remains a concern, prompting the search for a medication that can provide optimal pain control with minimal impact on the respiratory and circulatory systems. OBJECTIVES: The aim of this study was to observe the effects of different doses of esketamine combined with dexmedetomidine on reducing visual analog scale (VAS) scores during surgical interventions. METHODS: One hundred two patients who underwent PETD were randomly divided into a control group (group C: normal saline + dexmedetomidine), an E1 group (0.1 mg kg-1 esketamine + dexmedetomidine), and an E2 group (0.2 mg kg-1 esketamine + dexmedetomidine). The primary outcome was the maximum visual analogue scale (VAS) (score: 0 = no pain and 10 = worst pain) at six time points. The secondary outcomes included the Assessment of Alertness/Sedation Scale (OAA/S) score and mean arterial pressure (BP), heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO2) at 11 time points. The incidence of adverse reactions during and 24 h after the operation and patient satisfaction with the anesthesia were also recorded. RESULTS: Compared with those in group C, the VAS scores of patients in groups E1 and E2 were lower at T6, T7, and T9 (P < 0.05). From T4 to T10, the OAA/S scores of the E1 and E2 groups were both lower than those of group C (P < 0.05), and at the T4-T6 time points, the OAA/S score of the E2 group was lower than that of group E1 (P < 0.05). At T4 and T5, the HR and BP of patients in groups E1 and E2 were greater than those in group C (P < 0.05). Compared with those in group C, the incidences of intraoperative illusion, floating sensation, postoperative dizziness, and hyperalgesia in groups E1 and E2 were significantly greater (P < 0.01). There was no significant difference in patient RR, SpO2, or postoperative satisfaction with anesthesia among the three groups (P > 0.05). CONCLUSION: The combination of esketamine and dexmedetomidine can reduce VAS scores during certain stages of this type of surgery; it has minimal impact on respiration and circulation. However, this approach is associated with increased incidences of postoperative dizziness and psychiatric side effects, which may also affect patients' compliance with surgical instructions from medical staff. Patient satisfaction was not greater with dexmedetomidine combined with esketamine than with dexmedetomidine alone. TRIAL REGISTRATION: http://www.chictr.org.cn . Identifier: ChiCTR2300068206. Date of registration: 10 February 2023.
Subject(s)
Dexmedetomidine , Diskectomy, Percutaneous , Intervertebral Disc Displacement , Ketamine , Humans , Dexmedetomidine/administration & dosage , Female , Male , Double-Blind Method , Ketamine/administration & dosage , Adult , Middle Aged , Intervertebral Disc Displacement/surgery , Diskectomy, Percutaneous/methods , Analgesics/administration & dosage , Drug Therapy, Combination , Pain Measurement , Dose-Response Relationship, Drug , Endoscopy/methods , Pain, Postoperative/drug therapy , Treatment Outcome , Lumbar Vertebrae/surgeryABSTRACT
Exceptional points (EPs) have recently emerged as a new method for engineering the response of open physical systems, that is, systems that interact with the environment. The systems at the EPs exhibit a strong response to a small perturbation. Here, we show a method by which the sensitivity of silicon resonant sensors can be enhanced when operated at EPs. In our experiments, we use a pair of mechanically coupled silicon micromechanical resonators constituting a parity-time (PT)-symmetric dimer. Small perturbations introduced on the mechanically coupled spring cause the frequency to split from the EPs into the PT-symmetric regime without broadening the two spectrum linewidths, and this frequency splitting scales with the square root of the perturbation strength. The overall signal-to-noise ratio is still greatly enhanced, although the measured noise spectral density of the EP sensing scheme has a slight increase comparable to the traditional counterpart. Our results pave the way for resonant sensors with ultrahigh sensitivity.
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Ketamine is a racemic mixture of equal amounts of R-ketamine and S-ketamine and is well known to anesthesiologists for its unique dissociative anesthetic properties. The pharmacological properties of ketamine, namely, its sympathetic excitation, mild respiratory depression, and potent analgesia, are still highly valued in its use as an anesthetic for some patients. In particular, since its advent, S-ketamine has been widely used as an anesthetic in many countries due to its increased affinity for NMDA receptors and its enhanced anesthetic and analgesic effects. However, the anesthetic and analgesic mechanisms of S-ketamine are not fully understood. In addition to antagonizing NMDA receptors, a variety of other receptors or channels may be involved, but there are no relevant mechanistic summaries in the literature. Therefore, the purpose of this paper is to review the mechanisms of action of S-ketamine on relevant receptors and systems in the body that result in its pharmacological properties, such as anesthesia and analgesia, with the aim of providing a reference for its clinical applications and research.
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BACKGROUND: Cryptosporidium is a gastrointestinal protozoan that widely exists in nature, it is an established zoonotic pathogen. Infected cattle are considered to be associated with cryptosporidiosis outbreaks in humans. In the present study, we aimed to assess the prevalence and species distribution of Cryptosporidium in dairy cattle in Central Inner Mongolia. METHODS: We focused on the small subunit ribosomal RNA gene (SSU rRNA) of Cryptosporidium and 60-kDa glycoprotein gene (gp60) of Cryptosporidium parvum. We collected 505 dairy cattle manure samples from 6 sampling sites in Inner Mongolia in 2021; the samples were divided into 4 groups based on age. DNA extraction, polymerase chain reaction (PCR), sequence analysis, and restriction fragment length polymorphism (RFLP) using SspI and MboII restriction endonucleases were performed. RFLP analysis was performed to determine the prevalence and species distribution of Cryptosporidium. RESULTS: SSU rRNA PCR revealed that the overall prevalence of Cryptosporidium infection was 29.90% (151/505), with a prevalence of 37.67% (55/146) and 26.74% (96/359) in diarrheal and nondiarrheal samples, respectively; these differences were significant. The overall prevalence of Cryptosporidium infection at the 6 sampling sites ranged from 0 to 47.06% and that among the 4 age groups ranged from 18.50 to 43.81%. SSU rRNA sequence analysis and RFLP analysis revealed the presence of 4 Cryptosporidium species, namely, C. bovis (44.37%), C. andersoni (35.10%), C. ryanae (21.85%), and C. parvum (11.92%), along with a mixed infection involving two or three Cryptosporidium species. Cryptosporidium bovis or C. andersoni was the most common cause of infection in the four age groups. The subtype of C. parvum was successfully identified as IIdA via gp60 analysis; all isolates were identified as the subtype IIdA19G1. CONCLUSIONS: To the best of our knowledge, this is the first report of dairy cattle infected with four Cryptosporidium species in Inner Mongolia, China, along with a mixed infection involving two or three Cryptosporidium species, with C. bovis and C. andersoni as the dominant species. Moreover, this is the first study to identify C. parvum subtype IIdA19G1 in cattle in Inner Mongolia. Our study findings provide detailed information on molecular epidemiological investigation of bovine cryptosporidiosis in Inner Mongolia, suggesting that dairy cattle in this region are at risk of transmitting cryptosporidiosis to humans.
Subject(s)
Cattle Diseases , Coinfection , Cryptosporidiosis , Cryptosporidium , Humans , Animals , Cattle , Cryptosporidium/genetics , Cryptosporidiosis/epidemiology , Coinfection/veterinary , Prevalence , China/epidemiology , RNA, Ribosomal , Cattle Diseases/epidemiologyABSTRACT
Giardia duodenalis is a gastrointestinal protozoan ubiquitous in nature. It is a confirmed zoonotic pathogen, and cattle are considered a source of giardiasis outbreaks in humans. This study aimed to evaluate the prevalence and multilocus genotype (MLG) of G. duodenalis in dairy cattle in Central Inner Mongolia. This study was based on the small subunit ribosomal RNA (SSU rRNA), glutamate dehydrogenase (gdh), triosephosphate isomerase (tpi), and beta-giardin (bg) genes of G. duodenalis. DNA extraction, polymerase chain reaction (PCR), and sequence analysis were performed on 505 dairy cattle fecal samples collected in 2021 from six sampling sites and four age groups in Central Inner Mongolia to determine the prevalence and MLG distribution of G. duodenalis. The PCR results of SSU rRNA revealed that the overall prevalence of G. duodenalis was 29.5% (149/505) and that the overall prevalence of the diarrhea and nondiarrhea samples was 31.5% (46/146) and 28.5% (103/359), respectively; the difference was not significant (p > 0.05). SSU rRNA sequence analysis revealed that G. duodenalis assemblage E (91.1%, 133/146) was primarily detected and that assemblage A (8.9%, 13/146) was detected in 13 samples. The G. duodenalis-positive samples were PCR amplified and sequenced for gdh, tpi, and bg, from which 38, 47, and 70 amplified sequences were obtained, respectively. A combination of G. duodenalis assemblages A and E were detected in seven samples. Multilocus genotyping yielded 25 different assemblage E MLGs, which formed six subgroups. To the best of our knowledge, this is the first report regarding G. duodenalis infection in dairy cattle in Inner Mongolia, China. This study revealed that Inner Mongolian cattle pose a risk of giardiasis transmission to humans and that the distribution of local cattle G. duodenalis assemblage E MLGs is diverse. The findings of this study can bridge the knowledge gap in the molecular epidemiological investigation of giardiasis in Central Inner Mongolia.
Subject(s)
Giardia lamblia , Giardiasis , Animals , Cattle , China/epidemiology , Giardia lamblia/genetics , Giardiasis/epidemiology , Giardiasis/veterinary , Glutamate Dehydrogenase/genetics , Prevalence , Protozoan Proteins/genetics , RNA, Ribosomal/genetics , Triose-Phosphate Isomerase/geneticsABSTRACT
BACKGROUND: Exertional heatstroke (EHS) is an emergency with a high mortality rate, characterized by central nervous system dysfunctions. This study aims to establish a Heat acclimation/acclimatization (HA) rat model in locomotion to recapitulate the physical state of human in severe environment of high temperature and humidity, and investigate the mechanism of organism protection in HA. (2) Methods: Wistar rats were exposed to 36 °C and ran 2 h/d for 21 days, acquired thermal tolerance test was conducted to assess the thermotolerance and exercise ability. Core temperature and consumption of water and food were observed. Expression of HSP70 and HSP90 of different tissues were determined by WB. Pathological structure of brain tissue was detected with HE staining. Proteomics was used to identify the differently expressed proteins in cerebral cortex of different groups. And key molecules were identified by RT-PCR and WB. (3) Results: HA rats displayed stronger thermotolerance and exercised ability on acquired thermal tolerance test. Brain water content of HA + EHS group reduced compared with EHS group. HE staining revealed slighter brain injuries of HA + EHS group than that of EHS. Proteomics focused on cell death-related pathways and key molecules Aquaporin 4 (AQP4) related to cell edema. Identification results showed HA increased AQP4, Bcl-xl, ratio of p-Akt/AKT and Bcl-xl/Bax, down-regulated Cleaved Caspase-3. (4) Conclusions: This HA model can ameliorate brain injury of EHS by reducing cerebral edema and cell apoptosis, offering experimental evidence for EHS prophylaxis.
Subject(s)
Brain Injuries , Heat Stroke , Humans , Rats , Animals , Proto-Oncogene Proteins c-akt , Rats, Wistar , Heat-Shock Response , Acclimatization/physiology , Exercise/physiologyABSTRACT
Objective: Aeromonas caviae (A. caviae) is one of the major etiological agents in human intestinal infections reported to be associated with a broad spectrum of extra-intestinal infections with increasing incidence over recent years. Although previous studies have established its significance as a causative agent of both bloodstream and gastrointestinal infections, the characteristics of A. caviae that cause extra-intestinal infections remain unilluminated.In this single-center retrospective study, we investigated epidemiological characteristics, antimicrobial resistance genes and phenotypes, virulence genes, and phyloevolution of 47 clinical A. caviae isolated from patients with extra-intestinal infections from 2017 to 2020. Methods: A. caviae strains were identified by biochemical tests and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF/MS), ultimately confirmed to species level by whole-genome sequencing (WGS). Antimicrobial resistance and virulence genes were identified using the Comprehensive Antibiotic Resistance Database (CARD) and the virulence factor database (VFDB), respectively. Phylogenetic analysis of 47 clinical strains was performed by combining with 521 A. caviae strains from NCBI database. Results: A. caviae was an opportunistic pathogen in immunocompromised patients, especially those with underlying hepatobiliary diseases and malignancies. 19 out of 47 isolates were identified as multidrug resistance (MDR) strains. Piperacillin-tazobactam, levofloxacin, gentamicin, amikacin with a resistance rate of less than 10% remained as options to treat extra-intestinal infections. 24 out of 47 isolates exhibited non-susceptibility to cephalosporins and cephamycins, all of which carried ß-lactamase gene, including bla MOX, bla PER-3, bla OXA, bla NDM, and bla CphA. Most stains (98%, 46/47) carried at least one of the virulence genes, but extra-intestinal infections had a low mortality rate. Phylogenetic analysis indicated the risk of nosocomial transmission but revealed no outbreak. However, the emergence of MDR and ß-lactamase resistance genes in extra-intestinal isolates of A. caviae is becoming an increasing risk to public health and requires attention. Conclusions: This study strengthen our understanding of A.caviae isolated from extra-intestinal infections. It may contribute to the management of extra-intestinal infections as well as the prevention and control of drug resistance.
Subject(s)
Aeromonas caviae , Aeromonas , Anti-Infective Agents , Humans , Virulence/genetics , Anti-Bacterial Agents/pharmacology , Phylogeny , Retrospective Studies , Drug Resistance, Bacterial/genetics , Microbial Sensitivity Tests , beta-Lactamases/geneticsABSTRACT
@#Abstract: Objective To investigate the epidemiological characteristics of pathogens causing bloodstream infection in hematology patients during treatment and to compare the effects of allogeneic hematopoietic stem cell transplantation (HSCT) on them, so as to provide evidence for the diagnosis and treatment of bloodstream infection. Methods A total of 292 cases with bloodstream infection in hematology wards of the PLA General Hospital were collected from 2017 to 2021, which were divided into HSCT group and N-HSCT group according to whether performed HSCT or not. The epidemiological characteristics and influence of pathogenic bacteria in blood stream infection were analyzed and compared between the two groups. Results A total of 362 strains of pathogenic bacteria were collected from 292 cases, including 106 strains in HSCT group (84 cases) and 256 strains in N-HSCT group (208 cases). Bloodstream infections were more common in acute myeloid leukemia (130/392, 44.52%), followed by non-Hodgkin's lymphoma (74/292, 25.34%). The rate of once bloodstream infection in HSCT group was higher than that in N-HSCT Group, but the rate of twice bloodstream infections in N-HSCT group was higher. Gram-negative Bacilli were the most common pathogens (56.08%), with Escherichia coli being absolutely dominant (109/362, 30.11%), followed by Klebsiella pneumoniae (39/362, 10.77%). Coagulase-negative staphylococci (CoNS) (107/362, 29.56%) were the most common Gram-positive cocci. The detection rate of fungi in HSCT group (10/106, 9.43%) was significantly higher than that in N-HSCT Group (3.52%). The drug resistance rate of the common pathogenic bacteria was at a high level, and there was a certain proportion of multi-drug resistant strains (except for Pseudomonas aeruginosa). The resistance rates of CoNS to penicillin, gentamicin, moxifloxacin, clindamycin and rifampicin in HSCT group were higher than those in N-HSCT Group. The resistance rate of Escherichia coli to piperacillin/tazobactam, cephalosporins and etapenem in HSCT group was significantly higher than that in N-HSCT group. Conclusions The pathogens of blood stream infection in hematology patients are complicated and various. It is difficult for clinical diagnosis and treatment to detect multiple infections and multiple pathogens. HSCT patients have a higher risk of fungal bloodstream infection and more multi-drug resistant strains detected. Therefore, the identification of bloodstream infection and multi-drug resistant strains associated with HSCT patients should prompt surveillance.
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Objective: This study aimed to evaluate the effect of perioperative transcutaneous electrical acupoint stimulation (TEAS) on postoperative cognitive dysfunction (POCD) in older patients with lumbar spine surgery. Methods: Older patients (aged 60-80 years old) receiving lumbar spine surgery under general anesthesia were randomly divided into group A, 3-day intervention group; group B, 7-day intervention group; control group C, sham TEAS group, selected "Baihui" (GV 20) and "Dazhui" (GV 14) point was intervened once 30 min before operation with "HANS" transcutaneous electrical stimulation device, and then once a day after operation for 30 min each time. The primary outcome was the incidence of postoperative cognitive impairment assessed by the use of the Mini Mental Rating Scale (MMSE), patients developed POCD according to the Z score method. The secondary outcome was serum interleukin-6 (IL-6), tumor Necrosis factor α (TNF-α), neuron-specific enolase (NSE), and S100ß protein levels. Results: Three days after surgery, the incidence of POCD in groups A((22.4%)) and B ((18.3%)) were lower than those in group C ((42.9%)) (P < 0.05). There was no significant difference between groups A and B (P > 0.05). Seven days after surgery, the incidence of POCD in group B (18.3%) was lower than that in groups A (26.5%) and B (42.9%), and the comparison between groups B and C was statistically significant (P < 0.05). On the 3rd and 7th days after surgery, the levels of IL-6, TNF-α, NSE, and S100ß in the two TEAS groups were lower than those in the sham TEAS group (P < 0.01), but higher than the preoperative levels in the three groups (P < 0.01). Conclusion: It seems that Perioperative TEAS intervention could reduce the level of inflammatory factors IL-6, TNF-α in the blood of older patients with lumbar spine surgery, and reduce the incidence of POCD. Clinical trial registration: www.chictr.org.cn, identifier ChiCTR2200063030.
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Ticks were identified as arthropods that are pathogenic vectors. Dermacentor nuttalli is one of the dominant tick species in Inner Mongolia, and it carries and transmits a wide range of pathogenic microorganisms. However, at present, only the detection of D. nuttalli adult ticks and D. nuttalli different developmental stages carrying one specific pathogen, or the next-generation sequencing of D. nuttalli adult ticks were available. In this study, we investigated the microbial community structures of D. nuttalli in different growth stages under laboratory artificial feeding conditions. Total DNA was extracted from seven growth stages (female adult ticks, eggs, larval ticks, engorged larval ticks, nymphal ticks, engorged nymphal ticks, and second-generation adult ticks) obtained from laboratory artificial feeding of engorged D. nuttalli female ticks in Inner Mongolia. Then, the 16S rDNA V3-V4 hypervariable region was amplified to construct an Illumina PE250 library. Finally, 16S rRNA sequencing was performed on Illumina Novaseq 6000 platform. The sequencing data were analyzed using molecular biology software and platforms. The Illumina PE250 sequencing results showed that the egg stage had the highest diversity and number of species (28.74%, 98/341), while the engorged nymph stage had the lowest diversity and number of species (9.72%, 21/216). A total of 387 genera of 22 phyla were annotated in D. nuttalli, with 9 phyla and 57 genera found throughout all 7 growth stages. The dominant phylum was Proteobacteria; the dominant genera were Arsenophonus and Rickettsia; and the genera with the highest relative abundance in the 7 growth stages were Pseudomonas, Paenalcaligenes, Arsenophonus, Arsenophonus, Pseudomonas, Arsenophonus, and Rickettsia, respectively. Among the 23 exact species annotated, Brucella melitensis exhibits pathogeny that poses a serious threat to humans and animals. In this study, the microbial community composition at different growth stages of D. nuttalli was comprehensively analyzed for the first time.
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OBJECTIVE: The relationship of a diet low in fibre with mortality has not been evaluated. This study aims to assess the burden of non-communicable chronic diseases (NCD) attributable to a diet low in fibre globally from 1990 to 2019. DESIGN: All data were from the Global Burden of Disease (GBD) Study 2019, in which the mortality, disability-adjusted life-years (DALY) and years lived with disability (YLD) were estimated with Bayesian geospatial regression using data at global, regional and country level acquired from an extensively systematic review. SETTING: All data sourced from the GBD Study 2019. PARTICIPANTS: All age groups for both sexes. RESULTS: The age-standardised mortality rates (ASMR) declined in most GBD regions; however, in Southern sub-Saharan Africa, the ASMR increased from 4·07 (95 % uncertainty interval (UI) (2·08, 6·34)) to 4·60 (95 % UI (2·59, 6·90)), and in Central sub-Saharan Africa, the ASMR increased from 7·46 (95 % UI (3·64, 11·90)) to 9·34 (95 % UI (4·69, 15·25)). Uptrends were observed in the age-standardised YLD rates attributable to a diet low in fibre in a number of GBD regions. The burden caused by diabetes mellitus increased in Central Asia, Southern sub-Saharan Africa and Eastern Europe. CONCLUSIONS: The burdens of disease attributable to a diet low in fibre in Southern sub-Saharan Africa and Central sub-Saharan Africa and the age-standardised YLD rates in a number of GBD regions increased from 1990 to 2019. Therefore, greater efforts are needed to reduce the disease burden caused by a diet low in fibre.
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Melophagus ovinus (sheep ked) is one of the common ectoparasites in sheep. In addition to causing direct damage to the host through biting and sucking blood, sheep ked is a potential vector of helminths, protozoa, bacteria, and viruses. Sheep M. ovinus samples from three regions in Tibet were selected for DNA extraction. The 16S rDNA V3-V4 hypervariable region was amplified, after genomic DNA fragmentation, Illumina Hiseq libraries were constructed. The 16S rRNA sequencing and viral metagenomics sequencing were separately conducted on the Illumina Novaseq 6000 platform and molecular biology software and platforms were employed to analyze the sequencing data. Illumina PE250 sequencing results demonstrated that the dominant bacteria phylum in M. ovinus from Tibet, China was Proteobacteria, where 29 bacteria genera were annotated. The dominant bacterial genera were Bartonella, Wolbachia, and Arsenophonus; Bartonella chomelii, Wolbachia spp., and Arsenophonus spp. were the dominant bacterial species in M. ovinus from Tibet, China. We also detected Kluyvera intermedia, Corynebacterium maris DSM 45190, Planomicrobium okeanokoites, and Rhodococcus erythropolis, of which the relative abundance of Kluyvera intermedia was high. Illumina Hiseq sequencing results demonstrated that 4 virus orders were detected in M. ovinus from Tibet, China, and 3 samples were annotated into 29 families, 30 families, and 28 families of viruses, respectively. Virus families related to vertebrates and insects mainly included Mimiviridae, Marseilleviridae, Poxviridae, Ascoviridae, Iridoviridae, Baculoviridae, Hytrosaviridae, Nudiviridae, Polydnaviridae, Adomaviridae, Asfarviridae, Hepeviridae, Herpesviridae, and Retroviridae; at the species level, the relative abundance of Tupanvirus_soda_lake, Klosneuvirus_KNV1, and Indivirus_ILV1 was higher. African swine fever virus and many poxviruses from the family Poxviridae were detected, albeit their relative abundance was low. The dominant bacterial phylum of M. ovinus from Tibet, China was Proteobacteria, and the dominant bacterial genera were Bartonella, Wolbachia, and Arsenophonus, where 23 out of 29 annotated bacteria genera were first reported in M. ovinus. Kluyvera intermedia, Corynebacterium maris DSM 45190, Planomicrobium okeanokoites, and Rhodococcus erythropolis were detected for the first time. All DNA viruses detected in this study have been reported in M. ovinus for the first time.
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Gastric cancer (GC) is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide. Cancer-associated fibroblasts (CAFs), an important cell type in the tumor microenvironment, play an important role in GC development. In this review, we describe the current knowledge of CAFs' heterogeneity and their role in GC invasion and metastasis. Currently, CAF-targeted cancer therapies are being rapidly explored and developed. However, the heterogeneity of CAFs limits the application of this therapy, so it is urgent to find specific markers and divide them into different subpopulations. With the development of single-cell RNA sequencing technology, researchers have used this technology to classify CAFs in many tumors, but whether it is applicable to GC and other tumors needs further study. And we believe that this technology will be in the near future utilized to sort CAFs on the basis of different cell markers and functions, so as to target tumor-promoting CAFs and inhibit tumor progression. Targeting CAFs by cell surface markers or normalizing the activated CAFs subsets may be an effective therapy, alone or in combination with other therapeutic approaches for GC treatment. Therefore, in the coming decades, the interaction between CAFs and GC cells will be still the focus of our research.
Subject(s)
Cancer-Associated Fibroblasts , Stomach Neoplasms , Humans , Cancer-Associated Fibroblasts/pathology , Stomach Neoplasms/genetics , Cell Movement/genetics , Tumor Microenvironment , Fibroblasts/metabolismABSTRACT
Human adenovirus (HAdV) infection causes excessive inflammation associated with severe tissue injury, such as pneumonia. The molecules involved in the underlying inflammatory mechanisms remain to be elucidated. Receptor for advanced glycation end product (RAGE) is mainly expressed on immune cells and lung tissues, and it is a key factor in the initiation and development of inflammation. RAGE can be cleaved by metalloprotease 9 (MMP9) to release the extracellular segment, which is named soluble RAGE (sRAGE), into the intercellular space, where it can bind to RAGE ligands and block RAGE activation and subsequent inflammation. In our study, we enrolled HAdV-infected patients and their contacts to examine the relationship between sRAGE and inflammation induced by HAdV infection. The results showed that HAdV infection stimulated inflammatory cytokine secretion, increased such as high mobility group box 1 (HMGB1) levels, and suppressed sRAGE expression. sRAGE levels were significantly different between patients with or without pneumonia. We also found that MMP9 was significantly lower in patients with pneumonia, and it was positively correlated with sRAGE levels over 7 days after disease onset. The mitogen-activated protein kinase (MAPK) pathway is an important immune activation signaling pathway that is regulated by RAGE. We observed the activation of the MAPK pathway in the peripheral blood mononuclear cells (PBMCs) of patients. Negative correlations between sRAGE and phosphorylated JNK and p38 were observed. These results suggest that sRAGE is involved in HAdV-induced inflammatory responses, and might be a potential therapeutic target to alleviate the HAdV-induced excessive inflammation.
ABSTRACT
Objective: The clinical manifestations and treatment of three patients with hemodynamically unstable lupus myocarditis (LM) were analyzed. Methods: The clinical data of three patients with LM with hemodynamic instability, who were admitted to the emergency ICU of the south hospital of the Renji Hospital, School of Medicine, Shanghai Jiao Tong University of Medicine from January 2018 to December 2021, were collected and analyzed, and relevant literatures were reviewed. Results: Two of the three patients had the first onset of systemic lupus erythematosus. The other patient had mixed connective tissue disease in the past, and lupus was the main manifestation of this disease. At the onset of the disease, all patients had chest tightness and shortness of breath; two patients had a fever, and the markers of myocardial injury increased. Cardiac color Doppler ultrasound indicated that left ventricular ejection fraction decreased significantly. Cardiac insufficiency with cardiogenic shock rapidly appeared as the main manifestation. Two patients immediately started veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and ECMO was also started in one patient after a pacemaker placement was ineffective. For all three patients, high-dose hormones were given to control the primary disease, and then the ECMO machines were removed successfully. Conclusion: VA-ECMO treatment should be implemented in patients with hemodynamically unstable LM as soon as possible to maintain the patient's hemodynamics and help them overcome the crisis of cardiac dysfunction, allowing more time for primary disease treatment.
ABSTRACT
The vital roles of R2R3-MYB transcription factors (TFs) in regulating stress response and phytohormone signaling have been thoroughly studied in numerous plant species, but the functions of these TFs in rubber tree are poorly understood. Rubber tree is the most important source of natural rubber but often suffers from various abiotic and biotic stresses that cause severe yield losses each year. In this study, we reported a novel MYB44 gene in rubber tree (named HbMYB44) and revealed its biological function. HbMYB44 was highly similar to AtMYB44 and clustered into subgroup 22. Transient expression indicated that HbMYB44 is a nuclear localized protein and displays transactivation activity at the C-terminus. HbMYB44 was ubiquitously expressed in rubber tree, and its expression was strongly induced by multiple phytohormones, drought stress, wounding, and H2O2 treatments. Furthermore, overexpression of HbMYB44 in Arabidopsis (OE) demonstrated that OE plants significantly enhanced stress tolerance, i.e., salt stress, osmotic stress, and drought stress. Additionally, HbMYB44 promoted recovery from root growth inhibition of OE plants caused by exogenous phytohormones (including abscisic acid, methyl jasmonic acid, gibberellic acid 3, and salicylic acid), but the opposite effect was present in response to ethephon. Interestingly, HbMYB44 increased the expression of its homologous genes and interacting protein-encoding genes in OE plants. Overall, HbMYB44 plays versatile functions in modulating multiple phytohormone signaling pathways and stress tolerance.
ABSTRACT
Brassinolide (BR) plays an important role in plant growth, development, and the adaptation adversity process. Moreover, BRI1-EMS-SUPPRESSOR 1 (BES1) genes are crucial transcription factors (TFs) in the BR signaling pathway. To realize the function of HbBES1 family is helpful to improve genetic resources for rubber tree breeding. Based on the rubber tree database, we used bioinformatics to characterize physicochemical properties, gene structure, cis-elements, and expression patterns. These results indicated that there were nine BES1 members in rubber tree, which we named HbBES1-1 to HbBES1-9 and divided into two groups (I and II) based on their genetic relationships. HbBES1 genes in the same group shared similar gene structures and motifs. Cis-acting element analysis showed that the promoter sequences of HbBES1 genes contained many regulator elements that were related to hormone and stress, indicating that HbBES1 genes might be involved in the regulation of hormone and stress signal pathways. Our analysis of tissue specificity revealed that all of the nine HbBES1 members expressed highly in branches. Gene expression profiles under different hormone treatments showed that the HbBES1 gene family was induced to varying degrees under different hormones, HbBES1-3 and HbBES1-9 were extremely induced by ethylene (ETH). These results lay the foundation for further exploration of the molecular mechanism of the BES1 gene family, especially HbBES1-3 and HbBES1-9, regulating plant stress tolerance in rubber tree.