Dear Editor,The COVID-19 pandemic,caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has resulted in millions of deaths worldwide.It poses significant challenges in the management of immunocompr...Dear Editor,The COVID-19 pandemic,caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has resulted in millions of deaths worldwide.It poses significant challenges in the management of immunocompromised patients,particularly people with HIV(PWH).Whether PWH are more vulnerable to COVID with more adverse outcomes has been extensively studied,but the findings are inconsistent.Many cohort studies and meta-analyses support that PWH have a higher risk of SARSCoV-2 infection and more severe COVID-19 outcomes(Bertagnolio et al.,2022;Ssentongo et al.,2021).展开更多
People′s environmental tropism has an effect on their understanding of tourism-nature relationship,and also influences their attitudes to natural resources utilization and environmental protection.Taking Jiuzhaigou N...People′s environmental tropism has an effect on their understanding of tourism-nature relationship,and also influences their attitudes to natural resources utilization and environmental protection.Taking Jiuzhaigou National Park of China as a study case,the authors conducted some quantitative analyses with the tools of SPSS 16.0 and LISREL 8.7,to explore the influence of tourists′ environmental tropism on their attitudes to tourism and nature conservation in the natural tourist destination.Three hypotheses and the theoretic model of influences of tourists′ environmental tropism on their attitudes to tourism and nature conservation have been tested and accepted based on the Structural Equation Model analysis on survey data collected in Jiuzhaigou National Park of China.Some conclusions were drawn as follows: 1) tourists′ human-prioritized concept influences their cognition to tourism-nature relationship.This concept has a positive influence on their supportive attitudes to tourism,but a negative influence on their attitudes to nature conservation;2) tourists′ human-nature coordination concept has a positive influence on their supportive attitudes to both tourism and nature conservation,especially to the latter.This paper generally proves that human′s environmental tropism does have an influence on their attitudes to tourism and nature conservation in natural tourist destinations.展开更多
The cross-species infection of coronaviruses has resulted in several major epidemics since 2003.Porcine epidemic diarrhea virus(PEDV)is a devastating swine enteric coronavirus,which targets pigs as the only natural re...The cross-species infection of coronaviruses has resulted in several major epidemics since 2003.Porcine epidemic diarrhea virus(PEDV)is a devastating swine enteric coronavirus,which targets pigs as the only natural reservoir.In this study,the nucleic acid of PEDV was detected in rat fecal samples collected from pig farms.Further animal tests showed that PEDV can cause systemic infections in neonatal mice and rats via intracranial inoculation.The brain,lung,intestine and spleen were all targets for PEDV in rodents in contrast to the intestine being targeted in pigs.Morbidity and mortality vary via different infection routes.PEDV was also detectable in feces after infection,suggesting that the infected rodents were potential infectious sources.Moreover,the cerebral tropism of PEDV was verified in piglets via orally inoculation,which had not been identified before.In conclusion,our findings demonstrate that PEDV could cross the species barrier to infect mice and rats through different routes in experimental settings.Although it is highly devastating to piglets,PEDV changes the target organs and turns to be milder when meeting with new hosts.Based on these findings,more attention should be paid to the potential cross-species infection of PEDV.展开更多
AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in vario...AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.展开更多
HIV-1 co-receptor tropism is central for understanding the transmission and pathogenesis of HIV-1 infection. We performed a genome-wide comparison between the adaptive evolution of R5 and X4 variants from HIV-1 subtyp...HIV-1 co-receptor tropism is central for understanding the transmission and pathogenesis of HIV-1 infection. We performed a genome-wide comparison between the adaptive evolution of R5 and X4 variants from HIV-1 subtypes B and C. The results showed that R5 and X4 variants experienced differential evolutionary patterns and different HIV-1 genes encountered various positive selection pressures, suggesting that complex selection pressures are driving HIV-1 evolution. Compared with other hypervariable regions of Gp120, significantly more positively selected sites were detected in the V3 region of subtype B X4 variants, V2 region of subtype B R5 variants, and V1 and V4 regions of subtype C X4 variants, indicating an association of positive selection with co-receptor recognition/binding. Intriguingly, a significantly higher proportion (33.3% and 55.6%, P【0.05) of positively selected sites were identified in the C3 region than other conserved regions of Gp120 in all the analyzed HIV-1 variants, indicating that the C3 region might be more important to HIV-1 adaptation than previously thought. Approximately half of the positively selected sites identified in the env gene were identical between R5 and X4 variants. There were three common positively selected sites (96, 113 and 281) identified in Gp41 of all X4 and R5 variants from subtypes B and C. These sites might not only suggest a functional importance in viral survival and adaptation, but also imply a potential cross-immunogenicity between HIV-1 R5 and X4 variants, which has important implications for AIDS vaccine development.展开更多
The property theory of traditional Chinese medicine(TCM) has been practiced for thousands of years,playing a pivotal role in the clinical application of TCM. While advancements in energy metabolism,chemical compositio...The property theory of traditional Chinese medicine(TCM) has been practiced for thousands of years,playing a pivotal role in the clinical application of TCM. While advancements in energy metabolism,chemical composition analysis, machine learning, ion current modeling, and supercritical fluid technology have provided valuable insight into how aspects of TCM property theory may be measured, these studies only capture specific aspects of TCM property theory in isolation, overlooking the holistic perspective inherent in TCM. To systematically investigate the modern interpretation of the TCM property theory from multidimensional perspectives, we consulted the Chinese Pharmacopoeia(2020 edition) to compile a list of Chinese materia medica(CMM). Then, using the Latin names of each CMM and gut microbiota as keywords, we searched the PubMed database for relevant research on gut microbiota and CMM. The regulatory patterns of different herbs on gut microbiota were then summarized from the perspectives of the four natures, the five flavors and the meridian tropism. In terms of the four natures, we found that warm-natured medicines promoted the colonization of specific beneficial bacteria,while cold-natured medicines boosted populations of some beneficial bacteria while suppressing pathogenic bacteria. Analysis of the five flavors revealed that sweet-flavored and bitter-flavored CMMs positively influenced beneficial bacteria while inhibiting harmful bacteria. CMMs with different meridian tropism exhibited complex modulative patterns on gut microbiota, with Jueyin(Liver) and Taiyin(Lung) meridian CMMs generally exerting a stronger effect. The gut microbiota may be a biological indicator for characterizing the TCM property theory, which not only enhances our understanding of classic TCM theory but also contributes to its scientific advancement and application in healthcare.展开更多
Background: Mario Bertolotti, (1917) described LSTV-Lumbar spinal transitional vertebra as Bertolotti Syndrome a century ago and associated low back pain with it. Yet, it needs to be given significance in general orth...Background: Mario Bertolotti, (1917) described LSTV-Lumbar spinal transitional vertebra as Bertolotti Syndrome a century ago and associated low back pain with it. Yet, it needs to be given significance in general orthopaedic practice even now, and radiologists underreport it. LSTV is a congenital anatomical anomaly that Castellvi classified into four varying types. Purpose: I titled this phenomenon “Kiran Nandivada’s stuck blade in a grinder jar degenerative cascade by LSTV at L5-S1” to clearly explain how an abnormal mega-transverse apophysis with its various variations affects the weight-bearing mechanics as the L5-S1 which is a vital junction where the maximum body weight is directed into both the sacroiliac joints and if a transitional vertebra occurs it becomes detrimental and abnormally redirects the load-bearing forces and leads to a progressive degenerative cascade both proximally and distally. As the L5 vertebral rotations and other movements of flexion, extensions, lateral flexion are stuck like a bent grinder blade, the other areas of the region are damaged progressively as the pelvis, just like the grinder motor tries to move it, resulting in overheating and maybe even a burnout results in the form of facet arthritis, disc degeneration in the normal disc above, the transitional disc at L5-S1, foraminal osteophytes causing radiculopathy, sacroiliac joint arthritis. Material and Methods: Around 200 X-rays of children and adults with this congenital anomaly have been studied between 2020 and 2023. This is a retrospective study. Results: 1) Our study showed an Increased incidence of LSTV at 15%. 2) Patients ranged from asymptomatic, atypical lumbago to classical lumbago with sciatica and claudication. Findings supported facet and sacroiliac joint arthritis and the pain, relieved with physiotherapy, posture corrections, weight reduction, and lifestyle precautions, negating the need for local steroid injections, radiofrequency ablation or surgical excision as per our experience. Conclusion: Other dysplastic congenital manifestations like associated scoliosis, facet tropism and nerve root, and sacroiliac joint anomalies can co-exist. These radiological findings must be clearly explained to the patient so that the inherently progressive nature of this phenomenon is well understood and the patient can take the required precautions to slow them and suitable conservative treatment can be planned. In rare cases, radiofrequency ablation or even rarely a surgical resection could be beneficial, but the surgical approach could be complex as normal anatomy is changed. Hence, prior anaesthesia blocks and even scintigraphy are essential steps to clearly define and confirm the LSTV to be the actual cause of the pain.展开更多
Various studies have demonstrated the tremendous tropism of stem cells for malignant gliomas,making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells.However,little is know...Various studies have demonstrated the tremendous tropism of stem cells for malignant gliomas,making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells.However,little is known about the mechanisms underlying the glioma-induced tropism of stem cells.Soluble factors including chemokines or growth factors released and expressed by glioma cells at least mediate the tropism of stem cells for gliomas.Here we review the possible mechanisms of stem cells tropism for malignant gliomas.展开更多
AIM： To investigate the selective tropism of liver stem cells to hepatocellular carcinoma （HCC） in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC.METHODS： ...AIM： To investigate the selective tropism of liver stem cells to hepatocellular carcinoma （HCC） in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC.METHODS： WB-F344, a kind of rat liver stem cell, was infected with recombinant virus to establish a cell line with stable, high-level expressing enhanced green fluorescent protein （EGFP）. An animal model of HCC in Wistar rats was established by implanting HCC cells （CBRH7919） combined with an immunosuppressive drug. EGFP labeled liver stern cells were injected into caudal veins of the animals and distribution was observed at different time points after injection. SDF-1 and c-kit expression in non-tumor liver and tumor tissue were analysed by immunohistochemistry for the relationshiop between the expression and migration of liver stem cells. Furthermore, hepatic stern cells were injected via the portal vein, hepatic artery, caudal vein, or directly into the pericancerous liver tissue, respectively, and effects on migration, localization, and proliferation of the hepatic stern cells within the tumor tissue were observed and analyzed.RESULTS： Recombinant adenovirus could deliver the EGFP gene to hepatic stem cells. A new stem cell line, named WB-EGFP, was established that stably expressed EGFP. WB-EGFP cells still showed selective tropism towards HCC and EGFP expression was stable in vivo. According to immunohistochemistry results, SDF-1 may not be related to the mechanisms of tropism of hepatic stem cells. Different application sites affected the distribution of liver stem cells. Injection via the portal vein was superior with regard to selective migration, localization, and proliferation of the hepatic stem cells within the tumor tissue.CONCLUSION： Liver stem cells have the biological behavior of selective migration to HCC in vivo and they could localize and proliferate within HCC tissue stably expressing the target gene. Liver stem cells are a potential tool for a targeted gene therapy of HCC.展开更多
Objective: Lung-toxin Dispelling Formula No. 1, referred to as Respiratory Detox Shot(RDS), was developed based on a classical prescription of traditional Chinese medicine(TCM) and the theoretical understanding of her...Objective: Lung-toxin Dispelling Formula No. 1, referred to as Respiratory Detox Shot(RDS), was developed based on a classical prescription of traditional Chinese medicine(TCM) and the theoretical understanding of herbal properties within TCM. Therapeutic benefits of using RDS for both disease control and prevention, in the effort to contain the coronavirus disease 2019(COVID-19), have been shown. However,the biochemically active constituents of RDS and their mechanisms of action are still unclear. The goal of the present study is to clarify the material foundation and action mechanism of RDS.Methods: To conduct an analysis of RDS, an integrative analytical platform was constructed, including target prediction, protein–protein interaction(PPI) network, and cluster analysis;further, the hub genes involved in the disease-related pathways were identified, and the their corresponding compounds were used for in vitro validation of molecular docking predictions. The presence of these validated compounds was also measured in samples of the RDS formula to quantify the abundance of the biochemically active constituents. In our network pharmacological study, a total of 26 bioinformatic programs and databases were used, and six networks, covering the entire Zang-fu viscera, were constructed to comprehensively analyze the intricate connections among the compounds-targets-disease pathways-meridians of RDS.Results: For all 1071 known chemical constituents of the nine ingredients in RDS, identified from established TCM databases, 157 passed drug-likeness screening and led to 339 predicted targets in the constituent–target network. Forty-two hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target–constitu ent–disease network. Twelve disease pathways attributed to the Lung–Large Intestine meridians, with six and five attributed to the Kidney–Urinary Bladder and Stomach–Spleen meridians, respectively. Onehundred and eighteen candidate constituents showed a high binding affinity with SARS-coronavirus-23-chymotrypsin-like protease(3 CLpro), as indicated by molecular docking using computational pattern recognition. The in vitro activity of 22 chemical constituents of RDS was validated using the 3 CLproinhibition assay. Finally, using liquid chromatography mass spectrometry in data-independent analysis mode,the presence of seven out of these 22 constituents was confirmed and validated in an aqueous decoction of RDS, using reference standards in both non-targeted and targeted approaches.Conclusion: RDS acts primarily in the Lung–Large Intestine, Kidney–Urinary Bladder and Stomach–Spleen meridians, with other Zang-fu viscera strategically covered by all nine ingredients. In the context of TCM meridian theory, the multiple components and targets of RDS contribute to RDS’s dual effects of healthstrengthening and pathogen-eliminating. This results in general therapeutic effects for early COVID-19 control and prevention.展开更多
The mass mortality of pond-reared scattered mirror carp, Cyprinus carpio, caused by Thelohanellus kitauei, occurred at fish farms in Sichuan Province, southwest China. Morphological and molecular analyses were supplem...The mass mortality of pond-reared scattered mirror carp, Cyprinus carpio, caused by Thelohanellus kitauei, occurred at fish farms in Sichuan Province, southwest China. Morphological and molecular analyses were supplemented with histological evaluation of infected tissues to better understand the route of infection and the pathological effects of 1＂. kitauei on the fish host. The intestine of the diseased host was full of large cysts of the myxosporean. The cysts range from 2 cm to 3.6 cm in diameter. Histopathology indicated that T. kitauei first invaded the submucosa of the host intestine and then moved into the mucosa layers with the development of their spores, finally entering into the enteric cavity of the hosts after the disruption of mucosa layers. The pyriform spores of T. kitauei were surrounded by the transparent spore sheath, measuring 25.98/μm±0.95 μm in body length, 8.72 μm±0.51μm body width, and 7.86 μm±0.26 μm in body thickness. The single polar capsule was pyriform, measuring 14.73 μm±0.92μm in length and 6.82 μm±0.45μm in width, with eight to 10 turns of filament coils winding inside. Phylogenetic analysis based on the 18S small-subunit ribosomal DNA sequences indicated that minimal genetic differences were present between T. kitauei samples from South Korea and from China. Close affinity was found between the genus Thelohanellus and Myxobolus. Additionally, two polar capsule nuclei were found at the anterior end of the single polar capsule in spores of T. kitauei stained with hematoxylin and eosin, which suggested the separation of the genus Thelohanellus from Myxobolus.展开更多
OBJECTIVE: To study the meridian tropism(MT) for three Chinese medicines: Tinglizi(Semen Lepidii Apetali, TLZ), Yiyiren(Semen Coicis, YYR), Cheqianzi(Semen Plantaginis, CQZ) in vivo experiments.METHODS: The extracts o...OBJECTIVE: To study the meridian tropism(MT) for three Chinese medicines: Tinglizi(Semen Lepidii Apetali, TLZ), Yiyiren(Semen Coicis, YYR), Cheqianzi(Semen Plantaginis, CQZ) in vivo experiments.METHODS: The extracts of TLZ,YYR, CQZ were orally administered to rats at a dose 234, 700 and 350 mg/kg, respectively. The urinary excretion rate, loss in weight of rats and the electrolyte levels in the plasma were measured, in order to assess the mechanisms of the three traditional Chinese diuretic medicines.RESULTS: TLZ, YYR and CQZ exhibited obvious diuretic effect and reduced the weight of saline-loaded animals. All the three diuretic medicines differentially reduced various serum, urinary, lung, stomach, kidney and hormonal markers, thus indicating the different mechanisms of action and a close resemblance with their different meridian as per the MT theory.CONCLUSION: Our findings suggest that the three Traditional Chinese Medicine(TCM) medicines-TLZ,YYR and CQZ-possess different Shamisen meridian.This can support the regimen of treating the same disease with different therapies in TCM theory.展开更多
Objective:To evaluate parasite distribution and tissue tropism of Toxoplasma gondii tachyzoites in experimentally infected mice using real time QPCR.Methods:In this survey 16 Balb/c mice were inoculated with 1×10...Objective:To evaluate parasite distribution and tissue tropism of Toxoplasma gondii tachyzoites in experimentally infected mice using real time QPCR.Methods:In this survey 16 Balb/c mice were inoculated with 1×10~4 alive tachyzoites of Toxoplasma gondii RH strain.After 1,2,3 days post infection and the last day(before death),different tissues of mice including blood,brain,eye,liver,spleen,kidney,heart and muscle were harvested.Following tissues DNA extraction,the parasite burden was quantified using real time QPCR targeting the B1 gene(451 bp).Results:It showed that Toxoplasma after intraperitoneal injection was able to movement to various tissues in24 hours.Parasite burden was high in all tissues but the most number of parasites were observed in kidney,heart and liver,respectively.Conclusions:These data provide significant baseline information about Toxoplasma pathogenesis,vaccine monitoring and drug efficiency.展开更多
The coronavirus disease 2019(COVID-19)represents a global health and economic challenge.Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus(SARS-CoV-2)infection.The ...The coronavirus disease 2019(COVID-19)represents a global health and economic challenge.Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus(SARS-CoV-2)infection.The viral tropism pattern of SARS-CoV-2 can induce hepatic injuries either by itself or by worsening the conditions of patients with hepatic diseases.Besides,other factors have been reported to play a crucial role in the pathological forms of hepatic injuries induced by SARS-CoV-2,including cytokine storm,hypoxia,endothelial cells,and even some treatments for COVID-19.On the other hand,several groups of people could be at risk of hepatic COVID-19 complications,such as pregnant women and neonates.The present review outlines and discusses the interplay between SARS-CoV-2 infection and hepatic injury,hepatic illness comorbidity,and risk factors.Besides,it is focused on the vaccination process and the role of developed vac-cines in preventing hepatic injuries due to SARS-CoV-2 infection.展开更多
OBJECTIVE:To study the morphological basis of the role of Siqi(cold as winter,cool as autumn,warm as spring,hot as summer),Wuwei(five flavors:sweet,pungent,salty,sour,and bitter),and Guijing(meridian tropism) through ...OBJECTIVE:To study the morphological basis of the role of Siqi(cold as winter,cool as autumn,warm as spring,hot as summer),Wuwei(five flavors:sweet,pungent,salty,sour,and bitter),and Guijing(meridian tropism) through the use of information integration.METHODS:A14C-2-deoxy-glucose autoradiography method was adopted to determine the overall impact of treatment with 39 herbs on functions of various tissues and organs.Data was measured at 4hs after a single dose and following the last treatment of repeated doses for a week.Least-squares estimation was used and fitted for each herb regression effect of organs and tissues after singleand repeated treatment.The slope of the regression line represented the cumulative trend of the effect of the herbs(β),and the standard deviation of the slope(Sβ) was compared with those of the untreated animals(t 'test).All significantly cumulative effect trends were applied with an artificial neural network,which integrated the relationship among Siqi,Wuwei,and Guijing with tissues and organs.RESULTS:There is a certain relationship among the Siqi,Wuwei,Guijing and the anatomy of organs and tissues,but the different scores indicate that influence of Siqi,Wuwei,Guijing to anatomy of organs and tissues was a nonlinear state.CONCLUSION:Results demonstrated that the effects of Siqi,Wuwei,and Guijing have a morphological basis,and each concept was associated with multiple anatomical structures.展开更多
OBJECTIVE:To investigate whether Fuzi(Radix Aconiti Praeparata) has fewer "hot" characteristics when administered without Ganjiang(Rhizoma Zingiberis).METHODS:Differences in the thermotropism behaviors of mi...OBJECTIVE:To investigate whether Fuzi(Radix Aconiti Praeparata) has fewer "hot" characteristics when administered without Ganjiang(Rhizoma Zingiberis).METHODS:Differences in the thermotropism behaviors of mice treated either with Fuzi(Radix Aconiti Praeparata),Ganjiang(Rhizoma Zingiberis) or the combination of the two given intragastrically were investigated using the Animal Thermotropism Behavior Surveillance System.The water intake volume,oxygen consumption volume,adenosine triphosphatase(ATPase) activity,total antioxidant capacity(T-AOC) and total superoxide dismutase(T-SOD) activity were determined during the investigation.RESULTS:When Fuzi and Ganjiang were administered together,the rate at which mice remained on a warm plate("remaining rate") and the times and distances of their movement were all significantly reduced(P<0.05).Compared with the Normal group,the reduction was 55.1%,48.3% and 44.8%,while compared with the Fuzi group,the reduction was 57.6%,34.3% and 36.0%,indicating that "cold" tropism was significantly increased.Compared with the Normal and Fuzi groups,the ATPase activity and the respiratory oxygen consumption volume of the Fuzi + Ganjiang group were significantly increased(P<0.05),suggesting an improvement in energy metabolism and showing a "hot" characteristic when Fuzi and Ganjiang are present together.Additionally,the T-AOC and T-SOD activity were significantly enhanced(P<0.05).CONCLUSION:The behavior of mice tending toward "cold" tropism can be regarded as a quantitative reflection of Fuzi having fewer characteristics consistent w ith a "hot" nature when not used with Ganjiang,the functional mechanism of which may be a change in the ATPase activity in liver tissue.展开更多
Infectious bursal disease virus（IBDV）is responsible for the highly contagious infectious bursal disease of chickens.Further understanding the gene-function is necessary to design the tailored vaccine.The amino acid ...Infectious bursal disease virus（IBDV）is responsible for the highly contagious infectious bursal disease of chickens.Further understanding the gene-function is necessary to design the tailored vaccine.The amino acid residue 279,located on strand P_F of VP2,is one of the three residues that have been reported to be involved in cell-tropism but with some inconsistency.In this study,to further clarify the amino acids involved in the cell tropism of IBDV,a series of mutations about residue 279were introduced into the VP2 of vv IBDV Gx strain.With the reverse genetic system,we found single mutation of D279N,double mutations of D279N/A284T or Q253H/D279N were not enough to adapt IBDV to chicken embryo fibroblast（CEF）cell.To evaluate whether residue 279 could influence the replication and virulence of IBDV,the virus r Gx HT-279 with three mutations（Q253H/D279N/A284T）was rescued and evaluated.Results showed that the mutation of residue 279 in VP2had no efficient effects on both the replication efficiency in vitro and the virulence to SPF chickens of IBDV.In summary,the results demonstrated that residue 279 of VP2 did not contribute efficiently to cell tropism,replication efficiency,and virulence of IBDV at least in some strains.These findings provided further information for understanding the gene function of IBDV.展开更多
After infection and integration steps, HIV-1 transcriptions increase sharply and singly-spliced mRNAs are produced. These encode Env （gpl20 and gp41） and auxiliary proteins Vif, Vpr and VpU. The same localization wi...After infection and integration steps, HIV-1 transcriptions increase sharply and singly-spliced mRNAs are produced. These encode Env （gpl20 and gp41） and auxiliary proteins Vif, Vpr and VpU. The same localization within the unique structure of the mRNAs suggests that the VpU sequence prior to the Env could affect the Env polyprotein expression.The HIV-I infection process begins when the gpl20 subunit of the envelope glycoprotein complex interacts with its receptor（s） on the target cell. The V3 domain of gpl20 is the major determinant of cellular co-receptor binding. According to phenotypic information of HIVol isolates, sequences from the VpU to V3 regions （119 in R5- and 120 X4-tropic viruses; one per patient） were analysed. The binomial correlation phi coefficient was used to assess covariation among VpU and gpl20v3 signatures. Subsequently, average linkage hierarchical agglomerative clustering was performed. Beyond the classical V3 signatures （R5-viruses： SI1, E25D; X4-viruses： SllKR, E25KRQ）, other specific V3 and novel VpU signatures were found to be statistically associated with co-receptor usage. Several statistically significant associations between V3 and VpU mutations were also observed. The dendrogram showed two distinct large clusters： one associated with R5-tropic sequences （bootstrap=0.94）, involving： （a） H13NPv3, E25Dv3, Sllv3, T22Av3 and Q61Hvpu, （b） E25Av3 and L12Fvpu, （c） D44Evpu, R18Qv3 and D80Nvpu; and another associated with X4-tropic sequences （bootstrap=0.97）, involving： （i） E25Iv3 and V10Avpu, （ii） 0-1insVvpc, H13Rv3, I46Lvpc, I30Mv3 and 60-62delvpu, （iii） SllKRv3 and E25KRQv3. Some of these pairs of mutations were encoded always by one specific codon. These data indicate the possible VpU mutational patterns contributing to regulation of HIV-I tropism.展开更多
BACKGROUND Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)is the pathogen responsible for pandemic coronavirus disease 2019(COVID-19).It is a highly contagious virus which primarily affects the respiratory...BACKGROUND Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)is the pathogen responsible for pandemic coronavirus disease 2019(COVID-19).It is a highly contagious virus which primarily affects the respiratory tract,nevertheless,the lungs are not the only target organs of the virus.The intestinal tract could represent an additional tropism site for SARS-CoV-2.Several observations have collectively suggested that enteric infections can occur in COVID-19 patients.However,the detection of viral RNA in gastrointestinal(GI)tissue samples has not been adequately investigated and results are conflicting.AIM To detect the presence of SARS-CoV-2 RNA in intestinal mucosa samples and to evaluate histological features.METHODS The COVID-19 patients hospitalized at an Italian tertiary hospital from April 2020 to March 2021 were evaluated for enrollment in an observational,monocentric trial.The study population was composed of two groups of adult patients.In the first group(biopsy group,30 patients),patients were eligible for inclusion if they had mild to moderate disease and if they agreed to have a rectal biopsy;in the second group(surgical specimen group,6 patients),patients were eligible for inclusion if they underwent intestinal resection during index hospitalization.Fifty-nine intestinal mucosal samples were analyzed.RESULTS Viral RNA was not detectable in any of the rectal biopsies performed(0/53).Histological examination showed no enterocyte damage,but slight edema of the lamina propria with mild inflammatory lymphoplasmacytic infiltration.There was no difference in inflammatory infiltrates in patients with and without GI symptoms.SARS-CoV-2 RNA was detected in fecal samples in 6 cases out of 14 cases examined(42.9%).In the surgical specimen group,all patients underwent emergency intestinal resection.Viral RNA was detected in 2 surgical specimens of the 6 examined,both of which were from patients with active neoplastic disease.Histological examination also pointed out abundant macrophages,granulocytes and plasma cells infiltrating the muscular layer and adipose tissue,and focal vasculitis.CONCLUSION Mild-moderate COVID-19 may not be associated with rectal infection by the virus.More comprehensive autopsies or surgical specimens are needed to provide histological evidence of intestinal infection.展开更多
Emerging and re-emerging viruses from wild animals have seriously threatened the health of humans and domesticated animals in recent years.Herein,we isolated a new mammalian orthoreovirus(MRV),Pika/MRV/GCCDC7/2019(PMR...Emerging and re-emerging viruses from wild animals have seriously threatened the health of humans and domesticated animals in recent years.Herein,we isolated a new mammalian orthoreovirus(MRV),Pika/MRV/GCCDC7/2019(PMRV-GCCDC7),in the Qinghai-Tibet Plateau wild pika(Ochotona curzoniae).Though the PMRVGCCDC7 shows features of a typical reovirus with ten gene segments arranged in 3:3:4 in length,the virus belongs to an independent evolutionary branch compared to other MRVs based on phylogenetic tree analysis.The results of cellular susceptibility,species tropism,and replication kinetics of PMRV-GCCDC7 indicated the virus could infect four human cell lines(A549,Huh7,HCT,and LoVo)and six non-human cell lines,including Vero-E6,LLCMK2,BHK-21,N2a,MDCK,and RfKT cell,derived from diverse mammals,i.e.monkey,mice,canine and bat,which revealed the potential of PMRV-GCCDC7 to infect a variety of hosts.Infection of BALB/c mice with PMRVGCCDC7 via intranasal inoculation led to relative weight loss,lung tissue damage and inflammation with the increase of virus titer,but no serious respiratory symptoms and death occurred.The characterization of the new reovirus from a plateau-based wild animal has expanded our knowledge of the host range of MRV and provided insight into its risk of trans-species transmission and zoonotic diseases.展开更多
基金National Key Research and Development Project of China(2023YFC2306600)Key Program of the National Natural Science Foundation of China(82430070)+6 种基金Shanghai Pujiang Program(No.23PJ1410800)National Natural Science Foundation of China(82072260,32370168)Eastern Talent Plan Leading Project,Shanghai Hospital Development Center Foundation(SHDC12022121)Shanghai 2020“Science and Technology Innovation Action Plan”Medical Innovation Research Special(20Z11900900)Three-year Action Plan(2023-2025)Key Discipline Program on Public Health System Construction of Shanghai(GWVI-11.1-15)Construction of the Major Infectious Disease Medical Treatment System(GWVI-2.2).
文摘Dear Editor,The COVID-19 pandemic,caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has resulted in millions of deaths worldwide.It poses significant challenges in the management of immunocompromised patients,particularly people with HIV(PWH).Whether PWH are more vulnerable to COVID with more adverse outcomes has been extensively studied,but the findings are inconsistent.Many cohort studies and meta-analyses support that PWH have a higher risk of SARSCoV-2 infection and more severe COVID-19 outcomes(Bertagnolio et al.,2022;Ssentongo et al.,2021).
基金Under the auspices of Sino-British Fellowship Trust by British Academy (No.SG-47266)National Natural Science Foundation of China (No.49571031)Foundation of China Scholarship Council (No.2008619067)
文摘People′s environmental tropism has an effect on their understanding of tourism-nature relationship,and also influences their attitudes to natural resources utilization and environmental protection.Taking Jiuzhaigou National Park of China as a study case,the authors conducted some quantitative analyses with the tools of SPSS 16.0 and LISREL 8.7,to explore the influence of tourists′ environmental tropism on their attitudes to tourism and nature conservation in the natural tourist destination.Three hypotheses and the theoretic model of influences of tourists′ environmental tropism on their attitudes to tourism and nature conservation have been tested and accepted based on the Structural Equation Model analysis on survey data collected in Jiuzhaigou National Park of China.Some conclusions were drawn as follows: 1) tourists′ human-prioritized concept influences their cognition to tourism-nature relationship.This concept has a positive influence on their supportive attitudes to tourism,but a negative influence on their attitudes to nature conservation;2) tourists′ human-nature coordination concept has a positive influence on their supportive attitudes to both tourism and nature conservation,especially to the latter.This paper generally proves that human′s environmental tropism does have an influence on their attitudes to tourism and nature conservation in natural tourist destinations.
基金supported by the Basic Research Innovation Group Project of Gansu Province(No.25JRRA434)the National Natural Science Foundation of China(U22A20522).
文摘The cross-species infection of coronaviruses has resulted in several major epidemics since 2003.Porcine epidemic diarrhea virus(PEDV)is a devastating swine enteric coronavirus,which targets pigs as the only natural reservoir.In this study,the nucleic acid of PEDV was detected in rat fecal samples collected from pig farms.Further animal tests showed that PEDV can cause systemic infections in neonatal mice and rats via intracranial inoculation.The brain,lung,intestine and spleen were all targets for PEDV in rodents in contrast to the intestine being targeted in pigs.Morbidity and mortality vary via different infection routes.PEDV was also detectable in feces after infection,suggesting that the infected rodents were potential infectious sources.Moreover,the cerebral tropism of PEDV was verified in piglets via orally inoculation,which had not been identified before.In conclusion,our findings demonstrate that PEDV could cross the species barrier to infect mice and rats through different routes in experimental settings.Although it is highly devastating to piglets,PEDV changes the target organs and turns to be milder when meeting with new hosts.Based on these findings,more attention should be paid to the potential cross-species infection of PEDV.
基金supported by the National Natural Science Foundation of China,Nos.81870921(to YW),81974179(to ZZ),82271320(to ZZ),82071284(to YT)National Key R&D Program of China,No.2022YFA1603600(to ZZ),2019YFA0112000(to YT)+1 种基金Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY).
文摘AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.
基金supported by the National Natural Science Foundation of China (Grant No. 30600352)the "Top-notch Personnel" Project of Ji-angsu University, the National Basic Research Program of China (Grant No. 2006CB504200)the Open Research Fund Program of the State Key Laboratory of Virology of China (Grant No. 2009008)
文摘HIV-1 co-receptor tropism is central for understanding the transmission and pathogenesis of HIV-1 infection. We performed a genome-wide comparison between the adaptive evolution of R5 and X4 variants from HIV-1 subtypes B and C. The results showed that R5 and X4 variants experienced differential evolutionary patterns and different HIV-1 genes encountered various positive selection pressures, suggesting that complex selection pressures are driving HIV-1 evolution. Compared with other hypervariable regions of Gp120, significantly more positively selected sites were detected in the V3 region of subtype B X4 variants, V2 region of subtype B R5 variants, and V1 and V4 regions of subtype C X4 variants, indicating an association of positive selection with co-receptor recognition/binding. Intriguingly, a significantly higher proportion (33.3% and 55.6%, P【0.05) of positively selected sites were identified in the C3 region than other conserved regions of Gp120 in all the analyzed HIV-1 variants, indicating that the C3 region might be more important to HIV-1 adaptation than previously thought. Approximately half of the positively selected sites identified in the env gene were identical between R5 and X4 variants. There were three common positively selected sites (96, 113 and 281) identified in Gp41 of all X4 and R5 variants from subtypes B and C. These sites might not only suggest a functional importance in viral survival and adaptation, but also imply a potential cross-immunogenicity between HIV-1 R5 and X4 variants, which has important implications for AIDS vaccine development.
基金supported financially by the National Natural Science Foundation of China (No. 81973217)。
文摘The property theory of traditional Chinese medicine(TCM) has been practiced for thousands of years,playing a pivotal role in the clinical application of TCM. While advancements in energy metabolism,chemical composition analysis, machine learning, ion current modeling, and supercritical fluid technology have provided valuable insight into how aspects of TCM property theory may be measured, these studies only capture specific aspects of TCM property theory in isolation, overlooking the holistic perspective inherent in TCM. To systematically investigate the modern interpretation of the TCM property theory from multidimensional perspectives, we consulted the Chinese Pharmacopoeia(2020 edition) to compile a list of Chinese materia medica(CMM). Then, using the Latin names of each CMM and gut microbiota as keywords, we searched the PubMed database for relevant research on gut microbiota and CMM. The regulatory patterns of different herbs on gut microbiota were then summarized from the perspectives of the four natures, the five flavors and the meridian tropism. In terms of the four natures, we found that warm-natured medicines promoted the colonization of specific beneficial bacteria,while cold-natured medicines boosted populations of some beneficial bacteria while suppressing pathogenic bacteria. Analysis of the five flavors revealed that sweet-flavored and bitter-flavored CMMs positively influenced beneficial bacteria while inhibiting harmful bacteria. CMMs with different meridian tropism exhibited complex modulative patterns on gut microbiota, with Jueyin(Liver) and Taiyin(Lung) meridian CMMs generally exerting a stronger effect. The gut microbiota may be a biological indicator for characterizing the TCM property theory, which not only enhances our understanding of classic TCM theory but also contributes to its scientific advancement and application in healthcare.
文摘Background: Mario Bertolotti, (1917) described LSTV-Lumbar spinal transitional vertebra as Bertolotti Syndrome a century ago and associated low back pain with it. Yet, it needs to be given significance in general orthopaedic practice even now, and radiologists underreport it. LSTV is a congenital anatomical anomaly that Castellvi classified into four varying types. Purpose: I titled this phenomenon “Kiran Nandivada’s stuck blade in a grinder jar degenerative cascade by LSTV at L5-S1” to clearly explain how an abnormal mega-transverse apophysis with its various variations affects the weight-bearing mechanics as the L5-S1 which is a vital junction where the maximum body weight is directed into both the sacroiliac joints and if a transitional vertebra occurs it becomes detrimental and abnormally redirects the load-bearing forces and leads to a progressive degenerative cascade both proximally and distally. As the L5 vertebral rotations and other movements of flexion, extensions, lateral flexion are stuck like a bent grinder blade, the other areas of the region are damaged progressively as the pelvis, just like the grinder motor tries to move it, resulting in overheating and maybe even a burnout results in the form of facet arthritis, disc degeneration in the normal disc above, the transitional disc at L5-S1, foraminal osteophytes causing radiculopathy, sacroiliac joint arthritis. Material and Methods: Around 200 X-rays of children and adults with this congenital anomaly have been studied between 2020 and 2023. This is a retrospective study. Results: 1) Our study showed an Increased incidence of LSTV at 15%. 2) Patients ranged from asymptomatic, atypical lumbago to classical lumbago with sciatica and claudication. Findings supported facet and sacroiliac joint arthritis and the pain, relieved with physiotherapy, posture corrections, weight reduction, and lifestyle precautions, negating the need for local steroid injections, radiofrequency ablation or surgical excision as per our experience. Conclusion: Other dysplastic congenital manifestations like associated scoliosis, facet tropism and nerve root, and sacroiliac joint anomalies can co-exist. These radiological findings must be clearly explained to the patient so that the inherently progressive nature of this phenomenon is well understood and the patient can take the required precautions to slow them and suitable conservative treatment can be planned. In rare cases, radiofrequency ablation or even rarely a surgical resection could be beneficial, but the surgical approach could be complex as normal anatomy is changed. Hence, prior anaesthesia blocks and even scintigraphy are essential steps to clearly define and confirm the LSTV to be the actual cause of the pain.
文摘Various studies have demonstrated the tremendous tropism of stem cells for malignant gliomas,making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells.However,little is known about the mechanisms underlying the glioma-induced tropism of stem cells.Soluble factors including chemokines or growth factors released and expressed by glioma cells at least mediate the tropism of stem cells for gliomas.Here we review the possible mechanisms of stem cells tropism for malignant gliomas.
文摘AIM： To investigate the selective tropism of liver stem cells to hepatocellular carcinoma （HCC） in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC.METHODS： WB-F344, a kind of rat liver stem cell, was infected with recombinant virus to establish a cell line with stable, high-level expressing enhanced green fluorescent protein （EGFP）. An animal model of HCC in Wistar rats was established by implanting HCC cells （CBRH7919） combined with an immunosuppressive drug. EGFP labeled liver stern cells were injected into caudal veins of the animals and distribution was observed at different time points after injection. SDF-1 and c-kit expression in non-tumor liver and tumor tissue were analysed by immunohistochemistry for the relationshiop between the expression and migration of liver stem cells. Furthermore, hepatic stern cells were injected via the portal vein, hepatic artery, caudal vein, or directly into the pericancerous liver tissue, respectively, and effects on migration, localization, and proliferation of the hepatic stern cells within the tumor tissue were observed and analyzed.RESULTS： Recombinant adenovirus could deliver the EGFP gene to hepatic stem cells. A new stem cell line, named WB-EGFP, was established that stably expressed EGFP. WB-EGFP cells still showed selective tropism towards HCC and EGFP expression was stable in vivo. According to immunohistochemistry results, SDF-1 may not be related to the mechanisms of tropism of hepatic stem cells. Different application sites affected the distribution of liver stem cells. Injection via the portal vein was superior with regard to selective migration, localization, and proliferation of the hepatic stem cells within the tumor tissue.CONCLUSION： Liver stem cells have the biological behavior of selective migration to HCC in vivo and they could localize and proliferate within HCC tissue stably expressing the target gene. Liver stem cells are a potential tool for a targeted gene therapy of HCC.
基金the financial support from National Key Research and Development Program of China (No.2018YFC1707900).
文摘Objective: Lung-toxin Dispelling Formula No. 1, referred to as Respiratory Detox Shot(RDS), was developed based on a classical prescription of traditional Chinese medicine(TCM) and the theoretical understanding of herbal properties within TCM. Therapeutic benefits of using RDS for both disease control and prevention, in the effort to contain the coronavirus disease 2019(COVID-19), have been shown. However,the biochemically active constituents of RDS and their mechanisms of action are still unclear. The goal of the present study is to clarify the material foundation and action mechanism of RDS.Methods: To conduct an analysis of RDS, an integrative analytical platform was constructed, including target prediction, protein–protein interaction(PPI) network, and cluster analysis;further, the hub genes involved in the disease-related pathways were identified, and the their corresponding compounds were used for in vitro validation of molecular docking predictions. The presence of these validated compounds was also measured in samples of the RDS formula to quantify the abundance of the biochemically active constituents. In our network pharmacological study, a total of 26 bioinformatic programs and databases were used, and six networks, covering the entire Zang-fu viscera, were constructed to comprehensively analyze the intricate connections among the compounds-targets-disease pathways-meridians of RDS.Results: For all 1071 known chemical constituents of the nine ingredients in RDS, identified from established TCM databases, 157 passed drug-likeness screening and led to 339 predicted targets in the constituent–target network. Forty-two hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target–constitu ent–disease network. Twelve disease pathways attributed to the Lung–Large Intestine meridians, with six and five attributed to the Kidney–Urinary Bladder and Stomach–Spleen meridians, respectively. Onehundred and eighteen candidate constituents showed a high binding affinity with SARS-coronavirus-23-chymotrypsin-like protease(3 CLpro), as indicated by molecular docking using computational pattern recognition. The in vitro activity of 22 chemical constituents of RDS was validated using the 3 CLproinhibition assay. Finally, using liquid chromatography mass spectrometry in data-independent analysis mode,the presence of seven out of these 22 constituents was confirmed and validated in an aqueous decoction of RDS, using reference standards in both non-targeted and targeted approaches.Conclusion: RDS acts primarily in the Lung–Large Intestine, Kidney–Urinary Bladder and Stomach–Spleen meridians, with other Zang-fu viscera strategically covered by all nine ingredients. In the context of TCM meridian theory, the multiple components and targets of RDS contribute to RDS’s dual effects of healthstrengthening and pathogen-eliminating. This results in general therapeutic effects for early COVID-19 control and prevention.
基金Supported by the earmarked fund for China Agriculture Research System(No.CARS-46-08)the National Science Foundation for Young Scientists of China(No.31301863)the Major Scientific and Technological Innovation Project of Hubei Province(No.2015ABA045)
文摘The mass mortality of pond-reared scattered mirror carp, Cyprinus carpio, caused by Thelohanellus kitauei, occurred at fish farms in Sichuan Province, southwest China. Morphological and molecular analyses were supplemented with histological evaluation of infected tissues to better understand the route of infection and the pathological effects of 1＂. kitauei on the fish host. The intestine of the diseased host was full of large cysts of the myxosporean. The cysts range from 2 cm to 3.6 cm in diameter. Histopathology indicated that T. kitauei first invaded the submucosa of the host intestine and then moved into the mucosa layers with the development of their spores, finally entering into the enteric cavity of the hosts after the disruption of mucosa layers. The pyriform spores of T. kitauei were surrounded by the transparent spore sheath, measuring 25.98/μm±0.95 μm in body length, 8.72 μm±0.51μm body width, and 7.86 μm±0.26 μm in body thickness. The single polar capsule was pyriform, measuring 14.73 μm±0.92μm in length and 6.82 μm±0.45μm in width, with eight to 10 turns of filament coils winding inside. Phylogenetic analysis based on the 18S small-subunit ribosomal DNA sequences indicated that minimal genetic differences were present between T. kitauei samples from South Korea and from China. Close affinity was found between the genus Thelohanellus and Myxobolus. Additionally, two polar capsule nuclei were found at the anterior end of the single polar capsule in spores of T. kitauei stained with hematoxylin and eosin, which suggested the separation of the genus Thelohanellus from Myxobolus.
基金Supported by the National Basic Research Program of China(973 Program)Study on the Medicinal Properties of Xuanxie Lishui Traditional Chinese Medicine(No.2013CB531802)
文摘OBJECTIVE: To study the meridian tropism(MT) for three Chinese medicines: Tinglizi(Semen Lepidii Apetali, TLZ), Yiyiren(Semen Coicis, YYR), Cheqianzi(Semen Plantaginis, CQZ) in vivo experiments.METHODS: The extracts of TLZ,YYR, CQZ were orally administered to rats at a dose 234, 700 and 350 mg/kg, respectively. The urinary excretion rate, loss in weight of rats and the electrolyte levels in the plasma were measured, in order to assess the mechanisms of the three traditional Chinese diuretic medicines.RESULTS: TLZ, YYR and CQZ exhibited obvious diuretic effect and reduced the weight of saline-loaded animals. All the three diuretic medicines differentially reduced various serum, urinary, lung, stomach, kidney and hormonal markers, thus indicating the different mechanisms of action and a close resemblance with their different meridian as per the MT theory.CONCLUSION: Our findings suggest that the three Traditional Chinese Medicine(TCM) medicines-TLZ,YYR and CQZ-possess different Shamisen meridian.This can support the regimen of treating the same disease with different therapies in TCM theory.
基金prepared from Yousef Dadimoghaddam's MScthesis and supported by grant(no.90-31) from Deputy of Research,Mazandaran University of Medical Sciences.Sari,IranThe spousor or Junding organization had norole in the design or conduct of this research
文摘Objective:To evaluate parasite distribution and tissue tropism of Toxoplasma gondii tachyzoites in experimentally infected mice using real time QPCR.Methods:In this survey 16 Balb/c mice were inoculated with 1×10~4 alive tachyzoites of Toxoplasma gondii RH strain.After 1,2,3 days post infection and the last day(before death),different tissues of mice including blood,brain,eye,liver,spleen,kidney,heart and muscle were harvested.Following tissues DNA extraction,the parasite burden was quantified using real time QPCR targeting the B1 gene(451 bp).Results:It showed that Toxoplasma after intraperitoneal injection was able to movement to various tissues in24 hours.Parasite burden was high in all tissues but the most number of parasites were observed in kidney,heart and liver,respectively.Conclusions:These data provide significant baseline information about Toxoplasma pathogenesis,vaccine monitoring and drug efficiency.
文摘The coronavirus disease 2019(COVID-19)represents a global health and economic challenge.Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus(SARS-CoV-2)infection.The viral tropism pattern of SARS-CoV-2 can induce hepatic injuries either by itself or by worsening the conditions of patients with hepatic diseases.Besides,other factors have been reported to play a crucial role in the pathological forms of hepatic injuries induced by SARS-CoV-2,including cytokine storm,hypoxia,endothelial cells,and even some treatments for COVID-19.On the other hand,several groups of people could be at risk of hepatic COVID-19 complications,such as pregnant women and neonates.The present review outlines and discusses the interplay between SARS-CoV-2 infection and hepatic injury,hepatic illness comorbidity,and risk factors.Besides,it is focused on the vaccination process and the role of developed vac-cines in preventing hepatic injuries due to SARS-CoV-2 infection.
基金Support by National Natural Science Foundation Grant(Correlation Analysis Among Herb's Properties affecting the Multiple Parameters of the Blood and the Morphology of the Organism Structure,No.81473366)
文摘OBJECTIVE:To study the morphological basis of the role of Siqi(cold as winter,cool as autumn,warm as spring,hot as summer),Wuwei(five flavors:sweet,pungent,salty,sour,and bitter),and Guijing(meridian tropism) through the use of information integration.METHODS:A14C-2-deoxy-glucose autoradiography method was adopted to determine the overall impact of treatment with 39 herbs on functions of various tissues and organs.Data was measured at 4hs after a single dose and following the last treatment of repeated doses for a week.Least-squares estimation was used and fitted for each herb regression effect of organs and tissues after singleand repeated treatment.The slope of the regression line represented the cumulative trend of the effect of the herbs(β),and the standard deviation of the slope(Sβ) was compared with those of the untreated animals(t 'test).All significantly cumulative effect trends were applied with an artificial neural network,which integrated the relationship among Siqi,Wuwei,and Guijing with tissues and organs.RESULTS:There is a certain relationship among the Siqi,Wuwei,Guijing and the anatomy of organs and tissues,but the different scores indicate that influence of Siqi,Wuwei,Guijing to anatomy of organs and tissues was a nonlinear state.CONCLUSION:Results demonstrated that the effects of Siqi,Wuwei,and Guijing have a morphological basis,and each concept was associated with multiple anatomical structures.
基金Supported by National Natural Sciences Foundation(No. 81173571)National Basic Research Program of China (No.2007CB512607)
文摘OBJECTIVE:To investigate whether Fuzi(Radix Aconiti Praeparata) has fewer "hot" characteristics when administered without Ganjiang(Rhizoma Zingiberis).METHODS:Differences in the thermotropism behaviors of mice treated either with Fuzi(Radix Aconiti Praeparata),Ganjiang(Rhizoma Zingiberis) or the combination of the two given intragastrically were investigated using the Animal Thermotropism Behavior Surveillance System.The water intake volume,oxygen consumption volume,adenosine triphosphatase(ATPase) activity,total antioxidant capacity(T-AOC) and total superoxide dismutase(T-SOD) activity were determined during the investigation.RESULTS:When Fuzi and Ganjiang were administered together,the rate at which mice remained on a warm plate("remaining rate") and the times and distances of their movement were all significantly reduced(P<0.05).Compared with the Normal group,the reduction was 55.1%,48.3% and 44.8%,while compared with the Fuzi group,the reduction was 57.6%,34.3% and 36.0%,indicating that "cold" tropism was significantly increased.Compared with the Normal and Fuzi groups,the ATPase activity and the respiratory oxygen consumption volume of the Fuzi + Ganjiang group were significantly increased(P<0.05),suggesting an improvement in energy metabolism and showing a "hot" characteristic when Fuzi and Ganjiang are present together.Additionally,the T-AOC and T-SOD activity were significantly enhanced(P<0.05).CONCLUSION:The behavior of mice tending toward "cold" tropism can be regarded as a quantitative reflection of Fuzi having fewer characteristics consistent w ith a "hot" nature when not used with Ganjiang,the functional mechanism of which may be a change in the ATPase activity in liver tissue.
基金supported by a grant from National Natural Science Foundation of China(31430087)the Scientific and Technological Research Project of Harbin,China(2014AB3AN058)+2 种基金the Special Fund for Scientific and Technological Innovative Talents of Harbin,China(2014RFQYJ129)China-France Cai-Yuanpei Program(2011008007)the Modern Agro-industry Technology Research System of China(nycytx-42-G3-01)
文摘Infectious bursal disease virus（IBDV）is responsible for the highly contagious infectious bursal disease of chickens.Further understanding the gene-function is necessary to design the tailored vaccine.The amino acid residue 279,located on strand P_F of VP2,is one of the three residues that have been reported to be involved in cell-tropism but with some inconsistency.In this study,to further clarify the amino acids involved in the cell tropism of IBDV,a series of mutations about residue 279were introduced into the VP2 of vv IBDV Gx strain.With the reverse genetic system,we found single mutation of D279N,double mutations of D279N/A284T or Q253H/D279N were not enough to adapt IBDV to chicken embryo fibroblast（CEF）cell.To evaluate whether residue 279 could influence the replication and virulence of IBDV,the virus r Gx HT-279 with three mutations（Q253H/D279N/A284T）was rescued and evaluated.Results showed that the mutation of residue 279 in VP2had no efficient effects on both the replication efficiency in vitro and the virulence to SPF chickens of IBDV.In summary,the results demonstrated that residue 279 of VP2 did not contribute efficiently to cell tropism,replication efficiency,and virulence of IBDV at least in some strains.These findings provided further information for understanding the gene function of IBDV.
文摘After infection and integration steps, HIV-1 transcriptions increase sharply and singly-spliced mRNAs are produced. These encode Env （gpl20 and gp41） and auxiliary proteins Vif, Vpr and VpU. The same localization within the unique structure of the mRNAs suggests that the VpU sequence prior to the Env could affect the Env polyprotein expression.The HIV-I infection process begins when the gpl20 subunit of the envelope glycoprotein complex interacts with its receptor（s） on the target cell. The V3 domain of gpl20 is the major determinant of cellular co-receptor binding. According to phenotypic information of HIVol isolates, sequences from the VpU to V3 regions （119 in R5- and 120 X4-tropic viruses; one per patient） were analysed. The binomial correlation phi coefficient was used to assess covariation among VpU and gpl20v3 signatures. Subsequently, average linkage hierarchical agglomerative clustering was performed. Beyond the classical V3 signatures （R5-viruses： SI1, E25D; X4-viruses： SllKR, E25KRQ）, other specific V3 and novel VpU signatures were found to be statistically associated with co-receptor usage. Several statistically significant associations between V3 and VpU mutations were also observed. The dendrogram showed two distinct large clusters： one associated with R5-tropic sequences （bootstrap=0.94）, involving： （a） H13NPv3, E25Dv3, Sllv3, T22Av3 and Q61Hvpu, （b） E25Av3 and L12Fvpu, （c） D44Evpu, R18Qv3 and D80Nvpu; and another associated with X4-tropic sequences （bootstrap=0.97）, involving： （i） E25Iv3 and V10Avpu, （ii） 0-1insVvpc, H13Rv3, I46Lvpc, I30Mv3 and 60-62delvpu, （iii） SllKRv3 and E25KRQv3. Some of these pairs of mutations were encoded always by one specific codon. These data indicate the possible VpU mutational patterns contributing to regulation of HIV-I tropism.
基金approved by the Institutional Review Board of the Azienda Ospedaliero-Universitaria di Bologna,Italy(Approval No.2257/2020).
文摘BACKGROUND Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)is the pathogen responsible for pandemic coronavirus disease 2019(COVID-19).It is a highly contagious virus which primarily affects the respiratory tract,nevertheless,the lungs are not the only target organs of the virus.The intestinal tract could represent an additional tropism site for SARS-CoV-2.Several observations have collectively suggested that enteric infections can occur in COVID-19 patients.However,the detection of viral RNA in gastrointestinal(GI)tissue samples has not been adequately investigated and results are conflicting.AIM To detect the presence of SARS-CoV-2 RNA in intestinal mucosa samples and to evaluate histological features.METHODS The COVID-19 patients hospitalized at an Italian tertiary hospital from April 2020 to March 2021 were evaluated for enrollment in an observational,monocentric trial.The study population was composed of two groups of adult patients.In the first group(biopsy group,30 patients),patients were eligible for inclusion if they had mild to moderate disease and if they agreed to have a rectal biopsy;in the second group(surgical specimen group,6 patients),patients were eligible for inclusion if they underwent intestinal resection during index hospitalization.Fifty-nine intestinal mucosal samples were analyzed.RESULTS Viral RNA was not detectable in any of the rectal biopsies performed(0/53).Histological examination showed no enterocyte damage,but slight edema of the lamina propria with mild inflammatory lymphoplasmacytic infiltration.There was no difference in inflammatory infiltrates in patients with and without GI symptoms.SARS-CoV-2 RNA was detected in fecal samples in 6 cases out of 14 cases examined(42.9%).In the surgical specimen group,all patients underwent emergency intestinal resection.Viral RNA was detected in 2 surgical specimens of the 6 examined,both of which were from patients with active neoplastic disease.Histological examination also pointed out abundant macrophages,granulocytes and plasma cells infiltrating the muscular layer and adipose tissue,and focal vasculitis.CONCLUSION Mild-moderate COVID-19 may not be associated with rectal infection by the virus.More comprehensive autopsies or surgical specimens are needed to provide histological evidence of intestinal infection.
基金the National Key Research and Development Program of China(2021YFC0863400,2022YFC2604105).
文摘Emerging and re-emerging viruses from wild animals have seriously threatened the health of humans and domesticated animals in recent years.Herein,we isolated a new mammalian orthoreovirus(MRV),Pika/MRV/GCCDC7/2019(PMRV-GCCDC7),in the Qinghai-Tibet Plateau wild pika(Ochotona curzoniae).Though the PMRVGCCDC7 shows features of a typical reovirus with ten gene segments arranged in 3:3:4 in length,the virus belongs to an independent evolutionary branch compared to other MRVs based on phylogenetic tree analysis.The results of cellular susceptibility,species tropism,and replication kinetics of PMRV-GCCDC7 indicated the virus could infect four human cell lines(A549,Huh7,HCT,and LoVo)and six non-human cell lines,including Vero-E6,LLCMK2,BHK-21,N2a,MDCK,and RfKT cell,derived from diverse mammals,i.e.monkey,mice,canine and bat,which revealed the potential of PMRV-GCCDC7 to infect a variety of hosts.Infection of BALB/c mice with PMRVGCCDC7 via intranasal inoculation led to relative weight loss,lung tissue damage and inflammation with the increase of virus titer,but no serious respiratory symptoms and death occurred.The characterization of the new reovirus from a plateau-based wild animal has expanded our knowledge of the host range of MRV and provided insight into its risk of trans-species transmission and zoonotic diseases.
