Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is no...Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.展开更多
Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)iso...Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.展开更多
Transfer RNA(tRNA)-derived fragments,a new type of tRNA-derived small RNA(tsRNA),can be cleaved from tRNA by enzymes to regulate target gene expression at the transcriptional and translational levels.tsRNAs are not on...Transfer RNA(tRNA)-derived fragments,a new type of tRNA-derived small RNA(tsRNA),can be cleaved from tRNA by enzymes to regulate target gene expression at the transcriptional and translational levels.tsRNAs are not only degradation fragments but also have biological functions,including those in immune inflammation,metabolic disorders,and cell death.tsRNA dysregulation is closely associated with multiple diseases,including various cancers and acute pancreatitis(AP).AP is a common gastrointestinal disease,and its incidence increases annually.AP development is associated with tsRNAs,which regulate cell injury and induce inflammation,especially pyroptosis and ferroptosis.Notably,serum tRF36 has the potential to serve as a non-invasive diagnostic biomarker and leads to pancreatic acinar cell ferroptosis causing inflammation to promote AP.We show the characteristics of tsRNAs and their diagnostic value and function in AP,and discuss the potential opportunities and challenges of using tsRNAs in clinical applications and research.展开更多
Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limit...Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.展开更多
BACKGROUND Small cell lung cancer(SCLC)is the most malignant type of lung cancer.Even in the latent period and early stage of the tumor,SCLC is prone to produce distant metastases with complex and diverse clinical man...BACKGROUND Small cell lung cancer(SCLC)is the most malignant type of lung cancer.Even in the latent period and early stage of the tumor,SCLC is prone to produce distant metastases with complex and diverse clinical manifestations.SCLC is most closely related to paraneoplastic syndrome,and some cases present as paraneoplastic peripheral neuropathy(PPN).PPN in SCLC appears early,lacks specificity,and often occurs before diagnosis of the primary tumor.It is easy to be misdiagnosed as a primary disease of the nervous system,leading to missed diagnosis and delayed diagnosis and treatment.CASE SUMMARY This paper reports two cases of SCLC with limb weakness as the first symptom.The first symptoms of one patient were rash,limb weakness,and abnormal electromyography.The patient was repeatedly referred to the hospital for limb weakness and rash for>1 year,during which time,treatment with hormones and immunosuppressants did not lead to significant improvement,and the condition gradually aggravated.The patient was later diagnosed with SCLC,and the dyskinesia did not worsen as the dermatomyositis improved after antineoplastic and hormone therapy.The second case presented with limb numbness and weakness as the first symptom,but the patient did not pay attention to it.Later,the patient was diagnosed with SCLC after facial edema caused by tumor thrombus invading the vein.However,he was diagnosed with extensive SCLC and died 1 year after diagnosis.CONCLUSION The two cases had PPN and abnormal electromyography,highlighting its correlation with early clinical indicators of SCLC.展开更多
The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are...The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start networks.Here we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal cells.In this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)cDNA.To investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were used.Neurite outgrowth is evaluated through the segmentation and measurement of neural processes.These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth.These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22.DDQ-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-tubulin.Additionally,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth.Our findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara cteristics.The key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.展开更多
An investigation of sucking lice on the body surface of small mammals was carried out in the surrounding areas of Erhai Lake in Dali, Yunnan from 2003 to 2004. From investigation sites, 3 303 small mammal hosts were c...An investigation of sucking lice on the body surface of small mammals was carried out in the surrounding areas of Erhai Lake in Dali, Yunnan from 2003 to 2004. From investigation sites, 3 303 small mammal hosts were captured and identified into 7 families, 15 genera and 21 species in 4 orders (Rodentia, Insectivora, Scandentia and Carnivora), while t4 635 individuals of sucking lice collected from the body surface of the small mammal hosts are identified into 5 families, 6 genera and 21 species in the Order Anoplura, The sites stand alongside three cordilleras surrounding the Erhai Lake, namely Eastern Wuliang Mountain, Southern Ailao Mountain and Western Cangshan Mountain. The three confined oriented areas are different landscapes within the same zone where the longitude, latitude, altitude and fauna are homologous but isolated by Erhai Lake as inartificial barrier. The aim of this study was to recognize features of the species diversity, abundance, community structure, similarity and distribution of sucking lice in different landscapes within the same zone. The results showed the species diversity of sucking lice was very low with a very simple community structure. The distribution of sucking lice and their corresponding hosts are quite uneven among different oriented areas and this may imply that ecological environment influences the species composition and distribution of sucking lice and their corresponding hosts. A certain species of hosts usually have their fixed louse species. The similarity of sucking louse communities is highly consistent with the affinity of small mammal hosts in taxonomy. Species of sucking lice on the same small mammal host in different oriented areas of Erhai Lake are homologous. The results strongly suggest a close relationship of co-evolution between sucking lice and their hosts.展开更多
A thorough analysis on its natural environment as well as social economic status of the hilly-gullied loess region is presented. A small watershed, the dominant landscape unit of the region, has been singled out for f...A thorough analysis on its natural environment as well as social economic status of the hilly-gullied loess region is presented. A small watershed, the dominant landscape unit of the region, has been singled out for further and specific study on landscape pattern and function, its social and economic distinctions. The authors proposed several principles based on its eco-economic background study, which includes water balance and efficient use principle, co-development of grass and agro-forestry principle, location optimization principle. Integrated with detailed analysis of a small watershed, an eco-productive paradigm for the loess land's development based on a small watershed scale was worked out. It consists of circle pattern with villages at core for high efficient agriculture production, hierarchical pattern along the slope for eco-economic development, point-axis pattern for commodity production and circulation in small watersheds and core-margin pattern for exchanges among watersheds.展开更多
The definition and type of recreational belt around metropolis were introduced,the development principles of recreational spot around small and middle cities were analyzed.With Baoding City as an example,the empirical...The definition and type of recreational belt around metropolis were introduced,the development principles of recreational spot around small and middle cities were analyzed.With Baoding City as an example,the empirical analysis was conducted,and the development models of recreational spot around metropolis in Baoding City were put forward.展开更多
Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive malignancy with distinctive histological features: a nesting pattern of cellular growth within dense desmoplastic stroma, occurring in young ...Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive malignancy with distinctive histological features: a nesting pattern of cellular growth within dense desmoplastic stroma, occurring in young population with male predominance. The mean survival period is only about 1.5-2.5 years. The tumor has co-expressed epithelial, muscle, and neural markers in immunohistochemical studies. This work reports a 27-year-old man presenting with hematemesis and chronic constipation. Serial studies including endoscopy, upper gastrointestinal series, abdominal computed tomography and barium enema study showed disseminated involvement of visceral organs. The patient underwent aggressive surgery and received postoperative adjuvant chemotherapy consisting of 5-fluorouracil, cyclophosphamide, etoposide, doxorubicin, and cisplatin. He survived without any disease for 20 mo after the surgery. No standard treatment protocol has been established. Aggressive surgery combined with postoperative multi-agent adjuvant chemotherapy is justified not only to relieve symptoms but also to try to improve the outcome in this advanced DSRCT young patient.展开更多
With the increasing traffic demand, the closely built three or more tunnels with large section play a significant role in the tunnel construction. However, the interaction among tunnels has important influences on the...With the increasing traffic demand, the closely built three or more tunnels with large section play a significant role in the tunnel construction. However, the interaction among tunnels has important influences on the security and economy of tunnel engineering, and the calculation of pressure from the surrounding rock during the excavation is one of the problems that need to be solved urgently. Based on the practical engineering of three tunnels, the load model of three tunnels was proposed in consideration of the interaction and excavation sequence between tunnels. In comparison with the load model of single tunnel, the construction mechanical characteristics of the three tunnels were analyzed. The results show that the rock pressure of three tunnels calculated by the current tunnel design code is not reliable, and the interaction force increases with the spacing between tunnels.展开更多
To investigate the clinical and computed tomography(CT)features of desmoplastic small round cell tumor(DSRCT),we retrospectively analyzed the clinical presentations,treatment and outcome,as well as CT manifestations o...To investigate the clinical and computed tomography(CT)features of desmoplastic small round cell tumor(DSRCT),we retrospectively analyzed the clinical presentations,treatment and outcome,as well as CT manifestations of four cases of DSRCT confirmed by surgery and pathology.The CT manifestations of DSRCT were as follows:(1)multiple soft-tissue masses or diffuse peritoneal thickening in the abdomen and pelvis,with the dominant mass usually located in the pelvic cavity;(2)masses without an apparent organbased primary site;(3)mild to moderate homogeneous or heterogeneous enhancement in solid area on enhanced CT;and(4)secondary manifestations,such as ascites,hepatic metastases,lymphadenopathy,hydronephrosis and hydroureter.The prognosis and overall survival rates were generally poor.Commonly used treatment strategies including aggressive tumor resection,polychemotherapy,and radiotherapy,showed various therapeutic effects.CT of DSRCT shows characteristic features that are helpful in diagnosis.Early discovery and complete resection,coupled with postoperative adjuvant chemotherapy,are important for prognosis of DSRCT.Whole abdominopelvic rather than locoregional radiotherapy is more effective for unresectable DSRCT.展开更多
Prediction of tunneling-induced ground settlements is an essential task,particularly for tunneling in urban settings.Ground settlements should be limited within a tolerable threshold to avoid damages to aboveground st...Prediction of tunneling-induced ground settlements is an essential task,particularly for tunneling in urban settings.Ground settlements should be limited within a tolerable threshold to avoid damages to aboveground structures.Machine learning(ML)methods are becoming popular in many fields,including tunneling and underground excavations,as a powerful learning and predicting technique.However,the available datasets collected from a tunneling project are usually small from the perspective of applying ML methods.Can ML algorithms effectively predict tunneling-induced ground settlements when the available datasets are small?In this study,seven ML methods are utilized to predict tunneling-induced ground settlement using 14 contributing factors measured before or during tunnel excavation.These methods include multiple linear regression(MLR),decision tree(DT),random forest(RF),gradient boosting(GB),support vector regression(SVR),back-propagation neural network(BPNN),and permutation importancebased BPNN(PI-BPNN)models.All methods except BPNN and PI-BPNN are shallow-structure ML methods.The effectiveness of these seven ML approaches on small datasets is evaluated using model accuracy and stability.The model accuracy is measured by the coefficient of determination(R2)of training and testing datasets,and the stability of a learning algorithm indicates robust predictive performance.Also,the quantile error(QE)criterion is introduced to assess model predictive performance considering underpredictions and overpredictions.Our study reveals that the RF algorithm outperforms all the other models with the highest model prediction accuracy(0.9)and stability(3.0210^(-27)).Deep-structure ML models do not perform well for small datasets with relatively low model accuracy(0.59)and stability(5.76).The PI-BPNN architecture is proposed and designed for small datasets,showing better performance than typical BPNN.Six important contributing factors of ground settlements are identified,including tunnel depth,the distance between tunnel face and surface monitoring points(DTM),weighted average soil compressibility modulus(ACM),grouting pressure,penetrating rate and thrust force.展开更多
A desmoplastic small round cell tumor (DSRCT) is a rare, aggressive mesenchymal neoplasm. Although a DSRCT can develop at various sites, the intraabdominal site is the most common location. These tumors are found most...A desmoplastic small round cell tumor (DSRCT) is a rare, aggressive mesenchymal neoplasm. Although a DSRCT can develop at various sites, the intraabdominal site is the most common location. These tumors are found most commonly among young adolescents and the prognosis is extremely poor. Multimodal treatment with surgery, chemotherapy and radiotherapy is very important for these rare cases, and this treatment can improve patient survival. In this report, we describe the case of an 8-year-old boy diagnosed with DSRCT located in the retroperitoneal space. The patient has undergone surgical resection and adjuvant chemoradiation therapy, and is currently alive without disease recurrence.展开更多
In this article,authors review the current knowledge of Bartonella infection in small mammals including rodents,insectivores,bats and exotic small mammal pets and their vectors in Asia.Species of Bartonella are Gram-n...In this article,authors review the current knowledge of Bartonella infection in small mammals including rodents,insectivores,bats and exotic small mammal pets and their vectors in Asia.Species of Bartonella are Gram-negative intracellular bacteria that infect erythrocytes of various mammalian and non-mammalian animals and mainly transmitted by blood sucking arthropod vectors.The genus Bartonella includes several species of important human diseases with severe clinical signs.Several new Bartonella species were isolated from rodents and other small mammals,and from human patients in Asia.Bartonella species are identified using standard polymerase chain reaction amplification and a sequencing targeting two housekeeping genes(glt.A and rpoB) and the internal transcribed spacer fragment.Authors also discuss the implications in term of potential emerging zoonotic diseases.展开更多
Oxygen is one of the important substances for the survival of most life systems on the earth,and plateau and underground burrow systems are two typical hypoxic environments.Small mammals living in hypoxic environments...Oxygen is one of the important substances for the survival of most life systems on the earth,and plateau and underground burrow systems are two typical hypoxic environments.Small mammals living in hypoxic environments have evolved different adaptation strategies,which include increased oxygen delivery,metabolic regulation of physiological responses and other physiological responses that change tissue oxygen utilization.Multiomics predictions have also shown that these animals have evolved different adaptations to extreme environments.In particular,vascular endothelial growth factor(VEGF)and erythropoietin(EPO),which have specific functions in the control of O_(2) delivery,have evolved adaptively in small mammals in hypoxic environments.Naked mole-rats and blind mole-rats are typical hypoxic model animals as they have some resistance to cancer.This review primarily summarizes the main living environment of hypoxia tolerant small mammals,as well as the changes of phenotype,physiochemical characteristics and gene expression mode of their long-term living in hypoxia environment.展开更多
The aboveground biomass(AGB)of shrubs and small trees is the main component for the productivity and carbon storage of understory vegetation in subtropical secondary forests.However,few allometric models exist to accu...The aboveground biomass(AGB)of shrubs and small trees is the main component for the productivity and carbon storage of understory vegetation in subtropical secondary forests.However,few allometric models exist to accurately evaluate understory biomass.To estimate the AGB of five common shrub(diameter at base<5 cm,<5 m high)and one small tree species(<8 m high,trees’s seedling),206 individuals were harvested and species-specific and multi-species allometric models developed based on four predictors,height(H),stem diameter(D),crown area(Ca),and wood density(ρ).As expected,the six species possessed greater biomass in their stems compared with branches,with the lowest biomass in the leaves.Species-specific allometric models that employed stem diameter and the combined variables of D~2H andρDH as predictors accurately estimated the components and total AGB,with R^(2) values from 0.602 and 0.971.A multi-species shrub allometric model revealed that wood density×diameter×height(ρDH)was the best predictor,with R^(2) values ranging from between 0.81 and 0.89 for the components and total AGB,respectively.These results indicated that height(H)and diameter(D)were effective predictors for the models to estimate the AGB of the six species,and the introduction of wood density(ρ)improved their accuracy.The optimal models selected in this study could be applied to estimate the biomass of shrubs and small trees in subtropical regions.展开更多
Background: Weaning is known to result in barrier dysfunction and villus atrophy in the immediate post-weaning phase, and the magnitude of these responses is hypothesized to correlate with changes in the glutathione(G...Background: Weaning is known to result in barrier dysfunction and villus atrophy in the immediate post-weaning phase, and the magnitude of these responses is hypothesized to correlate with changes in the glutathione(GSH)redox system. Therefore, these parameters were simultaneously measured throughout the weaning phase, in piglets differing in birth weight category and weaning age, as these pre-weaning factors are important determinants for the weaning transition. Low birth weight(LBW) and normal birth weight(NBW) littermates were assigned to one of three weaning treatments;i.e. weaning at 3 weeks of age(3 w), weaning at 4 weeks of age(4 w) and removal from the sow at 3 d of age and fed a milk replacer until weaning at 3 weeks of age(3 d3 w). For each of these treatments, six LBW and six NBW piglets were euthanized at 0, 2, 5, 12 or 28 d post-weaning piglets, adding up 180 piglets.Results: Weaning increased the glutathione peroxidase activity on d 5 post-weaning in plasma, and duodenal and jejunal mucosa. Small intestinal glutathione-S-transferase activity gradually increased until d 12 post-weaning, and this was combined with a progressive rise of mucosal GSH up till d 12 post-weaning. Oxidation of the GSH redox status(GSH/GSSG Eh) was only observed in the small intestinal mucosa of 3 d3 w weaned piglets at d 5 postweaning. These piglets also demonstrated increased fluorescein isothiocyanate dextran(FD4) and horseradish peroxidase fluxes in the duodenum and distal jejunum during the experiment, and specifically demonstrated increased FD4 fluxes at d 2 to d 5 post-weaning. On the other hand, profound villus atrophy was observed during the weaning transition for all weaning treatments. Finally, LBW and NBW piglets did not demonstrate notable differences in GSH redox status, small intestinal barrier function and histo-morphology throughout the experiment.Conclusion: Although moderate changes in the GSH redox system were observed upon weaning, the GSH redox status remained at a steady state level in 3 w and 4 w weaned piglets and was therefore not associated with weaning induced villus atrophy. Conversely, 3 d3 w weaned piglets demonstrated GSH redox imbalance in the small intestinal mucosa, and this co-occurred with a temporal malfunction of their intestinal barrier function.展开更多
基金supported by China Scholarship Council(202208210093,to RJ)。
文摘Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.
基金supported by the NIH grants,R01 NS111801(to ZGZ)American Heart Association 16SDG29860003(to YZ)。
文摘Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.
基金Supported by the Central South University Innovation-Driven Research Programme,No.2023CXQD075。
文摘Transfer RNA(tRNA)-derived fragments,a new type of tRNA-derived small RNA(tsRNA),can be cleaved from tRNA by enzymes to regulate target gene expression at the transcriptional and translational levels.tsRNAs are not only degradation fragments but also have biological functions,including those in immune inflammation,metabolic disorders,and cell death.tsRNA dysregulation is closely associated with multiple diseases,including various cancers and acute pancreatitis(AP).AP is a common gastrointestinal disease,and its incidence increases annually.AP development is associated with tsRNAs,which regulate cell injury and induce inflammation,especially pyroptosis and ferroptosis.Notably,serum tRF36 has the potential to serve as a non-invasive diagnostic biomarker and leads to pancreatic acinar cell ferroptosis causing inflammation to promote AP.We show the characteristics of tsRNAs and their diagnostic value and function in AP,and discuss the potential opportunities and challenges of using tsRNAs in clinical applications and research.
基金supported by the National Natural Science Foundation of China,No.82271114the Natural Science Foundation of Zhejiang Province of China,No.LZ22H120001(both to ZLC).
文摘Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.
基金Supported by Science and Technology Plan Project of Jiaxing,No.2021AD30044Supporting Discipline of Neurology in Jiaxing,No.2023-ZC-006Affiliated Hospital of Jiaxing University,No.2020-QMX-16.
文摘BACKGROUND Small cell lung cancer(SCLC)is the most malignant type of lung cancer.Even in the latent period and early stage of the tumor,SCLC is prone to produce distant metastases with complex and diverse clinical manifestations.SCLC is most closely related to paraneoplastic syndrome,and some cases present as paraneoplastic peripheral neuropathy(PPN).PPN in SCLC appears early,lacks specificity,and often occurs before diagnosis of the primary tumor.It is easy to be misdiagnosed as a primary disease of the nervous system,leading to missed diagnosis and delayed diagnosis and treatment.CASE SUMMARY This paper reports two cases of SCLC with limb weakness as the first symptom.The first symptoms of one patient were rash,limb weakness,and abnormal electromyography.The patient was repeatedly referred to the hospital for limb weakness and rash for>1 year,during which time,treatment with hormones and immunosuppressants did not lead to significant improvement,and the condition gradually aggravated.The patient was later diagnosed with SCLC,and the dyskinesia did not worsen as the dermatomyositis improved after antineoplastic and hormone therapy.The second case presented with limb numbness and weakness as the first symptom,but the patient did not pay attention to it.Later,the patient was diagnosed with SCLC after facial edema caused by tumor thrombus invading the vein.However,he was diagnosed with extensive SCLC and died 1 year after diagnosis.CONCLUSION The two cases had PPN and abnormal electromyography,highlighting its correlation with early clinical indicators of SCLC.
基金supported by NIH grants AG079264(to PHR)and AG071560(to APR)。
文摘The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start networks.Here we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal cells.In this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)cDNA.To investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were used.Neurite outgrowth is evaluated through the segmentation and measurement of neural processes.These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth.These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22.DDQ-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-tubulin.Additionally,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth.Our findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara cteristics.The key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.
基金This project was supported by the Natural Science Foundation of China(30460125)
文摘An investigation of sucking lice on the body surface of small mammals was carried out in the surrounding areas of Erhai Lake in Dali, Yunnan from 2003 to 2004. From investigation sites, 3 303 small mammal hosts were captured and identified into 7 families, 15 genera and 21 species in 4 orders (Rodentia, Insectivora, Scandentia and Carnivora), while t4 635 individuals of sucking lice collected from the body surface of the small mammal hosts are identified into 5 families, 6 genera and 21 species in the Order Anoplura, The sites stand alongside three cordilleras surrounding the Erhai Lake, namely Eastern Wuliang Mountain, Southern Ailao Mountain and Western Cangshan Mountain. The three confined oriented areas are different landscapes within the same zone where the longitude, latitude, altitude and fauna are homologous but isolated by Erhai Lake as inartificial barrier. The aim of this study was to recognize features of the species diversity, abundance, community structure, similarity and distribution of sucking lice in different landscapes within the same zone. The results showed the species diversity of sucking lice was very low with a very simple community structure. The distribution of sucking lice and their corresponding hosts are quite uneven among different oriented areas and this may imply that ecological environment influences the species composition and distribution of sucking lice and their corresponding hosts. A certain species of hosts usually have their fixed louse species. The similarity of sucking louse communities is highly consistent with the affinity of small mammal hosts in taxonomy. Species of sucking lice on the same small mammal host in different oriented areas of Erhai Lake are homologous. The results strongly suggest a close relationship of co-evolution between sucking lice and their hosts.
文摘A thorough analysis on its natural environment as well as social economic status of the hilly-gullied loess region is presented. A small watershed, the dominant landscape unit of the region, has been singled out for further and specific study on landscape pattern and function, its social and economic distinctions. The authors proposed several principles based on its eco-economic background study, which includes water balance and efficient use principle, co-development of grass and agro-forestry principle, location optimization principle. Integrated with detailed analysis of a small watershed, an eco-productive paradigm for the loess land's development based on a small watershed scale was worked out. It consists of circle pattern with villages at core for high efficient agriculture production, hierarchical pattern along the slope for eco-economic development, point-axis pattern for commodity production and circulation in small watersheds and core-margin pattern for exchanges among watersheds.
文摘The definition and type of recreational belt around metropolis were introduced,the development principles of recreational spot around small and middle cities were analyzed.With Baoding City as an example,the empirical analysis was conducted,and the development models of recreational spot around metropolis in Baoding City were put forward.
文摘Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive malignancy with distinctive histological features: a nesting pattern of cellular growth within dense desmoplastic stroma, occurring in young population with male predominance. The mean survival period is only about 1.5-2.5 years. The tumor has co-expressed epithelial, muscle, and neural markers in immunohistochemical studies. This work reports a 27-year-old man presenting with hematemesis and chronic constipation. Serial studies including endoscopy, upper gastrointestinal series, abdominal computed tomography and barium enema study showed disseminated involvement of visceral organs. The patient underwent aggressive surgery and received postoperative adjuvant chemotherapy consisting of 5-fluorouracil, cyclophosphamide, etoposide, doxorubicin, and cisplatin. He survived without any disease for 20 mo after the surgery. No standard treatment protocol has been established. Aggressive surgery combined with postoperative multi-agent adjuvant chemotherapy is justified not only to relieve symptoms but also to try to improve the outcome in this advanced DSRCT young patient.
基金Project(2011CB01380) supported by the National Basic Research Program of ChinaProject(51178468) supported by the National Natural Science Foundation of ChinaProject(2011G013-B) supported by Science and Technology Development of Railways Department in China
文摘With the increasing traffic demand, the closely built three or more tunnels with large section play a significant role in the tunnel construction. However, the interaction among tunnels has important influences on the security and economy of tunnel engineering, and the calculation of pressure from the surrounding rock during the excavation is one of the problems that need to be solved urgently. Based on the practical engineering of three tunnels, the load model of three tunnels was proposed in consideration of the interaction and excavation sequence between tunnels. In comparison with the load model of single tunnel, the construction mechanical characteristics of the three tunnels were analyzed. The results show that the rock pressure of three tunnels calculated by the current tunnel design code is not reliable, and the interaction force increases with the spacing between tunnels.
文摘To investigate the clinical and computed tomography(CT)features of desmoplastic small round cell tumor(DSRCT),we retrospectively analyzed the clinical presentations,treatment and outcome,as well as CT manifestations of four cases of DSRCT confirmed by surgery and pathology.The CT manifestations of DSRCT were as follows:(1)multiple soft-tissue masses or diffuse peritoneal thickening in the abdomen and pelvis,with the dominant mass usually located in the pelvic cavity;(2)masses without an apparent organbased primary site;(3)mild to moderate homogeneous or heterogeneous enhancement in solid area on enhanced CT;and(4)secondary manifestations,such as ascites,hepatic metastases,lymphadenopathy,hydronephrosis and hydroureter.The prognosis and overall survival rates were generally poor.Commonly used treatment strategies including aggressive tumor resection,polychemotherapy,and radiotherapy,showed various therapeutic effects.CT of DSRCT shows characteristic features that are helpful in diagnosis.Early discovery and complete resection,coupled with postoperative adjuvant chemotherapy,are important for prognosis of DSRCT.Whole abdominopelvic rather than locoregional radiotherapy is more effective for unresectable DSRCT.
基金funded by the University Transportation Center for Underground Transportation Infrastructure(UTC-UTI)at the Colorado School of Mines under Grant No.69A3551747118 from the US Department of Transportation(DOT).
文摘Prediction of tunneling-induced ground settlements is an essential task,particularly for tunneling in urban settings.Ground settlements should be limited within a tolerable threshold to avoid damages to aboveground structures.Machine learning(ML)methods are becoming popular in many fields,including tunneling and underground excavations,as a powerful learning and predicting technique.However,the available datasets collected from a tunneling project are usually small from the perspective of applying ML methods.Can ML algorithms effectively predict tunneling-induced ground settlements when the available datasets are small?In this study,seven ML methods are utilized to predict tunneling-induced ground settlement using 14 contributing factors measured before or during tunnel excavation.These methods include multiple linear regression(MLR),decision tree(DT),random forest(RF),gradient boosting(GB),support vector regression(SVR),back-propagation neural network(BPNN),and permutation importancebased BPNN(PI-BPNN)models.All methods except BPNN and PI-BPNN are shallow-structure ML methods.The effectiveness of these seven ML approaches on small datasets is evaluated using model accuracy and stability.The model accuracy is measured by the coefficient of determination(R2)of training and testing datasets,and the stability of a learning algorithm indicates robust predictive performance.Also,the quantile error(QE)criterion is introduced to assess model predictive performance considering underpredictions and overpredictions.Our study reveals that the RF algorithm outperforms all the other models with the highest model prediction accuracy(0.9)and stability(3.0210^(-27)).Deep-structure ML models do not perform well for small datasets with relatively low model accuracy(0.59)and stability(5.76).The PI-BPNN architecture is proposed and designed for small datasets,showing better performance than typical BPNN.Six important contributing factors of ground settlements are identified,including tunnel depth,the distance between tunnel face and surface monitoring points(DTM),weighted average soil compressibility modulus(ACM),grouting pressure,penetrating rate and thrust force.
文摘A desmoplastic small round cell tumor (DSRCT) is a rare, aggressive mesenchymal neoplasm. Although a DSRCT can develop at various sites, the intraabdominal site is the most common location. These tumors are found most commonly among young adolescents and the prognosis is extremely poor. Multimodal treatment with surgery, chemotherapy and radiotherapy is very important for these rare cases, and this treatment can improve patient survival. In this report, we describe the case of an 8-year-old boy diagnosed with DSRCT located in the retroperitoneal space. The patient has undergone surgical resection and adjuvant chemoradiation therapy, and is currently alive without disease recurrence.
基金Supported by the French ANR CERoPath project(number ANR 07 BDIV 012)the French ANR BiodivHealthSEA project(number ANR 11 CPEL.002)
文摘In this article,authors review the current knowledge of Bartonella infection in small mammals including rodents,insectivores,bats and exotic small mammal pets and their vectors in Asia.Species of Bartonella are Gram-negative intracellular bacteria that infect erythrocytes of various mammalian and non-mammalian animals and mainly transmitted by blood sucking arthropod vectors.The genus Bartonella includes several species of important human diseases with severe clinical signs.Several new Bartonella species were isolated from rodents and other small mammals,and from human patients in Asia.Bartonella species are identified using standard polymerase chain reaction amplification and a sequencing targeting two housekeeping genes(glt.A and rpoB) and the internal transcribed spacer fragment.Authors also discuss the implications in term of potential emerging zoonotic diseases.
基金This work was supported by the National Natural Science Foundation of China,Grant No.U2004152.
文摘Oxygen is one of the important substances for the survival of most life systems on the earth,and plateau and underground burrow systems are two typical hypoxic environments.Small mammals living in hypoxic environments have evolved different adaptation strategies,which include increased oxygen delivery,metabolic regulation of physiological responses and other physiological responses that change tissue oxygen utilization.Multiomics predictions have also shown that these animals have evolved different adaptations to extreme environments.In particular,vascular endothelial growth factor(VEGF)and erythropoietin(EPO),which have specific functions in the control of O_(2) delivery,have evolved adaptively in small mammals in hypoxic environments.Naked mole-rats and blind mole-rats are typical hypoxic model animals as they have some resistance to cancer.This review primarily summarizes the main living environment of hypoxia tolerant small mammals,as well as the changes of phenotype,physiochemical characteristics and gene expression mode of their long-term living in hypoxia environment.
基金supported by the Special Major Science and Technology Project of Anhui Province(S202103b06020066)the 2020 Annual Graduate Innovation Fund of Anhui Agricultural University(2020YSJ-21)。
文摘The aboveground biomass(AGB)of shrubs and small trees is the main component for the productivity and carbon storage of understory vegetation in subtropical secondary forests.However,few allometric models exist to accurately evaluate understory biomass.To estimate the AGB of five common shrub(diameter at base<5 cm,<5 m high)and one small tree species(<8 m high,trees’s seedling),206 individuals were harvested and species-specific and multi-species allometric models developed based on four predictors,height(H),stem diameter(D),crown area(Ca),and wood density(ρ).As expected,the six species possessed greater biomass in their stems compared with branches,with the lowest biomass in the leaves.Species-specific allometric models that employed stem diameter and the combined variables of D~2H andρDH as predictors accurately estimated the components and total AGB,with R^(2) values from 0.602 and 0.971.A multi-species shrub allometric model revealed that wood density×diameter×height(ρDH)was the best predictor,with R^(2) values ranging from between 0.81 and 0.89 for the components and total AGB,respectively.These results indicated that height(H)and diameter(D)were effective predictors for the models to estimate the AGB of the six species,and the introduction of wood density(ρ)improved their accuracy.The optimal models selected in this study could be applied to estimate the biomass of shrubs and small trees in subtropical regions.
基金supported by a grant from the government agency for Innovation by Science and Technology (IWT-LO 100856)。
文摘Background: Weaning is known to result in barrier dysfunction and villus atrophy in the immediate post-weaning phase, and the magnitude of these responses is hypothesized to correlate with changes in the glutathione(GSH)redox system. Therefore, these parameters were simultaneously measured throughout the weaning phase, in piglets differing in birth weight category and weaning age, as these pre-weaning factors are important determinants for the weaning transition. Low birth weight(LBW) and normal birth weight(NBW) littermates were assigned to one of three weaning treatments;i.e. weaning at 3 weeks of age(3 w), weaning at 4 weeks of age(4 w) and removal from the sow at 3 d of age and fed a milk replacer until weaning at 3 weeks of age(3 d3 w). For each of these treatments, six LBW and six NBW piglets were euthanized at 0, 2, 5, 12 or 28 d post-weaning piglets, adding up 180 piglets.Results: Weaning increased the glutathione peroxidase activity on d 5 post-weaning in plasma, and duodenal and jejunal mucosa. Small intestinal glutathione-S-transferase activity gradually increased until d 12 post-weaning, and this was combined with a progressive rise of mucosal GSH up till d 12 post-weaning. Oxidation of the GSH redox status(GSH/GSSG Eh) was only observed in the small intestinal mucosa of 3 d3 w weaned piglets at d 5 postweaning. These piglets also demonstrated increased fluorescein isothiocyanate dextran(FD4) and horseradish peroxidase fluxes in the duodenum and distal jejunum during the experiment, and specifically demonstrated increased FD4 fluxes at d 2 to d 5 post-weaning. On the other hand, profound villus atrophy was observed during the weaning transition for all weaning treatments. Finally, LBW and NBW piglets did not demonstrate notable differences in GSH redox status, small intestinal barrier function and histo-morphology throughout the experiment.Conclusion: Although moderate changes in the GSH redox system were observed upon weaning, the GSH redox status remained at a steady state level in 3 w and 4 w weaned piglets and was therefore not associated with weaning induced villus atrophy. Conversely, 3 d3 w weaned piglets demonstrated GSH redox imbalance in the small intestinal mucosa, and this co-occurred with a temporal malfunction of their intestinal barrier function.