AIM:To evaluate visual outcomes of pars plana vitrectomy(PPV)combined with tissue plasminogen activator(tPA)-induced clot lysis and pneumatic displacement for submacular hemorrhage(SMH)in a cohort of closed-globe trau...AIM:To evaluate visual outcomes of pars plana vitrectomy(PPV)combined with tissue plasminogen activator(tPA)-induced clot lysis and pneumatic displacement for submacular hemorrhage(SMH)in a cohort of closed-globe trauma patients.METHODS:A retrospective,multicenter interventional case series involving 7 eyes of 7 patients who underwent PPV with subretinal tPA administration for SMH secondary to closed-globe injury were conducted.The primary outcome measure was the change in Snellen visual acuity.RESULTS:The mean age of patients was 32y(range:21-51y),with a mean follow-up duration of 4.6mo(range:1.1-14.9mo).The average best-corrected visual acuity(BCVA)was 20/1020 at baseline and 20/114 at the final visit,respectively(P=0.025).Preoperative BCVA was not a significant predictor of final BCVA(r=0.102,P=0.827).Final BCVA did not differ significantly between patients who underwent PPV within 14d of symptom onset and those who underwent surgery after 14d(P=0.57).All eyes received SF6 or C3F8 gas tamponade.CONCLUSION:Surgical intervention involving tPAmediated clot lysis and pneumatic displacement may yield visual benefits in trauma-induced SMH without underlying retinal vascular disease;however,larger prospective studies are warranted to confirm these findings.展开更多
BACKGROUND In vivo degradation of bone scaffolds is significantly influenced by osteoclast(OC)activity,which is orchestrated by the interplay between receptor activator of nuclear factor-kappa B ligand(RANKL)and osteo...BACKGROUND In vivo degradation of bone scaffolds is significantly influenced by osteoclast(OC)activity,which is orchestrated by the interplay between receptor activator of nuclear factor-kappa B ligand(RANKL)and osteoprotegerin(OPG).The ratio of RANKL/OPG is a crucial determinant of OC-mediated bone resorption,which plays an integral role in bone remodeling and scaffold degradation.Elevated levels of RANKL relative to OPG enhance osteoclastogenesis,thereby accelerating the degradation process essential for integrating bone scaffolds into the host tissue.AIM To elucidate the effects of OPG gene silencing on osteoclastogenesis within rat bone marrow-derived mesenchymal stem cells(BMSCs).By investigating these effects,the study aimed to provide deeper insights into the regulatory mechanisms that influence bone scaffold degradation,potentially leading to improved bone repair and regeneration strategies.METHODS We employed recombinant lentiviral plasmids to silence the OPG gene in rat BMSCs to achieve the aims.The efficacy of gene silencing was assessed using quantitative reverse transcription polymerase chain reaction and western blot analysis to measure the expression levels of OPG and RANKL.Tartrate-resistant acid phosphatase staining was utilized to evaluate the formation of OCs.Additionally,co-immunoprecipitation assays were conducted to explore the interactions between RANKL and OPG proteins,further assessing the biochemical pathways involved in osteoclastogenesis.RESULTS The silencing of the OPG gene in BMSCs resulted in a significant increase in the RANKL/OPG ratio,evidenced by decreased expression levels of OPG and increased levels of RANKL.Enhanced osteoclastogenesis was observed through tartrate-resistant acid phosphatase staining,which indicated a substantial rise in OC formation in response to the altered RANKL/OPG balance.The co-immunoprecipitation assays provided concrete evidence of the direct interaction between RANKL and OPG proteins,substantiating their pivotal roles in regulating OC activity.CONCLUSION The findings from this study underscore the critical role of the RANKL/OPG axis in osteoclastogenesis.Silencing of the OPG gene in BMSCs effectively increases the RANKL/OPG ratio,promoting OC activity and potentially enhancing bone scaffold degradation.This regulatory mechanism offers a promising avenue for modulating bone remodeling processes,which is essential for effective bone repair and the successful integration of bone scaffolds into damaged sites.Future research might focus on optimizing the control of this axis to better facilitate bone tissue engineering and regenerative therapies.展开更多
Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminog...Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminogen activator may come into contact with brain tissue.Therefore,a thorough assessment of its safety is required.In this study,we established a mouse model of intracerebral hemorrhage induced by type VII collagenase.We observed that the administration of recombinant tissue plasminogen activator without hematoma aspiration significantly improved the neurological function of mice with intracerebral hemorrhage,reduced pathological damage,and lowered the levels of apoptosis and autophagy in the tissue surrounding the hematoma.In an in vitro model of intracerebral hemorrhage using primary cortical neurons induced by hemin,the administration of recombinant tissue plasminogen activator suppressed neuronal apoptosis,autophagy,and endoplasmic reticulum stress.Transcriptome sequencing analysis revealed that recombinant tissue plasminogen activator upregulated the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway in neurons.Moreover,the phosphoinositide 3-kinase inhibitor LY294002 abrogated the neuroprotective effects of recombinant tissue plasminogen activator in inhibiting excessive apoptosis,autophagy,and endoplasmic reticulum stress.Furthermore,to specify the domain of recombinant tissue plasminogen activator responsible for its neuroprotective effects,various inhibitors were used to target distinct domains.It has been revealed that the epidermal growth factor receptor inhibitor AG-1478 reversed the effect of recombinant tissue plasminogen activator on the phosphoinositide 3-kinase/RAC-alpha serine/threonineprotein kinase/mammalian target of rapamycin pathway.These findings suggest that recombinant tissue plasminogen activator exerts a direct neuroprotective effect on neurons following intracerebral hemorrhage,possibly through activation of the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway.展开更多
Using cemented rockfill to replace coal pillars offers an effective solution for reducing solid waste while ensuring the safety of gob-side entries.However,achieving the balance among low cost,high waste recycling rat...Using cemented rockfill to replace coal pillars offers an effective solution for reducing solid waste while ensuring the safety of gob-side entries.However,achieving the balance among low cost,high waste recycling rates,and adequate strength remains a significant challenge for cemented rockfill.This study used a composite alkali activator to activate gangue cemented rockfill.The compressive strength,scanning electron microscopy,energy dispersive spectrometer,mercury intrusion porosimetry,X-ray diffraction,and thermogra-vimetric tests were carried out to investigate the effect of the composite alkali activator proportion on the compressive strength,micro-structure,and composition of the cemented rockfill.The calcium silicate hydrate(C–S–H)molecular model of cemented rockfill was con-structed to explore the fracture evolution of the nucleated molecular structure under tension.The results show that compressive strength initially increased and then decreased with the activator proportion,the optimal activator proportion of 1:2 resulted in a 31.25%increase in strength at 3 d.This reasonable activator proportion strengthens the pozzolanic effect of gangue,and consumes more calcium hydroxide to inhibit its agglomeration,ultimately achieving the densification of microstructure.The activator proportion inevitably substitutes calcium ions with sodium ions in the C–S–H molecular model.The 12%substitution of calcium ions increases the adhesion between silicon chain layers,which is beneficial to the interlayer stress transfer.This work proposes a method for preparing low-cost cemented rockfill from al-kali-activated gangue,which can be used for solid waste recycling and reducing cement consumption to achieve low-carbon goals.展开更多
The degradation of organic pollutants in water is a critical environmental challenge.The iron-doped MoS_(2) catalysts have demonstrated potential in activating peroxymonosulfate(PMS)for environmental remediation,but t...The degradation of organic pollutants in water is a critical environmental challenge.The iron-doped MoS_(2) catalysts have demonstrated potential in activating peroxymonosulfate(PMS)for environmental remediation,but they face challenges such as poor conductivity,limited electron transfer efficiency,and a scarcity of active sites.To address these issues,we successfully synthesized a nano-flowers FeS/MoS_(2) composite derived from polyoxometalates(NH_(4))_(3)[Fe(III)Mo_(6)O_(24)H_(6)]⋅6H_(2)O(denoted as FeMo6)as the bimetallic precursors.This synthesis strategy enhances the interaction between FeS and MoS_(2),thereby facilitating electron transfer.Notably,the introduction of sulfur vacancies in FeS/MoS_(2) exposes additional Mo4t active sites,promoting the redox cycle of Fe^(2+)/Fe^(3+) and accelerating the regeneration of Fe^(2+),which in turn enhances PMS activation.Therefore,a catalytic oxidation system of FeS/MoS_(2)/PMS is presented that primarily relies on SO_(4)^(⋅-)and⋅OH,with ^(1)O_(2) as a supplementary oxidant.This system exhibits exceptional degradation efficiency for p-chlorophenol(4-CP),achieving 100% degradation within 10 min over a wide pH range of 2.4–8.4.The robust performance and wide applicability of FeS/MoS_(2) catalyst make it a promising candidate in advanced oxidation processes(AOPs)for environmental remediation.展开更多
Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are inv...Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.展开更多
Avirulence effectors(Avrs),encoded by plant pathogens,can be recognized by plants harboring the corresponding resistance proteins,thereby initiating effector-triggered immunity(ETI).In susceptible plants,however,Avrs ...Avirulence effectors(Avrs),encoded by plant pathogens,can be recognized by plants harboring the corresponding resistance proteins,thereby initiating effector-triggered immunity(ETI).In susceptible plants,however,Avrs can function as effectors,facilitating infection via effector-triggered susceptibility(ETS).Mechanisms of Avr-mediated ETS remain largely unexplored.Here we report that the Magnaporthe oryzae effector Avr-PikD enters rice cells via the canonical cytoplasmic secretion pathway and suppresses rice basal defense.Avr-PikD interacts with an LSD1-like transcriptional activator AKIP30 of rice,and AKIP30 is also a positive regulator of rice immunity,whereas Avr-PikD impedes its nuclear localization and suppresses its transcriptional activity.In summary,M.oryzae delivers Avr-PikD into rice cells to facilitate ETS by inhibiting AKIP30-mediated transcriptional regulation of immune response against M.oryzae.展开更多
This study aims to further enhance the oil recovery of reservoirs in the Zhong-2 Block of the Gudao Oilfield by identifying the most effective microbial-flooding activator systems and applying them in the field.We beg...This study aims to further enhance the oil recovery of reservoirs in the Zhong-2 Block of the Gudao Oilfield by identifying the most effective microbial-flooding activator systems and applying them in the field.We began by analyzing the structure of the reservoirs'endogenous microbial communities to understand the potential impact of microbial flooding.This was followed by determining commonly used activator systems based on their abilities to stimulate oil-displacement functional bacteria.Through laboratory experiments on oil displacement efficiency and sweep characteristics,we determined the optimal activator injection method(injection ratio)and the requisite bacterial concentration for maximal microbial-flooding efficacy.Finally,we selected the optimal activator systems and applied them to field tests.Our findings suggest the target block is highly receptive to microbial-flooding.In terms of performance,the activator systems ranked as No.3>No.4>No.1>No.2.Interestingly,a deep activator system,when compared to the top-performing No.3 system,exhibited a higher bacterial concentration peak and longer peaking duration.Optimal oil displacement effects were observed at a 1:4 vol ratio between the No.3 activator and deep activator systems,with bacterial concentrations of up to 106 cells/mL or above.Field tests with the selected activator systems,following a specific injection protocol,demonstrated a notable increase in oil production and a reduction in water cut.展开更多
BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can sign...BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIM To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory environment.METHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BMSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs.Mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.展开更多
BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary...BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.展开更多
This study explores the diagnostic value of combining the Padua score with the thrombotic biomarker tissue plasminogen activator inhibitor-1(tPAI-1)for assessing the risk of deep vein thrombosis(DVT)in patients with p...This study explores the diagnostic value of combining the Padua score with the thrombotic biomarker tissue plasminogen activator inhibitor-1(tPAI-1)for assessing the risk of deep vein thrombosis(DVT)in patients with pulmonary heart disease.These patients often exhibit symptoms similar to venous thrombosis,such as dyspnea and bilateral lower limb swelling,complicating differential diagnosis.The Padua Prediction Score assesses the risk of venous thromboembolism(VTE)in hospitalized patients,while tPAI-1,a key fibrinolytic system inhibitor,indicates a hypercoagulable state.Clinical data from hospitalized patients with cor pulmonale were retrospectively analyzed.ROC curves compared the diagnostic value of the Padua score,tPAI-1 levels,and their combined model for predicting DVT risk.Results showed that tPAI-1 levels were significantly higher in DVT patients compared to non-DVT patients.The Padua score demonstrated a sensitivity of 82.61%and a specificity of 55.26%at a cutoff value of 3.The combined model had a significantly higher AUC than the Padua score alone,indicating better discriminatory ability in diagnosing DVT risk.The combination of the Padua score and tPAI-1 detection significantly improves the accuracy of diagnosing DVT risk in patients with pulmonary heart disease,reducing missed and incorrect diagnoses.This study provides a comprehensive assessment tool for clinicians,enhancing the diagnosis and treatment of patients with cor pulmonale complicated by DVT.Future research should validate these findings in larger samples and explore additional thrombotic biomarkers to optimize the predictive model.展开更多
Novel coal gangue-based persulfate catalyst(CG-FeCl_(2))was successfully synthesized by the means of calcinating under nitrogen atmosphere with the addition of ferrous chloride tetrahydrate(FeCl_(2)·_(4)H_(2)O).T...Novel coal gangue-based persulfate catalyst(CG-FeCl_(2))was successfully synthesized by the means of calcinating under nitrogen atmosphere with the addition of ferrous chloride tetrahydrate(FeCl_(2)·_(4)H_(2)O).The phase transformation of the prepared materials and gas products during the heating process are thoroughly investigated.It is suggested that ferrous chloride participated in the phase transformation and formed Si-O-Fe bonds.And the main gaseous products are H_(2)O,H_(2),and HCl during the heating process.Besides,the ability of CG-FeCl_(2) to activate peroxymonosulfate(PMS)for catalytic degradation of polycyclic aromatic hydrocarbons(PAHs)and phenol was deeply studied.More than 95%of naphthyl,phenanthrene and phenol were removed under optimizied conditions.In addition,1O_(2),·OH,and SO_(4)·−were involved in the CG-FeCl_(2)/PMS system from the free radical scavenging experiment,where 1O_(2) played a major role during the oxidation process.Furthermore,CG-FeCl_(2)/PMS system exhibited superior stability in a relatively wide pH range and the presence of common anion from related degradation experiments.Overall,the novel CG-FeCl_(2) is an efficient and environmentally friendly catalyst,displaying potential application prospect in the field of PAHs and phenol-contaminated wastewater treatment.展开更多
基金Supportea by DeNardo Education and Research Foundation GrantJeffrey T.Fort Innovation Fund+3 种基金Siteman Retina Research FundResearch to Prevent Blindness IncGetahun H is supported by Washington University in St.Louis School of Medicine Dean’s Medical Student Research Fellowship for the MD5 Yearlong Research ProgramGetahun H is also a recipient of a Research to Prevent Blindness Medical Student Eye Research Fellowship.
文摘AIM:To evaluate visual outcomes of pars plana vitrectomy(PPV)combined with tissue plasminogen activator(tPA)-induced clot lysis and pneumatic displacement for submacular hemorrhage(SMH)in a cohort of closed-globe trauma patients.METHODS:A retrospective,multicenter interventional case series involving 7 eyes of 7 patients who underwent PPV with subretinal tPA administration for SMH secondary to closed-globe injury were conducted.The primary outcome measure was the change in Snellen visual acuity.RESULTS:The mean age of patients was 32y(range:21-51y),with a mean follow-up duration of 4.6mo(range:1.1-14.9mo).The average best-corrected visual acuity(BCVA)was 20/1020 at baseline and 20/114 at the final visit,respectively(P=0.025).Preoperative BCVA was not a significant predictor of final BCVA(r=0.102,P=0.827).Final BCVA did not differ significantly between patients who underwent PPV within 14d of symptom onset and those who underwent surgery after 14d(P=0.57).All eyes received SF6 or C3F8 gas tamponade.CONCLUSION:Surgical intervention involving tPAmediated clot lysis and pneumatic displacement may yield visual benefits in trauma-induced SMH without underlying retinal vascular disease;however,larger prospective studies are warranted to confirm these findings.
基金Supported by the National Natural Science Foundation of China,No.82160192and Guangxi Science and Technology Program,No.2023AB23037.
文摘BACKGROUND In vivo degradation of bone scaffolds is significantly influenced by osteoclast(OC)activity,which is orchestrated by the interplay between receptor activator of nuclear factor-kappa B ligand(RANKL)and osteoprotegerin(OPG).The ratio of RANKL/OPG is a crucial determinant of OC-mediated bone resorption,which plays an integral role in bone remodeling and scaffold degradation.Elevated levels of RANKL relative to OPG enhance osteoclastogenesis,thereby accelerating the degradation process essential for integrating bone scaffolds into the host tissue.AIM To elucidate the effects of OPG gene silencing on osteoclastogenesis within rat bone marrow-derived mesenchymal stem cells(BMSCs).By investigating these effects,the study aimed to provide deeper insights into the regulatory mechanisms that influence bone scaffold degradation,potentially leading to improved bone repair and regeneration strategies.METHODS We employed recombinant lentiviral plasmids to silence the OPG gene in rat BMSCs to achieve the aims.The efficacy of gene silencing was assessed using quantitative reverse transcription polymerase chain reaction and western blot analysis to measure the expression levels of OPG and RANKL.Tartrate-resistant acid phosphatase staining was utilized to evaluate the formation of OCs.Additionally,co-immunoprecipitation assays were conducted to explore the interactions between RANKL and OPG proteins,further assessing the biochemical pathways involved in osteoclastogenesis.RESULTS The silencing of the OPG gene in BMSCs resulted in a significant increase in the RANKL/OPG ratio,evidenced by decreased expression levels of OPG and increased levels of RANKL.Enhanced osteoclastogenesis was observed through tartrate-resistant acid phosphatase staining,which indicated a substantial rise in OC formation in response to the altered RANKL/OPG balance.The co-immunoprecipitation assays provided concrete evidence of the direct interaction between RANKL and OPG proteins,substantiating their pivotal roles in regulating OC activity.CONCLUSION The findings from this study underscore the critical role of the RANKL/OPG axis in osteoclastogenesis.Silencing of the OPG gene in BMSCs effectively increases the RANKL/OPG ratio,promoting OC activity and potentially enhancing bone scaffold degradation.This regulatory mechanism offers a promising avenue for modulating bone remodeling processes,which is essential for effective bone repair and the successful integration of bone scaffolds into damaged sites.Future research might focus on optimizing the control of this axis to better facilitate bone tissue engineering and regenerative therapies.
基金supported by the National Natural Science Foundation of China,Nos.92148206,82071330(both to ZT)a grant from the Major Program of Hubei Province,No.2023BAA005(to ZT)+1 种基金a grant from the Key Research and Discovery Program of Hubei Province,No.2021BCA109(to ZT)the Research Foundation of Tongji Hospital,No.2022B37(to PZ)。
文摘Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminogen activator may come into contact with brain tissue.Therefore,a thorough assessment of its safety is required.In this study,we established a mouse model of intracerebral hemorrhage induced by type VII collagenase.We observed that the administration of recombinant tissue plasminogen activator without hematoma aspiration significantly improved the neurological function of mice with intracerebral hemorrhage,reduced pathological damage,and lowered the levels of apoptosis and autophagy in the tissue surrounding the hematoma.In an in vitro model of intracerebral hemorrhage using primary cortical neurons induced by hemin,the administration of recombinant tissue plasminogen activator suppressed neuronal apoptosis,autophagy,and endoplasmic reticulum stress.Transcriptome sequencing analysis revealed that recombinant tissue plasminogen activator upregulated the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway in neurons.Moreover,the phosphoinositide 3-kinase inhibitor LY294002 abrogated the neuroprotective effects of recombinant tissue plasminogen activator in inhibiting excessive apoptosis,autophagy,and endoplasmic reticulum stress.Furthermore,to specify the domain of recombinant tissue plasminogen activator responsible for its neuroprotective effects,various inhibitors were used to target distinct domains.It has been revealed that the epidermal growth factor receptor inhibitor AG-1478 reversed the effect of recombinant tissue plasminogen activator on the phosphoinositide 3-kinase/RAC-alpha serine/threonineprotein kinase/mammalian target of rapamycin pathway.These findings suggest that recombinant tissue plasminogen activator exerts a direct neuroprotective effect on neurons following intracerebral hemorrhage,possibly through activation of the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway.
基金supported by the Key Research and Development Special Tasks of Xinjiang,China (No.2022B01051-2)the National Natural Science Foundation of China (Nos.U23B2091,42372328,and 52478253)+1 种基金the Natural Science Foundation of Jiangsu Province,China (No.BK20240209)the Science and Technology Program Special Fund of Jiangsu Province (Frontier Leading Technology Basic Research) Major projects,China (No.BK 20222004)
文摘Using cemented rockfill to replace coal pillars offers an effective solution for reducing solid waste while ensuring the safety of gob-side entries.However,achieving the balance among low cost,high waste recycling rates,and adequate strength remains a significant challenge for cemented rockfill.This study used a composite alkali activator to activate gangue cemented rockfill.The compressive strength,scanning electron microscopy,energy dispersive spectrometer,mercury intrusion porosimetry,X-ray diffraction,and thermogra-vimetric tests were carried out to investigate the effect of the composite alkali activator proportion on the compressive strength,micro-structure,and composition of the cemented rockfill.The calcium silicate hydrate(C–S–H)molecular model of cemented rockfill was con-structed to explore the fracture evolution of the nucleated molecular structure under tension.The results show that compressive strength initially increased and then decreased with the activator proportion,the optimal activator proportion of 1:2 resulted in a 31.25%increase in strength at 3 d.This reasonable activator proportion strengthens the pozzolanic effect of gangue,and consumes more calcium hydroxide to inhibit its agglomeration,ultimately achieving the densification of microstructure.The activator proportion inevitably substitutes calcium ions with sodium ions in the C–S–H molecular model.The 12%substitution of calcium ions increases the adhesion between silicon chain layers,which is beneficial to the interlayer stress transfer.This work proposes a method for preparing low-cost cemented rockfill from al-kali-activated gangue,which can be used for solid waste recycling and reducing cement consumption to achieve low-carbon goals.
基金financially supported by the National Natural Science Foundation of China(52063024 and 51868052)the Natural Science Foundation of Jiangxi Province(20192ACBL21046)the National Science Foundation of State Key Laboratory of Structural Chemistry(20160013).
文摘The degradation of organic pollutants in water is a critical environmental challenge.The iron-doped MoS_(2) catalysts have demonstrated potential in activating peroxymonosulfate(PMS)for environmental remediation,but they face challenges such as poor conductivity,limited electron transfer efficiency,and a scarcity of active sites.To address these issues,we successfully synthesized a nano-flowers FeS/MoS_(2) composite derived from polyoxometalates(NH_(4))_(3)[Fe(III)Mo_(6)O_(24)H_(6)]⋅6H_(2)O(denoted as FeMo6)as the bimetallic precursors.This synthesis strategy enhances the interaction between FeS and MoS_(2),thereby facilitating electron transfer.Notably,the introduction of sulfur vacancies in FeS/MoS_(2) exposes additional Mo4t active sites,promoting the redox cycle of Fe^(2+)/Fe^(3+) and accelerating the regeneration of Fe^(2+),which in turn enhances PMS activation.Therefore,a catalytic oxidation system of FeS/MoS_(2)/PMS is presented that primarily relies on SO_(4)^(⋅-)and⋅OH,with ^(1)O_(2) as a supplementary oxidant.This system exhibits exceptional degradation efficiency for p-chlorophenol(4-CP),achieving 100% degradation within 10 min over a wide pH range of 2.4–8.4.The robust performance and wide applicability of FeS/MoS_(2) catalyst make it a promising candidate in advanced oxidation processes(AOPs)for environmental remediation.
基金supported by the Ministerio de Economía,Industria y Competitividad(Agencia Estatal de Investigación,AEI,to CGF and MP)Fondo Europeo de Desarrollo Regional(MINECO-FEDER)(PID2022-139016OA-I00,PDC2022-133441-I00,to CGF and MP),Generalitat de Catalunya(2021 SGR 00357+3 种基金to CGF and MP)co-financed by Secretaria d’Universitats i Recerca del Departament d’Empresai Coneixement de la Generalitat de Catalunya 2021(Llavor 00086,to CGF)the recipient of an Alzheimer’s Association Research Fellowship(AARF-21-848511)the Agència de Gestiód’Ajuts Universitaris i de Recerca(AGAUR)for her FI-SDUR fellowship(2021FISDU 00182).
文摘Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.
基金supported by grants from the National Natural Science Foundation of China(31401692,31901960,32272513,32001976)the Natural Science Foundation of Fujian Province(2019J01766,2023J011418,2020J05177)+3 种基金Fujian Provincial Science and Technology Key Project(2022NZ030014)External Cooperation Program of Fujian Academy of Agricultural Sciences(DWHZ-2024-23)State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crop Opening Project(SKL2019005)Project of Fujian Provincial Department of Education(JAT190627)。
文摘Avirulence effectors(Avrs),encoded by plant pathogens,can be recognized by plants harboring the corresponding resistance proteins,thereby initiating effector-triggered immunity(ETI).In susceptible plants,however,Avrs can function as effectors,facilitating infection via effector-triggered susceptibility(ETS).Mechanisms of Avr-mediated ETS remain largely unexplored.Here we report that the Magnaporthe oryzae effector Avr-PikD enters rice cells via the canonical cytoplasmic secretion pathway and suppresses rice basal defense.Avr-PikD interacts with an LSD1-like transcriptional activator AKIP30 of rice,and AKIP30 is also a positive regulator of rice immunity,whereas Avr-PikD impedes its nuclear localization and suppresses its transcriptional activity.In summary,M.oryzae delivers Avr-PikD into rice cells to facilitate ETS by inhibiting AKIP30-mediated transcriptional regulation of immune response against M.oryzae.
基金supported by the National Natural Science Foundation of China(No.82271914)Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(No.KYCX22_3382)Nantong Special Fund for Basic Research,China(No.JC12022021)。
文摘本文旨在研究TFEB activator 1(TA1)改善小胶质细胞自噬降解β淀粉样蛋白寡聚体(oligomeric amyloid-β,oAβ)的机制,探讨TA1对于阿尔茨海默病(Alzheimer’s disease,AD)体外小胶质细胞模型的治疗效果。在体外培养的原代小胶质细胞中,分别给予oAβ(1μmol/L)处理0、3、12、24 h,或以oAβ(1μmol/L)和TA1(1μmol/L)联合处理细胞12 h后,巴弗洛霉素A1(100 nmol/L)继续处理细胞1 h。采用荧光示踪法检测小胶质细胞内吞或降解oAβ1-42的水平;采用mCherry-EGFP-LC3的慢病毒转染原代小胶质细胞,检测自噬通量的变化;利用免疫荧光法检测oAβ1-42与溶酶体相关膜蛋白1(lysosome-associated membrane protein 1,LAMP1)或微管相关蛋白轻链3(microtuble-associated protein light chain 3,LC3)的共定位、TFEB核表达及自噬小体数量的变化;采用qRT-PCR法检测自噬基因Lamp1、Atg5、Map1lc3b的表达变化。结果显示:长时程oAβ暴露后,小胶质细胞内吞与降解oAβ的能力明显下降,细胞内自噬小体数量及自噬通量降低,自噬调节因子TFEB的核表达降低,自噬基因表达降低,引发oAβ的自噬降解受损;给予上述细胞TA1治疗后,可观察到TFEB的核表达明显上调,细胞内自噬基因表达上调,自噬通量恢复,小胶质细胞内吞与降解oAβ的能力得到明显恢复。因此,TA1可以通过上调小胶质细胞TFEB介导的自噬,改善AD小胶质细胞清除oAβ的能力,提示TA1可作为治疗AD的潜在药物。
基金funded by the National Natural Science Foun-dation of China(No.51974343)the China Postdoctoral Science Foundation(No.2021M703588)the Open Fund of Hubei Key Laboratory of Drilling and Production Engineering for Oil and Gas(Yangtze University)(No.YQZC202307).
文摘This study aims to further enhance the oil recovery of reservoirs in the Zhong-2 Block of the Gudao Oilfield by identifying the most effective microbial-flooding activator systems and applying them in the field.We began by analyzing the structure of the reservoirs'endogenous microbial communities to understand the potential impact of microbial flooding.This was followed by determining commonly used activator systems based on their abilities to stimulate oil-displacement functional bacteria.Through laboratory experiments on oil displacement efficiency and sweep characteristics,we determined the optimal activator injection method(injection ratio)and the requisite bacterial concentration for maximal microbial-flooding efficacy.Finally,we selected the optimal activator systems and applied them to field tests.Our findings suggest the target block is highly receptive to microbial-flooding.In terms of performance,the activator systems ranked as No.3>No.4>No.1>No.2.Interestingly,a deep activator system,when compared to the top-performing No.3 system,exhibited a higher bacterial concentration peak and longer peaking duration.Optimal oil displacement effects were observed at a 1:4 vol ratio between the No.3 activator and deep activator systems,with bacterial concentrations of up to 106 cells/mL or above.Field tests with the selected activator systems,following a specific injection protocol,demonstrated a notable increase in oil production and a reduction in water cut.
文摘BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIM To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory environment.METHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BMSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs.Mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.
基金Supported by Innovative Team of Jiangsu Province,No.CXTDA2017042Jiangsu Provincial Medical Youth Talent,No.QNRC2016508In-Hospital Project of Taizhou People's Hospital,No.ZL201930.
文摘BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.
基金Sichuan Province Medical Research Project Plan(Project No.S21113)。
文摘This study explores the diagnostic value of combining the Padua score with the thrombotic biomarker tissue plasminogen activator inhibitor-1(tPAI-1)for assessing the risk of deep vein thrombosis(DVT)in patients with pulmonary heart disease.These patients often exhibit symptoms similar to venous thrombosis,such as dyspnea and bilateral lower limb swelling,complicating differential diagnosis.The Padua Prediction Score assesses the risk of venous thromboembolism(VTE)in hospitalized patients,while tPAI-1,a key fibrinolytic system inhibitor,indicates a hypercoagulable state.Clinical data from hospitalized patients with cor pulmonale were retrospectively analyzed.ROC curves compared the diagnostic value of the Padua score,tPAI-1 levels,and their combined model for predicting DVT risk.Results showed that tPAI-1 levels were significantly higher in DVT patients compared to non-DVT patients.The Padua score demonstrated a sensitivity of 82.61%and a specificity of 55.26%at a cutoff value of 3.The combined model had a significantly higher AUC than the Padua score alone,indicating better discriminatory ability in diagnosing DVT risk.The combination of the Padua score and tPAI-1 detection significantly improves the accuracy of diagnosing DVT risk in patients with pulmonary heart disease,reducing missed and incorrect diagnoses.This study provides a comprehensive assessment tool for clinicians,enhancing the diagnosis and treatment of patients with cor pulmonale complicated by DVT.Future research should validate these findings in larger samples and explore additional thrombotic biomarkers to optimize the predictive model.
基金National Key R&D Program of China(2019YFC1904903 and 2020YFC1806504)China Postdoctoral Science Foundation(2020M680757)Fundamental Research Funds for the Central Universities(2022XJHH08).
文摘Novel coal gangue-based persulfate catalyst(CG-FeCl_(2))was successfully synthesized by the means of calcinating under nitrogen atmosphere with the addition of ferrous chloride tetrahydrate(FeCl_(2)·_(4)H_(2)O).The phase transformation of the prepared materials and gas products during the heating process are thoroughly investigated.It is suggested that ferrous chloride participated in the phase transformation and formed Si-O-Fe bonds.And the main gaseous products are H_(2)O,H_(2),and HCl during the heating process.Besides,the ability of CG-FeCl_(2) to activate peroxymonosulfate(PMS)for catalytic degradation of polycyclic aromatic hydrocarbons(PAHs)and phenol was deeply studied.More than 95%of naphthyl,phenanthrene and phenol were removed under optimizied conditions.In addition,1O_(2),·OH,and SO_(4)·−were involved in the CG-FeCl_(2)/PMS system from the free radical scavenging experiment,where 1O_(2) played a major role during the oxidation process.Furthermore,CG-FeCl_(2)/PMS system exhibited superior stability in a relatively wide pH range and the presence of common anion from related degradation experiments.Overall,the novel CG-FeCl_(2) is an efficient and environmentally friendly catalyst,displaying potential application prospect in the field of PAHs and phenol-contaminated wastewater treatment.
