Gordon Life Science Institute is the first Internet Research Institute ever established in the world. It is a non-profit institute. Those scientists who really dedicate themselves to science and loving science more th...Gordon Life Science Institute is the first Internet Research Institute ever established in the world. It is a non-profit institute. Those scientists who really dedicate themselves to science and loving science more than anything else can become its member. In the friendly door-opened Institute, they can maximize their time and energy to engage in their scientific creativity. They have also believed that science would be more truthful and wonderful if scientists do not have to spend a lot of time on funding application, and that great scientific findings and creations in history were often made by those who were least supported or funded but driven by interesting imagination and curiosity. Recollected in this review article is its establishing and developing processes, as well as its philosophy and accomplishments. Particularly, its productive and by-productive outcomes have covered the following five very hot topics in bioinformatics and drug development: 1) PseAAC and PseKNC;2) Disported key theory;3) Wenxiang diagram;4) Multi-label system prediction;5) 5-steps rule. Their impacts on the proteomics and genomics as well as drug development are substantially and awesome.展开更多
The impacts of coronavirus to our planet <span>are</span><span "=""><span> unprecedented;</span><i><span>i.e.</span></i><span>, </span>&...The impacts of coronavirus to our planet <span>are</span><span "=""><span> unprecedented;</span><i><span>i.e.</span></i><span>, </span></span><span>they are</span><span> going to eliminate the entire mankind. Driven by such horrible situation, some philosophical viewpoints have naturally happened. Whether the “World End” must come? If yes, when? During this waiting period, the best way to do science is via the Internet Institute, such as “Gordon Life Science Institute”, and the results thus achieved will be most rewarding.</span>展开更多
Established in 2004, Gordon Life Science Institute is the first Internet Research Institute in the world. It is a non-profit institute, a gift to science. Those scientists, who are really loving science more than anyt...Established in 2004, Gordon Life Science Institute is the first Internet Research Institute in the world. It is a non-profit institute, a gift to science. Those scientists, who are really loving science more than anything else and have shown fantastic creativity in science, can become the membership of such Institute. Their driving force is not funding but firmly belief that scientists will do much better science if they do not have to spend a lot of time for funding application, and that great scientific findings in history were often discovered by those who were without funding at all but driven by profound imagination and curiosity. Summarized in this review are also the accomplishments of the Gordon Life Science Institute and its future perspective.展开更多
In this review paper, the remarkable impacts of the first Internet Institute, the Gordon Life Science Institute, as well as its profound and far-reaching influence have been systematically and comprehensively presented.
Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understan...Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.展开更多
Hippo signaling is a highly conserved pathway central to diverse cellular processes.Dysregulation of this pathway not only leads to developmental abnormalities but is also closely related to the occurrence and progres...Hippo signaling is a highly conserved pathway central to diverse cellular processes.Dysregulation of this pathway not only leads to developmental abnormalities but is also closely related to the occurrence and progression of various cancers.Recent studies have uncovered that,in addition to the classical signaling cascade regulation,biomolecular condensates formed via phase separation play a key role in the spatiotemporal regulation of Hippo signaling.In this review,we provide a summary of the latest research progress on the regulation of the Hippo signaling pathway by phase separation,with a particular focus on transcriptional activation mediated by Yes-associated protein(YAP)/transcriptional coactivator with post-synaptic density-95,disks-large,and zonula occludens-1(PDZ)-binding domain(TAZ)condensates.Furthermore,we discuss the utility of chemical crosslinking combined with mass spectrometry to analyze the TAZ condensate interactome and examine the role of the protein fused in sarcoma(FUS)in modulating the biophysical properties of TAZ condensates,which in turn influence their transcriptional activity and pro-tumorigenic functions.These insights not only advance our understanding of Hippo signaling but also offer new perspectives for therapeutic interventions targeting diseases linked to dysregulated YAP/TAZ activity.展开更多
Bacterial pneumonia is one of the most common infectious diseases,a great threat to the health of children and the elderly.In the clinic,due to the extensive use of antibiotics,multi-drug-resistant bacteria have incre...Bacterial pneumonia is one of the most common infectious diseases,a great threat to the health of children and the elderly.In the clinic,due to the extensive use of antibiotics,multi-drug-resistant bacteria have increased in large numbers,seriously affects the treatment of patients with bacterial pneumonia.With the development of nanomedicine,it shows great potential in the treatment of bacterial pneumonia.In this review,it initially comprehensively describes the pathological process of bacterial pneumonia and the current status of its clinical treatment.Then it summarizes the strategies of nanomedicine for the treatment of bacterial pneumonia,including inorganic nanomaterials,polymer nanoparticles,natural source nanomaterials and artificial antimicrobial peptides,with a focus on novel nanomaterials for the treatment of bacterial pneumonia(biomimetic nanomaterials,nanovaccines and genetically engineered nanomaterials).Finally,the prospect of nanomedicine for bacterial pneumonia therapy is discussed in the hope of providing new ideas for the clinical treatment of bacterial pneumonia.展开更多
Lupus nephritis(LN)is one of the most common and serious complications of systemic lupus erythematosus,which can lead to end-stage renal disease,and is an important cause of death in patients with systemic lupus eryth...Lupus nephritis(LN)is one of the most common and serious complications of systemic lupus erythematosus,which can lead to end-stage renal disease,and is an important cause of death in patients with systemic lupus erythematosus.Treatment options include glucocorticoids,immunosuppressive agents and the addition of biologics.Recently,the therapeutic role of mesenchymal stem cells(MSCs)in LN has received extensive attention worldwide.MSCs can suppress autoimmunity,alleviate proteinuria and restore renal function by modulating the functions of various immune cells and reducing the secretion of inflammatory cytokines.Several clinical trials have investigated MSC treatment in LN with promising but sometimes inconsistent outcomes.This review summarizes the sources of MSCs and mechanisms in immunoregulation.Furthermore,it examines clinical trials evaluating the efficacy,safety,and limitations of MSC therapy in LN.By highlighting advances and ongoing challenges,this review underscores the potential of MSCs for LN treatment.More large-scale randomized controlled trials are needed to support the effectiveness of this therapy and pave the way for personalized and combinatorial therapeutic approaches.展开更多
Infectious wound healing is complicated with and limited by infection and oxidative stress at the wound site.In recent years,various evidences suggest that nanozymes with multiple enzymatic activities have enabled the...Infectious wound healing is complicated with and limited by infection and oxidative stress at the wound site.In recent years,various evidences suggest that nanozymes with multiple enzymatic activities have enabled the development of novel strategies for infectious wound healing.In this study,epigallocatechin gallate loaded polydopamine(P@E)was developed to act as a potent reactive oxygen species(ROS)scavenger for scavenging ROS,alleviating inflammatory responses,and promoting infectious wound healing.Combining with near infrared(NIR)irradiation,P@E presented excellent antibacterial ability of Escherichia coli(E.coli,93.6%)and methicillin-resistant Staphylococcus aureus(MRSA,87.6%).Specifically,P@E+NIR exhibited the most potent antioxidant,anti-inflammatory and cell proliferation behaviors through downregulating intracellular ROS levels(81.9%and 94.3%for NIH3T3 and RAW264.7 respectively)and inducible nitric oxide synthase(iNOS)expression level(55.7%),and up-regulating the expression levels of arginase-1(Arg-1,71.4%),heat shock protein 70(HSP70,48.6%)and platelet endothelial cell adhesion molecule(CD31,35.3%)compared to control group.Meanwhile,it also efficiently induced M2 directional polarization of lipopolysaccharide induced murine macrophages to achieve anti-inflammation,indicated by the down-regulation of CD86(86.2%),and up-regulation of CD206(85.6%).Significantly,it was also observed that P@E+NIR presented the excellent behaviors of inhibiting wound infection,alleviating wound inflammation,as well as promoting skin tissue repairing.Altogether,it has developed the strategy of using P@E combining with NIR irradiation for the synergistic enhanced healing of infectious skin wound,which can serve as a promising therapeutic strategy for its clinical treatment.展开更多
Acute lung injury(ALI)was characterized by excessive reactive oxygen species(ROS)levels and inflammatory response in the lung.Scavenging ROS could inhibit the excessive inflammatory response,further treating ALI.Herei...Acute lung injury(ALI)was characterized by excessive reactive oxygen species(ROS)levels and inflammatory response in the lung.Scavenging ROS could inhibit the excessive inflammatory response,further treating ALI.Herein,we designed a novel nanozyme(P@Co)comprised of polydopamine(PDA)nanoparticles(NPs)loading with ultra-small Co,combining with near infrared(NIR)irradiation,which could efficiently scavenge intracellular ROS and suppress inflammatory responses against ALI.For lipopolysaccharide(LPS)induced macrophages,P@Co+NIR presented excellent antioxidant and anti-inflammatory capacities through lowering intracellular ROS levels,decreasing the expression levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)as well as inducing macrophage M2 directional polarization.Significantly,it displayed the outstanding activities of lowering acute lung inflammation,relieving diffuse alveolar damage,and up-regulating heat shock protein 70(HSP70)expression,resulting in synergistic enhanced ALI therapy effect.It offers a novel strategy for the clinical treatment of ROS related diseases.展开更多
BACKGROUND Barrett esophagus(BE),a metaplastic adaptive process to gastrointestinal reflux,is associated with a higher risk of developing esophageal adenocarcinoma.However,the factors and mechanism that drive the mali...BACKGROUND Barrett esophagus(BE),a metaplastic adaptive process to gastrointestinal reflux,is associated with a higher risk of developing esophageal adenocarcinoma.However,the factors and mechanism that drive the malignant progression of BE is not well understood.AIM To investigate the role of bile acids,a component of the reflux fluid,in the malignant progression of BE.METHODS Using engineered green fluorescent protein-labeled adult tissue-resident stem cells isolated from BE clinical biopsies(BE-ASCs)as the target,we studied the effect of hydrophobic deoxycholic acid(DCA)and hydrophilic tetrahydroxylated bile acids(THBA)on cell viability by fluorescence intensity analysis,mucin production by dark density measurement,tissue structure by pathology analysis,expression of different pro-inflammatory factors gene by quantitative polymerase chain reaction and proteins by Western blot.RESULTS We found that hydrophobic DCA has cytotoxic and proinflammatory effects through activation of interleukin-1β(IL-1β)-nuclear factor kappa-B(NF-κB)inflammatory pathway on BE-ASCs.This action results in impaired cell viability,tissue intactness,reduced mucin production,and increased transition to disorganized atypical cells without intestinal features.In contrast,co-culture with hydrophilic THBA inhibited the IL-1β-NF-κB inflammatory pathway with maintenance of mature intestinal type cellular and histomorphology.CONCLUSION Our data indicates that the hydrophilic bile acid THBA can counteract the cytotoxic and proinflammatory effect of hydrophobic DCA and prevent the malignant progression of BE by inhibiting the IL-1β-NF-κB pathway.展开更多
It is extremely fearful for the pestilences covering our Earth. Does that mean the “World End” is around the corner? For the so-called “Atheists” originally proposed by Karl Max and Friedrich Engels, “there is a ...It is extremely fearful for the pestilences covering our Earth. Does that mean the “World End” is around the corner? For the so-called “Atheists” originally proposed by Karl Max and Friedrich Engels, “there is a Beginning, there must be an End”, meaning our Earth will finally no longer exist in the entire Universe by colliding with the other planet. According to Holly Bible, however, Jesus, will send out his angels to separate the wicked from the righteous and throw the former into the fiery furnace. For such a special time-period, many useful ideas or outcomes can be acquired by the Internet Institutes.展开更多
The damage of coronavirus to our Earth is unprecedented that is going to kill the entire human beings. Facing this kind of situation, there are two completely different kinds of viewpoints. According to the philosophy...The damage of coronavirus to our Earth is unprecedented that is going to kill the entire human beings. Facing this kind of situation, there are two completely different kinds of viewpoints. According to the philosophy of “Atheists” Karl Max and Friedrich Engels, “there is a Bigging, there must be an End”, meaning our Earth will eventually collide with the other planet and be destroyed completely. According to Holly Bible, however, Jesus, will come down again to bring Godly people to the Heaven and leave the remaining in the coronavirus-hell. During this waiting period, the “Internet Institutes” can provide the most useful knowledge for the other planets.展开更多
Traditional Chinese medicine(TCM)has been increasingly employed in the last decades in China for both preventing and treating a variety of cancers.3-epi-bufotalin is an active ingredient of TCM“Chanpi”with anti-tumo...Traditional Chinese medicine(TCM)has been increasingly employed in the last decades in China for both preventing and treating a variety of cancers.3-epi-bufotalin is an active ingredient of TCM“Chanpi”with anti-tumor potential.However,the effect and mechanism of 3-epi-bufotalin on colorectal cancers were not well disclosed.The present study demonstrated that 3-epi-bufotalin could reduce viability,trigger apoptosis,and block the cell cycle at the G2/M stage in colorectal cancer cell lines HT29,RKO,and COLO205 in vitro.Moreover,3-epi-bufotalin inhibited the JAK1/STAT3 signaling pathway.These results indicated the anti-proliferation ability of 3-epi-bufotalin in colorectal cancer cells.展开更多
OBJECTIVE: To confirm the anti-NPC effect of sanguinarine(SA) through a series of wet experiments.METHODS: NPC cell viability was determined by proliferation experiment. Cell clone formation experiment, cell scratch t...OBJECTIVE: To confirm the anti-NPC effect of sanguinarine(SA) through a series of wet experiments.METHODS: NPC cell viability was determined by proliferation experiment. Cell clone formation experiment, cell scratch test, transwell migration and invasion experiment and flow cytometry-based cell apoptosis assay were further performed. In addition, Western blotting was performed to investigate the cell signaling pathway. All the relevant experimental data were statistically processed using SPSS 16.0 software.RESULTS: The results showed that sanguinarine represented a time and dose dependent inhibition effects on NPC cell proliferation including the low differentiated CNE2 cells and high metastatic 5-8F cells, along with the cell cloning ability reduction. In addition, sanguinarine has a certain inhibitory effect on the invasion and migration of NPC cells. Mechanistically, sanguinarine displayed the anti-NPC effects mainly involved into the suppression of m TOR signaling and cell apoptosis, which is closely associated with the tumor growth and metastatic malignancy. CONCLUSIONS: Collectively, we discover that sanguinarine is a new high-efficiency anti-NPC monomer of Chinese medicine, with a value for the follow-up preclinical research.展开更多
Background:We aimed to explore the associations of adherence to an overall healthy lifestyle with cardiometabolic diseases(CMDs)among schoolteachers in China.Methods:We conducted a cross-sectional analysis among 2983 ...Background:We aimed to explore the associations of adherence to an overall healthy lifestyle with cardiometabolic diseases(CMDs)among schoolteachers in China.Methods:We conducted a cross-sectional analysis among 2983 teachers(aged 39.8±9.3 years,73.8%women)in Zhejiang Province,China.A healthy lifestyle score(0–7)was constructed based on seven low-risk factors:healthy diet,noncurrent smoking,noncurrent drinking,regular exercise,normal body mass index(BMI),adequate sleep duration,and limited sedentary behavior.CMDs included self-reported hyperlipidemia,hypertension,diabetes,coronary heart disease,and stroke.Multivariable-adjusted logistic regression models were used to evaluate the associations between healthy lifestyle and CMD.Results:A total of 493(16.5%)participants had at least one CMD,with hyperlipidemia,hypertension,and diabetes being the three leading CMDs.ach point increment in a healthy lifestyle score was associated with 20%lower odds of having CMD(p-trend<0.001).Compared with 0–3 low-risk factors,the odds ratios(ORs)and 95%confidence intervals(CIs)were 0.66(0.50–0.88)for 4 low-risk factors and 0.51(0.39–0.67)for 5–7 low-risk factors.We observed independent associations for normal BMI(OR=0.50,95%CI=0.40–0.63),noncurrent drinking(OR=0.53,95%CI=0.36–0.77),and limited sedentary behavior(OR=0.77,95%CI=0.62–0.96)in relation to CMD.Healthy diet(OR=0.75,95%CI=0.55–1.01)exhibited marginally significant association with CMD.Conclusions:Our findings suggest that adherence to an overall healthy lifestyle is associated with lower odds of CMD among schoolteachers.展开更多
Nasopharyngeal carcinoma(NPC)has been a focus of medical research for more than 100 years,with significant interest emerging over the last 58 years following the identification of the link between the disease and Epst...Nasopharyngeal carcinoma(NPC)has been a focus of medical research for more than 100 years,with significant interest emerging over the last 58 years following the identification of the link between the disease and Epstein-Barr virus(EBV)infection.NPC possesses several distinctive characteristics among human cancers,notably its well-documented global epidemiology,which reveals localized high-incidence regions primarily in Southeast Asia,particularly in the Southern provinces of China near the Pearl river,as well as in Greenland and North Africa.Epidemiological data indicate a marked male predominance,early disease onset,and a nearly 100%prevalence of latent EBV infection in the tumors.Due to lack of consistent pattern of cancer-related mutations in NPC genomes and excessive DNA-methylation in the tumor cells,NPC can be considered"an epigenetic cancer".Despite extensive researches,convincing biological explanations for these unique characteristics remain elusive.Recently,suggestive evidence has been published that specific local variants of EBV may represent major high risk factors.In spite of tumor and virus specific immunity,it has not been possible to use this for improved treatment.Ongoing studies on the role of the local microflora and tumor microenvironment are essential for a comprehensive understanding of host-EBV-tumor interactions.Ultimately,this knowledge aims to enhance diagnosis,disease fractionation,treatment strategies,and potentially prevention of NPC.展开更多
Acute lung injury(ALI)is a severe inflammatory condition with a high mortality rate,often precipitated by sepsis.The pathophysiology of ALI involves complex mechanisms,including inflammation,oxidative stress,and ferro...Acute lung injury(ALI)is a severe inflammatory condition with a high mortality rate,often precipitated by sepsis.The pathophysiology of ALI involves complex mechanisms,including inflammation,oxidative stress,and ferroptosis,a novel form of regulated cell death.This study explores the therapeutic potential of andrographolide(AG),a bioactive compound derived from Andrographis,in mitigating Lipopolysaccharide(LPS)-induced inflammation and ferroptosis.Our research employed in vitro experiments with RAW264.7 macrophage cells and in vivo studies using a murine model of LPS-induced ALI.The results indicate that AG significantly suppresses the production of pro-inflammatory cytokines and inhibits ferroptosis in LPS-stimulated RAW264.7 cells.In vivo,AG treatment markedly reduces lung edema,decreases inflammatory cell infiltration,and mitigates ferroptosis in lung tissues of LPS-induced ALI mice.These protective effects are mediated via the modulation of the Toll-like receptor 4(TLR4)/Kelch-like ECH-associated protein 1(Keap1)/Nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway.Molecular docking simulations identified the binding sites of AG on the TLR4 protein(Kd value:-33.5 kcal·mol^(-1)),and these interactions were further corroborated by Cellular Thermal Shift Assay(CETSA)and SPR assays.Collectively,our findings demonstrate that AG exerts potent anti-inflammatory and anti-ferroptosis effects in LPS-induced ALI by targeting TLR4 and modulating the Keap1/Nrf2 pathway.This study underscores AG's potential as a therapeutic agent for ALI and provides new insights into its underlying mechanisms of action.展开更多
Vertical forest structure is closely linked to multiple ecosystem characteristics,such as biodiversity,habitat,and productivity.Mixing tree species in planted forests has the potential to create diverse vertical fores...Vertical forest structure is closely linked to multiple ecosystem characteristics,such as biodiversity,habitat,and productivity.Mixing tree species in planted forests has the potential to create diverse vertical forest structures due to the different physiological and morphological traits of the composing tree species.However,the relative importance of species richness,species identity and species interactions for the variation in vertical forest structure remains unclear,mainly because traditional forest inventories do not observe vertical stand structure in detail.Terrestrial laser scanning(TLS),however,allows to study vertical forest structure in an unprecedented way.Therefore,we used TLS single scan data from 126 plots across three experimental planted forests of a largescale tree diversity experiment in Belgium to study the drivers of vertical forest structure.These plots were 9–11years old young pure and mixed forests,characterized by four levels of tree species richness ranging from monocultures to four-species mixtures,across twenty composition levels.We generated vertical plant profiles from the TLS data and derived six stand structural variables.Linear mixed models were used to test the effect of species richness on structural variables.Employing a hierarchical diversity interaction modelling framework,we further assessed species identity effect and various species interaction effects on the six stand structural variables.Our results showed that species richness did not significantly influence most of the stand structure variables,except for canopy height and foliage height diversity.Species identity on the other hand exhibited a significant impact on vertical forest structure across all sites.Species interaction effects were observed to be site-dependent due to varying site conditions and species pools,and rapidly growing tree species tend to dominate these interactions.Overall,our results highlighted the importance of considering both species identity and interaction effects in choosing suitable species combinations for forest management practices aimed at enhancing vertical forest structure.展开更多
The rapidly changing Antarctic sea ice has garnered significant interest. To enhance the prediction skill for sea ice and respond to the Sea Ice Prediction Network-South's latest call, this study presents the refo...The rapidly changing Antarctic sea ice has garnered significant interest. To enhance the prediction skill for sea ice and respond to the Sea Ice Prediction Network-South's latest call, this study presents the reforecast results of Antarctic sea-ice area and extent from December to June of the coming year with a Convolutional Long Short-Term Memory(Conv LSTM)Network. The reforecast experiments demonstrate that Conv LSTM captures the interannual and interseasonal variability of Antarctic sea ice successfully, and performs better than the European Centre for Medium-Range Weather Forecasts. Based on this, we present the prediction from December 2023 to June 2024, indicating that the Antarctic sea ice will remain at lows, but may not create a new record low. This research highlights the promising application of deep learning in Antarctic sea-ice prediction.展开更多
文摘Gordon Life Science Institute is the first Internet Research Institute ever established in the world. It is a non-profit institute. Those scientists who really dedicate themselves to science and loving science more than anything else can become its member. In the friendly door-opened Institute, they can maximize their time and energy to engage in their scientific creativity. They have also believed that science would be more truthful and wonderful if scientists do not have to spend a lot of time on funding application, and that great scientific findings and creations in history were often made by those who were least supported or funded but driven by interesting imagination and curiosity. Recollected in this review article is its establishing and developing processes, as well as its philosophy and accomplishments. Particularly, its productive and by-productive outcomes have covered the following five very hot topics in bioinformatics and drug development: 1) PseAAC and PseKNC;2) Disported key theory;3) Wenxiang diagram;4) Multi-label system prediction;5) 5-steps rule. Their impacts on the proteomics and genomics as well as drug development are substantially and awesome.
文摘The impacts of coronavirus to our planet <span>are</span><span "=""><span> unprecedented;</span><i><span>i.e.</span></i><span>, </span></span><span>they are</span><span> going to eliminate the entire mankind. Driven by such horrible situation, some philosophical viewpoints have naturally happened. Whether the “World End” must come? If yes, when? During this waiting period, the best way to do science is via the Internet Institute, such as “Gordon Life Science Institute”, and the results thus achieved will be most rewarding.</span>
文摘Established in 2004, Gordon Life Science Institute is the first Internet Research Institute in the world. It is a non-profit institute, a gift to science. Those scientists, who are really loving science more than anything else and have shown fantastic creativity in science, can become the membership of such Institute. Their driving force is not funding but firmly belief that scientists will do much better science if they do not have to spend a lot of time for funding application, and that great scientific findings in history were often discovered by those who were without funding at all but driven by profound imagination and curiosity. Summarized in this review are also the accomplishments of the Gordon Life Science Institute and its future perspective.
文摘In this review paper, the remarkable impacts of the first Internet Institute, the Gordon Life Science Institute, as well as its profound and far-reaching influence have been systematically and comprehensively presented.
基金funded by NIH-NIA R01AG061708 (to PHO)Patrick Grange Memorial Foundation (to PHO)+1 种基金A Long Swim (to PHO)CureSPG4 Foundation (to PHO)。
文摘Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.
基金supported by the National Natural Science Foundation of China(Nos.32570646,32370591 and 323B2012)the Zhejiang Provincial Natural Science Foundation of China(Nos.LRG25C060001 and LR21C060002)the Fundamental Research Funds for the Central Universities(No.226-2025-00028),China.
文摘Hippo signaling is a highly conserved pathway central to diverse cellular processes.Dysregulation of this pathway not only leads to developmental abnormalities but is also closely related to the occurrence and progression of various cancers.Recent studies have uncovered that,in addition to the classical signaling cascade regulation,biomolecular condensates formed via phase separation play a key role in the spatiotemporal regulation of Hippo signaling.In this review,we provide a summary of the latest research progress on the regulation of the Hippo signaling pathway by phase separation,with a particular focus on transcriptional activation mediated by Yes-associated protein(YAP)/transcriptional coactivator with post-synaptic density-95,disks-large,and zonula occludens-1(PDZ)-binding domain(TAZ)condensates.Furthermore,we discuss the utility of chemical crosslinking combined with mass spectrometry to analyze the TAZ condensate interactome and examine the role of the protein fused in sarcoma(FUS)in modulating the biophysical properties of TAZ condensates,which in turn influence their transcriptional activity and pro-tumorigenic functions.These insights not only advance our understanding of Hippo signaling but also offer new perspectives for therapeutic interventions targeting diseases linked to dysregulated YAP/TAZ activity.
基金supported by the Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation(Nos.2023GXNSFDA026023 and 2024GXNSFAA010089)the Key Research&Development Program of Guangxi(No.Gui Ke AB22080088)+2 种基金the National Natural Science Foundation of China(No.82360372)the First-class Discipline Innovation-driven Talent Program of Guangxi Medical Universitythe Major Talent Project of Guangxi Autonomous Region。
文摘Bacterial pneumonia is one of the most common infectious diseases,a great threat to the health of children and the elderly.In the clinic,due to the extensive use of antibiotics,multi-drug-resistant bacteria have increased in large numbers,seriously affects the treatment of patients with bacterial pneumonia.With the development of nanomedicine,it shows great potential in the treatment of bacterial pneumonia.In this review,it initially comprehensively describes the pathological process of bacterial pneumonia and the current status of its clinical treatment.Then it summarizes the strategies of nanomedicine for the treatment of bacterial pneumonia,including inorganic nanomaterials,polymer nanoparticles,natural source nanomaterials and artificial antimicrobial peptides,with a focus on novel nanomaterials for the treatment of bacterial pneumonia(biomimetic nanomaterials,nanovaccines and genetically engineered nanomaterials).Finally,the prospect of nanomedicine for bacterial pneumonia therapy is discussed in the hope of providing new ideas for the clinical treatment of bacterial pneumonia.
基金Supported by Natural Science Foundation of Zhejiang Province,No.LY23H050005Zhejiang Medical Technology Project,No.2020KY439,No.2022RC009,No.2024KY645,and No.2024KY697.
文摘Lupus nephritis(LN)is one of the most common and serious complications of systemic lupus erythematosus,which can lead to end-stage renal disease,and is an important cause of death in patients with systemic lupus erythematosus.Treatment options include glucocorticoids,immunosuppressive agents and the addition of biologics.Recently,the therapeutic role of mesenchymal stem cells(MSCs)in LN has received extensive attention worldwide.MSCs can suppress autoimmunity,alleviate proteinuria and restore renal function by modulating the functions of various immune cells and reducing the secretion of inflammatory cytokines.Several clinical trials have investigated MSC treatment in LN with promising but sometimes inconsistent outcomes.This review summarizes the sources of MSCs and mechanisms in immunoregulation.Furthermore,it examines clinical trials evaluating the efficacy,safety,and limitations of MSC therapy in LN.By highlighting advances and ongoing challenges,this review underscores the potential of MSCs for LN treatment.More large-scale randomized controlled trials are needed to support the effectiveness of this therapy and pave the way for personalized and combinatorial therapeutic approaches.
基金financially supported by the Natural Science Foundation of Guangxi(Nos.2022GXNSFAA035505 and 2024GXNSFAA010164)the Key Research&Development Program of Guangxi(No.GuiKe2024AB08057)+1 种基金the Guangxi Medical and Health Suitable Technology Development and Popularization Applications Project(Nos.S2023093 and S2021084)the Major Talent Project of Guangxi Autonomous Region.
文摘Infectious wound healing is complicated with and limited by infection and oxidative stress at the wound site.In recent years,various evidences suggest that nanozymes with multiple enzymatic activities have enabled the development of novel strategies for infectious wound healing.In this study,epigallocatechin gallate loaded polydopamine(P@E)was developed to act as a potent reactive oxygen species(ROS)scavenger for scavenging ROS,alleviating inflammatory responses,and promoting infectious wound healing.Combining with near infrared(NIR)irradiation,P@E presented excellent antibacterial ability of Escherichia coli(E.coli,93.6%)and methicillin-resistant Staphylococcus aureus(MRSA,87.6%).Specifically,P@E+NIR exhibited the most potent antioxidant,anti-inflammatory and cell proliferation behaviors through downregulating intracellular ROS levels(81.9%and 94.3%for NIH3T3 and RAW264.7 respectively)and inducible nitric oxide synthase(iNOS)expression level(55.7%),and up-regulating the expression levels of arginase-1(Arg-1,71.4%),heat shock protein 70(HSP70,48.6%)and platelet endothelial cell adhesion molecule(CD31,35.3%)compared to control group.Meanwhile,it also efficiently induced M2 directional polarization of lipopolysaccharide induced murine macrophages to achieve anti-inflammation,indicated by the down-regulation of CD86(86.2%),and up-regulation of CD206(85.6%).Significantly,it was also observed that P@E+NIR presented the excellent behaviors of inhibiting wound infection,alleviating wound inflammation,as well as promoting skin tissue repairing.Altogether,it has developed the strategy of using P@E combining with NIR irradiation for the synergistic enhanced healing of infectious skin wound,which can serve as a promising therapeutic strategy for its clinical treatment.
基金financially supported by the Key Research&Development Program of Guangxi(No.GuiKeAB22080088)the Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation(No.2023GXNSFDA026023)+3 种基金the Natural Science Foundation of Guangxi(No.2023JJA140322)the National Natural Science Foundation of China(No.82360372)the High-level Medical Expert Training Program of Guangxi“139 Plan Funding(No.G202003010)the Medical Appropriate Technology Development and Popularization and Application Project of Guangxi(No.S2020099)。
文摘Acute lung injury(ALI)was characterized by excessive reactive oxygen species(ROS)levels and inflammatory response in the lung.Scavenging ROS could inhibit the excessive inflammatory response,further treating ALI.Herein,we designed a novel nanozyme(P@Co)comprised of polydopamine(PDA)nanoparticles(NPs)loading with ultra-small Co,combining with near infrared(NIR)irradiation,which could efficiently scavenge intracellular ROS and suppress inflammatory responses against ALI.For lipopolysaccharide(LPS)induced macrophages,P@Co+NIR presented excellent antioxidant and anti-inflammatory capacities through lowering intracellular ROS levels,decreasing the expression levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)as well as inducing macrophage M2 directional polarization.Significantly,it displayed the outstanding activities of lowering acute lung inflammation,relieving diffuse alveolar damage,and up-regulating heat shock protein 70(HSP70)expression,resulting in synergistic enhanced ALI therapy effect.It offers a novel strategy for the clinical treatment of ROS related diseases.
文摘BACKGROUND Barrett esophagus(BE),a metaplastic adaptive process to gastrointestinal reflux,is associated with a higher risk of developing esophageal adenocarcinoma.However,the factors and mechanism that drive the malignant progression of BE is not well understood.AIM To investigate the role of bile acids,a component of the reflux fluid,in the malignant progression of BE.METHODS Using engineered green fluorescent protein-labeled adult tissue-resident stem cells isolated from BE clinical biopsies(BE-ASCs)as the target,we studied the effect of hydrophobic deoxycholic acid(DCA)and hydrophilic tetrahydroxylated bile acids(THBA)on cell viability by fluorescence intensity analysis,mucin production by dark density measurement,tissue structure by pathology analysis,expression of different pro-inflammatory factors gene by quantitative polymerase chain reaction and proteins by Western blot.RESULTS We found that hydrophobic DCA has cytotoxic and proinflammatory effects through activation of interleukin-1β(IL-1β)-nuclear factor kappa-B(NF-κB)inflammatory pathway on BE-ASCs.This action results in impaired cell viability,tissue intactness,reduced mucin production,and increased transition to disorganized atypical cells without intestinal features.In contrast,co-culture with hydrophilic THBA inhibited the IL-1β-NF-κB inflammatory pathway with maintenance of mature intestinal type cellular and histomorphology.CONCLUSION Our data indicates that the hydrophilic bile acid THBA can counteract the cytotoxic and proinflammatory effect of hydrophobic DCA and prevent the malignant progression of BE by inhibiting the IL-1β-NF-κB pathway.
文摘It is extremely fearful for the pestilences covering our Earth. Does that mean the “World End” is around the corner? For the so-called “Atheists” originally proposed by Karl Max and Friedrich Engels, “there is a Beginning, there must be an End”, meaning our Earth will finally no longer exist in the entire Universe by colliding with the other planet. According to Holly Bible, however, Jesus, will send out his angels to separate the wicked from the righteous and throw the former into the fiery furnace. For such a special time-period, many useful ideas or outcomes can be acquired by the Internet Institutes.
文摘The damage of coronavirus to our Earth is unprecedented that is going to kill the entire human beings. Facing this kind of situation, there are two completely different kinds of viewpoints. According to the philosophy of “Atheists” Karl Max and Friedrich Engels, “there is a Bigging, there must be an End”, meaning our Earth will eventually collide with the other planet and be destroyed completely. According to Holly Bible, however, Jesus, will come down again to bring Godly people to the Heaven and leave the remaining in the coronavirus-hell. During this waiting period, the “Internet Institutes” can provide the most useful knowledge for the other planets.
基金This work was supported by the Guizhou Provincial Science and Technology Program(QKHZC[2020]4Y154)Science and Technology Plan of Zunyi(ZSKHSZ[2018]18)+3 种基金Science and Technology Plan of Zunyi(ZSKHHZ[2020]83)the Xinmiao Funding of Zunyi Medical University(QKPTRC[2019]022)City School Joint Fund of Zunyi(ZSKHHZ[2021]277)the Innovation Talent Team of Zunyi(ZSKRC[2019]1).
文摘Traditional Chinese medicine(TCM)has been increasingly employed in the last decades in China for both preventing and treating a variety of cancers.3-epi-bufotalin is an active ingredient of TCM“Chanpi”with anti-tumor potential.However,the effect and mechanism of 3-epi-bufotalin on colorectal cancers were not well disclosed.The present study demonstrated that 3-epi-bufotalin could reduce viability,trigger apoptosis,and block the cell cycle at the G2/M stage in colorectal cancer cell lines HT29,RKO,and COLO205 in vitro.Moreover,3-epi-bufotalin inhibited the JAK1/STAT3 signaling pathway.These results indicated the anti-proliferation ability of 3-epi-bufotalin in colorectal cancer cells.
基金Supported by Project for Department of Science and Technology of Guangxi Zhuang Autonomous Region,China,Screening,Product Development and Mechanism Research of Anti-Nasopharyngeal Cancer Chinese Medicine Monomers (AB19110052)Natural Science Foundation of Guangxi,China,Epstein-Barr Virus Infection and UpRegulation Mechanism of Invasion and Migration-Related Proteins S100A8 and S100A9 in Nasopharyngeal Carcinoma Cells (2015GXNSFAA139215)National Natural Science Foundation of China,Quantification,Validation,Functional Analysis and Construction of Regulatory Pathway of i TRAQ Serum Protein Molecular Markers in Nasopharyngeal Carcinoma (81260405)。
文摘OBJECTIVE: To confirm the anti-NPC effect of sanguinarine(SA) through a series of wet experiments.METHODS: NPC cell viability was determined by proliferation experiment. Cell clone formation experiment, cell scratch test, transwell migration and invasion experiment and flow cytometry-based cell apoptosis assay were further performed. In addition, Western blotting was performed to investigate the cell signaling pathway. All the relevant experimental data were statistically processed using SPSS 16.0 software.RESULTS: The results showed that sanguinarine represented a time and dose dependent inhibition effects on NPC cell proliferation including the low differentiated CNE2 cells and high metastatic 5-8F cells, along with the cell cloning ability reduction. In addition, sanguinarine has a certain inhibitory effect on the invasion and migration of NPC cells. Mechanistically, sanguinarine displayed the anti-NPC effects mainly involved into the suppression of m TOR signaling and cell apoptosis, which is closely associated with the tumor growth and metastatic malignancy. CONCLUSIONS: Collectively, we discover that sanguinarine is a new high-efficiency anti-NPC monomer of Chinese medicine, with a value for the follow-up preclinical research.
基金Key R&D Program of China,Grant/Award Number:2021YFA1301001。
文摘Background:We aimed to explore the associations of adherence to an overall healthy lifestyle with cardiometabolic diseases(CMDs)among schoolteachers in China.Methods:We conducted a cross-sectional analysis among 2983 teachers(aged 39.8±9.3 years,73.8%women)in Zhejiang Province,China.A healthy lifestyle score(0–7)was constructed based on seven low-risk factors:healthy diet,noncurrent smoking,noncurrent drinking,regular exercise,normal body mass index(BMI),adequate sleep duration,and limited sedentary behavior.CMDs included self-reported hyperlipidemia,hypertension,diabetes,coronary heart disease,and stroke.Multivariable-adjusted logistic regression models were used to evaluate the associations between healthy lifestyle and CMD.Results:A total of 493(16.5%)participants had at least one CMD,with hyperlipidemia,hypertension,and diabetes being the three leading CMDs.ach point increment in a healthy lifestyle score was associated with 20%lower odds of having CMD(p-trend<0.001).Compared with 0–3 low-risk factors,the odds ratios(ORs)and 95%confidence intervals(CIs)were 0.66(0.50–0.88)for 4 low-risk factors and 0.51(0.39–0.67)for 5–7 low-risk factors.We observed independent associations for normal BMI(OR=0.50,95%CI=0.40–0.63),noncurrent drinking(OR=0.53,95%CI=0.36–0.77),and limited sedentary behavior(OR=0.77,95%CI=0.62–0.96)in relation to CMD.Healthy diet(OR=0.75,95%CI=0.55–1.01)exhibited marginally significant association with CMD.Conclusions:Our findings suggest that adherence to an overall healthy lifestyle is associated with lower odds of CMD among schoolteachers.
文摘Nasopharyngeal carcinoma(NPC)has been a focus of medical research for more than 100 years,with significant interest emerging over the last 58 years following the identification of the link between the disease and Epstein-Barr virus(EBV)infection.NPC possesses several distinctive characteristics among human cancers,notably its well-documented global epidemiology,which reveals localized high-incidence regions primarily in Southeast Asia,particularly in the Southern provinces of China near the Pearl river,as well as in Greenland and North Africa.Epidemiological data indicate a marked male predominance,early disease onset,and a nearly 100%prevalence of latent EBV infection in the tumors.Due to lack of consistent pattern of cancer-related mutations in NPC genomes and excessive DNA-methylation in the tumor cells,NPC can be considered"an epigenetic cancer".Despite extensive researches,convincing biological explanations for these unique characteristics remain elusive.Recently,suggestive evidence has been published that specific local variants of EBV may represent major high risk factors.In spite of tumor and virus specific immunity,it has not been possible to use this for improved treatment.Ongoing studies on the role of the local microflora and tumor microenvironment are essential for a comprehensive understanding of host-EBV-tumor interactions.Ultimately,this knowledge aims to enhance diagnosis,disease fractionation,treatment strategies,and potentially prevention of NPC.
基金supported by China-ASEAN International Innovative Center for Health Industry of Traditional Chinese Medicine(No.AD20297142)Guangxi Collaborative Innovation Center for Scientific Achievements Transformation and Applicationon Traditional Chinese Medicine(No.05020058)。
文摘Acute lung injury(ALI)is a severe inflammatory condition with a high mortality rate,often precipitated by sepsis.The pathophysiology of ALI involves complex mechanisms,including inflammation,oxidative stress,and ferroptosis,a novel form of regulated cell death.This study explores the therapeutic potential of andrographolide(AG),a bioactive compound derived from Andrographis,in mitigating Lipopolysaccharide(LPS)-induced inflammation and ferroptosis.Our research employed in vitro experiments with RAW264.7 macrophage cells and in vivo studies using a murine model of LPS-induced ALI.The results indicate that AG significantly suppresses the production of pro-inflammatory cytokines and inhibits ferroptosis in LPS-stimulated RAW264.7 cells.In vivo,AG treatment markedly reduces lung edema,decreases inflammatory cell infiltration,and mitigates ferroptosis in lung tissues of LPS-induced ALI mice.These protective effects are mediated via the modulation of the Toll-like receptor 4(TLR4)/Kelch-like ECH-associated protein 1(Keap1)/Nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway.Molecular docking simulations identified the binding sites of AG on the TLR4 protein(Kd value:-33.5 kcal·mol^(-1)),and these interactions were further corroborated by Cellular Thermal Shift Assay(CETSA)and SPR assays.Collectively,our findings demonstrate that AG exerts potent anti-inflammatory and anti-ferroptosis effects in LPS-induced ALI by targeting TLR4 and modulating the Keap1/Nrf2 pathway.This study underscores AG's potential as a therapeutic agent for ALI and provides new insights into its underlying mechanisms of action.
基金Mengxi Wang holds a doctoral scholarship from the China scholarship council(CSC:202003270025)。
文摘Vertical forest structure is closely linked to multiple ecosystem characteristics,such as biodiversity,habitat,and productivity.Mixing tree species in planted forests has the potential to create diverse vertical forest structures due to the different physiological and morphological traits of the composing tree species.However,the relative importance of species richness,species identity and species interactions for the variation in vertical forest structure remains unclear,mainly because traditional forest inventories do not observe vertical stand structure in detail.Terrestrial laser scanning(TLS),however,allows to study vertical forest structure in an unprecedented way.Therefore,we used TLS single scan data from 126 plots across three experimental planted forests of a largescale tree diversity experiment in Belgium to study the drivers of vertical forest structure.These plots were 9–11years old young pure and mixed forests,characterized by four levels of tree species richness ranging from monocultures to four-species mixtures,across twenty composition levels.We generated vertical plant profiles from the TLS data and derived six stand structural variables.Linear mixed models were used to test the effect of species richness on structural variables.Employing a hierarchical diversity interaction modelling framework,we further assessed species identity effect and various species interaction effects on the six stand structural variables.Our results showed that species richness did not significantly influence most of the stand structure variables,except for canopy height and foliage height diversity.Species identity on the other hand exhibited a significant impact on vertical forest structure across all sites.Species interaction effects were observed to be site-dependent due to varying site conditions and species pools,and rapidly growing tree species tend to dominate these interactions.Overall,our results highlighted the importance of considering both species identity and interaction effects in choosing suitable species combinations for forest management practices aimed at enhancing vertical forest structure.
基金supported by the National Key R&D Program of China (Grant No.2022YFE0106300)the National Natural Science Foundation of China (Grant Nos.41941009 and 42006191)+2 种基金the China Postdoctoral Science Foundation (Grant No.2023M741526)the Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai) (Grant Nos.SML2022SP401 and SML2023SP207)the Program of Marine Economy Development Special Fund under Department of Natural Resources of Guangdong Province (Grant No.GDNRC [2022]18)。
文摘The rapidly changing Antarctic sea ice has garnered significant interest. To enhance the prediction skill for sea ice and respond to the Sea Ice Prediction Network-South's latest call, this study presents the reforecast results of Antarctic sea-ice area and extent from December to June of the coming year with a Convolutional Long Short-Term Memory(Conv LSTM)Network. The reforecast experiments demonstrate that Conv LSTM captures the interannual and interseasonal variability of Antarctic sea ice successfully, and performs better than the European Centre for Medium-Range Weather Forecasts. Based on this, we present the prediction from December 2023 to June 2024, indicating that the Antarctic sea ice will remain at lows, but may not create a new record low. This research highlights the promising application of deep learning in Antarctic sea-ice prediction.
