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.
Ulva prolifera green tides are becoming aworldwide environmental problem,especially in the Yellow Sea,China.However,the effects of the occurrence of U.prolifera green tides on the community organization and stability ...Ulva prolifera green tides are becoming aworldwide environmental problem,especially in the Yellow Sea,China.However,the effects of the occurrence of U.prolifera green tides on the community organization and stability of surrounding microbiomes have still not been de-termined.Here,the prokaryotic microbial community network stability and assembly char-acteristics were systematically analyzed and compared between the green tide and non-green tide periods.U.prolifera blooms weaken the community complexity and robustness of surrounding microbiomes,increasing fragmentation and decreasing diversity.Bacteria and archaea exhibited distinct community distributions and assembly patterns under the influ-ence of green tides,and bacterial communities were more sensitive to outbreaks of green tides.The bacterial communities exhibited a greater niche breadth and a lower phyloge-netic distance during the occurrence of U.prolifera green tides compared to those during the non-green tide period while archaeal communities remained unchanged,suggesting that the bacterial communities underwent stronger homogeneous selection and more sensitive to green tide blooms than the archaeal communities.Piecewise structural equation model analysis revealed that the different responses of major prokaryotic microbial groups,such as Cyanobacteria,to environmental variables during green tides,were influenced by the variations in pH and nitrate during green tides and correlated with the salinity gradient during the non-green tide period.This study elucidates the response of the adaptability,associations,and stability of surrounding microbiomes to outbreaks of U.prolifera green tides.展开更多
Drought stress orchestrates a phosphorylation-dependent signaling cascade that reprograms transcriptional networks to enhance crop resilience.Through a large-scale transgenic screening,we identified ZmCRK5A,a Ca^(2+)-...Drought stress orchestrates a phosphorylation-dependent signaling cascade that reprograms transcriptional networks to enhance crop resilience.Through a large-scale transgenic screening,we identified ZmCRK5A,a Ca^(2+)-independent calcium-dependent protein kinase(CDPK)-related kinase,as a master regulator of drought tolerance in maize.Mechanistically,ZmCRK5A directly phosphorylates the MYB transcriptional repressor ZmSMH4(Single MYB Histone 4)at three conserved serine residues(Ser42/43/59)within its SANT domain,as demonstrated by in vitro kinase assays and site-directed mutagenesis.This post-translational modification abolishes Zm SMH4's DNA-binding capacity to ACC cis-elements,thereby de-repressing the potassium influx channel gene Zm KCH1(K^(+)Channel 1).Functional validation revealed that Zm KCH1 overexpression confers drought resilience through optimized stomatal dynamics and water retention,whereas clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)-generated zmkch1 mutants display hypersensitivity to water deficit.Crucially,field evaluations demonstrated preserved grain yield alongside enhanced drought tolerance in plants with activated Zm CRK5A-Zm SMH4-Zm KCH1 signaling.Our findings delineate a kinase-transcription factor-ion channel axis that dynamically fine-tunes drought responses while maintaining productivity,providing a strategic framework for engineering stress-adapted crops without yield penalties.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
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
The most unethical behaviors in science are of falsifying data and stealing ideas from previous investigators. But for publishing papers with high similarity and editing papers with coercion, it is necessary to carry ...The most unethical behaviors in science are of falsifying data and stealing ideas from previous investigators. But for publishing papers with high similarity and editing papers with coercion, it is necessary to carry out a concrete analysis case by case.展开更多
Compared with the rice-acid soup inoculated with single starter,the synergistically intensifi ed rice-acid soup inoculated with Lactobacillus paracasei H4-11(L.paracasei H4-11)and Kluyveromyces marxianus L1-1(K.marxia...Compared with the rice-acid soup inoculated with single starter,the synergistically intensifi ed rice-acid soup inoculated with Lactobacillus paracasei H4-11(L.paracasei H4-11)and Kluyveromyces marxianus L1-1(K.marxianus L1-1)contained more fl avor compounds.Organic acids mainly included L-lactic acid and the main volatile fl avor component was ethyl acetate.Moreover,the signal intensity of astringency and bitterness and the total concentration of volatile sulfur compounds were reduced.The combined analysis results of RNA sequencing(RNA-seq)technology and 4D label-free quantitative(4D LFQ)proteomics explained the fl avor formation pathways in rice-acid soup inoculated with L.paracasei H4-11 and K.marxianus L1-1.In L.paracasei H4-11,L-lactate dehydrogenase,phosphoglucomutase,acetate kinase,alcohol dehydrogenase and acetyl-CoA were up-regulated and D-lactate dehydrogenase and N-Acetyltransferase were down-regulated.In K.marxianus L1-1,Acetyl-CoA,acetaldehyde dehydrogenase,acyl-coenzyme A,N-acetyltransferase,and L-lactate dehydrogenase were up-regulated and hexokinase,alcohol dehydrogenase,and alcohol O-acetyltransferase were down-regulated.The above up-regulation and down-regulation synergistically promoted the formation of characteristic fl avor compounds(mainly L-lactic acid and ethyl acetate).Enzyme-linked immunoassay(ELISA)and parallel reaction monitoring(PRM)quantitative analysis respectively verifi ed that 5 key metabolic enzymes and 27 proteins in L.paracasei H4-11 and K.marxianus L1-1 were associated with the characteristic fl avor of rice-acid soup,as confi rmed by the quantitative results of 4D LFQ.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
Environmental changes along an altitudinal gradient can facilitate the differentiation of life-history features in ectothermic species,but little attention has been devoted to the reciprocal influence of altitude and ...Environmental changes along an altitudinal gradient can facilitate the differentiation of life-history features in ectothermic species,but little attention has been devoted to the reciprocal influence of altitude and alpine slope directionality on life-history variation.According to life-history theory,increased environmental stress causes a change in reproductive allocation from number to quality of offspring,as well as a stronger trade-off between size and number of offspring.To clarify the influence of environmental pressures on the life-history features of the Qinghai toad-headed lizard Phrynocephalus vlangalii along an altitudinal cline,we surveyed late pregnant females from 3 populations of low(2,600 m),middle(3,400 m),and high(3,600 m)elevations in the Dangjin Mountain of Gansu,China from July to October 2019,and compared their inter-population differences in maternal body size,reproductive characteristics,offspring growth,and locomotor performance.Because of lower temperatures,higher humidity,and lower light intensity caused by slope aspect and altitude,the middle-altitude region experienced stronger environmental stress than the high-and low-altitude regions.Our results showed that females were larger at middle-and high-altitude sites and smaller at the low-altitude site,following Bergmann’s rule.We also found that females from low-altitude population gave birth earlier than those from the middle and high altitudes.Our results showed a shift in the offspring size-number trade-off of P.vlangalii in response to colder and harsher environments,with lizards from the alpine steppe(i.e.the middle-and high-altitude habitats)producing fewer but larger offspring than those from the warm steppe(i.e.the low-altitude habitat).Low-altitude juveniles grew faster than high-altitude ones,but at the same rates as middle-altitude juveniles.This result demonstrates that the growth of P.vlangalii was associated with temperature and light intensity.Our findings contribute to enhancing our understanding of the altitudinal variation in life-history features of plateau ectotherms and their phenotypic plasticity or local adaptation.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
Parkinson's disease(PD),a chronic and com-mon neurodegenerative disease,is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-...Parkinson's disease(PD),a chronic and com-mon neurodegenerative disease,is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein.Type 2 diabetes mellitus(T2DM)is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion.Extensive evidence has con-firmed shared pathogenic mechanisms underlying PD and T2DM,such as oxidative stress caused by insulin resistance,mitochondrial dysfunction,inflammation,and disorders of energy metabolism.Conventional drugs for treating T2DM,such as metformin and glucagon-like peptide-1 receptor ago-nists,affect nerve repair.Even drugs for treating PD,such as levodopa,can affect insulin secretion.This review sum-marizes the relationship between PD and T2DM and related therapeutic drugs from the perspective of insulin signaling pathways in the brain.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 Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limi...BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.展开更多
To explore the mechanism of sperm dysfunction caused by dibutyl phthalate(DBP),the effects of DBP on intracellular[Ca^(2+)]and[pH],reactive oxygen species(ROS),lipid peroxidation(LPO),mitochondrial permeability transi...To explore the mechanism of sperm dysfunction caused by dibutyl phthalate(DBP),the effects of DBP on intracellular[Ca^(2+)]and[pH],reactive oxygen species(ROS),lipid peroxidation(LPO),mitochondrial permeability transition pore(mPTP)opening,mitochondrial membrane potential(MMP),adenosine triphosphate(ATP)levels,phosphorylation of protein kinase A(PKA)substrate proteins and phosphotyrosine(p-Tyr)proteins,sperm motility,spontaneous acrosome reaction,and tail bending were examined in mouse spermatozoa.At 100μg/mL,DBP significantly increased tail bending and[Ca^(2+)]i.Interestingly,DBP showed biphasic effects on[pH]i.DBP at 10–100μg/mL significantly decreased sperm motility.Similarly,Ca^(2+)ionophore A23187 decreased[pH]_(i)sperm motility,suggesting that DBP-induced excessive[Ca^(2+)]_(i)decreased sperm motility.DBP significantly increased ROS and LPO.DBP at 100μg/mL significantly decreased mPTP closing,MMP,and ATP levels in spermatozoa,as did H2O2,indicative of ROS-mediatedmitochondrial dysfunction caused by DBP.DBP as well as H2O2 increased p-Tyr sperm proteins and phosphorylated PKA substrate sperm proteins.DBP at 1–10μg/mL significantly increased the spontaneous acrosome reaction,suggesting that DBP can activate sperm capacitation.Altogether,DBP showed a biphasic effect on intracellular signaling in spermatozoa.At concentrations relevant to seminal ortho-phthalate levels,DBP activates[pH]i,protein tyrosine kinases and PKA via physiological levels of ROS generation,potentiating sperm capacitation.DBP at high doses excessively raises[Ca^(2+)]_(i)and ROS and disrupts[pH]i,impairing the mitochondrial function,tail structural integrity,and sperm motility.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
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supported by the National Key Research and Development Program of China(No.2022YFC2807500)Laoshan Laboratory(No.LSKJ202203201)+1 种基金the National Natural Science Foundation of China(Nos.42206147,42120104006 and 42176111)the Natural Science Foundation of Shandong Province(Nos.ZR2022QD046,ZR2021QD051).
文摘Ulva prolifera green tides are becoming aworldwide environmental problem,especially in the Yellow Sea,China.However,the effects of the occurrence of U.prolifera green tides on the community organization and stability of surrounding microbiomes have still not been de-termined.Here,the prokaryotic microbial community network stability and assembly char-acteristics were systematically analyzed and compared between the green tide and non-green tide periods.U.prolifera blooms weaken the community complexity and robustness of surrounding microbiomes,increasing fragmentation and decreasing diversity.Bacteria and archaea exhibited distinct community distributions and assembly patterns under the influ-ence of green tides,and bacterial communities were more sensitive to outbreaks of green tides.The bacterial communities exhibited a greater niche breadth and a lower phyloge-netic distance during the occurrence of U.prolifera green tides compared to those during the non-green tide period while archaeal communities remained unchanged,suggesting that the bacterial communities underwent stronger homogeneous selection and more sensitive to green tide blooms than the archaeal communities.Piecewise structural equation model analysis revealed that the different responses of major prokaryotic microbial groups,such as Cyanobacteria,to environmental variables during green tides,were influenced by the variations in pH and nitrate during green tides and correlated with the salinity gradient during the non-green tide period.This study elucidates the response of the adaptability,associations,and stability of surrounding microbiomes to outbreaks of U.prolifera green tides.
基金supported by National Key Research and Development Program of China(2022YFF1001600)BeijingNatural Science Foundation(5244040)+1 种基金STI2030-Major Projects(2030ZD0407101)China Postdoctoral Science Foundation(2022M723435)。
文摘Drought stress orchestrates a phosphorylation-dependent signaling cascade that reprograms transcriptional networks to enhance crop resilience.Through a large-scale transgenic screening,we identified ZmCRK5A,a Ca^(2+)-independent calcium-dependent protein kinase(CDPK)-related kinase,as a master regulator of drought tolerance in maize.Mechanistically,ZmCRK5A directly phosphorylates the MYB transcriptional repressor ZmSMH4(Single MYB Histone 4)at three conserved serine residues(Ser42/43/59)within its SANT domain,as demonstrated by in vitro kinase assays and site-directed mutagenesis.This post-translational modification abolishes Zm SMH4's DNA-binding capacity to ACC cis-elements,thereby de-repressing the potassium influx channel gene Zm KCH1(K^(+)Channel 1).Functional validation revealed that Zm KCH1 overexpression confers drought resilience through optimized stomatal dynamics and water retention,whereas clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)-generated zmkch1 mutants display hypersensitivity to water deficit.Crucially,field evaluations demonstrated preserved grain yield alongside enhanced drought tolerance in plants with activated Zm CRK5A-Zm SMH4-Zm KCH1 signaling.Our findings delineate a kinase-transcription factor-ion channel axis that dynamically fine-tunes drought responses while maintaining productivity,providing a strategic framework for engineering stress-adapted crops without yield penalties.
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.
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.
文摘The most unethical behaviors in science are of falsifying data and stealing ideas from previous investigators. But for publishing papers with high similarity and editing papers with coercion, it is necessary to carry out a concrete analysis case by case.
基金funded by National Natural Science Foundation of China(32060530)Guizhou University,Gui Da Te Gang He Zi(2022)39,Science and Technology Project of Guizhou Province,Qian Ke He Zhicheng[2022]Zhongdian 001-2,Qian Ke He Zhicheng[2022]Zhongdian 003-3+1 种基金Industry-University-Research Cooperation Project of Guizhou University(701/700465172217)China Scholarship Council(201906670006).
文摘Compared with the rice-acid soup inoculated with single starter,the synergistically intensifi ed rice-acid soup inoculated with Lactobacillus paracasei H4-11(L.paracasei H4-11)and Kluyveromyces marxianus L1-1(K.marxianus L1-1)contained more fl avor compounds.Organic acids mainly included L-lactic acid and the main volatile fl avor component was ethyl acetate.Moreover,the signal intensity of astringency and bitterness and the total concentration of volatile sulfur compounds were reduced.The combined analysis results of RNA sequencing(RNA-seq)technology and 4D label-free quantitative(4D LFQ)proteomics explained the fl avor formation pathways in rice-acid soup inoculated with L.paracasei H4-11 and K.marxianus L1-1.In L.paracasei H4-11,L-lactate dehydrogenase,phosphoglucomutase,acetate kinase,alcohol dehydrogenase and acetyl-CoA were up-regulated and D-lactate dehydrogenase and N-Acetyltransferase were down-regulated.In K.marxianus L1-1,Acetyl-CoA,acetaldehyde dehydrogenase,acyl-coenzyme A,N-acetyltransferase,and L-lactate dehydrogenase were up-regulated and hexokinase,alcohol dehydrogenase,and alcohol O-acetyltransferase were down-regulated.The above up-regulation and down-regulation synergistically promoted the formation of characteristic fl avor compounds(mainly L-lactic acid and ethyl acetate).Enzyme-linked immunoassay(ELISA)and parallel reaction monitoring(PRM)quantitative analysis respectively verifi ed that 5 key metabolic enzymes and 27 proteins in L.paracasei H4-11 and K.marxianus L1-1 were associated with the characteristic fl avor of rice-acid soup,as confi rmed by the quantitative results of 4D LFQ.
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supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA20050201)the National Natural Science Fund of China(31861143023).
文摘Environmental changes along an altitudinal gradient can facilitate the differentiation of life-history features in ectothermic species,but little attention has been devoted to the reciprocal influence of altitude and alpine slope directionality on life-history variation.According to life-history theory,increased environmental stress causes a change in reproductive allocation from number to quality of offspring,as well as a stronger trade-off between size and number of offspring.To clarify the influence of environmental pressures on the life-history features of the Qinghai toad-headed lizard Phrynocephalus vlangalii along an altitudinal cline,we surveyed late pregnant females from 3 populations of low(2,600 m),middle(3,400 m),and high(3,600 m)elevations in the Dangjin Mountain of Gansu,China from July to October 2019,and compared their inter-population differences in maternal body size,reproductive characteristics,offspring growth,and locomotor performance.Because of lower temperatures,higher humidity,and lower light intensity caused by slope aspect and altitude,the middle-altitude region experienced stronger environmental stress than the high-and low-altitude regions.Our results showed that females were larger at middle-and high-altitude sites and smaller at the low-altitude site,following Bergmann’s rule.We also found that females from low-altitude population gave birth earlier than those from the middle and high altitudes.Our results showed a shift in the offspring size-number trade-off of P.vlangalii in response to colder and harsher environments,with lizards from the alpine steppe(i.e.the middle-and high-altitude habitats)producing fewer but larger offspring than those from the warm steppe(i.e.the low-altitude habitat).Low-altitude juveniles grew faster than high-altitude ones,but at the same rates as middle-altitude juveniles.This result demonstrates that the growth of P.vlangalii was associated with temperature and light intensity.Our findings contribute to enhancing our understanding of the altitudinal variation in life-history features of plateau ectotherms and their phenotypic plasticity or local adaptation.
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.
基金supported by the National Natural Science Foundation of China(32161143021)the Iran National Science Foundation(4001873)+1 种基金the Henan Province Natural Science Foundation of China(182300410313)Henan University graduate Talent Program of Henan Province(SYLYC2023092).
文摘Parkinson's disease(PD),a chronic and com-mon neurodegenerative disease,is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein.Type 2 diabetes mellitus(T2DM)is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion.Extensive evidence has con-firmed shared pathogenic mechanisms underlying PD and T2DM,such as oxidative stress caused by insulin resistance,mitochondrial dysfunction,inflammation,and disorders of energy metabolism.Conventional drugs for treating T2DM,such as metformin and glucagon-like peptide-1 receptor ago-nists,affect nerve repair.Even drugs for treating PD,such as levodopa,can affect insulin secretion.This review sum-marizes the relationship between PD and T2DM and related therapeutic drugs from the perspective of insulin signaling pathways in the brain.
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.
基金Supported by the Ministry of Science and Technology of China,No.2021YFA1101502。
文摘BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.
基金supported by the National Research Foundation of Republic of Korea(NRF)grant funded by the Republic of Korea government(MSIT)(No.2022R1A2C1007831).
文摘To explore the mechanism of sperm dysfunction caused by dibutyl phthalate(DBP),the effects of DBP on intracellular[Ca^(2+)]and[pH],reactive oxygen species(ROS),lipid peroxidation(LPO),mitochondrial permeability transition pore(mPTP)opening,mitochondrial membrane potential(MMP),adenosine triphosphate(ATP)levels,phosphorylation of protein kinase A(PKA)substrate proteins and phosphotyrosine(p-Tyr)proteins,sperm motility,spontaneous acrosome reaction,and tail bending were examined in mouse spermatozoa.At 100μg/mL,DBP significantly increased tail bending and[Ca^(2+)]i.Interestingly,DBP showed biphasic effects on[pH]i.DBP at 10–100μg/mL significantly decreased sperm motility.Similarly,Ca^(2+)ionophore A23187 decreased[pH]_(i)sperm motility,suggesting that DBP-induced excessive[Ca^(2+)]_(i)decreased sperm motility.DBP significantly increased ROS and LPO.DBP at 100μg/mL significantly decreased mPTP closing,MMP,and ATP levels in spermatozoa,as did H2O2,indicative of ROS-mediatedmitochondrial dysfunction caused by DBP.DBP as well as H2O2 increased p-Tyr sperm proteins and phosphorylated PKA substrate sperm proteins.DBP at 1–10μg/mL significantly increased the spontaneous acrosome reaction,suggesting that DBP can activate sperm capacitation.Altogether,DBP showed a biphasic effect on intracellular signaling in spermatozoa.At concentrations relevant to seminal ortho-phthalate levels,DBP activates[pH]i,protein tyrosine kinases and PKA via physiological levels of ROS generation,potentiating sperm capacitation.DBP at high doses excessively raises[Ca^(2+)]_(i)and ROS and disrupts[pH]i,impairing the mitochondrial function,tail structural integrity,and sperm motility.
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.
