Gordon Life Science Institute and Its Impacts on Computational Biology and Drug Development

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.

Coronavirus and Gordon Life Science Institute

The impacts of coronavirus to our planet are unprecedented;i.e., they are 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.

The Development of Gordon Life Science Institute: Its Driving Force and Accomplishments

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.

The Remarkable Impacts of Gordon Life Science Institute

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.

3-epi-bufotalin suppresses the proliferation in colorectal cancer cells through the inhibition of the JAK1/STAT3 signaling pathway

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.

The Implication of “I Am the Alpha and the Omega” to Internet Institutes

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.

Noah’s Ark and Internet Institutes: When and Why?

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.

The Most Important Ethical Concerns in Science

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.

Integrative proteomic-transcriptomic analysis revealed the lifestyles of Lactobacillus paracasei H4-11 and Kluyveromyces marxianus L1-1 under co-cultivation conditions

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.

Presence of a long nuclear-localization signal sequence in homeodomain transcription factor Nkx 1.2

Homeodomains,a 60-amino acid sequence encoded by 180 nucleotides,are highly conserved DNA-binding motifs that are present in a variety of transcription factors in species ranging from yeast to humans.The NKX proteins belong to the homeodomain(HD)-containing transcription factor family.They play vital roles in the regulation of morphogenesis.NKX1-2 is one member of the NKX subfamily.At present,information about its nuclear localization signal(NLS)sequence is limited.We studied the NLS sequence of zebrafish Nkx1.2 by introducing sequence changes such as deletion,mutation,and truncation,and identified an NLS motif(QNRRTKWKKQ)that is localized at the C-terminus of the homeodomain.Moreover,the deletion of two amino acid residues(RR)in this NLS motif prevents Nkx1.2 from entering the nucleus,indicating that the two amino acids are essential for Nkx1.2 nuclear localization.However,the NLS motif alone is unable to target cytoplasmic protein glutathione S-transferase(GST)to the nucleus.An intact homeodomain is necessary for mediating the complete nuclear transport of cytoplasmic protein.Unlike most nuclear import proteins with short NLS sequences,a long NLS is present in zebrafish Nkx1.2.We also demonstrated that the sequences of homeodomain of NKX1.2 are well conserved among different species.This study is informative to verify the function of the NKX1.2 protein.

CES1 is associated with cisplatin resistance and poor prognosis of head and neck squamous cell carcinoma

Background:Head and neck squamous cell carcinoma(HNSCC)is a prevalent form of cancer globally,with chemoresistance posing a major challenge in treatment outcomes.The efficacy of the commonly used chemotherapeutic agent,cisplatin,is diminished in patients with poor prognoses.Methods:Various bioinformatics databases were utilized to examine Carboxylesterase 1(CES1)gene expression,clinicopathologic features,patient survival analysis,and gene function.An organoid model of HNSCC was established,along with the induction of drug-resistant HNSCC in the organoid model.CES1 expression was assessed using qRT-PCR and Western Blot,and differential markers were identified through transcriptome sequencing.Knockdown and overexpression models of CES1 were created in SCC-9 and patient-derived organoid(PDO)cells using shRNA and lentivirus to investigate the tumor biology and cisplatin resistance associated with CES1.Results:Research in bioinformatics has uncovered a strong correlation between the expression level of CES1 and the prognosis of HNSCC.The data suggests a significant link between CES1 expression and tobacco smoking.RNA-sequencing revealed a notable increase in CES1 expression in HNSCC-PDOcis-R cells compared to the parental PDO cells.Subsequently,we performed in vitro studies by HNSCC-PDO and SCC-9 and found that CES1-overexpressing cells exhibited reduced sensitivity to cisplatin and stronger tumor malignant biological behavior compared with CES1-knockdown cells.Conclusion:The observed association between CES1 expression and tobacco smoking implies a potential influence of smoking on the efficacy of cisplatin-based chemotherapy in HNSCC through the regulation of CES1 expression.

Re-searching nasopharyngeal carcinoma

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.

Regulatory role of peroxynitrite in advanced glycation end products mediated diabetic cardiovascular complications

The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of formation.Nitric oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.

Unravelling the role of the combined effect of metallic charge transfer channel and SiO_(x) overlayer in the Zr/Si-Fe_(2)O_(3):Au:SiO_(x) nanorod arrays to boost photoelectrochemical water splitting

Hematite(α-Fe_(2)O_(3)) based photoanodes have been extensively studied due to various intriguing features that make them viable candidates for a photoelectrochemical(PEC) water splitting photoanode.Herein,we propose a Zr-doped Fe_(2)O_(3) photoanode decorated with facilely spin-coated Au nanoparticles(NPs) and microwave-assisted attached Si co-doping in conjunction with a SiO_(x) overlayer that displayed a remarkable photocurrent density of 2.01 mA/cm^(2) at 1.23 V vs.RHE.The kinetic dynamics at the photoelectrode/-electrolyte interface was examined by employing systematic electrochemical investigations.The Au NPs played a dual role in increasing PEC water splitting.First,the Schottky interface that was formed between Au NPs and Zr-Fe_(2)O_(3) lectrode ensured the prevention of electron flow from the photoanode to the metal,increasing the number of available charges as well as suppressing surface charge recombination.Second,Au extracted photoholes from the bulk of the Zr-Fe_(2)O_(3) and transported them to the outer SiO_(x) overlayer,while the SiO_(x) overlayer efficiently collected the photoholes and promoted the hole injection into the electrolyte.Further,Si co-doping enhanced bulk conductivity by reducing bulk charge transfer resistance and improving charge carrier density.This study outlines a technique to design a metallic charge transfer path with an overlayer for solar energy conversion.

Pathogenic genes associated with Parkinson’s disease:molecular mechanism overview

Parkinson’s disease(PD)is a common neurodegenerative disease in the elderly,accounting for more than 1%of the population aged 65 years.Monogenic inheritance is relatively rare in PD,accounting for approximately 5%to 10%of PD patients,and there is a growing body of evidence suggesting that multiple genetic risk factors play a significant role in the pathogenesis of PD.Several groups have identified and reported a number of genes carrying mutations associated with affected family members.Mutated genes associated with PD are also candidates for idiopathic PD,and these genes may also carry other mutation sites that increase risk.When multiple genetic risk factors are combined,the risk of PD is increased to a greater extent,and to unravel the pathogenic pathways that lead to different forms of PD.This review focuses on the association of PD genes,such as Parkinson Disease 1-24(PARK1-24),glucosylceramidase(GBA),GTP cyclohydrolase 1(GCH1),fibroblast growth factor 20(FGF20),nuclear receptor-related factor 1(NURR1),NUS1 dehydrodolichyl diphosphate synthase subunit(NUS1),diacylglycerol Lipase Beta(DAGLB),transmembrane protein(TMEM),ubiquinol-cytochrome c reductase core protein 1(UQCRC1),glycoprotein non-metastatic melanoma protein B protein(GPNMB),dynactin 1(DCTN1),LDL receptor related protein 10(LRP10),monoamine oxidase(MAO),ataxin 2(ATXN2),microtubule associated protein tau(MAPT),pantothenate kinase 2(PANK2),spastic parapplegia type 11(SPG11),polymer gamma(POLG),TATA-box binding protein associated factor 1(TAF1),dual specificity tyrosine phosphorylation regulated kinase 1A(Dyrk1a),and crystallin alpha A(CRYAA),with the pathogenesis of PD.We introduce what is currently known about the molecular genetics of PD to help explain the molecular mechanisms leading to the neurodegenerative disease.

Interleukin-35: A key player managing pre-diabetes and chronic inflammatory type 1 autoimmune diabetes

Interleukin-35(IL-35)is a novel protein comprising IL-12αand IL-27βchains.The IL12A and EBI3 genes are responsible for its production.The study of IL-35 has experienced a substantial increase in interest in recent years,as demonstrated by many research papers.Recent clinical studies have shown that individuals who do not have a C-peptide have notably reduced amounts of IL-35 in their blood serum.This is accompanied by a drop in the percentage of IL-35+Treg cells,regulatory B cells,and CD8+FOXP3+cells that produce IL-35.This article em-phasizes the potential significance of IL-35 expression in governing the immune response and its involvement in chronic inflammatory autoimmune diabetes in pancreatic inflammation.It demonstrates IL-35's ability to regulate cytokine proportions,modulate B cells,and protect against autoimmune diabetes.However,further investigation is necessary to ascertain the precise mechanism of IL-35,and meticulous planning is essential for clinical studies.

Highly Aligned Ternary Nanofiber Matrices Loaded with MXene Expedite Regeneration of Volumetric Muscle Loss

Current therapeutic approaches for volumetric muscle loss(VML)face challenges due to limited graft availability and insufficient bioactivities.To overcome these limitations,tissue-engineered scaffolds have emerged as a promising alternative.In this study,we developed aligned ternary nanofibrous matrices comprised of poly(lactide-co-ε-caprolactone)integrated with collagen and Ti_(3)C_(2)T_(x)MXene nanoparticles(NPs)(PCM matrices),and explored their myogenic potential for skeletal muscle tissue regeneration.The PCM matrices demonstrated favorable physicochemical properties,including structural uniformity,alignment,microporosity,and hydrophilicity.In vitro assays revealed that the PCM matrices promoted cellular behaviors and myogenic differentiation of C2C12 myoblasts.Moreover,in vivo experiments demonstrated enhanced muscle remodeling and recovery in mice treated with PCM matrices following VML injury.Mechanistic insights from next-generation sequencing revealed that MXene NPs facilitated protein and ion availability within PCM matrices,leading to elevated intracellular Ca^(2+)levels in myoblasts through the activation of inducible nitric oxide synthase(i NOS)and serum/glucocorticoid regulated kinase 1(SGK1),ultimately promoting myogenic differentiation via the m TOR-AKT pathway.Additionally,upregulated i NOS and increased NO–contributed to myoblast proliferation and fiber fusion,thereby facilitating overall myoblast maturation.These findings underscore the potential of MXene NPs loaded within highly aligned matrices as therapeutic agents to promote skeletal muscle tissue recovery.

SiRAP2-12,a Positive Regulatory Factor,Effectively Improves the Waterlogging Tolerance of Foxtail Millet(Setaria italica)

Foxtail millet(Setaria italica)growth was inhibited because of waterlogging stress,which has caused yield reduc-tion.ERF family plays an important role to plant adversity tolerance.In our study,we obtained 19,819 differential expressed genes(DEGs)between the two treatments based on the RNA-seq sequencing of foxtail millet of water-logging stress.Furthermore,a total of 28 ERF family members were obtained,which have a complete open read-ing frame.We studied the evolution and function of SiERF family and how they affected the waterlogging tolerance.It was found that SiERF1A/B/C(GenBank ID:OR775217,OR775219,OR775218)and SiRAP2-12(GenBank ID:OR775216)have similar functions to the known waterlogging tolerance genes of other plants.Among them,the SiRAP2-12 expression was obviously significantly up-regulated in foxtail millet after 5d water-logging stress.After SiRAP2-12 was silenced,the activity of defense enzymes in millet decreased significantly.In details,superoxide dismutase(SOD),catalase(CAT)and peroxidase(POD),the osmotic regulator proline(Pro),and the activity of the anaerobic respiratory enzyme alcohol dehydrogenase(ADH)content were decreased by 78.61%,29.52%,79.95%,19.41%and 54.77%,respectively.In contrast,the relative electrical conductivity contents(REC),malondialdehyde(MDA),and hydrogen peroxide(H_(2)O_(2))of the foxtail millet subjected to virus-induced gene silencing clearly increased by 1.03-fold,36.09%,and 15.21%,respectively.The content of sodium(Na^(+))in the SiRAP2-12-silenced foxtail millet also increased,but that of potassium(K^(+))decreased.Interestingly,we found that ethylene content was significantly reduced.Further,the SiAOC1 expression,an essential gene for ethylene synthesis,was inhibited in SiRAP2-12-silenced foxtail millet after waterlogging stress.Taken together,we hypothesized that SiRAP2-12 might be a positive regulator of millet tolerance to waterlogging stress.

Influences of Skin and Base Types on the Soothing Assessment of Cosmetic Products

In order to assess the responses of different skin types stimulated by tape stripping,after which two kinds of brand cosmetics of cream and hydrogel,were separately applied to evaluate the individual soothing effect of the product on different skin types.A total of 30 volunteers aged 18~65 years were recruited,which were divided into four groups(oily,dry,normal and combined)according to the self-oiling ability of facial and T zones.Four 3 cm×3 cm of skins on inner forearm of each volunteer were chosen and randomly marked as blank,negative control,soothing cream and soothing gel.The blank area was kept untreated,and the remaining areas were tape-stripped by 10 times(Transparent universal 1527C-1,3M China Co.,Ltd.,)to disrupt the skin corneum and induce erythema.Images,erythema index(EI)and transcutaneous water loss rate(TEWL)of the marked skin areas before and 5 min after tape-stripping were taken to assess the distinct responses of different skin type to the taping treatment;Ten minutes after tape-stripping,The soothing products were applied to the test area,the skin images,EI and TEWL at 20 min and 50 min(corresponding to 30 min and 60 min after tape-stripping,respectively)were measured after cosmetics application to compare and evaluate the soothing effects of cream and hydrogel on different skin types.Results showed that different skin displayed diverse reactions to the tape-stripping,and the oily skin was more sensitive with longer duration of erythema than other skin types.After the application of soothing products,both cream and hydrogel could relieve skin erythema,while the soothing effects are dependent both on skin types and the cosmetic base materials:Hydrogel has a better efficacy in alleviating erythema and TEWL of dry skin,while the cream was more effective on normal,oily and combined skin types.The results suggest that the modelling method for soothing evaluation should consider the skin types of the volunteers,and the cosmetics of different base materials might have the target skin types.

Fusobacterium nucleatum-induced imbalance in microbiome-derived butyric acid levels promotes the occurrence and development of colorectal cancer

BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignant tumors globally.Recent reports suggest that Fusobacterium nucleatum(F.nucleatum)contributes to the initiation,progression,and prognosis of CRC.Butyrate,a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber,is known to inhibit various cancers.This study is designed to explore whether F.nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid.AIM To investigate the mechanism by which F.nucleatum affects CRC occurrence and development.METHODS Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F.nucleatum.Additionally,DLD-1 and HCT116 cell lines were exposed to sodium butyrate(NaB)and F.nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function.RESULTS Our research indicates that the prevalence of F.nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts,while the prevalence of butyrate-producing bacteria is notably lower.In mice colonized with F.nucleatum,the population of butyrate-producing bacteria decreased,resulting in altered levels of butyric acid,a key intestinal metabolite of butyrate.Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells.Consequently,this leads to modulated production of adenosine triphosphate and reactive oxygen species,thereby inhibiting cancer cell prolif-eration.Additionally,NaB triggers the adenosine monophosphate-activated protein kinase(AMPK)signaling pathway,blocks the cell cycle in HCT116 and DLD-1 cells,and curtails the proliferation of CRC cells.The combined presence of F.nucleatum and NaB attenuated the effects of the latter.By employing small interfering RNA to suppress AMPK,it was demonstrated that AMPK is essential for NaB’s inhibition of CRC cell proliferation.CONCLUSION F.nucleatum can promote cancer progression through its inhibitory effect on butyric acid,via the AMPK signaling pathway.