Available online Further oxidation of NH3produced via photocatalytic N_(2)fixation represents a promising strategy to enhance the economic value of N_(2)fixation.This work employs first-principles density functional t...Available online Further oxidation of NH3produced via photocatalytic N_(2)fixation represents a promising strategy to enhance the economic value of N_(2)fixation.This work employs first-principles density functional theory(DFT)calculations to demonstrate that incorporating Co into Ni O improves both N_(2)adsorption and activation as well as M-N electron exchange intensity.Guided by these predictions,a novel Co single-atom photocatalyst supported by nanoconfined Ni O@C nanosheets was synthesized using a direct metal atomization method,achieving high HNO_(3)production(60.54%).NH_(4)^(+)and NO_(3)^(-)production rates during N_(2)photofixation reached 67.97μmol g_(cat)^(-1)h^(-1)and 104.28μmol g_(cat)^(-1)h^(-1),respectively.The overall N_(2)→NH_(3)→HNO_(3)photofixation pathway was validated through in-situ diffuse reflectance infrared Fourier transform spectroscopy(DRIFTS)and^(15)N isotopic labeling.Mechanistic studies reveal that Co single-atom introduction serves as an electron trap,enhancing photogenerated electron accumulation with a five-fold increase in carrier density compared to Ni O@C,as observed via in-situ X-ray photoelectron spectroscopy(XPS).This synergistic effect between electron traps and N2adsorption/activation sites at Co single-atom centers supports rapid N_(2)reduction kinetics.Additionally,nanoconfined ink-bottle pores in the carbon layer impede NH_(3)desorption,further boosting NO_(3)-production.This work offers a comprehensive approach to optimizing N_(2)photofixation through electron regulation and surface reaction kinetics.展开更多
This study investigated whether changes in circulating tumor cell(CTC) numbers reflect tumor progression and treatment efficacy in esophageal squamous cell carcinoma(ESCC). A 47-year-old male patient with ESCC is pres...This study investigated whether changes in circulating tumor cell(CTC) numbers reflect tumor progression and treatment efficacy in esophageal squamous cell carcinoma(ESCC). A 47-year-old male patient with ESCC is presented in this case study. The patient was evaluated for a series of serum tumor markers and subjected to radiological examinations before and after surgery and during follow-up over the course of five years. In addition, the CTCs in 7.5 m L of peripheral blood were enriched by magneticactivated cell sorting negative selection and identified by immunofluorescence staining. Serum tumor markers remained within normal ranges and were discordant with imaging scans during the follow-up. Initially, one CTC was detected in the peripheral blood sample, and 14 were observed seven days after the operation. After 12 wk, subcutaneous metastases and bone metastases occurred, and the number of CTCs increased to 84. After 48 wk, lung metastases were noted, and the CTC level was 21. At 104 wk, the number of CTCs was 14, and disease recurrence was detected by positron emission tomography-computed tomography. The CTC counts were in accord with the imaging studies at several time points. The additional information provided by CTC enumeration could thus facilitate monitoring of disease status and treatment efficacy and provide support for treatment decisions.展开更多
Neuroinflammation has been recognized to play a critical role in the pathogenesis of Alzheimer＇s disease （AD）, which is pathologically characterized by the accumulation of senile plaques containing activated microg...Neuroinflammation has been recognized to play a critical role in the pathogenesis of Alzheimer＇s disease （AD）, which is pathologically characterized by the accumulation of senile plaques containing activated microglia and amyloid β-peptides （Aβ）. In the present study, we examined the neuroprotective effects of hydrogen sulfide （H2S） on neuroinflammation in rats with Aβ1-40 hippocampal injection. We found that Aβ-induced rats exhibited a disorder of pyramidal cell layer arrangement, and a decrease of mean pyramidal cell number in the CA1 hippocampal region compared with those in sham operated rats. NaHS （a donor of H2S, 5.6 mg/kg/d, i.p.） treatment for 3 weeks rescued neuronal cell death significantly. Moreover, we found that H2S dramatically suppressed the release of TNF-α, IL-1β and IL-6 in the hippocampus. Consistently, both immunohistochemistry and Western blotting assays showed that H2S inhibited the upregulation of COX-2 and the activation of NF-κB in the hippocampus. In conclusion, our data indicate that H2S suppresses neuroinflammation via inhibition of the NF-κB activation pathway in the Aβ-induced rat model and has potential value for AD therapy.展开更多
Oxysterol binding protein like 2(OSBPL2), an important regulator in cellular lipid metabolism and transport, was identified as a novel deafness-causal gene in our previous work. To resemble the phenotypic features of ...Oxysterol binding protein like 2(OSBPL2), an important regulator in cellular lipid metabolism and transport, was identified as a novel deafness-causal gene in our previous work. To resemble the phenotypic features of OSBPL2 mutation in animal models and elucidate the potential genotypephenotype associations, the OSBPL2-disrupted Bama miniature(BM) pig model was constructed using CRISPR/Cas9-mediated gene editing, somatic cell nuclear transfer(SCNT) and embryo transplantation approaches, and then subjected to phenotypic characterization of auditory function and serum lipid profiles. The OSBPL2-disrupted pigs displayed progressive hearing loss(HL) with degeneration/apoptosis of cochlea hair cells(HCs) and morphological abnormalities in HC stereocilia, as well as hypercholesterolaemia. High-fat diet(HFD) feeding aggravated the development of HL and led to more severe hypercholesterolaemia. The dual phenotypes of progressive HL and hypercholesterolaemia resembled in OSBPL2-disrupted pigs confirmed the implication of OSBPL2 mutation in nonsydromic hearing loss(NSHL) and contributed to the potential linkage between auditory dysfunction and dyslipidaemia/hypercholesterolaemia.展开更多
Objective:To explore the role that ceramide plays in the activation of mitogen-activated protein kinases(MAPKs)during cerebral ischemia and reperfusion.Methods:Rats were subjected to ischemia by the fourvessel occlusi...Objective:To explore the role that ceramide plays in the activation of mitogen-activated protein kinases(MAPKs)during cerebral ischemia and reperfusion.Methods:Rats were subjected to ischemia by the fourvessel occlusion(4-VO)method.The sphingomyelinase inhibitor TPCK was administered to the CA1 subregion of the rat hippocampus before inducing ischemia.Western blot was used to examine the activity of extracellular-signal regulated kinase(ERK)and c-Jun N-terminal protein kinase(JNK)using antibodies against ERK,JNK and diphosphorylated ERK and JNK.Results:At lh reperfusion post-ischemia,JNK reached its peak activity while ERK was undergoing a sharp inactivation(P〈0.05).The level of diphosphorylated JNK was significantly reduced but the sharp inactivation of ERK was visibly reversed(P〈0.05)by the sphingomyelinase inhibitor.Conclusion:The ceramide signaling pathway is up-regulated through sphingomyelin hydrolysis in brain ischemia,promoting JNK activation and suppressing ERK activation,culminating in the ischemic lesion.展开更多
Many studies have shown that(5R)-5-hydroxytriptolide is the optimal modified analogue of triptolide, possessing comparable immunosuppressive activity but much lower cytotoxicity than triptolide. Whether(5R)-5-hydroxyt...Many studies have shown that(5R)-5-hydroxytriptolide is the optimal modified analogue of triptolide, possessing comparable immunosuppressive activity but much lower cytotoxicity than triptolide. Whether(5R)-5-hydroxytriptolide has preventive effects on neuroinflammation is unclear. This study was designed to pretreat primary astrocytes from the brains of neonatal Sprague-Dawley rats with 20, 100 and 500 nM(5R)-5-hydroxytriptolide for 1 hour before establishing an in vitro neuroinflammation model with 1.0 μg/mL lipopolysaccharide for 24 hours. The generation of nitric oxide was detected by Griess reagents. Astrocyte marker glial fibrillary acidic protein was measured by immunohistochemical staining. The levels of tumor necrosis factor-α and interleukin-1β in the culture supernatant were assayed by enzyme linked immunosorbent assay. Nuclear factor-κB/p65 expression was examined by immunofluorescence staining. The phosphorylation of inhibitor of nuclear factor IκB-α and the location of nuclear factor-κB/P65 were determined using western blot assay. Our data revealed that(5R)-5-hydroxytriptolide inhibited the generation of nitric oxide, tumor necrosis factor-α and interleukin-1β from primary astrocytes activated by lipopolysaccharide, decreased the positive reaction intensity of glial fibrillary acidic protein, reduced the expression of tumor necrosis factor alpha and interleukin-1β in culture supernatant, inhibited the phosphorylation of IκB-α and the translocation of nuclear factor-κB/P65 to the nucleus. These results have confirmed that(5R)-5-hydroxytriptolide inhibits lipopolysaccharide-induced glial inflammatory response and provides cytological experimental data for(5R)-5-hydroxytriptolide in the treatment of neurodegenerative diseases.展开更多
Increased accumulation and/or impaired utilization of fatty acid in extra-adipose tissues are implicated in the pathogenesis of insulin resistance and type 2 diabetes. Pyruvate dehydrogenase kinase 4 （Pdk4） is a key...Increased accumulation and/or impaired utilization of fatty acid in extra-adipose tissues are implicated in the pathogenesis of insulin resistance and type 2 diabetes. Pyruvate dehydrogenase kinase 4 （Pdk4） is a key enzyme involved in fatty oxidation and energy expenditure, and its expression can be repressed by pro-inflammatory stimuli. Previously, we have shown that class II transactivator （CIITA） mediates the adverse effect of interferon gamma （IFN-7） in skeletal muscle cells by cooperating with hypermethylated in cancer 1 （HIC1） to repress silent informa- tion regulator 1 （SIRT1） transcription. Building upon this finding, we report here that CIITA interacted with HIC1 via the GTP-binding domain （GBD） while HIC1 interacted with CIITA via the BTB/POZ domain. The GBD domain was required for CIITA to repress SIRT1 transcription probably acting as a bridge for CIITA to bind to HIC1 and consequently to bind to the SIRT1 promoter. IFN-7 stimulation, CIITA over-expression, or HIC1 over- expression repressed Pdk4 promoter activity while silencing either CIITA or HIC1 normalized Pdk4 expression in the presence of IFN-7. An increase in SIRT1 expression or activity partially rescued Pdk4 expression in the pre- sence of CIITA, but SIRT1 inhibition abrogated Pdk4 normalization even in the absence of CIITA. Taken together, our data have identified a HIC1-CIITA-SIRT1 axis that regulates Pdk4 transcription in response to IFN-7 stimula- tion.展开更多
In this paper,we proposed an innovation diffusion model with three compartments to investigate the diffusion of an innovation(product)in a particular region.The model exhibits two equilibria,namely,the adopter-free an...In this paper,we proposed an innovation diffusion model with three compartments to investigate the diffusion of an innovation(product)in a particular region.The model exhibits two equilibria,namely,the adopter-free and an interior equilibrium.The existence and local stability of the adopter-free and interior equilibria are explored in terms of the effective Basic Influence Number(BIN)R_(A).It is investigated that the adopter free steady-state is stable if R_(A)<1.By consideringτ(the adoption experience of the adopters)as the bifurcation parameter,we have been able to obtain the critical value ofτresponsible for the periodic solutions due to Hopf bifurcation.The direction and stability analysis of bifurcating periodic solutions has been performed by using the arguments of normal form theory and the center manifold theorem.Exhaustive numerical simulations in the support of analytical results have been presented.展开更多
BACKGROUND Wnt/FZD-mediated signaling pathways are activated in more than 90%of hepatocellular carcinoma(HCC)cell lines.As a well-known secretory glycoprotein,Wnt3 can interact with FZD receptors on the cell surface,t...BACKGROUND Wnt/FZD-mediated signaling pathways are activated in more than 90%of hepatocellular carcinoma(HCC)cell lines.As a well-known secretory glycoprotein,Wnt3 can interact with FZD receptors on the cell surface,thereby activating the Wnt/β-catenin signaling pathway.However,the N-glycosylation modification site of Wnt3 and the effect of this modification on the biological function of the protein are still unclear.AIM To investigate the effect of Wnt3 N-glycosylation on the biological function of HCC cells.METHODS Site-directed mutagenesis was used to verify the Wnt3 N-glycosylation sites,actinomycin D treatment was used to detect the stability of Wnt3 after site-directed mutation,the binding of the N-glycosylation site-directed mutant Wnt3 to FZD7 was observed by laser confocal microscopy,and the effects of the N-glycosylation site-directed mutation of Wnt3 on the Wnt/β-catenin signaling pathway and the progression of HCC cells were detected by western blot and cell function experiments.RESULTS Wnt3 has two N-glycosylation-modified sites(Asn90 and Asn301);when a single site at amino acid 301 is mutated,the stability of Wnt3 is weakened;the binding ability of Wnt3 to FZD7 decreases when both sites are mutated simultaneously;and the level of proteins related to the Wnt/β-catenin signaling pathway is downregulated.Cell proliferation,migration and invasion are also weakened in the case of single 301 site and double-site mutations.CONCLUSION These results indicate that by inhibiting the N-glycosylation of Wnt3,the proliferation,migration,invasion and colony formation abilities of liver cancer cells can be weakened,which might provide new therapeutic strategies for clinical liver cancer in the future.展开更多
Coal has a highly complex chemical structure,similar to polymers,coal is a macromolecular structure composed of a large number of“similar compounds”,which is called the basic structural unit.Understanding coal struc...Coal has a highly complex chemical structure,similar to polymers,coal is a macromolecular structure composed of a large number of“similar compounds”,which is called the basic structural unit.Understanding coal structure is the basis of its transformation and utilization.Shendong(SD)coal was analyzed by FTIR,XRD,XPS,and NMR.The results show that SD coal normalized structure formula is C_(100)H_(68.5)O_(35.7)N_(1.2)S_(0.2)and the average number of aromatic rings is 1.98.-CH_(2)-content accounts for about 82%in aliphatic CeH region,and the ratio of ether bond CeO,aromatic ether C-O and C=O is about 2:1:11 in oxygen-containing functional group region.The d_(002),L_(C),L_(a)and N_(C)of S_(D)coal microcrystalline structure parameters are 0.1832 nm,1.4688 nm,2.0852 nm and 9.017,respectively.Aromatic carbon and aliphatic carbon ratios of SD coal are 55.67%and 29.97%,aromatic cluster size and average methylene chain length are 0.224 and 1.817.Based on these structural parameters,molecular model of SD coal was constructed with^(13)C SSNMR experimental spectra as a reference.The model was constructed with an atom composition of C_(214)H_(214)O_(49)N_(2)S.展开更多
The pyrolysis process of Shendong coal(SD)was first studied by combining the characteristics of thermal gravimetric(TG),pyrolysis-gas chromatography/mass spectrometry(Py-GC/MS)and Gray-King assay(GK).The results show ...The pyrolysis process of Shendong coal(SD)was first studied by combining the characteristics of thermal gravimetric(TG),pyrolysis-gas chromatography/mass spectrometry(Py-GC/MS)and Gray-King assay(GK).The results show that the order of coke yields is G-K(76.35%(mass))>TG(73.11%(mass))>Py(70.03%(mass)).G-K coke yield caused by condensation reaction and secondary reaction accounts for 3.08%(mass)and 3.24%(mass),respectively.Compared with slow pyrolysis,fast pyrolysis has stronger fracture ability to coal molecules and can obtain more O-compounds,mono-ring aromatics and aliphatics.Especially,the content of phenolics increases significantly from 15.49%to 35.17%,but the content of multi-ring aromatics decreases from 23.13%to 2.36%.By comparing the compositions of Py primary tar and G-K final tar,it is found that secondary reactions occurred during G-K pyrolysis process include the cleavage of alkane and esters,condensation of mono-ring aromatics with low carbon alkene,ring opening,isomerization of tri-ring aromatics,hydrogenation of aromatics and acids.展开更多
AIM： TO investigate the role of a-fetoprotein （AFP）, a cancer-associated fetal glycoprotein, in glucocorticoidinduced precocious maturation in rat colon. METHODS： Colons from suckling Sprague-Dawley rats were used...AIM： TO investigate the role of a-fetoprotein （AFP）, a cancer-associated fetal glycoprotein, in glucocorticoidinduced precocious maturation in rat colon. METHODS： Colons from suckling Sprague-Dawley rats were used in this study. Corticosterone acetate at a dose of 100 μg/g body weight was given to normal pups on days 7, 9 and 11 after birth to induce hypercorticoidism. Control animals were injected with identical volumes of normal saline. Some rats receiving corticosterone 7 d after birth were also treated with mifepristone （RU38486）, a glucocorticoid cytoplasm receptor antagonist to investigate the effects of glucocorticoids （GCs）. The morphological changes of the crypt depth and villous height of the villous zone in colon were observed as indicesof colon maturation. Expression levels of AFP in colons were detected by reverse transcriptase polymerase chain reaction and Western blotting. To identify the cellular lo- calization of AFP in developing rat colons, double-immu- nofluorescent staining was performed using antibodies to specific mesenchymal cell marker and AFP. RESULTS： Corticosterone increased the crypt depth and villous height in the colon of 8- and 10-d-old rats with hypercorticoidism compared with that in the control ani- mals （120% in 8-d-old rats and 118% in 10-d-old rats in villous height, P = 0.021; 145% in 8-d-old rats and 124% in 10-d-old rats in crypt depth, P = 0.017）. These increases were accompanied by an increase of AFP ex- pression in both mRNA and protein （2.5-folds in 8-d- old and 2.5-folds in 10-d-old rats higher than in control animals, P = 0.035; 1.8-folds in 8-d-old and 1.3-folds in 10-d-old rats higher than in control animals, P = 0.023）. Increased crypt depth and villous height and increased expression of AFP in the colon of rats with hypercorti- coidism were blocked by mifepristone. Both had positive staining for AFP or vimentin, and overlapped in mesen- chymal cells at each tested colon. CONCLUSION： GCs promote the development of rat colon. AFP appears to be involved, in part, in mediating the effects of GCs in the developmental colon.展开更多
In December 2019,a new strain of coronavirus was discovered in China,and the World Health Organization declared it a pandemic in March 2020.The majority of people with coronavirus disease 19(COVID-19)exhibit no or onl...In December 2019,a new strain of coronavirus was discovered in China,and the World Health Organization declared it a pandemic in March 2020.The majority of people with coronavirus disease 19(COVID-19)exhibit no or only mild symptoms such as fever,cough,anosmia,and headache.Meanwhile,approximately 15%develop a severe lung infection over the course of 10 d,resulting in respiratory failure,which can lead to multi-organ failure,coagulopathy,and death.Since the beginning of the pandemic,it appears that there has been consideration that preexisting chronic liver disease may predispose to deprived consequences in conjunction with COVID-19.Furthermore,extensive liver damage has been linked to immune dysfunction and coagulopathy,which leads to a more severe COVID-19 outcome.Besides that,people with COVID-19 frequently have abnormal liver function,with more significant elevations in alanine aminotransferase and aspartate aminotransferase in patients with severe COVID-19 compared to those with mild/moderate disease.This review focuses on the pathogenesis of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection in the liver,as well as the use of liver chemistry as a prognostic tool during COVID-19.We also evaluate the findings for viral infection of hepatocytes,and look into the potential mechanisms behind SARS-CoV-2-related liver damage.展开更多
Small non-coding RNAs with important regulatory roles are not confined to eukaryotes. Recent work has uncovered a growing number of bacterial small RNAs （sRNAs）, some of which have been shown to regulate critical ce...Small non-coding RNAs with important regulatory roles are not confined to eukaryotes. Recent work has uncovered a growing number of bacterial small RNAs （sRNAs）, some of which have been shown to regulate critical cellular processes. Computational approaches, in combination with molecular experiments, have played an important role in the identification of these sRNAs. At present, there is no information on the presence of small non-coding RNAs and their genes in the Agrobacterium tumefaciens genome. To identify potential sRNAs in this important bacterium, deep sequencing of the short RNA populations isolated from Agrobacterium tumefaciens C58 was carried out. From a data set of more than 10,000 short sequences, 16 candidate sRNAs have been tentatively identified based on computational analysis. All of these candidates can form stem-loop structures by RNA folding predictions and the majority of the secondary structures are rich in GC base-pairs：：Some are followed by a short stretch of U residues, indicative of a rho-independent transcription terminator, whereas some of the short RNAs are found in the stem region of the hairpin, indicative of eukaryotic-like sRNAs. Experimental strategies will need to be used to verify these candidates. The study of an expanded list of candidate sRNAs in Agrobacterium will allow a more complete understanding of the range of roles played by regulatory RNAs in prokaryotes.展开更多
Overexpression of heat shock protein 27(HSP27)in gastric cancer is correlated with poor clinical prognosis.Melatonin,an endogenous hormone,shows promise in gastric cancer therapy.However,there is limited study on the ...Overexpression of heat shock protein 27(HSP27)in gastric cancer is correlated with poor clinical prognosis.Melatonin,an endogenous hormone,shows promise in gastric cancer therapy.However,there is limited study on the biological activity of HSP27 in response to melatonin treatment.In this study,we show an anti-proliferative action of melatonin on human gastric cancer cell lines BGC-823 and MGC-803.Biochemically,the inhibitory effect of melatonin is accompanied by the upregulation of HSP27 phosphorylation level.Transfection of gastric cancer cells with HSP27-specific siRNA effectively reduces HSP27 phosphorylation and potentiated melatonininduced inhibitory effect on cell proliferation.The reduction of cyclin D1 in melatonin-treated cells is also aggravated by HSP27 depletion.Moreover,melatonin stimulation increases p38 phosphorylation.Pretreatment with p38 inhibitor SB203580 not only remarkably suppresses melatonin-induced HSP27 phosphorylation,but also augment the inhibitory effect of melatonin on cyclin D1 expression as well as cell proliferation.Taken together,our study indicates the protective pathway of p38/HSP27 against melatonin-induced inhibitory effect on gastric cancer cell proliferation,suggesting that combined with p38/HSP27 pathway inhibitor,the therapeutic efficacy of melatonin on gastric cancer may be improved.展开更多
Objective： To study the effect of interferon-alpha IFN-α in the serum of SLE patients on the differentiation and maturation of dendritic cells （DCs） derived from CD34^＋ hematopoietic precursor cells （HPCs）. Met...Objective： To study the effect of interferon-alpha IFN-α in the serum of SLE patients on the differentiation and maturation of dendritic cells （DCs） derived from CD34^＋ hematopoietic precursor cells （HPCs）. Methods： Serum samples from SLE patients and normal controls were collected and the concentration of IFN-α detected by ELISA. CD34^＋HPCs were purified from cord blood by a magnetic cell sorting system （MACS）, and cultured to differentiate to DCs. Normal serum, normal serum with exogenous IFN-α, SLE serum with raised levels of IFN-α, or SLE serum with anfi-IFN-α neutralizing antibody was added to the culture medium. The phenotype of DCs was analyzed by flow cytometry （FCM） and the capacity of DCs to stimulate allogenic T lymphocyte proliferation was evaluated in a mixed lymphocyte reaction by the Cell Counting Kit-8. Cytokine production was assessed by ELISA. Results： Serum levels of IFN-α were significantly higher in SLE patients than in normal controls and this correlated positively with disease activity. Cultured in SLE serum with raised levels of IFN-α, CD34^＋ HPCs could differentiate into DCs that expressed higher levels of HLA-DR, CD80 and CD86, and showed an enhanced allogenic T-cell stimulatory capacity, while producing lower levels of IL-12 and higher amounts of IL-10 compared with those DCs cultured in normal serum. Conclusion： Increased levels of IFN-α in SLE serum promotes the differentiation and maturation of DCs derived from CD34^＋ HPCs and could contribute to the pathogenesis of SLE.展开更多
Gene expression can be modulated at DNA,RNA,or protein levels,with targeted protein degradation(TPD)representing a well-established and effective strategy for manipulating protein function.TPD enables the selective el...Gene expression can be modulated at DNA,RNA,or protein levels,with targeted protein degradation(TPD)representing a well-established and effective strategy for manipulating protein function.TPD enables the selective elimination of proteins,protein condensates,or organelles via cellular degradation pathways,such as the ubiquitin-proteasome system,autophagy,or endocytosis,through induced proximity mechanisms.While TPD has had a transformative impact in biomedical research over the past two decades,its applications in plant science research has lagged behind.This gap stems from the dominance of RNA interference and CRISPR technologies,as well as the complexity and cost of chemical,macromolecular,and recombinant degrader platforms in plants.The recent development of genetically encoded chimeric protein degraders(GE-CPDs)offers a timely and promising alternative.These transgene-based systems offer a plant-adaptable,precise,tunable,and conditional means for controlling endogenous protein levels,opening new avenues for studying dynamic biological processes and engineering complex traits in crops.As genome engineering technologies continue to advance,GE-CPDs are poised to become a versatile and scalable platform for plant biology research and agricultural applications.In this review,we highlight five key opportunities-Selective-Targeting,Co-Targeting,Organelle-Targeting,Conditional-Targeting,and Synthetic Engineering(SCOCS)-that illustrate the emerging importance of TPD technologies,especially GE-CPDs,in advancing plant science.We argue that the field is well-positioned to harness the full potential of TPD for next-generation crop improvement.展开更多
About two thousand years ago,Hippocrates observed that“walking is man's best medicine”[1],a notion increasingly validated in modern society.The benefits of physical activity in preventing chronic diseases and in...About two thousand years ago,Hippocrates observed that“walking is man's best medicine”[1],a notion increasingly validated in modern society.The benefits of physical activity in preventing chronic diseases and in improving longevity have been extensively studied[2].展开更多
Protein translation is a tightly regulated cellular process that is essential for gene expression and protein synthesis.The deregulation of this process is increasingly recognized as a critical factor in the pathogene...Protein translation is a tightly regulated cellular process that is essential for gene expression and protein synthesis.The deregulation of this process is increasingly recognized as a critical factor in the pathogenesis of various human diseases.In this review,we discuss how deregulated translation can lead to aberrant protein synthesis,altered cellular functions,and disease progression.We explore the key mechanisms contributing to the deregulation of protein translation,including functional alterations in translation factors,tRNA,mRNA,and ribosome function.Deregulated translation leads to abnormal protein expression,disrupted cellular signaling,and perturbed cellular functions-all of which contribute to disease pathogenesis.The development of ribosome profiling techniques along with mass spectrometry-based proteomics,mRNA sequencing and single-cell approaches have opened new avenues for detecting diseases related to translation errors.Importantly,we highlight recent advances in therapies targeting translation-related disorders and their potential applications in neurodegenerative diseases,cancer,infectious diseases,and cardiovascular diseases.Moreover,the growing interest lies in targeted therapies aimed at restoring precise control over translation in diseased cells is discussed.In conclusion,this comprehensive review underscores the critical role of protein translation in disease and its potential as a therapeutic target.Advancements in understanding the molecular mechanisms of protein translation deregulation,coupled with the development of targeted therapies,offer promising avenues for improving disease outcomes in various human diseases.Additionally,it will unlock doors to the possibility of precision medicine by offering personalized therapies and a deeper understanding of the molecular underpinnings of diseases in the future.展开更多
Infectious microbes that spread easily in healthcare facilities remain as the severe threat for the public health,especially among immunocompromised populations.Given the intricate problem of dramatic increase in resi...Infectious microbes that spread easily in healthcare facilities remain as the severe threat for the public health,especially among immunocompromised populations.Given the intricate problem of dramatic increase in resistance to common biocides,the development of safe and efficient biocide formulated agents to alleviate drug resistance is highly demanding.In this study,Schiff-base ligands were successfully formed on natural biopolymer of epsilon-poly-L-lysine(ε-PL)decorated aldehyde functionalized mesoporous silica SBA-15(CHO-SBA-15)for the selective coordination of silver ions,which was affirmed by various physicochemical methods.Besides the identified broad-spectrum antibacterial activities,the as-prepared Schiff-base silver nanocomplex(CHO-SBA-15/ε-PL/Ag,CLA-1)exhibited an improved inhibitory effect on infectious pathogen growth typified by Escherichia coli and Staphylococcus aureus in comparison with two control silver complexes without Schiff-base conjugates,SBA-15/ε-PL/Ag and CHO-SBA-15/Ag,respectively.In addition,CLA-1 remarkably inhibited the growth of Mycobacterium tuberculosis due to the excellent antimicrobial activity of silver species.Significantly,CLA-1 kills Candida albicans cells,inhibits biofilm formation,and eliminates preformed biofilms,with no development of resistance during continuous serial passaging.The antifungal activity is connected to disruption of bacterial cell membranes and increased levels of intracellular reactive oxygen species.In mouse models of multidrug-resistant C.albicans infection,CLA-1 exhibited efficient in vivo fungicidal efficacy superior to two antifungal drugs,amphotericin B and fluconazole.Moreover,CLA-1 treatment induces negligible toxicity against normal tissues with safety.Therefore,this study reveals the pivotal role of the molecular design of Schiff-base silver nanocomplex formation on biopolymer surface-functionalized silica mesopores as a green and efficient nanoplatform to tackle infectious microbes.展开更多
基金supported by the National Natural Science Foundation of China(No.62004143)the Key Research and Development Program of Gansu Province-Industrial Project under Grant(No.25YFGA058)+4 种基金the Key Talent Project Foundation of Gansu Province(No.2025RCXM066)the Gansu Provincial Department of Education:Industrial Support Plan Project(No.2025CYZC-005)the Key R&D Program of Hubei Province(No.2022BAA084)the Science and Technology Project of Lanzhou(No.2024-3-42)the Fundamental Research Funds for the Central Universities(No.331920240059)。
文摘Available online Further oxidation of NH3produced via photocatalytic N_(2)fixation represents a promising strategy to enhance the economic value of N_(2)fixation.This work employs first-principles density functional theory(DFT)calculations to demonstrate that incorporating Co into Ni O improves both N_(2)adsorption and activation as well as M-N electron exchange intensity.Guided by these predictions,a novel Co single-atom photocatalyst supported by nanoconfined Ni O@C nanosheets was synthesized using a direct metal atomization method,achieving high HNO_(3)production(60.54%).NH_(4)^(+)and NO_(3)^(-)production rates during N_(2)photofixation reached 67.97μmol g_(cat)^(-1)h^(-1)and 104.28μmol g_(cat)^(-1)h^(-1),respectively.The overall N_(2)→NH_(3)→HNO_(3)photofixation pathway was validated through in-situ diffuse reflectance infrared Fourier transform spectroscopy(DRIFTS)and^(15)N isotopic labeling.Mechanistic studies reveal that Co single-atom introduction serves as an electron trap,enhancing photogenerated electron accumulation with a five-fold increase in carrier density compared to Ni O@C,as observed via in-situ X-ray photoelectron spectroscopy(XPS).This synergistic effect between electron traps and N2adsorption/activation sites at Co single-atom centers supports rapid N_(2)reduction kinetics.Additionally,nanoconfined ink-bottle pores in the carbon layer impede NH_(3)desorption,further boosting NO_(3)-production.This work offers a comprehensive approach to optimizing N_(2)photofixation through electron regulation and surface reaction kinetics.
基金Supported by Grants from the High-tech R and D Program,No.2012AA020206,No.2014CBA02002,and No.2013ZX10002009-001-004State Key Projects for Basic Research,No.2011CB910703+1 种基金National Natural Science Foundation of China,No.81372591 and No.81321091the Center for Marine Medicine and Rescue of Tsinghua University of China
文摘This study investigated whether changes in circulating tumor cell(CTC) numbers reflect tumor progression and treatment efficacy in esophageal squamous cell carcinoma(ESCC). A 47-year-old male patient with ESCC is presented in this case study. The patient was evaluated for a series of serum tumor markers and subjected to radiological examinations before and after surgery and during follow-up over the course of five years. In addition, the CTCs in 7.5 m L of peripheral blood were enriched by magneticactivated cell sorting negative selection and identified by immunofluorescence staining. Serum tumor markers remained within normal ranges and were discordant with imaging scans during the follow-up. Initially, one CTC was detected in the peripheral blood sample, and 14 were observed seven days after the operation. After 12 wk, subcutaneous metastases and bone metastases occurred, and the number of CTCs increased to 84. After 48 wk, lung metastases were noted, and the CTC level was 21. At 104 wk, the number of CTCs was 14, and disease recurrence was detected by positron emission tomography-computed tomography. The CTC counts were in accord with the imaging studies at several time points. The additional information provided by CTC enumeration could thus facilitate monitoring of disease status and treatment efficacy and provide support for treatment decisions.
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions(No.Jx10131801095 to HongZhou)
文摘Neuroinflammation has been recognized to play a critical role in the pathogenesis of Alzheimer＇s disease （AD）, which is pathologically characterized by the accumulation of senile plaques containing activated microglia and amyloid β-peptides （Aβ）. In the present study, we examined the neuroprotective effects of hydrogen sulfide （H2S） on neuroinflammation in rats with Aβ1-40 hippocampal injection. We found that Aβ-induced rats exhibited a disorder of pyramidal cell layer arrangement, and a decrease of mean pyramidal cell number in the CA1 hippocampal region compared with those in sham operated rats. NaHS （a donor of H2S, 5.6 mg/kg/d, i.p.） treatment for 3 weeks rescued neuronal cell death significantly. Moreover, we found that H2S dramatically suppressed the release of TNF-α, IL-1β and IL-6 in the hippocampus. Consistently, both immunohistochemistry and Western blotting assays showed that H2S inhibited the upregulation of COX-2 and the activation of NF-κB in the hippocampus. In conclusion, our data indicate that H2S suppresses neuroinflammation via inhibition of the NF-κB activation pathway in the Aβ-induced rat model and has potential value for AD therapy.
基金supported by grants from the National Natural Science Foundation of China (81771000 and 31571302)the Key Research and Development Program of Jiangsu Province (Social Development: BE2016762)+2 种基金the Key Project of Science and Technology Innovation of Nanjing Medical University (2017NJMUCX001)grants from the China Postdoctoral Science Foundation (2016M600431)the Jiangsu Planned Projects for Postdoctoral Research Funds (1601071B)
文摘Oxysterol binding protein like 2(OSBPL2), an important regulator in cellular lipid metabolism and transport, was identified as a novel deafness-causal gene in our previous work. To resemble the phenotypic features of OSBPL2 mutation in animal models and elucidate the potential genotypephenotype associations, the OSBPL2-disrupted Bama miniature(BM) pig model was constructed using CRISPR/Cas9-mediated gene editing, somatic cell nuclear transfer(SCNT) and embryo transplantation approaches, and then subjected to phenotypic characterization of auditory function and serum lipid profiles. The OSBPL2-disrupted pigs displayed progressive hearing loss(HL) with degeneration/apoptosis of cochlea hair cells(HCs) and morphological abnormalities in HC stereocilia, as well as hypercholesterolaemia. High-fat diet(HFD) feeding aggravated the development of HL and led to more severe hypercholesterolaemia. The dual phenotypes of progressive HL and hypercholesterolaemia resembled in OSBPL2-disrupted pigs confirmed the implication of OSBPL2 mutation in nonsydromic hearing loss(NSHL) and contributed to the potential linkage between auditory dysfunction and dyslipidaemia/hypercholesterolaemia.
基金supported by grants from the National Natural Science Foundation of China (No.30871200)the Practice and Innovation Training Program for Students in Colleges and Universities of Jiangsu Province (NO.20090370)
文摘Objective:To explore the role that ceramide plays in the activation of mitogen-activated protein kinases(MAPKs)during cerebral ischemia and reperfusion.Methods:Rats were subjected to ischemia by the fourvessel occlusion(4-VO)method.The sphingomyelinase inhibitor TPCK was administered to the CA1 subregion of the rat hippocampus before inducing ischemia.Western blot was used to examine the activity of extracellular-signal regulated kinase(ERK)and c-Jun N-terminal protein kinase(JNK)using antibodies against ERK,JNK and diphosphorylated ERK and JNK.Results:At lh reperfusion post-ischemia,JNK reached its peak activity while ERK was undergoing a sharp inactivation(P〈0.05).The level of diphosphorylated JNK was significantly reduced but the sharp inactivation of ERK was visibly reversed(P〈0.05)by the sphingomyelinase inhibitor.Conclusion:The ceramide signaling pathway is up-regulated through sphingomyelin hydrolysis in brain ischemia,promoting JNK activation and suppressing ERK activation,culminating in the ischemic lesion.
基金supported by the National Natural Science Foundation of China,No.81402932(to YQC)
文摘Many studies have shown that(5R)-5-hydroxytriptolide is the optimal modified analogue of triptolide, possessing comparable immunosuppressive activity but much lower cytotoxicity than triptolide. Whether(5R)-5-hydroxytriptolide has preventive effects on neuroinflammation is unclear. This study was designed to pretreat primary astrocytes from the brains of neonatal Sprague-Dawley rats with 20, 100 and 500 nM(5R)-5-hydroxytriptolide for 1 hour before establishing an in vitro neuroinflammation model with 1.0 μg/mL lipopolysaccharide for 24 hours. The generation of nitric oxide was detected by Griess reagents. Astrocyte marker glial fibrillary acidic protein was measured by immunohistochemical staining. The levels of tumor necrosis factor-α and interleukin-1β in the culture supernatant were assayed by enzyme linked immunosorbent assay. Nuclear factor-κB/p65 expression was examined by immunofluorescence staining. The phosphorylation of inhibitor of nuclear factor IκB-α and the location of nuclear factor-κB/P65 were determined using western blot assay. Our data revealed that(5R)-5-hydroxytriptolide inhibited the generation of nitric oxide, tumor necrosis factor-α and interleukin-1β from primary astrocytes activated by lipopolysaccharide, decreased the positive reaction intensity of glial fibrillary acidic protein, reduced the expression of tumor necrosis factor alpha and interleukin-1β in culture supernatant, inhibited the phosphorylation of IκB-α and the translocation of nuclear factor-κB/P65 to the nucleus. These results have confirmed that(5R)-5-hydroxytriptolide inhibits lipopolysaccharide-induced glial inflammatory response and provides cytological experimental data for(5R)-5-hydroxytriptolide in the treatment of neurodegenerative diseases.
基金supported,in part,by the National Natural Science Foundation of China(31200645)the Natural Science Foundation of Jiangsu Province(BK20141498)a grant from Jiangsu Jiankang Vocational University(JK201405)
文摘Increased accumulation and/or impaired utilization of fatty acid in extra-adipose tissues are implicated in the pathogenesis of insulin resistance and type 2 diabetes. Pyruvate dehydrogenase kinase 4 （Pdk4） is a key enzyme involved in fatty oxidation and energy expenditure, and its expression can be repressed by pro-inflammatory stimuli. Previously, we have shown that class II transactivator （CIITA） mediates the adverse effect of interferon gamma （IFN-7） in skeletal muscle cells by cooperating with hypermethylated in cancer 1 （HIC1） to repress silent informa- tion regulator 1 （SIRT1） transcription. Building upon this finding, we report here that CIITA interacted with HIC1 via the GTP-binding domain （GBD） while HIC1 interacted with CIITA via the BTB/POZ domain. The GBD domain was required for CIITA to repress SIRT1 transcription probably acting as a bridge for CIITA to bind to HIC1 and consequently to bind to the SIRT1 promoter. IFN-7 stimulation, CIITA over-expression, or HIC1 over- expression repressed Pdk4 promoter activity while silencing either CIITA or HIC1 normalized Pdk4 expression in the presence of IFN-7. An increase in SIRT1 expression or activity partially rescued Pdk4 expression in the pre- sence of CIITA, but SIRT1 inhibition abrogated Pdk4 normalization even in the absence of CIITA. Taken together, our data have identified a HIC1-CIITA-SIRT1 axis that regulates Pdk4 transcription in response to IFN-7 stimula- tion.
文摘In this paper,we proposed an innovation diffusion model with three compartments to investigate the diffusion of an innovation(product)in a particular region.The model exhibits two equilibria,namely,the adopter-free and an interior equilibrium.The existence and local stability of the adopter-free and interior equilibria are explored in terms of the effective Basic Influence Number(BIN)R_(A).It is investigated that the adopter free steady-state is stable if R_(A)<1.By consideringτ(the adoption experience of the adopters)as the bifurcation parameter,we have been able to obtain the critical value ofτresponsible for the periodic solutions due to Hopf bifurcation.The direction and stability analysis of bifurcating periodic solutions has been performed by using the arguments of normal form theory and the center manifold theorem.Exhaustive numerical simulations in the support of analytical results have been presented.
基金Supported by National Natural Science Foundation of China,No.81560390the Guizhou Medical University Cultivation Project of the National Natural Science Foundation of China,No.22NSFCP02Basic Research Project of Science and Technology Department of Guizhou Province,No.ZK[2024]General 136.
文摘BACKGROUND Wnt/FZD-mediated signaling pathways are activated in more than 90%of hepatocellular carcinoma(HCC)cell lines.As a well-known secretory glycoprotein,Wnt3 can interact with FZD receptors on the cell surface,thereby activating the Wnt/β-catenin signaling pathway.However,the N-glycosylation modification site of Wnt3 and the effect of this modification on the biological function of the protein are still unclear.AIM To investigate the effect of Wnt3 N-glycosylation on the biological function of HCC cells.METHODS Site-directed mutagenesis was used to verify the Wnt3 N-glycosylation sites,actinomycin D treatment was used to detect the stability of Wnt3 after site-directed mutation,the binding of the N-glycosylation site-directed mutant Wnt3 to FZD7 was observed by laser confocal microscopy,and the effects of the N-glycosylation site-directed mutation of Wnt3 on the Wnt/β-catenin signaling pathway and the progression of HCC cells were detected by western blot and cell function experiments.RESULTS Wnt3 has two N-glycosylation-modified sites(Asn90 and Asn301);when a single site at amino acid 301 is mutated,the stability of Wnt3 is weakened;the binding ability of Wnt3 to FZD7 decreases when both sites are mutated simultaneously;and the level of proteins related to the Wnt/β-catenin signaling pathway is downregulated.Cell proliferation,migration and invasion are also weakened in the case of single 301 site and double-site mutations.CONCLUSION These results indicate that by inhibiting the N-glycosylation of Wnt3,the proliferation,migration,invasion and colony formation abilities of liver cancer cells can be weakened,which might provide new therapeutic strategies for clinical liver cancer in the future.
基金financed by the Department of education of Gansu Province:Young Doctor Fund Project(2022QB-029)the Fundamental Research Funds for the Central Universities(31920240125-06,31920240059)+1 种基金the Scientific Research Project of Introducing Talents of Northwest Minzu University(xbmuyjrc202215,xbmuyjrc202216)the National Natural Science Foundation of China(22178289).
文摘Coal has a highly complex chemical structure,similar to polymers,coal is a macromolecular structure composed of a large number of“similar compounds”,which is called the basic structural unit.Understanding coal structure is the basis of its transformation and utilization.Shendong(SD)coal was analyzed by FTIR,XRD,XPS,and NMR.The results show that SD coal normalized structure formula is C_(100)H_(68.5)O_(35.7)N_(1.2)S_(0.2)and the average number of aromatic rings is 1.98.-CH_(2)-content accounts for about 82%in aliphatic CeH region,and the ratio of ether bond CeO,aromatic ether C-O and C=O is about 2:1:11 in oxygen-containing functional group region.The d_(002),L_(C),L_(a)and N_(C)of S_(D)coal microcrystalline structure parameters are 0.1832 nm,1.4688 nm,2.0852 nm and 9.017,respectively.Aromatic carbon and aliphatic carbon ratios of SD coal are 55.67%and 29.97%,aromatic cluster size and average methylene chain length are 0.224 and 1.817.Based on these structural parameters,molecular model of SD coal was constructed with^(13)C SSNMR experimental spectra as a reference.The model was constructed with an atom composition of C_(214)H_(214)O_(49)N_(2)S.
基金financed by the Department of Education of Gansu Province:Young Doctor Fund Project(2022QB-029)the Fundamental Research Funds for the Central Universities(31920240059,3192024125-06)+1 种基金the Scientific Research Project of Introducing Talents of Northwest Minzu University(xbmuyjrc202215)the National Natural Science Foundation of China(22178289).
文摘The pyrolysis process of Shendong coal(SD)was first studied by combining the characteristics of thermal gravimetric(TG),pyrolysis-gas chromatography/mass spectrometry(Py-GC/MS)and Gray-King assay(GK).The results show that the order of coke yields is G-K(76.35%(mass))>TG(73.11%(mass))>Py(70.03%(mass)).G-K coke yield caused by condensation reaction and secondary reaction accounts for 3.08%(mass)and 3.24%(mass),respectively.Compared with slow pyrolysis,fast pyrolysis has stronger fracture ability to coal molecules and can obtain more O-compounds,mono-ring aromatics and aliphatics.Especially,the content of phenolics increases significantly from 15.49%to 35.17%,but the content of multi-ring aromatics decreases from 23.13%to 2.36%.By comparing the compositions of Py primary tar and G-K final tar,it is found that secondary reactions occurred during G-K pyrolysis process include the cleavage of alkane and esters,condensation of mono-ring aromatics with low carbon alkene,ring opening,isomerization of tri-ring aromatics,hydrogenation of aromatics and acids.
文摘AIM： TO investigate the role of a-fetoprotein （AFP）, a cancer-associated fetal glycoprotein, in glucocorticoidinduced precocious maturation in rat colon. METHODS： Colons from suckling Sprague-Dawley rats were used in this study. Corticosterone acetate at a dose of 100 μg/g body weight was given to normal pups on days 7, 9 and 11 after birth to induce hypercorticoidism. Control animals were injected with identical volumes of normal saline. Some rats receiving corticosterone 7 d after birth were also treated with mifepristone （RU38486）, a glucocorticoid cytoplasm receptor antagonist to investigate the effects of glucocorticoids （GCs）. The morphological changes of the crypt depth and villous height of the villous zone in colon were observed as indicesof colon maturation. Expression levels of AFP in colons were detected by reverse transcriptase polymerase chain reaction and Western blotting. To identify the cellular lo- calization of AFP in developing rat colons, double-immu- nofluorescent staining was performed using antibodies to specific mesenchymal cell marker and AFP. RESULTS： Corticosterone increased the crypt depth and villous height in the colon of 8- and 10-d-old rats with hypercorticoidism compared with that in the control ani- mals （120% in 8-d-old rats and 118% in 10-d-old rats in villous height, P = 0.021; 145% in 8-d-old rats and 124% in 10-d-old rats in crypt depth, P = 0.017）. These increases were accompanied by an increase of AFP ex- pression in both mRNA and protein （2.5-folds in 8-d- old and 2.5-folds in 10-d-old rats higher than in control animals, P = 0.035; 1.8-folds in 8-d-old and 1.3-folds in 10-d-old rats higher than in control animals, P = 0.023）. Increased crypt depth and villous height and increased expression of AFP in the colon of rats with hypercorti- coidism were blocked by mifepristone. Both had positive staining for AFP or vimentin, and overlapped in mesen- chymal cells at each tested colon. CONCLUSION： GCs promote the development of rat colon. AFP appears to be involved, in part, in mediating the effects of GCs in the developmental colon.
文摘In December 2019,a new strain of coronavirus was discovered in China,and the World Health Organization declared it a pandemic in March 2020.The majority of people with coronavirus disease 19(COVID-19)exhibit no or only mild symptoms such as fever,cough,anosmia,and headache.Meanwhile,approximately 15%develop a severe lung infection over the course of 10 d,resulting in respiratory failure,which can lead to multi-organ failure,coagulopathy,and death.Since the beginning of the pandemic,it appears that there has been consideration that preexisting chronic liver disease may predispose to deprived consequences in conjunction with COVID-19.Furthermore,extensive liver damage has been linked to immune dysfunction and coagulopathy,which leads to a more severe COVID-19 outcome.Besides that,people with COVID-19 frequently have abnormal liver function,with more significant elevations in alanine aminotransferase and aspartate aminotransferase in patients with severe COVID-19 compared to those with mild/moderate disease.This review focuses on the pathogenesis of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection in the liver,as well as the use of liver chemistry as a prognostic tool during COVID-19.We also evaluate the findings for viral infection of hepatocytes,and look into the potential mechanisms behind SARS-CoV-2-related liver damage.
文摘Small non-coding RNAs with important regulatory roles are not confined to eukaryotes. Recent work has uncovered a growing number of bacterial small RNAs （sRNAs）, some of which have been shown to regulate critical cellular processes. Computational approaches, in combination with molecular experiments, have played an important role in the identification of these sRNAs. At present, there is no information on the presence of small non-coding RNAs and their genes in the Agrobacterium tumefaciens genome. To identify potential sRNAs in this important bacterium, deep sequencing of the short RNA populations isolated from Agrobacterium tumefaciens C58 was carried out. From a data set of more than 10,000 short sequences, 16 candidate sRNAs have been tentatively identified based on computational analysis. All of these candidates can form stem-loop structures by RNA folding predictions and the majority of the secondary structures are rich in GC base-pairs：：Some are followed by a short stretch of U residues, indicative of a rho-independent transcription terminator, whereas some of the short RNAs are found in the stem region of the hairpin, indicative of eukaryotic-like sRNAs. Experimental strategies will need to be used to verify these candidates. The study of an expanded list of candidate sRNAs in Agrobacterium will allow a more complete understanding of the range of roles played by regulatory RNAs in prokaryotes.
基金supported by the Training Programs of Innovation and Entrepreneurship for Undergraduates by Jiangsu Province(201810312018Z)to Jun Du,Chenchen Zhu,Kaiquan Lithe Training Programs of Innovation and Entrepreneurship for Undergraduates by Nanjing Medical University to Jun Du,Yuting Wang
文摘Overexpression of heat shock protein 27(HSP27)in gastric cancer is correlated with poor clinical prognosis.Melatonin,an endogenous hormone,shows promise in gastric cancer therapy.However,there is limited study on the biological activity of HSP27 in response to melatonin treatment.In this study,we show an anti-proliferative action of melatonin on human gastric cancer cell lines BGC-823 and MGC-803.Biochemically,the inhibitory effect of melatonin is accompanied by the upregulation of HSP27 phosphorylation level.Transfection of gastric cancer cells with HSP27-specific siRNA effectively reduces HSP27 phosphorylation and potentiated melatonininduced inhibitory effect on cell proliferation.The reduction of cyclin D1 in melatonin-treated cells is also aggravated by HSP27 depletion.Moreover,melatonin stimulation increases p38 phosphorylation.Pretreatment with p38 inhibitor SB203580 not only remarkably suppresses melatonin-induced HSP27 phosphorylation,but also augment the inhibitory effect of melatonin on cyclin D1 expression as well as cell proliferation.Taken together,our study indicates the protective pathway of p38/HSP27 against melatonin-induced inhibitory effect on gastric cancer cell proliferation,suggesting that combined with p38/HSP27 pathway inhibitor,the therapeutic efficacy of melatonin on gastric cancer may be improved.
基金supported by Jiangsu Province Natural Science Fund(BK2004148)Nanjing Medical Technology Development Project(YKK06068)
文摘Objective： To study the effect of interferon-alpha IFN-α in the serum of SLE patients on the differentiation and maturation of dendritic cells （DCs） derived from CD34^＋ hematopoietic precursor cells （HPCs）. Methods： Serum samples from SLE patients and normal controls were collected and the concentration of IFN-α detected by ELISA. CD34^＋HPCs were purified from cord blood by a magnetic cell sorting system （MACS）, and cultured to differentiate to DCs. Normal serum, normal serum with exogenous IFN-α, SLE serum with raised levels of IFN-α, or SLE serum with anfi-IFN-α neutralizing antibody was added to the culture medium. The phenotype of DCs was analyzed by flow cytometry （FCM） and the capacity of DCs to stimulate allogenic T lymphocyte proliferation was evaluated in a mixed lymphocyte reaction by the Cell Counting Kit-8. Cytokine production was assessed by ELISA. Results： Serum levels of IFN-α were significantly higher in SLE patients than in normal controls and this correlated positively with disease activity. Cultured in SLE serum with raised levels of IFN-α, CD34^＋ HPCs could differentiate into DCs that expressed higher levels of HLA-DR, CD80 and CD86, and showed an enhanced allogenic T-cell stimulatory capacity, while producing lower levels of IL-12 and higher amounts of IL-10 compared with those DCs cultured in normal serum. Conclusion： Increased levels of IFN-α in SLE serum promotes the differentiation and maturation of DCs derived from CD34^＋ HPCs and could contribute to the pathogenesis of SLE.
基金supported by grants from the Biological Breeding-National Science and Technology Major Project(2023ZD04073)the National Natural Science Foundation of China(32470282)+1 种基金the Major Project of Hubei Hongshan Laboratory(2022hszd016)the Fundamental Research Funds for the Central Universities to G.X.
文摘Gene expression can be modulated at DNA,RNA,or protein levels,with targeted protein degradation(TPD)representing a well-established and effective strategy for manipulating protein function.TPD enables the selective elimination of proteins,protein condensates,or organelles via cellular degradation pathways,such as the ubiquitin-proteasome system,autophagy,or endocytosis,through induced proximity mechanisms.While TPD has had a transformative impact in biomedical research over the past two decades,its applications in plant science research has lagged behind.This gap stems from the dominance of RNA interference and CRISPR technologies,as well as the complexity and cost of chemical,macromolecular,and recombinant degrader platforms in plants.The recent development of genetically encoded chimeric protein degraders(GE-CPDs)offers a timely and promising alternative.These transgene-based systems offer a plant-adaptable,precise,tunable,and conditional means for controlling endogenous protein levels,opening new avenues for studying dynamic biological processes and engineering complex traits in crops.As genome engineering technologies continue to advance,GE-CPDs are poised to become a versatile and scalable platform for plant biology research and agricultural applications.In this review,we highlight five key opportunities-Selective-Targeting,Co-Targeting,Organelle-Targeting,Conditional-Targeting,and Synthetic Engineering(SCOCS)-that illustrate the emerging importance of TPD technologies,especially GE-CPDs,in advancing plant science.We argue that the field is well-positioned to harness the full potential of TPD for next-generation crop improvement.
基金supported by grants from the National Natural Science Foundation of China(Nos.92057207,92357303,92254308,32271223,and 32021003)the National Key Research and Development Program of China(No.2024YFA1306102).
文摘About two thousand years ago,Hippocrates observed that“walking is man's best medicine”[1],a notion increasingly validated in modern society.The benefits of physical activity in preventing chronic diseases and in improving longevity have been extensively studied[2].
基金supported by the National Natural Science Foundations of China[No.82073075]the Central Plains Science and Technology Innovation Leading Talents[No.224200510015]Natural Science Foundation of Henan[No.222102310029]。
文摘Protein translation is a tightly regulated cellular process that is essential for gene expression and protein synthesis.The deregulation of this process is increasingly recognized as a critical factor in the pathogenesis of various human diseases.In this review,we discuss how deregulated translation can lead to aberrant protein synthesis,altered cellular functions,and disease progression.We explore the key mechanisms contributing to the deregulation of protein translation,including functional alterations in translation factors,tRNA,mRNA,and ribosome function.Deregulated translation leads to abnormal protein expression,disrupted cellular signaling,and perturbed cellular functions-all of which contribute to disease pathogenesis.The development of ribosome profiling techniques along with mass spectrometry-based proteomics,mRNA sequencing and single-cell approaches have opened new avenues for detecting diseases related to translation errors.Importantly,we highlight recent advances in therapies targeting translation-related disorders and their potential applications in neurodegenerative diseases,cancer,infectious diseases,and cardiovascular diseases.Moreover,the growing interest lies in targeted therapies aimed at restoring precise control over translation in diseased cells is discussed.In conclusion,this comprehensive review underscores the critical role of protein translation in disease and its potential as a therapeutic target.Advancements in understanding the molecular mechanisms of protein translation deregulation,coupled with the development of targeted therapies,offer promising avenues for improving disease outcomes in various human diseases.Additionally,it will unlock doors to the possibility of precision medicine by offering personalized therapies and a deeper understanding of the molecular underpinnings of diseases in the future.
基金supported by the National Key R&D Programs of China(No.2018YFC0311003 to H.B.)the National Natural Science Foundation of China(No.U1703118 to J.C.)+5 种基金the Natural Science Foundation of Jiangsu Province(No.BK20181364 to J.C.)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD,to J.C.)the Cooperative Project between Southeast University and Nanjing Medical University(No.2018DN0004 to J.C.)the National Science Foundation of the Jiangsu Higher Education Institutions of China(No.18KJA310002 to H.B.,No.19KJA310003 to J.C)the Jiangsu Specially Appointed Professor and Jiangsu Medical Specialist Programs of China(to H.B.)Jiangsu Province“Innovative and Entrepreneurial Team”Program.
文摘Infectious microbes that spread easily in healthcare facilities remain as the severe threat for the public health,especially among immunocompromised populations.Given the intricate problem of dramatic increase in resistance to common biocides,the development of safe and efficient biocide formulated agents to alleviate drug resistance is highly demanding.In this study,Schiff-base ligands were successfully formed on natural biopolymer of epsilon-poly-L-lysine(ε-PL)decorated aldehyde functionalized mesoporous silica SBA-15(CHO-SBA-15)for the selective coordination of silver ions,which was affirmed by various physicochemical methods.Besides the identified broad-spectrum antibacterial activities,the as-prepared Schiff-base silver nanocomplex(CHO-SBA-15/ε-PL/Ag,CLA-1)exhibited an improved inhibitory effect on infectious pathogen growth typified by Escherichia coli and Staphylococcus aureus in comparison with two control silver complexes without Schiff-base conjugates,SBA-15/ε-PL/Ag and CHO-SBA-15/Ag,respectively.In addition,CLA-1 remarkably inhibited the growth of Mycobacterium tuberculosis due to the excellent antimicrobial activity of silver species.Significantly,CLA-1 kills Candida albicans cells,inhibits biofilm formation,and eliminates preformed biofilms,with no development of resistance during continuous serial passaging.The antifungal activity is connected to disruption of bacterial cell membranes and increased levels of intracellular reactive oxygen species.In mouse models of multidrug-resistant C.albicans infection,CLA-1 exhibited efficient in vivo fungicidal efficacy superior to two antifungal drugs,amphotericin B and fluconazole.Moreover,CLA-1 treatment induces negligible toxicity against normal tissues with safety.Therefore,this study reveals the pivotal role of the molecular design of Schiff-base silver nanocomplex formation on biopolymer surface-functionalized silica mesopores as a green and efficient nanoplatform to tackle infectious microbes.
