The published article titled“MicroRNA-98-5p Inhibits Cell Proliferation and Induces Cell Apoptosis in Hepatocellular Carcinoma via Targeting IGF2BP1”has been retracted from Oncology Research,Vol.25,No.7,2017,pp.1117...The published article titled“MicroRNA-98-5p Inhibits Cell Proliferation and Induces Cell Apoptosis in Hepatocellular Carcinoma via Targeting IGF2BP1”has been retracted from Oncology Research,Vol.25,No.7,2017,pp.1117–1127.展开更多
BACKGROUND Pelvic squamous cell carcinoma of unknown primary(CUP)is extremely rare,accounting for less than one percent of all CUP cases,and its infrequency has lim-ited the development of standardized diagnostic and ...BACKGROUND Pelvic squamous cell carcinoma of unknown primary(CUP)is extremely rare,accounting for less than one percent of all CUP cases,and its infrequency has lim-ited the development of standardized diagnostic and treatment guidelines.CASE SUMMARY A 77-year-old female with a history of resected lung adenocarcinoma presented with worsening constipation.Imaging revealed a 2.5 cm mass adjacent to the right levator ani muscle.Biopsy confirmed poorly differentiated squamous cell carcinoma,positive for pancytokeratin and p40,and negative for p16,cytokeratin 7,cytokeratin 20,and neuroendocrine markers.No primary lesion was identified despite extensive evaluation.She underwent five cycles of 5-fluorouracil(1000 mg/m^(2) continuous infusion,days 1-4)and mitomycin-C(10 mg/m^(2) on day 1)with concurrent pelvic radiotherapy(50.4 Gy in 28 fractions).Follow-up imaging demonstrated complete remission sustained for 12 months.Electrocorticography performance status improved from 2 at diagnosis to 1 during follow-up.CONCLUSION This case highlights the potential role of chemoradiotherapy in managing pelvic squamous cell CUP,achieving durable remission in selected patients.展开更多
Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The...Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.展开更多
The behaviour of nanofertilizers(NFs)in plant-soil systems can differ from that of conventional chemical fertilizers due to their peculiar chemical-physical properties.Their effectiveness is still poorly understood.In...The behaviour of nanofertilizers(NFs)in plant-soil systems can differ from that of conventional chemical fertilizers due to their peculiar chemical-physical properties.Their effectiveness is still poorly understood.In this study,we evaluated the P fertilization potential of a novel nanosized FePO4NF(FePNF)in a plant-soil microcosm in a pot experiment.The efficacies of FePNF and a conventional P fertilizer(triple superphosphate,TSP)in sustaining the growth of cucumber plants were evaluated.Plants were grown for 28 d on a P-deficient soil,and determinations were made of plant growth parameters,mineral nutrient concentrations in plant tissues,P availability in soil,activities of soil enzymes involved in C,N,P,and S mineralization,and soil microbial community structure.No significant differences were found in plant dry weight,leaf area,chlorophyll content,or root growth between the FePNF and TSP treatments.Conversely,P availability in soil and P concentration in plant tissues at the end of the plant growth period were significantly higher after TSP fertilization compared to FePNF fertilization,whereas no significant differences were observed for other nutrients.Among the measured soil enzyme activities,there were no significant differences in the activities of soil acid phosphatase,β-glucosidase,and arylsulfatase between the FePNF and TSP treatments,while soil alkaline phosphatase activity was higher in the TSP treatment than in the FePNF treatment and the protease activity was higher in the FePNF treatment than in the TSP treatment.The FePNF and TSP treatments showed significant differences in soil archaeal,bacterial,and fungal community structures,although the microbial community profiles generally clustered closer to each other in the two treatments.We concluded that FePNF can be an efficient alternative to the conventional P fertilizer TSP.展开更多
phoD and pqqC gene occurrence in bacteria allows them to mobilize phosphorus(P)by mineralizing organic P(Po)and solubilizing inorganic P(Pi),respectively.Community characteristics of phoD-and pqqC-harboring bacteria(p...phoD and pqqC gene occurrence in bacteria allows them to mobilize phosphorus(P)by mineralizing organic P(Po)and solubilizing inorganic P(Pi),respectively.Community characteristics of phoD-and pqqC-harboring bacteria(phoD-and pqqC-HB,respectively)mediate P cycling.However,whether the microbial community assembly and keystone taxa of phoD-and pqqC-HB regulate P availability and distinct regulatory pathways between these two genes remain unclear.In this study,soil microbial community characteristics and P availability were investigated in four long-term(38-year)fertilization regimes:control with no fertilizer(CK),P fertilizer(PF),nitrogen(N)and P fertilizers(NP),and N fertilizer,P fertilizer,and manure(NPM).The N addition treatments(NP and NPM)significantly changed the community composition and increased the abundances of phoD-and pqqC-HB compared to the no-N addition treatments(CK and PF).Stochastic processes dominated the community assembly of both phoD-and pqqC-HB,and the relative contributions of stochasticity increased with N addition.Furthermore,the N addition treatments resulted in greater network complexity and higher abundances of keystone taxa of phoD-and pqqC-HB compared to those of the no-N addition treatments.The keystone taxa implicated in P cycling were also associated with carbon(C)and N cycling processes.Microbial community composition and assembly processes were the main factors driving labile Pi for phoD-HB,whereas keystone taxa contributed the most to labile Pi for pqqC-HB.These results emphasize that distinct mechanisms of phoD-and pqqC-HB regulate P availability under fertilization management and underline the significance of microbial community assembly and keystone taxa in soil ecological functions,offering fresh perspectives on comprehending the biological processes facilitated by microorganisms in enhancing soil quality.展开更多
High-pressure β-Sn germanium may transform into diverse metastable allotropes with distinctive nanostructures and unique physical properties via multiple pathways under decompression.However,the mechanism and transit...High-pressure β-Sn germanium may transform into diverse metastable allotropes with distinctive nanostructures and unique physical properties via multiple pathways under decompression.However,the mechanism and transition kinetics remain poorly understood.Here,we investigate the formation of metastable phases and nanostructures in germanium via controllable transition pathways of β-Sn Ge under rapid decompression at different rates.High-resolution transmission electron microscopy reveals three distinct metastable phases with the distinctive nanostructures:an almost perfect st12 Ge crystal,nanosized bc8/r8 structures with amorphous boundaries,and amorphous Ge with nanosized clusters (0.8–2.5 nm).Fast in situ x-ray diffraction and x-ray absorption measurements indicate that these nanostructured products form in certain pressure regions via distinct kinetic pathways and are strongly correlated with nucleation rates and electronic transitions mediated by compression rate,temperature,and stress.This work provides deep insight into the controllable synthesis of metastable materials with unique crystal symmetries and nanostructures for potential applications.展开更多
BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanis...BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins.However,research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC(HNCSCC),particularly in Asian populations,remains limited.This retrospective study surveyed 62 patients with HNSCC(2011-2020),excluding those with facial warts or other skin cancer.AIM To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations.METHODS All patients underwent wide excision and biopsy.Immunohistochemical staining for HPV,p16,and p53 yielded positive and negative results.The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency.RESULTS Of the 62 patients,20(32.26%)were male,with an average age of 82.27 years(range 26-103 years).High-risk included 19 cases(30.65%),with the eyelid and lip being the most common sites(five cases,8.06%).Middle-risk included 43 cases(69.35%),with the cheek being the most common(29 cases,46.77%).The p16 expression was detected in 24 patients(38.71%),p53 expression in 42 patients(72.58%),and HPV in five patients(8.06%).No significant association was found between p16 expression and the presence of HPV(P>0.99),with a positive predictive value of 8.33%.CONCLUSION This study revealed that p16,a surrogate HPV marker in oropharyngeal SCC,is not reliable in HNCSCC,providing valuable insights for further research in Asian populations.展开更多
The DNA replication stress(RS)response is crucial for maintaining cellular homeostasis and promoting physiological longevity.However,the mechanisms by which long-lived species,such as bats,regulate RS to maintain geno...The DNA replication stress(RS)response is crucial for maintaining cellular homeostasis and promoting physiological longevity.However,the mechanisms by which long-lived species,such as bats,regulate RS to maintain genomic stability remain unclear.Also,recent studies have uncovered noncanonical roles of ribosome-associated factors in maintaining genomic stability.In this study,somatic skin fibroblasts from the long-lived big-footed bat(Myotis pilosus)were examined,with results showing that bat cells exhibited enhanced RS tolerance compared to mouse cells.Comparative transcriptome analysis under RS conditions revealed pronounced species-specific transcriptional differences,including robust up-regulation of ribosome biogenesis genes in bat cells and a markedly reduced activation of the P53 signaling pathway.These features emphasize a distinct homeostatic strategy in bat cells.Nuclear fragile X mental retardation-interacting protein 1(Nufip1),a ribosome-associated factor highly expressed in bat fibroblasts,was identified as a potential integrator of ribosomal and P53 signaling via its association with ribosomal protein S27-like(Rps27l).These findings provide direct cellular and molecular evidence for a noncanonical RS response in bats,highlighting a deeper understanding of the biological characteristics and genomic maintenance mechanisms of long-lived species.展开更多
Melanomas are aggressive cancers,with a high rate of metastatic disease.Cutaneous(CM)and uveal(UM)melanomas are intrinsically different diseases,and most cell death inducers effective for CM do not function for UM.Thi...Melanomas are aggressive cancers,with a high rate of metastatic disease.Cutaneous(CM)and uveal(UM)melanomas are intrinsically different diseases,and most cell death inducers effective for CM do not function for UM.This is primarily due to the fact the eye is an immunologically privileged organ,and it fails to achieve the efficacy of immune checkpoint inhibitors(ICIs)comparable to that for CM.However,approaches utilizing specific melanomaassociated antigens are being developed for metastatic forms of CM and UM.The most promising to date are gp100 and tyrosinase related protein 1(TYRP1),primarily for the design of targeting chimeric molecules and for autologous T-/NK-cell products with a chimeric antigen receptor.The difference in the mutational profile of apoptosis-related genes in CM and UM also makes counterproductive the use of the same drugs re-activators of the intrinsic pathway of apoptosis.Therefore,the discovery of novel pathways of regulated cell death such as ferroptosis and cuproptosis may help in the development of new drugs for melanomas resistant to already available inducers of regulated cell death.Here we consistently discuss the latest advances in the therapy of melanomas,and above all-UM,which is classified as an orphan disease.展开更多
Research on human motion prediction has made significant progress due to its importance in the development of various artificial intelligence applications.However,effectively capturing spatio-temporal features for smo...Research on human motion prediction has made significant progress due to its importance in the development of various artificial intelligence applications.However,effectively capturing spatio-temporal features for smoother and more precise human motion prediction remains a challenge.To address these issues,a robust human motion prediction method via integration of spatial and temporal cues(RISTC)has been proposed.This method captures sufficient spatio-temporal correlation of the observable sequence of human poses by utilizing the spatio-temporal mixed feature extractor(MFE).In multi-layer MFEs,the channel-graph united attention blocks extract the augmented spatial features of the human poses in the channel and spatial dimension.Additionally,multi-scale temporal blocks have been designed to effectively capture complicated and highly dynamic temporal information.Our experiments on the Human3.6M and Carnegie Mellon University motion capture(CMU Mocap)datasets show that the proposed network yields higher prediction accuracy than the state-of-the-art methods.展开更多
Silicosis,a major persistent occupational disease in China,is a progressive and irreversible pulmonary fibrosis disease with unclear pathogenesis.Cellular senescence,a state of stable cell cycle arrest that is recogni...Silicosis,a major persistent occupational disease in China,is a progressive and irreversible pulmonary fibrosis disease with unclear pathogenesis.Cellular senescence,a state of stable cell cycle arrest that is recognized as a key underlying factor in age-related fibroproliferative disorders,plays an important role in chronic lung diseases,particularly pulmonary fibrosis.We previously reported that SiO2-stimulated mice and alveolar type II epithelial cells develop cellular senescence,which is involved in silicosis formation in alveolar type II epithelial cells[1].Cellular senescence may play an important role in silicosis development;however,the exact underlying mechanisms are not fully understood.展开更多
BACKGROUND Colorectal cancer(CRC)is a common malignant tumor of the digestive tract worldwide,characterized by high incidence and mortality rates.AIM To investigate the expression of serum apurinic/apyrimidinic endonu...BACKGROUND Colorectal cancer(CRC)is a common malignant tumor of the digestive tract worldwide,characterized by high incidence and mortality rates.AIM To investigate the expression of serum apurinic/apyrimidinic endonuclease 1 autoantibodies(APE1-AAbs),peripheral pentraxin-3(PTX-3),and miR-486-3p in patients with CRC undergoing radical surgery and their relationship with postoperative recurrence and metastasis.METHODS A retrospective analysis was conducted on the clinical data of 154 CRC patients who underwent laparoscopic radical surgery in our hospital from January 2022 to January 2024.Patients were followed for one year postoperatively and divided into an occurrence group(n=28)and a non-occurrence group(n=126)based on whether they experienced recurrence or metastasis.The clinical data and the expression levels of APE1-AAbs,PTX-3,and miR-486-3p were compared between the two groups.Multivariate logistic regression analysis was performed to identify risk factors for postoperative recurrence and metastasis in CRC patients.The relationship of APE1-AAbs,PTX-3,and miR-486-3p with postoperative recurrence and metastasis was analyzed using Spearman correlation analysis.Receiver operating characteristic curves were drawn to evaluate the predictive value of serum APE1-AAbs,PTX-3,and miR-486-3p levels alone and their combination for postoperative recurrence and metastasis in CRC.RESULTS The occurrence group had significantly higher proportions of patients with an age≥60 years,lymph node metastasis,stage III disease,poor differentiation,tumor diameter>5 cm,and higher platelet count,carcinoembryonic antigen,and carbohydrate antigen 19-9 levels than the non-occurrence group(P<0.05).The expression levels of APE1-AAbs,PTX-3,and miR-486-3p in the occurrence group were significantly higher than those in the non-occurrence group(P<0.05).Multivariate logistic regression analysis showed that lymph node metastasis,stage III disease,poor differentiation,and elevated levels of APE1-AAbs,PTX-3,and miR-486-3p were risk factors for postoperative recurrence and metastasis in CRC patients(odds ratio>1,P<0.05).Spearman correlation analysis revealed that the levels of APE1-AAbs,PTX-3,and miR-486-3p were positively correlated with postoperative recurrence and metastasis in CRC patients(r=0.642,0.653,and 0.631,respectively,P<0.05).Receiver operating characteristic curve analysis showed that the area under the curve values for APE1-AAbs,PTX-3,and miR-486-3p levels alone and their combination in predicting postoperative recurrence and metastasis in CRC were 0.764,0.783,0.806,and 0.875,respectively,with the combination significantly outperforming individual markers(P<0.05).CONCLUSION Serum APE1-AAbs,PTX-3,and miR-486-3p levels are higher in CRC patients with postoperative recurrence and metastasis.These three markers are risk factors for postoperative recurrence and metastasis in CRC and can be used as predictive biomarkers.The combined detection of these markers has higher predictive value compared to individual tests.展开更多
Let p be a prime. For any finite p-group G, the deep transfers T H,G ' : H / H ' → G ' / G " from the maximal subgroups H of index (G:H) = p in G to the derived subgroup G ' are introduced as an ...Let p be a prime. For any finite p-group G, the deep transfers T H,G ' : H / H ' → G ' / G " from the maximal subgroups H of index (G:H) = p in G to the derived subgroup G ' are introduced as an innovative tool for identifying G uniquely by means of the family of kernels ùd(G) =(ker(T H,G ')) (G: H) = p. For all finite 3-groups G of coclass cc(G) = 1, the family ùd(G) is determined explicitly. The results are applied to the Galois groups G =Gal(F3 (∞)/ F) of the Hilbert 3-class towers of all real quadratic fields F = Q(√d) with fundamental discriminants d > 1, 3-class group Cl3(F) □ C3 × C3, and total 3-principalization in each of their four unramified cyclic cubic extensions E/F. A systematic statistical evaluation is given for the complete range 1 d 7, and a few exceptional cases are pointed out for 1 d 8.展开更多
AIM:To highlight the importance of microRNA(miRNA)-21-5p in directing the phosphatase and tensin homolog(PTEN)gene to control the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)...AIM:To highlight the importance of microRNA(miRNA)-21-5p in directing the phosphatase and tensin homolog(PTEN)gene to control the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)pathway in retinal pigment epithelial(RPE)cells in humans subjected to photodamage.METHODS:Human adult RPE cell line-19(ARPE-19)was cultured in vitro and randomly divided into control,damage,overexpression,negative,and PI3K/Akt blocker groups to establish a photodamage model of ARPE-19 cells.The models were subjected to 24h of light exposure,after which the corresponding indices were detected.The cell counting kit-8 assay quantified cell viability,while flow cytometry determined apoptosis rates.The miRNA-21 mimics and miRNA mimic NC were transfected into ARPE-19 cells using a transient transfection technique.Quantitative reverse transcription polymerase chain reaction(SYBR Green)and Western blotting analyzed expression levels of miRNA-21-5p,PTEN,p-PI3K/PI3K,p-mTOR/mTOR,and p-Akt/Akt.Statistical analyses comprised one-way analysis of variance and the Student-Newman-Keuls test for multiple group comparisons.RESULTS:The photodamage group demonstrated reduced cell survival rates than the control group(P<0.01).The overexpression group exhibited higher cell survival rates than the injury group(P<0.01).The negative group showed no difference in viability(P>0.05).The PI3K/Akt blocker group demonstrated lower cell viability,compared with the overexpression group(P<0.01).CONCLUSION:miRNA-21-5p significantly increases ARPE-19 cell survival after photodamage and inhibits lightinduced ARPE-19 cell apoptosis,suggesting that it may play a protective role in RPE by activating the PI3K/Akt/mTOR pathway while downregulating PTEN expression.展开更多
The strong association between human papillomavirus(HPV)infection and oropharyngeal squamous cell carcinoma(SCC)is well-documented,with p16 expression serving as a reliable predictor of HPV involvement.HPV-related tum...The strong association between human papillomavirus(HPV)infection and oropharyngeal squamous cell carcinoma(SCC)is well-documented,with p16 expression serving as a reliable predictor of HPV involvement.HPV-related tumors are characterized by distinct mechanisms affecting p16 and p53 protein pathways.However,the prevalence of HPV and the combined predictive utility of p16 and p53 expression in head and neck cutaneous SCC remain less explored,necessitating further research to understand their role in this subset of SCC.HPV,p16,and p53 statuses were determined using immunohistochemistry staining methods rather than more sensitive techniques such as polymerase chain reaction or HPV genotyping,limiting the ability to assess specific area HPV types poten-tially associated with prognosis.Further studies assessing multiple molecular markers in head and neck cutaneous patients will better predict the diverse outcomes and potentially the type of treatment targeted to those markers.展开更多
BACKGROUND Differential diagnosis among atypical hyperplasia(AH)(including reparative hyperplasia and intestinal metaplasia),low-grade dysplasia(LGD),high-grade dysplasia(HGD),and adenocarcinoma(AC)in gastric mucosal ...BACKGROUND Differential diagnosis among atypical hyperplasia(AH)(including reparative hyperplasia and intestinal metaplasia),low-grade dysplasia(LGD),high-grade dysplasia(HGD),and adenocarcinoma(AC)in gastric mucosal biopsies is challenging due to histomorphological overlaps,variability in pathological diagnosis consistency,and limited reproducibility.AIM To evaluate the diagnostic utility of P53,Ki67,P504S,and IMP3 in gastric cancer and its precancerous lesions,focusing on their effectiveness in distinguishing AH,LGD,HGD,and AC.METHODS From January 2018 to September 2020,a total of 185 gastric mucosal biopsy specimens were analyzed according to the pathological diagnostic criteria outlined in the World Health Organization Classification of Digestive System Tumors(2019).The specimens were categorized into four groups:AH,LGD,HGD,and AC.Immunohistochemistry was employed to assess the expression status of P53,Ki67,P504S,and IMP3.Intergroup comparisons were performed using theχ^(2)test or Fisher's exact probability test to compare the differences in immunohistochemical markers across the distinct lesion groups.RESULTS The expression rate of P504S was highest in the LGD group(53.3%,16/30),while IMP3 expression was highest in the AC group(41.9%,26/62),followed by the HGD group(33.3%).Significant differences in P504S and IMP3 expression levels were observed among the four lesion groups(P<0.001).Pairwise comparisons revealed statistically significant differences in P504S expression between the AH group and the LGD,HGD,and AC groups(P<0.001),as well as significant variations in IMP3 expression between the AH group and the HGD and AC groups,and between the LGD group and the HGD and AC groups(P<0.001).Additionally,significant correlations were found between P504S and the polarity expression pattern of Ki67,and between IMP3 and the mutation expression pattern of P53(P<0.001).The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.CONCLUSION P504S is highly expressed in LGD and is associated with the Ki67“polarity”expression pattern.IMP3 is highly expressed in HGD/AC and is correlated with the P53 mutation expression pattern.The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.The rational use of P504S,Ki67,IMP3,and p53 can help distinguish gastric cancer and precancerous lesions,improving the early cancer diagnosis rate.展开更多
Head and neck cutaneous squamous cell carcinoma(HNCSCC)remains underexplored compared to oropharyngeal squamous cell carcinoma,particularly in relation to human papillomavirus(HPV)and molecular markers such as p16 and...Head and neck cutaneous squamous cell carcinoma(HNCSCC)remains underexplored compared to oropharyngeal squamous cell carcinoma,particularly in relation to human papillomavirus(HPV)and molecular markers such as p16 and p53.While p16 is a well-established surrogate for HPV in oropharyngeal cancer,our review highlights its unreliable role in HNCSCC,where positivity is instead associated with recurrence and metastasis.Similarly,p53 illustrates a dual role-wild-type as a genomic safeguard,mutated as an oncogenic driver-complicating prognostication.Methodological considerations,including the limitations of immunohistochemistry for HPV detection,underscore the need for multi-method and molecular validation in future studies.Ultraviolet radiation is posited as a key modifier of p16 function,decoupling expression from tumor suppression.To contextualize these findings,we draw parallels to glioblastoma(GBM),where subclonal evolution,p53 dysfunction,and intratumoral heterogeneity drive relapse despite aggressive multimodal therapies.GBM exemplifies how bulk-level biomarker generalizations often obscure dynamic cellular ecosystems,reinforcing the necessity of single-cell and spatial approaches.Multi-omics integration-encompassing genome,transcriptome,proteome,and tumor microenvironment mapping-coupled with single-cell RNA sequencing and spatial transcriptomics,offers a path forward for resolving subclonal dynamics in both HNCSCC and GBM.These technologies provide the resolution needed to track tumor-immunestromal co-evolution,identify therapy-resistant clones,and anticipate recurrence.We argue for a N-of-1,patient-and cell-centric paradigm that reframes biomarkers not as static surrogates but as dynamic readouts of cancer evolution across time and tissue contexts.Conceptually,we propose kinetic and microenvironmental frameworks(e.g.,“load-and-lock”barriers;dormancy and immunesynapse stabilization)as hypothesis-generating avenues to stall clonal handoffs and improve outcome prediction.Together,these perspectives argue for revised biomarker frameworks in HNCSCC and ethically inclusive,mechanism-anchored studies that bridge discovery with individualized care.By bridging insights from HNCSCC with the lessons of GBM,this review underscores the need for ethically inclusive,mechanistically informed frameworks that integrate subclonal evolution,biomarker re-interpretation,and precision-personalized hybrid models.Such an approach will be essential for advancing from one-size-fits-all strategies to individualized lifetime cancer care.展开更多
Heme peroxygenases exhibit remarkable catalytic versatility in facilitating a wide array of oxidative reactions under mild conditions,eliminating the need for coenzymes and intricate electron transport systems.This un...Heme peroxygenases exhibit remarkable catalytic versatility in facilitating a wide array of oxidative reactions under mild conditions,eliminating the need for coenzymes and intricate electron transport systems.This unique character underscores their essentiality and potential as promising tools in synthetic biology.Recent advancements in enzyme engineering have significantly enhanced the catalytic performance of both natural and artificial peroxygenases.Extensive engineering efforts have been directed towards unspecific peroxygenases and fatty acid peroxygenases,aiming to expand their substrate specificities,and enhance reaction selectivities,as well as increase enzyme stability.Furthermore,innovative strategies such as dual-functional small molecule-assisted systems and H_(2)O_(2) tunnel engineering have been harnessed to transform P450 monooxygenases into highly efficient peroxygenases,capable of catalyzing reactions with a variety of unnatural substrates.This review consolidates the latest progress in the engineered and artificial heme peroxygenases,emphasizing their catalytic performances as potent biocatalysts for sustainable organic synthesis.展开更多
文摘The published article titled“MicroRNA-98-5p Inhibits Cell Proliferation and Induces Cell Apoptosis in Hepatocellular Carcinoma via Targeting IGF2BP1”has been retracted from Oncology Research,Vol.25,No.7,2017,pp.1117–1127.
文摘BACKGROUND Pelvic squamous cell carcinoma of unknown primary(CUP)is extremely rare,accounting for less than one percent of all CUP cases,and its infrequency has lim-ited the development of standardized diagnostic and treatment guidelines.CASE SUMMARY A 77-year-old female with a history of resected lung adenocarcinoma presented with worsening constipation.Imaging revealed a 2.5 cm mass adjacent to the right levator ani muscle.Biopsy confirmed poorly differentiated squamous cell carcinoma,positive for pancytokeratin and p40,and negative for p16,cytokeratin 7,cytokeratin 20,and neuroendocrine markers.No primary lesion was identified despite extensive evaluation.She underwent five cycles of 5-fluorouracil(1000 mg/m^(2) continuous infusion,days 1-4)and mitomycin-C(10 mg/m^(2) on day 1)with concurrent pelvic radiotherapy(50.4 Gy in 28 fractions).Follow-up imaging demonstrated complete remission sustained for 12 months.Electrocorticography performance status improved from 2 at diagnosis to 1 during follow-up.CONCLUSION This case highlights the potential role of chemoradiotherapy in managing pelvic squamous cell CUP,achieving durable remission in selected patients.
基金supported by the National Natural Science Foundation of China,Nos. 82173806 and U1803281Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science,Nos. 2021-I2M-1-030 and 2022-I2M-2-002Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No. 2022-JKCS-08 (all to RL)。
文摘Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.
基金supported by the Joint Project 2016 and the Joint Project 2019,developed by the University of Verona and Fabbrica Cooperativa Perfosfati Cerea,Italy。
文摘The behaviour of nanofertilizers(NFs)in plant-soil systems can differ from that of conventional chemical fertilizers due to their peculiar chemical-physical properties.Their effectiveness is still poorly understood.In this study,we evaluated the P fertilization potential of a novel nanosized FePO4NF(FePNF)in a plant-soil microcosm in a pot experiment.The efficacies of FePNF and a conventional P fertilizer(triple superphosphate,TSP)in sustaining the growth of cucumber plants were evaluated.Plants were grown for 28 d on a P-deficient soil,and determinations were made of plant growth parameters,mineral nutrient concentrations in plant tissues,P availability in soil,activities of soil enzymes involved in C,N,P,and S mineralization,and soil microbial community structure.No significant differences were found in plant dry weight,leaf area,chlorophyll content,or root growth between the FePNF and TSP treatments.Conversely,P availability in soil and P concentration in plant tissues at the end of the plant growth period were significantly higher after TSP fertilization compared to FePNF fertilization,whereas no significant differences were observed for other nutrients.Among the measured soil enzyme activities,there were no significant differences in the activities of soil acid phosphatase,β-glucosidase,and arylsulfatase between the FePNF and TSP treatments,while soil alkaline phosphatase activity was higher in the TSP treatment than in the FePNF treatment and the protease activity was higher in the FePNF treatment than in the TSP treatment.The FePNF and TSP treatments showed significant differences in soil archaeal,bacterial,and fungal community structures,although the microbial community profiles generally clustered closer to each other in the two treatments.We concluded that FePNF can be an efficient alternative to the conventional P fertilizer TSP.
基金supported by the National Key Research and Development Program of China(No.2022YFD 1901601)the National Natural Science Foundation of China(No.42107360)the Fundamental Research Funds for the Central Universities,China(No.2452021032).
文摘phoD and pqqC gene occurrence in bacteria allows them to mobilize phosphorus(P)by mineralizing organic P(Po)and solubilizing inorganic P(Pi),respectively.Community characteristics of phoD-and pqqC-harboring bacteria(phoD-and pqqC-HB,respectively)mediate P cycling.However,whether the microbial community assembly and keystone taxa of phoD-and pqqC-HB regulate P availability and distinct regulatory pathways between these two genes remain unclear.In this study,soil microbial community characteristics and P availability were investigated in four long-term(38-year)fertilization regimes:control with no fertilizer(CK),P fertilizer(PF),nitrogen(N)and P fertilizers(NP),and N fertilizer,P fertilizer,and manure(NPM).The N addition treatments(NP and NPM)significantly changed the community composition and increased the abundances of phoD-and pqqC-HB compared to the no-N addition treatments(CK and PF).Stochastic processes dominated the community assembly of both phoD-and pqqC-HB,and the relative contributions of stochasticity increased with N addition.Furthermore,the N addition treatments resulted in greater network complexity and higher abundances of keystone taxa of phoD-and pqqC-HB compared to those of the no-N addition treatments.The keystone taxa implicated in P cycling were also associated with carbon(C)and N cycling processes.Microbial community composition and assembly processes were the main factors driving labile Pi for phoD-HB,whereas keystone taxa contributed the most to labile Pi for pqqC-HB.These results emphasize that distinct mechanisms of phoD-and pqqC-HB regulate P availability under fertilization management and underline the significance of microbial community assembly and keystone taxa in soil ecological functions,offering fresh perspectives on comprehending the biological processes facilitated by microorganisms in enhancing soil quality.
基金supported by the National Nature Science Foundation of China(NSFC)(Grant No.11974033)Xuqiang Liu acknowledges support from the National Postdoctoral Foundation Project of China under Grant No.GZC20230215+2 种基金the National Nature Science Foundation of China under Grants No.12404001The XRD measurements at room and high temperatures were performed at the 4W2 HPStation of the Beijing Synchrotron Radiation Facility(BSRF)and beamline 15U1 of the Shanghai Synchrotron Radiation Facility(SSRF)In situ high-pressure,low-temperature XRD measurements were conducted at sector 16 ID-B,HPCAT of the Advanced Photon Source,and were supported by DOE-NNSA under Award No.DE-NA0001974.
文摘High-pressure β-Sn germanium may transform into diverse metastable allotropes with distinctive nanostructures and unique physical properties via multiple pathways under decompression.However,the mechanism and transition kinetics remain poorly understood.Here,we investigate the formation of metastable phases and nanostructures in germanium via controllable transition pathways of β-Sn Ge under rapid decompression at different rates.High-resolution transmission electron microscopy reveals three distinct metastable phases with the distinctive nanostructures:an almost perfect st12 Ge crystal,nanosized bc8/r8 structures with amorphous boundaries,and amorphous Ge with nanosized clusters (0.8–2.5 nm).Fast in situ x-ray diffraction and x-ray absorption measurements indicate that these nanostructured products form in certain pressure regions via distinct kinetic pathways and are strongly correlated with nucleation rates and electronic transitions mediated by compression rate,temperature,and stress.This work provides deep insight into the controllable synthesis of metastable materials with unique crystal symmetries and nanostructures for potential applications.
基金Supported by the National Research Foundation of Korea,No.2020R1A2C1100891Soonchunhyang University Research Fund,No.2024-05-014.
文摘BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins.However,research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC(HNCSCC),particularly in Asian populations,remains limited.This retrospective study surveyed 62 patients with HNSCC(2011-2020),excluding those with facial warts or other skin cancer.AIM To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations.METHODS All patients underwent wide excision and biopsy.Immunohistochemical staining for HPV,p16,and p53 yielded positive and negative results.The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency.RESULTS Of the 62 patients,20(32.26%)were male,with an average age of 82.27 years(range 26-103 years).High-risk included 19 cases(30.65%),with the eyelid and lip being the most common sites(five cases,8.06%).Middle-risk included 43 cases(69.35%),with the cheek being the most common(29 cases,46.77%).The p16 expression was detected in 24 patients(38.71%),p53 expression in 42 patients(72.58%),and HPV in five patients(8.06%).No significant association was found between p16 expression and the presence of HPV(P>0.99),with a positive predictive value of 8.33%.CONCLUSION This study revealed that p16,a surrogate HPV marker in oropharyngeal SCC,is not reliable in HNCSCC,providing valuable insights for further research in Asian populations.
基金supported by the Applied Basic Research Programs of Science and Technology Commission Foundation of Yunnan Province(202401AT070186 to K.Q.L.,202201AS070044 to B.Z.)Yunnan Province(202305AH340006 to B.Z.)Kunming Science and Technology Bureau(2022SCP007 to B.Z.)。
文摘The DNA replication stress(RS)response is crucial for maintaining cellular homeostasis and promoting physiological longevity.However,the mechanisms by which long-lived species,such as bats,regulate RS to maintain genomic stability remain unclear.Also,recent studies have uncovered noncanonical roles of ribosome-associated factors in maintaining genomic stability.In this study,somatic skin fibroblasts from the long-lived big-footed bat(Myotis pilosus)were examined,with results showing that bat cells exhibited enhanced RS tolerance compared to mouse cells.Comparative transcriptome analysis under RS conditions revealed pronounced species-specific transcriptional differences,including robust up-regulation of ribosome biogenesis genes in bat cells and a markedly reduced activation of the P53 signaling pathway.These features emphasize a distinct homeostatic strategy in bat cells.Nuclear fragile X mental retardation-interacting protein 1(Nufip1),a ribosome-associated factor highly expressed in bat fibroblasts,was identified as a potential integrator of ribosomal and P53 signaling via its association with ribosomal protein S27-like(Rps27l).These findings provide direct cellular and molecular evidence for a noncanonical RS response in bats,highlighting a deeper understanding of the biological characteristics and genomic maintenance mechanisms of long-lived species.
基金supported by the Russian Science Foundation,project no.23-14-00285。
文摘Melanomas are aggressive cancers,with a high rate of metastatic disease.Cutaneous(CM)and uveal(UM)melanomas are intrinsically different diseases,and most cell death inducers effective for CM do not function for UM.This is primarily due to the fact the eye is an immunologically privileged organ,and it fails to achieve the efficacy of immune checkpoint inhibitors(ICIs)comparable to that for CM.However,approaches utilizing specific melanomaassociated antigens are being developed for metastatic forms of CM and UM.The most promising to date are gp100 and tyrosinase related protein 1(TYRP1),primarily for the design of targeting chimeric molecules and for autologous T-/NK-cell products with a chimeric antigen receptor.The difference in the mutational profile of apoptosis-related genes in CM and UM also makes counterproductive the use of the same drugs re-activators of the intrinsic pathway of apoptosis.Therefore,the discovery of novel pathways of regulated cell death such as ferroptosis and cuproptosis may help in the development of new drugs for melanomas resistant to already available inducers of regulated cell death.Here we consistently discuss the latest advances in the therapy of melanomas,and above all-UM,which is classified as an orphan disease.
基金supported by the National Key R&D Program of China(No.2018YFB1305200)the Natural Science Foundation of Zhejiang Province(No.LGG21F030011)。
文摘Research on human motion prediction has made significant progress due to its importance in the development of various artificial intelligence applications.However,effectively capturing spatio-temporal features for smoother and more precise human motion prediction remains a challenge.To address these issues,a robust human motion prediction method via integration of spatial and temporal cues(RISTC)has been proposed.This method captures sufficient spatio-temporal correlation of the observable sequence of human poses by utilizing the spatio-temporal mixed feature extractor(MFE).In multi-layer MFEs,the channel-graph united attention blocks extract the augmented spatial features of the human poses in the channel and spatial dimension.Additionally,multi-scale temporal blocks have been designed to effectively capture complicated and highly dynamic temporal information.Our experiments on the Human3.6M and Carnegie Mellon University motion capture(CMU Mocap)datasets show that the proposed network yields higher prediction accuracy than the state-of-the-art methods.
文摘Silicosis,a major persistent occupational disease in China,is a progressive and irreversible pulmonary fibrosis disease with unclear pathogenesis.Cellular senescence,a state of stable cell cycle arrest that is recognized as a key underlying factor in age-related fibroproliferative disorders,plays an important role in chronic lung diseases,particularly pulmonary fibrosis.We previously reported that SiO2-stimulated mice and alveolar type II epithelial cells develop cellular senescence,which is involved in silicosis formation in alveolar type II epithelial cells[1].Cellular senescence may play an important role in silicosis development;however,the exact underlying mechanisms are not fully understood.
文摘BACKGROUND Colorectal cancer(CRC)is a common malignant tumor of the digestive tract worldwide,characterized by high incidence and mortality rates.AIM To investigate the expression of serum apurinic/apyrimidinic endonuclease 1 autoantibodies(APE1-AAbs),peripheral pentraxin-3(PTX-3),and miR-486-3p in patients with CRC undergoing radical surgery and their relationship with postoperative recurrence and metastasis.METHODS A retrospective analysis was conducted on the clinical data of 154 CRC patients who underwent laparoscopic radical surgery in our hospital from January 2022 to January 2024.Patients were followed for one year postoperatively and divided into an occurrence group(n=28)and a non-occurrence group(n=126)based on whether they experienced recurrence or metastasis.The clinical data and the expression levels of APE1-AAbs,PTX-3,and miR-486-3p were compared between the two groups.Multivariate logistic regression analysis was performed to identify risk factors for postoperative recurrence and metastasis in CRC patients.The relationship of APE1-AAbs,PTX-3,and miR-486-3p with postoperative recurrence and metastasis was analyzed using Spearman correlation analysis.Receiver operating characteristic curves were drawn to evaluate the predictive value of serum APE1-AAbs,PTX-3,and miR-486-3p levels alone and their combination for postoperative recurrence and metastasis in CRC.RESULTS The occurrence group had significantly higher proportions of patients with an age≥60 years,lymph node metastasis,stage III disease,poor differentiation,tumor diameter>5 cm,and higher platelet count,carcinoembryonic antigen,and carbohydrate antigen 19-9 levels than the non-occurrence group(P<0.05).The expression levels of APE1-AAbs,PTX-3,and miR-486-3p in the occurrence group were significantly higher than those in the non-occurrence group(P<0.05).Multivariate logistic regression analysis showed that lymph node metastasis,stage III disease,poor differentiation,and elevated levels of APE1-AAbs,PTX-3,and miR-486-3p were risk factors for postoperative recurrence and metastasis in CRC patients(odds ratio>1,P<0.05).Spearman correlation analysis revealed that the levels of APE1-AAbs,PTX-3,and miR-486-3p were positively correlated with postoperative recurrence and metastasis in CRC patients(r=0.642,0.653,and 0.631,respectively,P<0.05).Receiver operating characteristic curve analysis showed that the area under the curve values for APE1-AAbs,PTX-3,and miR-486-3p levels alone and their combination in predicting postoperative recurrence and metastasis in CRC were 0.764,0.783,0.806,and 0.875,respectively,with the combination significantly outperforming individual markers(P<0.05).CONCLUSION Serum APE1-AAbs,PTX-3,and miR-486-3p levels are higher in CRC patients with postoperative recurrence and metastasis.These three markers are risk factors for postoperative recurrence and metastasis in CRC and can be used as predictive biomarkers.The combined detection of these markers has higher predictive value compared to individual tests.
文摘Let p be a prime. For any finite p-group G, the deep transfers T H,G ' : H / H ' → G ' / G " from the maximal subgroups H of index (G:H) = p in G to the derived subgroup G ' are introduced as an innovative tool for identifying G uniquely by means of the family of kernels ùd(G) =(ker(T H,G ')) (G: H) = p. For all finite 3-groups G of coclass cc(G) = 1, the family ùd(G) is determined explicitly. The results are applied to the Galois groups G =Gal(F3 (∞)/ F) of the Hilbert 3-class towers of all real quadratic fields F = Q(√d) with fundamental discriminants d > 1, 3-class group Cl3(F) □ C3 × C3, and total 3-principalization in each of their four unramified cyclic cubic extensions E/F. A systematic statistical evaluation is given for the complete range 1 d 7, and a few exceptional cases are pointed out for 1 d 8.
文摘AIM:To highlight the importance of microRNA(miRNA)-21-5p in directing the phosphatase and tensin homolog(PTEN)gene to control the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)pathway in retinal pigment epithelial(RPE)cells in humans subjected to photodamage.METHODS:Human adult RPE cell line-19(ARPE-19)was cultured in vitro and randomly divided into control,damage,overexpression,negative,and PI3K/Akt blocker groups to establish a photodamage model of ARPE-19 cells.The models were subjected to 24h of light exposure,after which the corresponding indices were detected.The cell counting kit-8 assay quantified cell viability,while flow cytometry determined apoptosis rates.The miRNA-21 mimics and miRNA mimic NC were transfected into ARPE-19 cells using a transient transfection technique.Quantitative reverse transcription polymerase chain reaction(SYBR Green)and Western blotting analyzed expression levels of miRNA-21-5p,PTEN,p-PI3K/PI3K,p-mTOR/mTOR,and p-Akt/Akt.Statistical analyses comprised one-way analysis of variance and the Student-Newman-Keuls test for multiple group comparisons.RESULTS:The photodamage group demonstrated reduced cell survival rates than the control group(P<0.01).The overexpression group exhibited higher cell survival rates than the injury group(P<0.01).The negative group showed no difference in viability(P>0.05).The PI3K/Akt blocker group demonstrated lower cell viability,compared with the overexpression group(P<0.01).CONCLUSION:miRNA-21-5p significantly increases ARPE-19 cell survival after photodamage and inhibits lightinduced ARPE-19 cell apoptosis,suggesting that it may play a protective role in RPE by activating the PI3K/Akt/mTOR pathway while downregulating PTEN expression.
文摘The strong association between human papillomavirus(HPV)infection and oropharyngeal squamous cell carcinoma(SCC)is well-documented,with p16 expression serving as a reliable predictor of HPV involvement.HPV-related tumors are characterized by distinct mechanisms affecting p16 and p53 protein pathways.However,the prevalence of HPV and the combined predictive utility of p16 and p53 expression in head and neck cutaneous SCC remain less explored,necessitating further research to understand their role in this subset of SCC.HPV,p16,and p53 statuses were determined using immunohistochemistry staining methods rather than more sensitive techniques such as polymerase chain reaction or HPV genotyping,limiting the ability to assess specific area HPV types poten-tially associated with prognosis.Further studies assessing multiple molecular markers in head and neck cutaneous patients will better predict the diverse outcomes and potentially the type of treatment targeted to those markers.
基金Supported by The Science and Technology Research Project of Anyang,No.2022C01SF074。
文摘BACKGROUND Differential diagnosis among atypical hyperplasia(AH)(including reparative hyperplasia and intestinal metaplasia),low-grade dysplasia(LGD),high-grade dysplasia(HGD),and adenocarcinoma(AC)in gastric mucosal biopsies is challenging due to histomorphological overlaps,variability in pathological diagnosis consistency,and limited reproducibility.AIM To evaluate the diagnostic utility of P53,Ki67,P504S,and IMP3 in gastric cancer and its precancerous lesions,focusing on their effectiveness in distinguishing AH,LGD,HGD,and AC.METHODS From January 2018 to September 2020,a total of 185 gastric mucosal biopsy specimens were analyzed according to the pathological diagnostic criteria outlined in the World Health Organization Classification of Digestive System Tumors(2019).The specimens were categorized into four groups:AH,LGD,HGD,and AC.Immunohistochemistry was employed to assess the expression status of P53,Ki67,P504S,and IMP3.Intergroup comparisons were performed using theχ^(2)test or Fisher's exact probability test to compare the differences in immunohistochemical markers across the distinct lesion groups.RESULTS The expression rate of P504S was highest in the LGD group(53.3%,16/30),while IMP3 expression was highest in the AC group(41.9%,26/62),followed by the HGD group(33.3%).Significant differences in P504S and IMP3 expression levels were observed among the four lesion groups(P<0.001).Pairwise comparisons revealed statistically significant differences in P504S expression between the AH group and the LGD,HGD,and AC groups(P<0.001),as well as significant variations in IMP3 expression between the AH group and the HGD and AC groups,and between the LGD group and the HGD and AC groups(P<0.001).Additionally,significant correlations were found between P504S and the polarity expression pattern of Ki67,and between IMP3 and the mutation expression pattern of P53(P<0.001).The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.CONCLUSION P504S is highly expressed in LGD and is associated with the Ki67“polarity”expression pattern.IMP3 is highly expressed in HGD/AC and is correlated with the P53 mutation expression pattern.The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.The rational use of P504S,Ki67,IMP3,and p53 can help distinguish gastric cancer and precancerous lesions,improving the early cancer diagnosis rate.
文摘Head and neck cutaneous squamous cell carcinoma(HNCSCC)remains underexplored compared to oropharyngeal squamous cell carcinoma,particularly in relation to human papillomavirus(HPV)and molecular markers such as p16 and p53.While p16 is a well-established surrogate for HPV in oropharyngeal cancer,our review highlights its unreliable role in HNCSCC,where positivity is instead associated with recurrence and metastasis.Similarly,p53 illustrates a dual role-wild-type as a genomic safeguard,mutated as an oncogenic driver-complicating prognostication.Methodological considerations,including the limitations of immunohistochemistry for HPV detection,underscore the need for multi-method and molecular validation in future studies.Ultraviolet radiation is posited as a key modifier of p16 function,decoupling expression from tumor suppression.To contextualize these findings,we draw parallels to glioblastoma(GBM),where subclonal evolution,p53 dysfunction,and intratumoral heterogeneity drive relapse despite aggressive multimodal therapies.GBM exemplifies how bulk-level biomarker generalizations often obscure dynamic cellular ecosystems,reinforcing the necessity of single-cell and spatial approaches.Multi-omics integration-encompassing genome,transcriptome,proteome,and tumor microenvironment mapping-coupled with single-cell RNA sequencing and spatial transcriptomics,offers a path forward for resolving subclonal dynamics in both HNCSCC and GBM.These technologies provide the resolution needed to track tumor-immunestromal co-evolution,identify therapy-resistant clones,and anticipate recurrence.We argue for a N-of-1,patient-and cell-centric paradigm that reframes biomarkers not as static surrogates but as dynamic readouts of cancer evolution across time and tissue contexts.Conceptually,we propose kinetic and microenvironmental frameworks(e.g.,“load-and-lock”barriers;dormancy and immunesynapse stabilization)as hypothesis-generating avenues to stall clonal handoffs and improve outcome prediction.Together,these perspectives argue for revised biomarker frameworks in HNCSCC and ethically inclusive,mechanism-anchored studies that bridge discovery with individualized care.By bridging insights from HNCSCC with the lessons of GBM,this review underscores the need for ethically inclusive,mechanistically informed frameworks that integrate subclonal evolution,biomarker re-interpretation,and precision-personalized hybrid models.Such an approach will be essential for advancing from one-size-fits-all strategies to individualized lifetime cancer care.
文摘Heme peroxygenases exhibit remarkable catalytic versatility in facilitating a wide array of oxidative reactions under mild conditions,eliminating the need for coenzymes and intricate electron transport systems.This unique character underscores their essentiality and potential as promising tools in synthetic biology.Recent advancements in enzyme engineering have significantly enhanced the catalytic performance of both natural and artificial peroxygenases.Extensive engineering efforts have been directed towards unspecific peroxygenases and fatty acid peroxygenases,aiming to expand their substrate specificities,and enhance reaction selectivities,as well as increase enzyme stability.Furthermore,innovative strategies such as dual-functional small molecule-assisted systems and H_(2)O_(2) tunnel engineering have been harnessed to transform P450 monooxygenases into highly efficient peroxygenases,capable of catalyzing reactions with a variety of unnatural substrates.This review consolidates the latest progress in the engineered and artificial heme peroxygenases,emphasizing their catalytic performances as potent biocatalysts for sustainable organic synthesis.
