Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chem...Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.展开更多
To clarify the formation and distribution of feldspar dissolution pores and predict the distribution of high-quality reservoir in gravity flow sandstone of the 7^(th) member of Triassic Yanchang Formation(Chang 7 Memb...To clarify the formation and distribution of feldspar dissolution pores and predict the distribution of high-quality reservoir in gravity flow sandstone of the 7^(th) member of Triassic Yanchang Formation(Chang 7 Member)in the Ordos Basin,thin sections,scanning electron microscopy,energy spectrum analysis,X-ray diffraction whole rock analysis,and dissolution experiments are employed in this study to investigate the characteristics and control factors of feldspar dissolution pores.The results show that:(1)Three types of diagenetic processes are observed in the feldspar of Chang 7 sandstone in the study area:secondary overgrowth of feldspar,replacement by clay and calcite,and dissolution of detrital feldspar.(2)The feldspar dissolution of Chang 7 tight sandstone is caused by organic acid,and is further affected by the type of feldspar,the degree of early feldspar alteration,and the buffering effect of mica debris on organic acid.(3)Feldspars have varying degrees of dissolution.Potassium feldspar is more susceptible to dissolution than plagioclase.Among potassium feldspar,orthoclase is more soluble than microcline,and unaltered feldspar is more soluble than early kaolinized or sericitized feldspar.(4)The dissolution experiment demonstrated that the presence of mica can hinder the dissolution of feldspar.Mica of the same mass has a significantly stronger capacity to consume organic acids than feldspar.(5)Dissolution pores in feldspar of Chang 7 Member are more abundant in areas with low mica content,and they improve the reservoir physical properties,while in areas with high mica content,the number of feldspar dissolution pores decreases significantly.展开更多
BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC...BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.展开更多
BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has sho...BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.展开更多
Genome sequencing has revealed frequent mutations in Ras homolog family member A(RHOA)among various cancers with unique aberrant profiles and pathogenic effects,especially in peripheral T-cell lymphoma(PTCL).The discr...Genome sequencing has revealed frequent mutations in Ras homolog family member A(RHOA)among various cancers with unique aberrant profiles and pathogenic effects,especially in peripheral T-cell lymphoma(PTCL).The discrete positional distribution and types of RHOA amino acid substitutions vary according to the tumor type,thereby leading to different functional and biological properties,which provide new insight into the molecular pathogenesis and potential targeted therapies for various tumors.However,the similarities and discrepancies in characteristics of RHOA mutations among various histologic subtypes of PTCL have not been fully elucidated.Herein we highlight the inconsistencies and complexities of the type and location of RHOA mutations and demonstrate the contribution of RHOA variants to the pathogenesis of PTCL by combining epigenetic abnormalities and activating multiple downstream pathways.The promising potential of targeting RHOA as a therapeutic modality is also outlined.This review provides new insight in the field of personalized medicine to improve the clinical outcomes for patients.展开更多
BACKGROUND Hospice care plays an important role in improving the quality of life of advanced cancer patients,but controversy remains over whether age affects the attitudes of family members toward hospice care.AIM To ...BACKGROUND Hospice care plays an important role in improving the quality of life of advanced cancer patients,but controversy remains over whether age affects the attitudes of family members toward hospice care.AIM To investigate the attitudes of family members of advanced cancer patients of different ages toward hospice care.METHODS The study participants were 175 family members of patients with advanced cancer from January 2020 and October 2022.The participants were divided into youth(<40 years,n=65),middle-aged(40–60 years,n=59),and elderly(>60 years,n=51)groups.Researchers investigated and compared the degree of awareness regarding hospice care,attitudes,and whether the family members of patients would choose hospice care.RESULTS Among the family members of 175 patients,approximately 28%(49/175)were aware of hospice care.Awareness of hospice care,the proportion of hospice care acceptance and adaptation attitudes,and the proportion of those who chose hospice care in the youth group were higher in the middle-aged and elderly groups(P<0.05).No statistically significant difference was found in these three indicators between the middle-aged and elderly groups(P>0.05).Hospice care was chosen mainly to relieve pain and reduce unnecessary treatment,whereas the reasons for not choosing hospice care were mainly distrust and ethical concerns.CONCLUSION The family members of patients with advanced cancer had relatively low awareness of hospice care,while youth had a higher awareness of hospice care,acceptance,and adaptation attitudes,and were more willing to choose hospice care.展开更多
Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China,where the depositional p...Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China,where the depositional process is regarded confusing. The microfacies, construction types, and depositional model of the Member Deng-2 marginal microbial mound-bank complex have been investigated using unmanned aerial vehicle photography, outcrop section investigation, thin section identification,and seismic reflections in the southwestern Sichuan Basin. The microbialite lithologic textures in this region include thrombolite, dendrolite, stromatolite, fenestral stromatolite, spongiostromata stone,oncolite, aggregated grainstone, and botryoidal grapestone. Based on the comprehensive analysis of“depositional fabrics-lithology-microfacies”, an association between a fore mound, mound framework,and back mound subfacies has been proposed based on water depth, current direction, energy level and lithologic assemblages. The microfacies of the mound base, mound core, mound flank, mound cap, and mound flat could be recognized among the mound framework subfacies. Two construction types of marginal microbial mound-bank complex have been determined based on deposition location, mound scale, migration direction, and sedimentary facies association. Type Jinkouhe microbial mound constructions(TJMMCs) develop along the windward margin owing to their proximity to the seaward subfacies fore mound, with a northeastwardly migrated microbial mound on top of the mud mound,exhibiting the characteristics of large-sized mounds and small-sized banks in the surrounding area. Type E'bian microbial mound constructions(TEMMCs) primarily occur on the leeward margin, resulting from the presence of onshore back mound subfacies, with the smaller southwestward migrated microbial mounds existing on a thicker microbial flat. The platform margin microbial mound depositional model can be correlated with certain lateral comparison profile and seismic reflection structures in the 2D seismic section, which can provide references for future worldwide exploration. Microbial mounds with larger buildups and thicker vertical reservoirs are typically targeted on the windward margin, while small-sized microbial mounds and flats with better lateral connections are typically focused on the leeward margin.展开更多
The types,occurrence and composition of authigenic clay minerals in argillaceous limestone of sepiolite-bearing strata of the first member of the Middle Permian Maokou Formation(Mao-1 Member)in eastern Sichuan Basin w...The types,occurrence and composition of authigenic clay minerals in argillaceous limestone of sepiolite-bearing strata of the first member of the Middle Permian Maokou Formation(Mao-1 Member)in eastern Sichuan Basin were investigated through outcrop section measurement,core observation,thin section identification,argon ion polishing,X-ray diffraction,scanning electron microscope,energy spectrum analysis and laser ablation-inductively coupled plasma-mass spectrometry.The diagenetic evolution sequence of clay minerals was clarified,and the sedimentary-diagenetic evolution model of clay minerals was established.The results show that authigenic sepiolite minerals were precipitated in the Si4+and Mg2+-rich cool aragonite sea and sepiolite-bearing strata were formed in the Mao-1 Member.During burial diagenesis,authigenic clay minerals undergo two possible evolution sequences.First,from the early diagenetic stage A to the middle diagenetic stage A1,the sepiolite kept stable in the shallow-buried environment lack of Al3+.It began to transform into stevensite in the middle diagenetic stage A2,and then evolved into disordered talc in the middle diagenetic stage B1and finally into talc in the period from the middle diagenetic stage B2to the late diagenetic stage.Thus,the primary diagenetic evolution sequence of authigenic clay minerals,i.e.sepiolite-stevensite-disordered talc-talc,was formed in the Mao-1 Member.Second,in the early diagenetic stage A,as Al3+carried by the storm and upwelling currents was involved in the diagenetic process,trace of sepiolite started to evolve into smectite,and a part of smectite turned into chlorite.From the early diagenetic stage B to the middle diagenesis stage A1,a part of smectite evolved to illite/smectite mixed layer(I/S).The I/S evolved initially into illite from the middle diagenesis stage A2to the middle diagenesis stage B2,and then totally into illite in the late diagenesis stage.Thus,the secondary diagenetic evolution sequence of authigenic clay minerals,i.e.sepiolite-smectite-chlorite/illite,was formed in the Mao-1 Member.The types and evolution of authigenic clay minerals in argillaceous limestone of sepiolite-bearing strata are significant for petroleum geology in two aspects.First,sepiolite can adsorb and accumulate a large amount of organic matters,thereby effectively improving the quality and hydrocarbon generation potential of the source rocks of the Mao-1 Member.Second,the evolution from sepiolite to talc is accompanied by the formation of numerous organic matter pores and clay shrinkage pores/fractures,as well as the releasing of the Mg2+-rich diagenetic fluid,which allows for the dolomitization of limestone within or around the sag.As a result,the new assemblages of self-generation and self-accumulation,and lower/side source and upper/lateral reservoir,are created in the Middle Permian,enhancing the hydrocarbon accumulation efficiency.展开更多
Bladder cancer is a urological tumor with high rates of recurrence despite recent advances in novel therapies.Many proteins involved in the molecular mechanisms are currently an enigma,especially the transmembrane 9 s...Bladder cancer is a urological tumor with high rates of recurrence despite recent advances in novel therapies.Many proteins involved in the molecular mechanisms are currently an enigma,especially the transmembrane 9 superfamily member 1 which has an unclear function.Wei et al published the function and mechanism of this protein,and showed that it could participate in the proliferation,migration and invasion of tumor cells in bladder cancer,therefore treatments directed against this protein may be beneficial in avoiding this condition.展开更多
In this editorial we comment on the article by Wei et al,published in the recent issue of the World Journal of Clinical Oncology.The authors investigated the role of Transmembrane 9 superfamily member 1(TM9SF1)protein...In this editorial we comment on the article by Wei et al,published in the recent issue of the World Journal of Clinical Oncology.The authors investigated the role of Transmembrane 9 superfamily member 1(TM9SF1)protein in bladder cancer(BC)carcinogenesis.Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines.These cell lines were then subject to cell counting kit 8,wound-healing assay,transwell assay,and flow cytometry.Proliferation,migration,and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression.TM9SF1 silencing inhibited proliferation,migration and invasion of BC cells.The authors conclude that TM9SF1 may be an oncogene in bladder cancer pathogenesis.展开更多
Objective: To investigate the associated collateral stigma of the family members of schizophrenia patients and analyze its current status and influencing factors. Methods: The Link Depreciation-Discrimination Percepti...Objective: To investigate the associated collateral stigma of the family members of schizophrenia patients and analyze its current status and influencing factors. Methods: The Link Depreciation-Discrimination Perception Scale was used to investigate the status quo of the associated stigma of the family members of 169 schizophrenia patients diagnosed in 4 hospitals in a certain province. The results of the investigation were analyzed and summarized. Results: The detection rate of stigma associated with the family members of schizophrenia patients was 72.78%, with a score of 28.41 ± 3.92 points. The main influencing factors were the family member’s education level, the patient’s illness duration, the family member’s occupation, and the family-patient relationship. Conclusion: The detection rate of stigma associated with schizophrenia was relatively high. This requires increased attention and appropriate nursing intervention.展开更多
Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways...Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.展开更多
Tubular members subject to combined pitting corrosion and crack damage were numerically studied to clarify the reduction of ultimate strength and failure behavior,based on numerical models validated against available ...Tubular members subject to combined pitting corrosion and crack damage were numerically studied to clarify the reduction of ultimate strength and failure behavior,based on numerical models validated against available experi-ments.The effects of length,location and inclined angle of a crack under combined damage were studied to disclose the mechanism of interaction between the crack and corrosion pits.The methods,named as linear superposition directly accumulating the effects of solo crack and solo pitting damage,as well as crack projection transferring an inclined crack to a transverse one,were discussed and verified in the view of assessing ultimate strength of tubular members with combined damage.It was shown that the former is practical but complex while the next always over-estimates the residual strength.Besides,the location and inclined angle of a crack have a subtle effect on the reduction of ultimate strength under combined damage,especially at higher level of pitting damage,due to the synergistic effect between corrosion pits and cracks.Such effect can lead to early occurrence of plasticity and local buckling by inducing stress interaction between crack tips and pits,and causing more significant strength reduction compared with a solo type of damage.A practical method was proposed to determine the loss ratio of cross-sectional area on the equivalent weakest section of a damaged member.Based on the loss ratio,a formula was presented to predict the ultimate strength of damaged members with combined damage,showing good applicability.展开更多
To explore the genesis of the laminated calcite veins developed in the black shale of Chang 73 submember of the Ordos Basin,the petrology,microstructure and geochemistry of calcite veins are studied using thin section...To explore the genesis of the laminated calcite veins developed in the black shale of Chang 73 submember of the Ordos Basin,the petrology,microstructure and geochemistry of calcite veins are studied using thin sections,fluid inclusions,trace elements and isotopic geochemistry.The source,the time of formation,the mechanism of formation,and the dynamic background of the veins are discussed.The veins are mostly made up of calcite,mixed with lenticular or spindle-shape solid wall rock inclusions.Three structures are identified in the calcite minerals:fibrous,rhombic cleavage,and wedge-like structure.Trace elements and isotopes of carbon and oxygen confirm that the calcite veins were formed from a high density hydrothermal fluid.It is assumed that calcite veins formed prior to wall rock consolidation during the formation of the Qinling Orogenic Belt in the Middle and Late Triassic.The results show that the sedimentary sources of Chang 73 submember were influenced by hydrothermal materials besides terrigenous detritus.The fibrous calcite is different from the fibrous calcite reported in the morphology and mechanism of formation.In this way,the research complements and improves the morphology and the mechanism of formation of fibrous calcite.展开更多
According to the theory of sequence stratigraphy based on continental transgressive-regressive(T-R)cycles,a 500 m continuous core taken from the second member of Kongdian Formation(Kong 2 Member)of Paleogene in Well G...According to the theory of sequence stratigraphy based on continental transgressive-regressive(T-R)cycles,a 500 m continuous core taken from the second member of Kongdian Formation(Kong 2 Member)of Paleogene in Well G108-8 in the Cangdong Sag,Bohai Bay Basin,was tested and analyzed to clarify the high-frequency cycles of deep-water fine-grained sedimentary rocks in lacustrine basins.A logging vectorgraph in red pattern was plotted,and then a sequence stratigraphic framework with five-order high-frequency cycles was formed for the fine-grained sedimentary rocks in the Kong 2 Member.The high-frequency cycles of fine-grained sedimentary rocks were characterized by using different methods and at different scales.It is found that the fifth-order T cycles record a high content of terrigenous clastic minerals,a low paleosalinity,a relatively humid paleoclimate and a high density of laminae,while the fifth-order R cycles display a high content of carbonate minerals,a high paleosalinity,a dry paleoclimate and a low density of laminae.The changes in high-frequency cycles controlled the abundance and type of organic matter.The T cycles exhibit relatively high TOC and abundant endogenous organic matters in water in addition to terrigenous organic matters,implying a high primary productivity of lake for the generation and enrichment of shale oil.展开更多
基金National Yang Ming Chiao Tung University Far Eastern Memorial Hospital Joint Research Programs(NYCU-FEMH 109DN03,110DN06,111DN04,112DN05).
文摘Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.
基金Supported by the National Natural Science Foundation of China(42202176)CNPC-Southwest University of Petroleum Innovation Consortium Cooperation Project(2020CX050103).
文摘To clarify the formation and distribution of feldspar dissolution pores and predict the distribution of high-quality reservoir in gravity flow sandstone of the 7^(th) member of Triassic Yanchang Formation(Chang 7 Member)in the Ordos Basin,thin sections,scanning electron microscopy,energy spectrum analysis,X-ray diffraction whole rock analysis,and dissolution experiments are employed in this study to investigate the characteristics and control factors of feldspar dissolution pores.The results show that:(1)Three types of diagenetic processes are observed in the feldspar of Chang 7 sandstone in the study area:secondary overgrowth of feldspar,replacement by clay and calcite,and dissolution of detrital feldspar.(2)The feldspar dissolution of Chang 7 tight sandstone is caused by organic acid,and is further affected by the type of feldspar,the degree of early feldspar alteration,and the buffering effect of mica debris on organic acid.(3)Feldspars have varying degrees of dissolution.Potassium feldspar is more susceptible to dissolution than plagioclase.Among potassium feldspar,orthoclase is more soluble than microcline,and unaltered feldspar is more soluble than early kaolinized or sericitized feldspar.(4)The dissolution experiment demonstrated that the presence of mica can hinder the dissolution of feldspar.Mica of the same mass has a significantly stronger capacity to consume organic acids than feldspar.(5)Dissolution pores in feldspar of Chang 7 Member are more abundant in areas with low mica content,and they improve the reservoir physical properties,while in areas with high mica content,the number of feldspar dissolution pores decreases significantly.
文摘BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.
基金Supported by 2020 Guangxi Zhuang Autonomous Region Health Care Commission Self-Financing Research Projects,No.Z202000962023 Guangxi University Young and Middle-Aged Teachers’Basic Research Ability Improvement Project,No.2023KY0091+1 种基金National Natural Science Foundation of China,No.82260241the Natural Science Foundation of Guangxi Province,No.2015GXNSFAA139171 and No.2020GXNSFAA259053.
文摘BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.
基金This work was supported by the Natural Science Foundation of Guangdong Province(Grant No.2019A1515011354).
文摘Genome sequencing has revealed frequent mutations in Ras homolog family member A(RHOA)among various cancers with unique aberrant profiles and pathogenic effects,especially in peripheral T-cell lymphoma(PTCL).The discrete positional distribution and types of RHOA amino acid substitutions vary according to the tumor type,thereby leading to different functional and biological properties,which provide new insight into the molecular pathogenesis and potential targeted therapies for various tumors.However,the similarities and discrepancies in characteristics of RHOA mutations among various histologic subtypes of PTCL have not been fully elucidated.Herein we highlight the inconsistencies and complexities of the type and location of RHOA mutations and demonstrate the contribution of RHOA variants to the pathogenesis of PTCL by combining epigenetic abnormalities and activating multiple downstream pathways.The promising potential of targeting RHOA as a therapeutic modality is also outlined.This review provides new insight in the field of personalized medicine to improve the clinical outcomes for patients.
文摘BACKGROUND Hospice care plays an important role in improving the quality of life of advanced cancer patients,but controversy remains over whether age affects the attitudes of family members toward hospice care.AIM To investigate the attitudes of family members of advanced cancer patients of different ages toward hospice care.METHODS The study participants were 175 family members of patients with advanced cancer from January 2020 and October 2022.The participants were divided into youth(<40 years,n=65),middle-aged(40–60 years,n=59),and elderly(>60 years,n=51)groups.Researchers investigated and compared the degree of awareness regarding hospice care,attitudes,and whether the family members of patients would choose hospice care.RESULTS Among the family members of 175 patients,approximately 28%(49/175)were aware of hospice care.Awareness of hospice care,the proportion of hospice care acceptance and adaptation attitudes,and the proportion of those who chose hospice care in the youth group were higher in the middle-aged and elderly groups(P<0.05).No statistically significant difference was found in these three indicators between the middle-aged and elderly groups(P>0.05).Hospice care was chosen mainly to relieve pain and reduce unnecessary treatment,whereas the reasons for not choosing hospice care were mainly distrust and ethical concerns.CONCLUSION The family members of patients with advanced cancer had relatively low awareness of hospice care,while youth had a higher awareness of hospice care,acceptance,and adaptation attitudes,and were more willing to choose hospice care.
基金jointly funded by projects supported by the National Natural Science Foundation of China(Grant No.41872150)the Joint Funds of the National Natural Science Foundation of China(Grant No.U19B6003)Major Scientific and Technological Projects of CNPC during the 13th five-year plan(No.2019A-02-10)。
文摘Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China,where the depositional process is regarded confusing. The microfacies, construction types, and depositional model of the Member Deng-2 marginal microbial mound-bank complex have been investigated using unmanned aerial vehicle photography, outcrop section investigation, thin section identification,and seismic reflections in the southwestern Sichuan Basin. The microbialite lithologic textures in this region include thrombolite, dendrolite, stromatolite, fenestral stromatolite, spongiostromata stone,oncolite, aggregated grainstone, and botryoidal grapestone. Based on the comprehensive analysis of“depositional fabrics-lithology-microfacies”, an association between a fore mound, mound framework,and back mound subfacies has been proposed based on water depth, current direction, energy level and lithologic assemblages. The microfacies of the mound base, mound core, mound flank, mound cap, and mound flat could be recognized among the mound framework subfacies. Two construction types of marginal microbial mound-bank complex have been determined based on deposition location, mound scale, migration direction, and sedimentary facies association. Type Jinkouhe microbial mound constructions(TJMMCs) develop along the windward margin owing to their proximity to the seaward subfacies fore mound, with a northeastwardly migrated microbial mound on top of the mud mound,exhibiting the characteristics of large-sized mounds and small-sized banks in the surrounding area. Type E'bian microbial mound constructions(TEMMCs) primarily occur on the leeward margin, resulting from the presence of onshore back mound subfacies, with the smaller southwestward migrated microbial mounds existing on a thicker microbial flat. The platform margin microbial mound depositional model can be correlated with certain lateral comparison profile and seismic reflection structures in the 2D seismic section, which can provide references for future worldwide exploration. Microbial mounds with larger buildups and thicker vertical reservoirs are typically targeted on the windward margin, while small-sized microbial mounds and flats with better lateral connections are typically focused on the leeward margin.
基金Supported by the Enterprise Innovation and Development Joint Fund of National Natural Science Foundation of China(U19B6003)National Natural Science Foundation of China(41872150)。
文摘The types,occurrence and composition of authigenic clay minerals in argillaceous limestone of sepiolite-bearing strata of the first member of the Middle Permian Maokou Formation(Mao-1 Member)in eastern Sichuan Basin were investigated through outcrop section measurement,core observation,thin section identification,argon ion polishing,X-ray diffraction,scanning electron microscope,energy spectrum analysis and laser ablation-inductively coupled plasma-mass spectrometry.The diagenetic evolution sequence of clay minerals was clarified,and the sedimentary-diagenetic evolution model of clay minerals was established.The results show that authigenic sepiolite minerals were precipitated in the Si4+and Mg2+-rich cool aragonite sea and sepiolite-bearing strata were formed in the Mao-1 Member.During burial diagenesis,authigenic clay minerals undergo two possible evolution sequences.First,from the early diagenetic stage A to the middle diagenetic stage A1,the sepiolite kept stable in the shallow-buried environment lack of Al3+.It began to transform into stevensite in the middle diagenetic stage A2,and then evolved into disordered talc in the middle diagenetic stage B1and finally into talc in the period from the middle diagenetic stage B2to the late diagenetic stage.Thus,the primary diagenetic evolution sequence of authigenic clay minerals,i.e.sepiolite-stevensite-disordered talc-talc,was formed in the Mao-1 Member.Second,in the early diagenetic stage A,as Al3+carried by the storm and upwelling currents was involved in the diagenetic process,trace of sepiolite started to evolve into smectite,and a part of smectite turned into chlorite.From the early diagenetic stage B to the middle diagenesis stage A1,a part of smectite evolved to illite/smectite mixed layer(I/S).The I/S evolved initially into illite from the middle diagenesis stage A2to the middle diagenesis stage B2,and then totally into illite in the late diagenesis stage.Thus,the secondary diagenetic evolution sequence of authigenic clay minerals,i.e.sepiolite-smectite-chlorite/illite,was formed in the Mao-1 Member.The types and evolution of authigenic clay minerals in argillaceous limestone of sepiolite-bearing strata are significant for petroleum geology in two aspects.First,sepiolite can adsorb and accumulate a large amount of organic matters,thereby effectively improving the quality and hydrocarbon generation potential of the source rocks of the Mao-1 Member.Second,the evolution from sepiolite to talc is accompanied by the formation of numerous organic matter pores and clay shrinkage pores/fractures,as well as the releasing of the Mg2+-rich diagenetic fluid,which allows for the dolomitization of limestone within or around the sag.As a result,the new assemblages of self-generation and self-accumulation,and lower/side source and upper/lateral reservoir,are created in the Middle Permian,enhancing the hydrocarbon accumulation efficiency.
文摘Bladder cancer is a urological tumor with high rates of recurrence despite recent advances in novel therapies.Many proteins involved in the molecular mechanisms are currently an enigma,especially the transmembrane 9 superfamily member 1 which has an unclear function.Wei et al published the function and mechanism of this protein,and showed that it could participate in the proliferation,migration and invasion of tumor cells in bladder cancer,therefore treatments directed against this protein may be beneficial in avoiding this condition.
文摘In this editorial we comment on the article by Wei et al,published in the recent issue of the World Journal of Clinical Oncology.The authors investigated the role of Transmembrane 9 superfamily member 1(TM9SF1)protein in bladder cancer(BC)carcinogenesis.Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines.These cell lines were then subject to cell counting kit 8,wound-healing assay,transwell assay,and flow cytometry.Proliferation,migration,and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression.TM9SF1 silencing inhibited proliferation,migration and invasion of BC cells.The authors conclude that TM9SF1 may be an oncogene in bladder cancer pathogenesis.
文摘Objective: To investigate the associated collateral stigma of the family members of schizophrenia patients and analyze its current status and influencing factors. Methods: The Link Depreciation-Discrimination Perception Scale was used to investigate the status quo of the associated stigma of the family members of 169 schizophrenia patients diagnosed in 4 hospitals in a certain province. The results of the investigation were analyzed and summarized. Results: The detection rate of stigma associated with the family members of schizophrenia patients was 72.78%, with a score of 28.41 ± 3.92 points. The main influencing factors were the family member’s education level, the patient’s illness duration, the family member’s occupation, and the family-patient relationship. Conclusion: The detection rate of stigma associated with schizophrenia was relatively high. This requires increased attention and appropriate nursing intervention.
基金supported by the German Research Council(Deutsche Forschungsgemeinschaft,HA3309/3-1/2,HA3309/6-1,HA3309/7-1)。
文摘Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.
基金supported by the National Natural Science Foundation of China(Grant No.51879124)。
文摘Tubular members subject to combined pitting corrosion and crack damage were numerically studied to clarify the reduction of ultimate strength and failure behavior,based on numerical models validated against available experi-ments.The effects of length,location and inclined angle of a crack under combined damage were studied to disclose the mechanism of interaction between the crack and corrosion pits.The methods,named as linear superposition directly accumulating the effects of solo crack and solo pitting damage,as well as crack projection transferring an inclined crack to a transverse one,were discussed and verified in the view of assessing ultimate strength of tubular members with combined damage.It was shown that the former is practical but complex while the next always over-estimates the residual strength.Besides,the location and inclined angle of a crack have a subtle effect on the reduction of ultimate strength under combined damage,especially at higher level of pitting damage,due to the synergistic effect between corrosion pits and cracks.Such effect can lead to early occurrence of plasticity and local buckling by inducing stress interaction between crack tips and pits,and causing more significant strength reduction compared with a solo type of damage.A practical method was proposed to determine the loss ratio of cross-sectional area on the equivalent weakest section of a damaged member.Based on the loss ratio,a formula was presented to predict the ultimate strength of damaged members with combined damage,showing good applicability.
文摘To explore the genesis of the laminated calcite veins developed in the black shale of Chang 73 submember of the Ordos Basin,the petrology,microstructure and geochemistry of calcite veins are studied using thin sections,fluid inclusions,trace elements and isotopic geochemistry.The source,the time of formation,the mechanism of formation,and the dynamic background of the veins are discussed.The veins are mostly made up of calcite,mixed with lenticular or spindle-shape solid wall rock inclusions.Three structures are identified in the calcite minerals:fibrous,rhombic cleavage,and wedge-like structure.Trace elements and isotopes of carbon and oxygen confirm that the calcite veins were formed from a high density hydrothermal fluid.It is assumed that calcite veins formed prior to wall rock consolidation during the formation of the Qinling Orogenic Belt in the Middle and Late Triassic.The results show that the sedimentary sources of Chang 73 submember were influenced by hydrothermal materials besides terrigenous detritus.The fibrous calcite is different from the fibrous calcite reported in the morphology and mechanism of formation.In this way,the research complements and improves the morphology and the mechanism of formation of fibrous calcite.
基金Supported by the National Major Research and Development Project(2020YFA0710504,2022YFF0801204)PetroChina Science and Technology Major Project(2019E-26)。
文摘According to the theory of sequence stratigraphy based on continental transgressive-regressive(T-R)cycles,a 500 m continuous core taken from the second member of Kongdian Formation(Kong 2 Member)of Paleogene in Well G108-8 in the Cangdong Sag,Bohai Bay Basin,was tested and analyzed to clarify the high-frequency cycles of deep-water fine-grained sedimentary rocks in lacustrine basins.A logging vectorgraph in red pattern was plotted,and then a sequence stratigraphic framework with five-order high-frequency cycles was formed for the fine-grained sedimentary rocks in the Kong 2 Member.The high-frequency cycles of fine-grained sedimentary rocks were characterized by using different methods and at different scales.It is found that the fifth-order T cycles record a high content of terrigenous clastic minerals,a low paleosalinity,a relatively humid paleoclimate and a high density of laminae,while the fifth-order R cycles display a high content of carbonate minerals,a high paleosalinity,a dry paleoclimate and a low density of laminae.The changes in high-frequency cycles controlled the abundance and type of organic matter.The T cycles exhibit relatively high TOC and abundant endogenous organic matters in water in addition to terrigenous organic matters,implying a high primary productivity of lake for the generation and enrichment of shale oil.