Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer(GC)/gastroesophageal junction cancer(GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy(LTG) fo...Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer(GC)/gastroesophageal junction cancer(GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy(LTG) for GC/GEJC patients who have received preoperative therapy(PT) has come to the fore. This study aims to analyze the safety and feasibility of LTG after PT for GC/GEJC patients.Methods: We retrospectively analyzed the data of 511 patients with GC/GEJC undergoing LTG, of which 405received LTG(LTG group) and 106 received PT+LTG(PT-LTG group) at Nanfang Hospital between June 2018and September 2022. The surgical outcomes were compared between the two groups.Results: The surgical duration was significantly longer in the PT-LTG group(P<0.001), while the incidence of intraoperative complications(P=1.000), postoperative complications(LTG group vs. PT-LTG group: 26.2% vs.23.6%, P=0.587), the classification of complication severity(P=0.271), and postoperative recovery was similar between two groups. Notably, the incidence of anastomotic complications of esophagojejunostomy was also comparable between the two groups(LTG group vs. PT-LTG group: 5.9% vs. 5.7%, P=0.918). The univariate and multivariate analysis confirmed that positive proximal margin [positive vs. negative: odds ratio(OR)=14.094, 95%confidence interval(95% CI): 2.639-75.260, P=0.002], rather than PT, has an impact on anastomotic complications after LTG(OR=0.945, 95% CI: 0.371-2.408, P=0.905).Conclusions: PT did not increase the surgical risk of LTG for GC/GEJC. Therefore, considering the positive effect of PT on long-term survival, the broader application of PT and LTG for GC/GEJC is supported by our findings.展开更多
The concept of community is of great significance in guiding the innovation of the mechanism of industry-education integration,which can promote the integration of industry-education integration from"integration&...The concept of community is of great significance in guiding the innovation of the mechanism of industry-education integration,which can promote the integration of industry-education integration from"integration"to real"integration".We summarize the current situation of the development of industry-teaching integration mode through research,point out the"four deviations"in the development of industry-teaching integration,analyze the causes of deviations,and put forward the research strategy of"four synergistic"innovation mechanism for industry-teaching integration based on the concept of community,i.e.,synergistic development of community planning It proposes the research strategy of"four synergies"innovation mechanism based on the concept of community,namely the synergy of community planning and development,the synergy of community governance concept,the synergy of community multi-party educating mechanism,and the synergy of community fusion effect system,so as to establish collaborative ties,build a new form of cooperation concepts,safeguard the docking of talent supply and demand,and enhance the effect of integration of industry and education.展开更多
Akebia trifoliata subsp.australis is a well-known medicinal and potential woody oil plant in China.The limited genetic information available for A.trifoliata subsp.australis has hindered its exploitation.Here,a high-q...Akebia trifoliata subsp.australis is a well-known medicinal and potential woody oil plant in China.The limited genetic information available for A.trifoliata subsp.australis has hindered its exploitation.Here,a high-quality chromosomelevel genome sequence of A.trifoliata subsp.australis is reported.The de novo genome assembly of 682.14 Mb was generated with a scaffold N50 of 43.11 Mb.The genome includes 25,598 protein-coding genes,and 71.18%(485.55 Mb)of the assembled sequences were identi fi ed as repetitive sequences.An ongoing massive burst of long terminal repeat(LTR)insertions,which occurred~1.0 million years ago,has contributed a large proportion of LTRs in the genome of A.trifoliata subsp.australis.Phylogenetic analysis shows that A.trifoliata subsp.australis is closely related to Aquilegia coerulea and forms a clade with Papaver somniferum and Nelumbo nucifera,which supports the well-established hypothesis of a close relationship between basal eudicot species.The expansion of UDP-glucoronosyl and UDP-glucosyl transferase gene families and fi-amyrin synthase-like genes and the exclusive contraction of terpene synthase gene families may be responsible for the abundant oleanane-type triterpenoids in A.trifoliata subsp.australis.Furthermore,the acyl-ACP desaturase gene family,including 12 stearoyl-acyl-carrier protein desaturase(SAD)genes,has expanded exclusively.A combined transcriptome and fatty-acid analysis of seeds at fi ve developmental stages revealed that homologs of SADs,acyl-lipid desaturase omega fatty acid desaturases(FADs),and oleosins were highly expressed,consistent with the rapid increase in the content of fatty acids,especially unsaturated fatty acids.The genomic sequences of A.trifoliata subsp.australis will be a valuable resource for comparative genomic analyses and molecular breeding.展开更多
Objective: This study aimed to determine the impact of type 2 diabetes mellitus(T2 DM) on clinical outcomes of gastric cancer(GC) patients and explore whether metformin use and good glycemic control could reverse it.M...Objective: This study aimed to determine the impact of type 2 diabetes mellitus(T2 DM) on clinical outcomes of gastric cancer(GC) patients and explore whether metformin use and good glycemic control could reverse it.Methods: Clinicopathologic data of consecutive GC patients who underwent gastrectomy at Nanfang Hospital between October 2004 and December 2015 were included. Propensity score matching(PSM) was performed to balance the important factors of the disease status between non-T2 DM and T2 DM group. The last follow-up time was January 2019.Results: A total of 1,692 eligible patients(1,621 non-T2 DM vs. 71 T2 DM) were included. After PSM, nonT2 DM group(n=139) and T2 DM group(n=71) were more balanced in baseline variables. The 5-year cancerspecific survival(CSS) rate in T2 DM group(47.0%) was inferior to that in non-T2 DM group(58.0%), but did not reach statistical significance [hazard ratio(HR)=1.319, 95% confidence interval(95% CI): 0.868-2.005, P=0.192].While the 5-year progress-free survival(PFS) rate of T2 DM group(40.6%) is significantly worse than that in nonT2 DM group(56.3%)(HR=1.516, 95% CI: 1.004-2.290, P=0.045). Univariate and multivariate analyses showed that T2 DM was an independent risk factor for PFS but not for CSS. In T2 DM group, metformin use subgroup was associated with superior 5-year CSS and PFS in compared with non-metformin use subgroup, although the difference was not statistically significant(5-year CSS: 48.0% vs. 45.4%, HR=0.680, 95% CI: 0.352-1.313,P=0.246;5-year PFS: 43.5% vs. 35.7%, HR=0.763, 95% CI: 0.400-1.454, P=0.406). The 5-year CSS rate was47.5% in good glycemic control subgroup and 44.1% in poor glycemic control subgroup(HR=0.826, 95% CI:0.398-1.713, P=0.605). And both two subgroups yielded a similar 5-year PFS rate(42.2% vs. 36.3%, HR=0.908,95% CI: 0.441-1.871, P=0.792).Conclusions: DM promoted disease progress of GC after gastrectomy but had not yet led to the significant discrepancy of CSS. For GC patients with T2 DM, metformin use was associated with superior survival but without statistical significance, while better glycemic control could not improve the prognosis.展开更多
As the most common internal modification of mRNA,Ne-methyladenosine(m^(6)A)and its regulators modulate gene expression and play critical roles in various biological and patholog-ical processes including tumorigenesis....As the most common internal modification of mRNA,Ne-methyladenosine(m^(6)A)and its regulators modulate gene expression and play critical roles in various biological and patholog-ical processes including tumorigenesis.It was reported previously that m^(6)A methyltransferase(writer),methyltransferase-like 3(METTL3)adds m^(6)A in primary microRNAs(pri-miRNAs)and fa-cilitates its processing into precursor miRNAs(pre-miRNAs).However,it is unknown whether m^(6)A modification also plays a role in the maturation process of pre-miRNAs and(if so)whether such a function contributes to tumorigenesis.Here,we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia(AML)patients,especially in relapsed patients,and plays an onco-genic role in AML.Moreover,YTHDF2 promotes expression of miR-126-3p(also known as miR-126,as it is the main product of precursor miR-126(pre-miR-126)),a miRNA that was reported as an oncomiRNA in AML,through facilitating the processing of pre-miR-126 into mature miR-126.Mechanistically,YTHDF2 recognizes m^(6)A modification in pre-miR-126 and recruits AGO2,a regulator of pre-miRNA processing,to promote the maturation of pre-miR-126.YTHDF2 posi-tively and negatively correlates with miR-126 and miR-126's downstream target genes,respec-tively,in AML patients,and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis,indi-cating that miR-126 is a functionally important target of YTHDF2 in AML.Overall,our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the ther-apeutic potential of targeting this axis for AML treatment,but also suggest that m^(6)A plays a role in pre-miRNA processing that contributes to tumorigenesis.展开更多
As one of the most studied ribonucleic acid(RNA)modifications in eukaryotes,N^(6)-methyladenosine(m^(6)A)has been shown to play a predominant role in controlling gene expression and influence physiological and patholo...As one of the most studied ribonucleic acid(RNA)modifications in eukaryotes,N^(6)-methyladenosine(m^(6)A)has been shown to play a predominant role in controlling gene expression and influence physiological and pathological processes such as oncogenesis and tumor progression.Writer and eraser proteins,acting opposite to deposit and remove m^(6)A epigenetic marks,respectively,shape the cellular m^(6)A landscape,while reader proteins preferentially recognize m^(6)A modifications and mediate fate decision of the methylated RNAs,including RNA synthesis,splicing,exportation,translation,and stability.Therefore,RNA metabolism in cells is greatly influenced by these three classes of m^(6)A regulators.Aberrant expression of m^(6)A regulators has been widely reported in various types of cancer,leading to cancer initiation,progression,and drug resistance.The close links between m^(6)A and cancer shed light on the potential use of m^(6)A methylation and its regulators as prognostic biomarkers and drug targets for cancer therapy.Given the notable effects of m^(6)A in reversing chemoresistance and enhancing immune therapy,it is a promising target for combined therapy.Herein,we summarize the recent discoveries on m^(6)A and its regulators,emphasizing their influences on RNA metabolism,their dysregulation and impacts in diverse malignancies,and discuss the clinical implications of m^(6)A modification in cancer.展开更多
Background: Previous studies have revealed that diabetes mellitus (DM) promotes disease progress of gastric cancer (GC). This study aimed to further investigating whether DM advanced lymph nodes (LNs) metastasis in GC...Background: Previous studies have revealed that diabetes mellitus (DM) promotes disease progress of gastric cancer (GC). This study aimed to further investigating whether DM advanced lymph nodes (LNs) metastasis in GC.Methods: The clinicopathologic data of GC patients with >15 examined LN (ELN) between October 2004 and December 2019 from a prospectively maintained database were included. The observational outcomes included the number (N3b status) and anatomical distribution (N3 stations) of metastatic LN (MLN).Results: A total of 2142 eligible patients were included in the study between October 2004 and December 2019. N3 stations metastasis (26.8% in DMvs. 19.3% in non-DM,P = 0.026) and N3b status (18.8% in DMvs. 12.8% in non-DM,P = 0.039) were more advanced in the DM group, and multivariate logistic regression analyses confirmed that DM was an independent factor of developing N3 stations metastasis (odds ratio [OR] = 1.771,P= 0.011) and N3b status (OR= 1.752,P= 0.028). Also, multivariate analyses determined DM was independently associated with more MLN (β = 1.424,P = 0.047). The preponderance of N3 stations metastasis (DMvs. non-DM, T1-2: 2.2%vs. 4.9%, T3: 29.0%vs. 20.3%, T4a: 38.9%vs. 25.8%, T4b: 50.0%vs. 36.6%;ELN16-29: 8.6%vs. 10.4%, ELN30-44: 27.9%vs. 20.5%, ELN ≥ 45: 37.7%vs. 25.3%), N3b status (DMvs. non-DM, T1-2: 0%vs. 1.7%, T3: 16.1%vs. 5.1%, T4a: 27.8%vs. 19.1%, T4b: 44.0%vs. 28.0%;ELN16-29: 8.6%vs. 7.9%, ELN30-44: 18.0%vs. 11.8%, ELN ≥ 45: 26.4%vs. 17.3%), and the number of MLN (DMvs. non-DM, T1-2: 0.4vs. 1.1, T3: 8.6vs. 5.2, T4a: 9.7vs. 8.6, T4b: 17.0vs. 12.8;ELN16-29: 3.6vs. 4.6, ELN30-44: 5.8vs. 5.5, ELN ≥ 45: 12.0vs. 7.7) of DM group increased with the advancement of primary tumor depth stage and raising of ELN.Conclusions: DM was an independent risk factor for promoting LN metastasis. The preponderance of LN involvement in the DM group was aggravated with the advancement of tumor depth.展开更多
Background:Multiple myeloma(MM)is a hematologic malignancy characterized by the accumulation of aberrant plasma cells within the bone marrow.The high frequent mutation of family with sequence similarity 46,member C(FA...Background:Multiple myeloma(MM)is a hematologic malignancy characterized by the accumulation of aberrant plasma cells within the bone marrow.The high frequent mutation of family with sequence similarity 46,member C(FAM46C)is closely related with the occurrence and progression of MM.Recently,FAM46C has been identified as a non-canonical poly(A)polymerase(PAP)that functions as a tumor suppressor in MM.This study aimed to elucidate the structural features of this novel non-canonical PAP and how MM-related mutations affect the structural and biochemical properties of FAM46C,eventually advancing our understandings towards FAM46C mutation-related MM occurrence.Methods:We purified and crystallized a mammalian FAM46C construct,and solved its structure.Next,we characterized the property of FAM46C as a PAP through a combination of structural analysis,site-directed mutagenesis and biochemical assays,and by comparison with its homolog FAM46B.Finally,we structurally analyzed MM-related FAM46C mutations and tested the enzymatic activity of corresponding mutants.Results:We determined the crystal structure of a mammalian FAM46C protein at 2.35 A,and confirmed that FAM46C preferentially consumed adenosine triphosphate(ATP)and extended A-rich RNA substrates.FAM46C showed a weaker PAP activity than its homolog FAM46B,and this difference was largely dependent on the residue variance at particular sites.Of them,residues at positions 77,290,and 298 of mouse FAM46C weremost important for the divergence in enzymatic activity.Among the MM-associated FAM46C mutants,those residing at the catalytic site(D90G and D90H)or putative RNA-binding site(I155L,S156F,D182Y,F184L,Y247V,andM270V)showed abolished or compromised PAP activity of FAM46C,while N72A and S248A did not severely affect the PAP activity.FAM46C mutants D90G,D90H,I155L,S156F,F184L,Y247V,and M270V had significantly lower inhibitory effect on apoptosis of RPMI-8226 cells as compared to wild-type FAM46C.Conclusions:FAM46C is a prokaryotic-like PAP with preference forA-richRNA substrates,and showed distinct enzymatic efficiency with its homolog FAM46B.The MM-related missense mutations of FAM46C lead to various structural and biochemical outcomes to the protein.展开更多
Beta-glucan has been shown to have a beneficial effect on gastrointestinal health.This experiment was conducted to investigate the effects ofβ-glucan isolated from Agrobacterium sp.ZX09 on growth performance and inte...Beta-glucan has been shown to have a beneficial effect on gastrointestinal health.This experiment was conducted to investigate the effects ofβ-glucan isolated from Agrobacterium sp.ZX09 on growth performance and intestinal health of weaning pigs.A total of 108 weaned pigs(21 d of age;6.05±0.36 kg)were randomly divided into 3 groups(6 pens/group;6 pigs/pen),and the groups were each treated with the following diets:1)basal diet,2)basal diet supplemented with 20 mg/kg olaquindox,3)basal diet supplemented with 200 mg/kgβ-glucan,for 21 d.Compared with the control group,pigs fed with200 mg/kgβ-glucan had greaterBW,average daily gain and duodenal villus height to crypt depth ratio(P<0.05).Olaquindox increased the duodenal or jejunal villus height of pigs compared withβ-glucan.Compared with the control group,β-glucan tended to increase the occludin mRNA expression in the jejunum(0.05<P<0.10).Beta-glucan enriched the beneficial microbiota in the ileum of pigs(P<0.05).In conclusion,β-glucan may promote growth performance by improving intestinal health and increasing beneficial microbiota of weaned pigs.The study results will provide valuable theoretical guidance for the utilization ofβ-glucan in weaned pigs.展开更多
Due to space limitation,mutual coupling occurs almost invisibly in array antennas.In this paper,the mutual coupling effects on the two most popular categories of array antennas,i.e.,phased arrays and multiple-input mu...Due to space limitation,mutual coupling occurs almost invisibly in array antennas.In this paper,the mutual coupling effects on the two most popular categories of array antennas,i.e.,phased arrays and multiple-input multiple-output(MIMO)antennas,are reviewed.Some misconceptions regarding the mutual coupling effects are uncovered.It is shown that the steering pattern of a phased array at an arbitrary scan-ning angle can be readily calculated once the embedded radiation patterns of the array elements(including the mutual coupling effect)are obtained.As antenna spacing decreases,absorption loss increases,yet the phase terms tend to add up constructively as antenna spacing reduces,which may overcompensate the absorption loss due to mutual coupling.Thus,the array efficiency may be increased by reducing the antenna spacing.A patch antenna array is used to illustrate this phenomenon.It is further shown that while mutual coupling tends to reduce the correlation of two-element arrays,it has a negligible effect on the overall correlations of larger arrays.Finally,various mutual coupling reduction techniques are briefly presented.Two feasible techniques for large planar arrays are used to illustrate the benefits of array decoupling.展开更多
基金supported by grants from the Clinical Research Program of Nanfang Hospital, Southern Medical University (No.2021CR001 and No.2021CR013)Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer (No.2020B 121201004)“Climbing Program”, Special Fund of Guangdong Province (No.pdjh2022a0093 and No.pdjh2023a0098)。
文摘Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer(GC)/gastroesophageal junction cancer(GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy(LTG) for GC/GEJC patients who have received preoperative therapy(PT) has come to the fore. This study aims to analyze the safety and feasibility of LTG after PT for GC/GEJC patients.Methods: We retrospectively analyzed the data of 511 patients with GC/GEJC undergoing LTG, of which 405received LTG(LTG group) and 106 received PT+LTG(PT-LTG group) at Nanfang Hospital between June 2018and September 2022. The surgical outcomes were compared between the two groups.Results: The surgical duration was significantly longer in the PT-LTG group(P<0.001), while the incidence of intraoperative complications(P=1.000), postoperative complications(LTG group vs. PT-LTG group: 26.2% vs.23.6%, P=0.587), the classification of complication severity(P=0.271), and postoperative recovery was similar between two groups. Notably, the incidence of anastomotic complications of esophagojejunostomy was also comparable between the two groups(LTG group vs. PT-LTG group: 5.9% vs. 5.7%, P=0.918). The univariate and multivariate analysis confirmed that positive proximal margin [positive vs. negative: odds ratio(OR)=14.094, 95%confidence interval(95% CI): 2.639-75.260, P=0.002], rather than PT, has an impact on anastomotic complications after LTG(OR=0.945, 95% CI: 0.371-2.408, P=0.905).Conclusions: PT did not increase the surgical risk of LTG for GC/GEJC. Therefore, considering the positive effect of PT on long-term survival, the broader application of PT and LTG for GC/GEJC is supported by our findings.
基金this paper is supposed by National Natural Science Foundation of China(12074289)Zhejiang Provincial Natural Science Foundation of China(Y23A040004)+2 种基金Teaching Reform Project of Zhejiang Province(jg20220509)Scientific Research Project of Zhejiang Graduate Education Association(2023-016)The 14th Five-year Teaching Reform Project of Zhejiang Province(jg20220522)。
文摘The concept of community is of great significance in guiding the innovation of the mechanism of industry-education integration,which can promote the integration of industry-education integration from"integration"to real"integration".We summarize the current situation of the development of industry-teaching integration mode through research,point out the"four deviations"in the development of industry-teaching integration,analyze the causes of deviations,and put forward the research strategy of"four synergistic"innovation mechanism for industry-teaching integration based on the concept of community,i.e.,synergistic development of community planning It proposes the research strategy of"four synergies"innovation mechanism based on the concept of community,namely the synergy of community planning and development,the synergy of community governance concept,the synergy of community multi-party educating mechanism,and the synergy of community fusion effect system,so as to establish collaborative ties,build a new form of cooperation concepts,safeguard the docking of talent supply and demand,and enhance the effect of integration of industry and education.
基金the Natural Science Foundation of Hunan Province(2019JJ50475)Key Scientific Research Projects of Hunan Education Department(18A448)Foundation of Hunan Double First-rate Discipline Construction Pr ojects of Bioengineering and Key Lab oratory of Resea rch and Utilizati on of Ethnomedicinal Plant Resources of Hunan Province,and the National Science Foundation(81874334).
文摘Akebia trifoliata subsp.australis is a well-known medicinal and potential woody oil plant in China.The limited genetic information available for A.trifoliata subsp.australis has hindered its exploitation.Here,a high-quality chromosomelevel genome sequence of A.trifoliata subsp.australis is reported.The de novo genome assembly of 682.14 Mb was generated with a scaffold N50 of 43.11 Mb.The genome includes 25,598 protein-coding genes,and 71.18%(485.55 Mb)of the assembled sequences were identi fi ed as repetitive sequences.An ongoing massive burst of long terminal repeat(LTR)insertions,which occurred~1.0 million years ago,has contributed a large proportion of LTRs in the genome of A.trifoliata subsp.australis.Phylogenetic analysis shows that A.trifoliata subsp.australis is closely related to Aquilegia coerulea and forms a clade with Papaver somniferum and Nelumbo nucifera,which supports the well-established hypothesis of a close relationship between basal eudicot species.The expansion of UDP-glucoronosyl and UDP-glucosyl transferase gene families and fi-amyrin synthase-like genes and the exclusive contraction of terpene synthase gene families may be responsible for the abundant oleanane-type triterpenoids in A.trifoliata subsp.australis.Furthermore,the acyl-ACP desaturase gene family,including 12 stearoyl-acyl-carrier protein desaturase(SAD)genes,has expanded exclusively.A combined transcriptome and fatty-acid analysis of seeds at fi ve developmental stages revealed that homologs of SADs,acyl-lipid desaturase omega fatty acid desaturases(FADs),and oleosins were highly expressed,consistent with the rapid increase in the content of fatty acids,especially unsaturated fatty acids.The genomic sequences of A.trifoliata subsp.australis will be a valuable resource for comparative genomic analyses and molecular breeding.
基金supported by the National Natural Science Foundation of China (No.81872013)Clinical Research Program of Nanfang Hospital, Southern Medical University (No.2018CR017)+1 种基金National Key Clinical Specialty Discipline Construction Program of China (No.[2012]121)Science and Technology Planning Project of Guangdong Province (No.2017B020226005)。
文摘Objective: This study aimed to determine the impact of type 2 diabetes mellitus(T2 DM) on clinical outcomes of gastric cancer(GC) patients and explore whether metformin use and good glycemic control could reverse it.Methods: Clinicopathologic data of consecutive GC patients who underwent gastrectomy at Nanfang Hospital between October 2004 and December 2015 were included. Propensity score matching(PSM) was performed to balance the important factors of the disease status between non-T2 DM and T2 DM group. The last follow-up time was January 2019.Results: A total of 1,692 eligible patients(1,621 non-T2 DM vs. 71 T2 DM) were included. After PSM, nonT2 DM group(n=139) and T2 DM group(n=71) were more balanced in baseline variables. The 5-year cancerspecific survival(CSS) rate in T2 DM group(47.0%) was inferior to that in non-T2 DM group(58.0%), but did not reach statistical significance [hazard ratio(HR)=1.319, 95% confidence interval(95% CI): 0.868-2.005, P=0.192].While the 5-year progress-free survival(PFS) rate of T2 DM group(40.6%) is significantly worse than that in nonT2 DM group(56.3%)(HR=1.516, 95% CI: 1.004-2.290, P=0.045). Univariate and multivariate analyses showed that T2 DM was an independent risk factor for PFS but not for CSS. In T2 DM group, metformin use subgroup was associated with superior 5-year CSS and PFS in compared with non-metformin use subgroup, although the difference was not statistically significant(5-year CSS: 48.0% vs. 45.4%, HR=0.680, 95% CI: 0.352-1.313,P=0.246;5-year PFS: 43.5% vs. 35.7%, HR=0.763, 95% CI: 0.400-1.454, P=0.406). The 5-year CSS rate was47.5% in good glycemic control subgroup and 44.1% in poor glycemic control subgroup(HR=0.826, 95% CI:0.398-1.713, P=0.605). And both two subgroups yielded a similar 5-year PFS rate(42.2% vs. 36.3%, HR=0.908,95% CI: 0.441-1.871, P=0.792).Conclusions: DM promoted disease progress of GC after gastrectomy but had not yet led to the significant discrepancy of CSS. For GC patients with T2 DM, metformin use was associated with superior survival but without statistical significance, while better glycemic control could not improve the prognosis.
基金supported in part by the U.S.National Institutes of Health(NIH)grants R01 CA243386(J.C.),R01 CA271497,R01 CA214965(J.C.),R01 CA236399(J.C.),R01 DK124116(J.C)The Simms/Mann Family Foundation(J.C.).J.C.is a Leukemia&Lymphoma Society(LLS)Scholar and is supported by the LLS 2022 Scholar CDP Achievement Award.
文摘As the most common internal modification of mRNA,Ne-methyladenosine(m^(6)A)and its regulators modulate gene expression and play critical roles in various biological and patholog-ical processes including tumorigenesis.It was reported previously that m^(6)A methyltransferase(writer),methyltransferase-like 3(METTL3)adds m^(6)A in primary microRNAs(pri-miRNAs)and fa-cilitates its processing into precursor miRNAs(pre-miRNAs).However,it is unknown whether m^(6)A modification also plays a role in the maturation process of pre-miRNAs and(if so)whether such a function contributes to tumorigenesis.Here,we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia(AML)patients,especially in relapsed patients,and plays an onco-genic role in AML.Moreover,YTHDF2 promotes expression of miR-126-3p(also known as miR-126,as it is the main product of precursor miR-126(pre-miR-126)),a miRNA that was reported as an oncomiRNA in AML,through facilitating the processing of pre-miR-126 into mature miR-126.Mechanistically,YTHDF2 recognizes m^(6)A modification in pre-miR-126 and recruits AGO2,a regulator of pre-miRNA processing,to promote the maturation of pre-miR-126.YTHDF2 posi-tively and negatively correlates with miR-126 and miR-126's downstream target genes,respec-tively,in AML patients,and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis,indi-cating that miR-126 is a functionally important target of YTHDF2 in AML.Overall,our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the ther-apeutic potential of targeting this axis for AML treatment,but also suggest that m^(6)A plays a role in pre-miRNA processing that contributes to tumorigenesis.
基金Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2021A1515010425National Key R&D Program of China,Grant/Award Number:2020YFA0112403Ministry of Science and Technology of the People’s Republic of China。
文摘As one of the most studied ribonucleic acid(RNA)modifications in eukaryotes,N^(6)-methyladenosine(m^(6)A)has been shown to play a predominant role in controlling gene expression and influence physiological and pathological processes such as oncogenesis and tumor progression.Writer and eraser proteins,acting opposite to deposit and remove m^(6)A epigenetic marks,respectively,shape the cellular m^(6)A landscape,while reader proteins preferentially recognize m^(6)A modifications and mediate fate decision of the methylated RNAs,including RNA synthesis,splicing,exportation,translation,and stability.Therefore,RNA metabolism in cells is greatly influenced by these three classes of m^(6)A regulators.Aberrant expression of m^(6)A regulators has been widely reported in various types of cancer,leading to cancer initiation,progression,and drug resistance.The close links between m^(6)A and cancer shed light on the potential use of m^(6)A methylation and its regulators as prognostic biomarkers and drug targets for cancer therapy.Given the notable effects of m^(6)A in reversing chemoresistance and enhancing immune therapy,it is a promising target for combined therapy.Herein,we summarize the recent discoveries on m^(6)A and its regulators,emphasizing their influences on RNA metabolism,their dysregulation and impacts in diverse malignancies,and discuss the clinical implications of m^(6)A modification in cancer.
基金Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer(No.2020B121201004)Guangdong Provincial Major Talents Project(No.2019JC05 Y361)+3 种基金Science and Technology Planning Project of Guangdong Province(No. 2017B020226005)"Climbing Program" , Special Fund of Guangdong Province(No. pdjh2021b0098)National Natural Science Foundation of China(No. 81902444)Science and Technology Program of Guangzhou(No. 201903010072)。
文摘Background: Previous studies have revealed that diabetes mellitus (DM) promotes disease progress of gastric cancer (GC). This study aimed to further investigating whether DM advanced lymph nodes (LNs) metastasis in GC.Methods: The clinicopathologic data of GC patients with >15 examined LN (ELN) between October 2004 and December 2019 from a prospectively maintained database were included. The observational outcomes included the number (N3b status) and anatomical distribution (N3 stations) of metastatic LN (MLN).Results: A total of 2142 eligible patients were included in the study between October 2004 and December 2019. N3 stations metastasis (26.8% in DMvs. 19.3% in non-DM,P = 0.026) and N3b status (18.8% in DMvs. 12.8% in non-DM,P = 0.039) were more advanced in the DM group, and multivariate logistic regression analyses confirmed that DM was an independent factor of developing N3 stations metastasis (odds ratio [OR] = 1.771,P= 0.011) and N3b status (OR= 1.752,P= 0.028). Also, multivariate analyses determined DM was independently associated with more MLN (β = 1.424,P = 0.047). The preponderance of N3 stations metastasis (DMvs. non-DM, T1-2: 2.2%vs. 4.9%, T3: 29.0%vs. 20.3%, T4a: 38.9%vs. 25.8%, T4b: 50.0%vs. 36.6%;ELN16-29: 8.6%vs. 10.4%, ELN30-44: 27.9%vs. 20.5%, ELN ≥ 45: 37.7%vs. 25.3%), N3b status (DMvs. non-DM, T1-2: 0%vs. 1.7%, T3: 16.1%vs. 5.1%, T4a: 27.8%vs. 19.1%, T4b: 44.0%vs. 28.0%;ELN16-29: 8.6%vs. 7.9%, ELN30-44: 18.0%vs. 11.8%, ELN ≥ 45: 26.4%vs. 17.3%), and the number of MLN (DMvs. non-DM, T1-2: 0.4vs. 1.1, T3: 8.6vs. 5.2, T4a: 9.7vs. 8.6, T4b: 17.0vs. 12.8;ELN16-29: 3.6vs. 4.6, ELN30-44: 5.8vs. 5.5, ELN ≥ 45: 12.0vs. 7.7) of DM group increased with the advancement of primary tumor depth stage and raising of ELN.Conclusions: DM was an independent risk factor for promoting LN metastasis. The preponderance of LN involvement in the DM group was aggravated with the advancement of tumor depth.
基金National Key R&D Program of China,Grant/Award Number:2018YFA0508300National Natural Science Foundation of China,Grant/Award Numbers:81772977,31722016,31470729+1 种基金Natural Science Foundation of Guangdong Province,Grant/Award Numbers:2019TX05Y598,2014TQ01R584,2014A030312015Innovative Team Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory,Grant/Award Number:2018GZR110103002。
文摘Background:Multiple myeloma(MM)is a hematologic malignancy characterized by the accumulation of aberrant plasma cells within the bone marrow.The high frequent mutation of family with sequence similarity 46,member C(FAM46C)is closely related with the occurrence and progression of MM.Recently,FAM46C has been identified as a non-canonical poly(A)polymerase(PAP)that functions as a tumor suppressor in MM.This study aimed to elucidate the structural features of this novel non-canonical PAP and how MM-related mutations affect the structural and biochemical properties of FAM46C,eventually advancing our understandings towards FAM46C mutation-related MM occurrence.Methods:We purified and crystallized a mammalian FAM46C construct,and solved its structure.Next,we characterized the property of FAM46C as a PAP through a combination of structural analysis,site-directed mutagenesis and biochemical assays,and by comparison with its homolog FAM46B.Finally,we structurally analyzed MM-related FAM46C mutations and tested the enzymatic activity of corresponding mutants.Results:We determined the crystal structure of a mammalian FAM46C protein at 2.35 A,and confirmed that FAM46C preferentially consumed adenosine triphosphate(ATP)and extended A-rich RNA substrates.FAM46C showed a weaker PAP activity than its homolog FAM46B,and this difference was largely dependent on the residue variance at particular sites.Of them,residues at positions 77,290,and 298 of mouse FAM46C weremost important for the divergence in enzymatic activity.Among the MM-associated FAM46C mutants,those residing at the catalytic site(D90G and D90H)or putative RNA-binding site(I155L,S156F,D182Y,F184L,Y247V,andM270V)showed abolished or compromised PAP activity of FAM46C,while N72A and S248A did not severely affect the PAP activity.FAM46C mutants D90G,D90H,I155L,S156F,F184L,Y247V,and M270V had significantly lower inhibitory effect on apoptosis of RPMI-8226 cells as compared to wild-type FAM46C.Conclusions:FAM46C is a prokaryotic-like PAP with preference forA-richRNA substrates,and showed distinct enzymatic efficiency with its homolog FAM46B.The MM-related missense mutations of FAM46C lead to various structural and biochemical outcomes to the protein.
基金supported by National Key Research and Development Program of China(2018YFD0501100)Science and Technology Program of Changsha(kq2004078)+3 种基金Science and technology program of Changsha(kq1907074)the Innovation Team of Key areas of the Ministry of Science and Technologythe Science and Technology Leadership Program of Hunan Province(2019RS3021)Sichuan Synlight Biotech Ltd and Research Foundation of Education Bureau of Hunan Province,China(18B476)。
文摘Beta-glucan has been shown to have a beneficial effect on gastrointestinal health.This experiment was conducted to investigate the effects ofβ-glucan isolated from Agrobacterium sp.ZX09 on growth performance and intestinal health of weaning pigs.A total of 108 weaned pigs(21 d of age;6.05±0.36 kg)were randomly divided into 3 groups(6 pens/group;6 pigs/pen),and the groups were each treated with the following diets:1)basal diet,2)basal diet supplemented with 20 mg/kg olaquindox,3)basal diet supplemented with 200 mg/kgβ-glucan,for 21 d.Compared with the control group,pigs fed with200 mg/kgβ-glucan had greaterBW,average daily gain and duodenal villus height to crypt depth ratio(P<0.05).Olaquindox increased the duodenal or jejunal villus height of pigs compared withβ-glucan.Compared with the control group,β-glucan tended to increase the occludin mRNA expression in the jejunum(0.05<P<0.10).Beta-glucan enriched the beneficial microbiota in the ileum of pigs(P<0.05).In conclusion,β-glucan may promote growth performance by improving intestinal health and increasing beneficial microbiota of weaned pigs.The study results will provide valuable theoretical guidance for the utilization ofβ-glucan in weaned pigs.
基金This work was supported in part by National Natural Science Foundation of China(No.61801366)Natural Science Foundation of Shaanxi Province(No.2020JM-078)Innovation Team Research Fund of Shaanxi Province(No.2019TD-013)。
文摘Due to space limitation,mutual coupling occurs almost invisibly in array antennas.In this paper,the mutual coupling effects on the two most popular categories of array antennas,i.e.,phased arrays and multiple-input multiple-output(MIMO)antennas,are reviewed.Some misconceptions regarding the mutual coupling effects are uncovered.It is shown that the steering pattern of a phased array at an arbitrary scan-ning angle can be readily calculated once the embedded radiation patterns of the array elements(including the mutual coupling effect)are obtained.As antenna spacing decreases,absorption loss increases,yet the phase terms tend to add up constructively as antenna spacing reduces,which may overcompensate the absorption loss due to mutual coupling.Thus,the array efficiency may be increased by reducing the antenna spacing.A patch antenna array is used to illustrate this phenomenon.It is further shown that while mutual coupling tends to reduce the correlation of two-element arrays,it has a negligible effect on the overall correlations of larger arrays.Finally,various mutual coupling reduction techniques are briefly presented.Two feasible techniques for large planar arrays are used to illustrate the benefits of array decoupling.
