As-cast Al-Si alloys always face low ductility because of coarseα-Al grains and large lamellar eutectic Si.Although B-containing refiners and Sr modifiers could refine theα-Al grains and eutectic Si respec-tively,si...As-cast Al-Si alloys always face low ductility because of coarseα-Al grains and large lamellar eutectic Si.Although B-containing refiners and Sr modifiers could refine theα-Al grains and eutectic Si respec-tively,simultaneous addition leads to an invalid effect of Sr because B-containing refiner has a poison-ing effect(PE)on Sr modifier in the Al-10Si-B-Sr alloys.The present work achieves both refinement ofα-Al grains and modification of Si merely by the addition of 500 ppm La in Al-10Si-0.02B-0.015Sr alloy,which greatly enhances the ductility and tensile strength.Sr-B interaction in the Al-10Si-0.02B-0.015Sr melt results in a consumption of Sr by forming Sr-B intermetallic compound.CALPHAD-type calculations reveal that Sr concentration in liquid before eutectic reaction becomes a key parameter to estimate the alloying modification effect.The addition of La forms LaB 6 and thereby releases Sr to protect the Sr modification effect.First-principles calculations illustrate that both Sr and La are benefi-cial to the formation of twin boundaries in Si particles due to their negative formation energy of twin boundaries.The formed LaB 6 has a semicoherent interface withα-Al with the orientation relationship of[110]_(LaB6)//[110]_(Al) and(111)_(LaB6)//(111)_(Al),demonstrating that LaB 6 is an efficient nucleation site forα-Al,which contributes to the refinement ofα-Al in the Al-10Si-0.05La-0.02B-0.015Sr alloy.Our findings re-veal the micro-mechanism of refinement during the solidification process and develop an effective and simple way to obtain high-performance Al alloys.展开更多
Background:To date,there is no approved blood-based biomarker for breast cancer detection.Herein,we aimed to assess semaphorin 4C(SEMA4C),a pivotal protein involved in breast cancer progression,as a serum diagnostic b...Background:To date,there is no approved blood-based biomarker for breast cancer detection.Herein,we aimed to assess semaphorin 4C(SEMA4C),a pivotal protein involved in breast cancer progression,as a serum diagnostic biomarker.Methods:We included 6,213 consecutive inpatients from Tongji Hospital,Qilu Hospital,and Hubei Cancer Hospital.Training cohort and two validation cohorts were introduced for diagnostic exploration and validation.A pan-cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid tumors.Breast cancer patients who underwent mass excision prior to modified radical mastectomy were also analyzed.We hypothesized that increased pretreatment serum SEMA4C levels,measured using optimized in-house enzymelinked immunosorbent assay kits,could detect breast cancer.The endpoints were diagnostic performance,including area under the receiver operating characteristic curve(AUC),sensitivity,and specificity.Post-surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification.There was no restriction on disease stage for eligibilities.Results:We included 2667 inpatients with breast lesions,2378 patients with other solid tumors,and 1168 healthy participants.Specifically,118 patients with breast cancer were diagnosed with stage 0(5.71%),620 with stage I(30.00%),966 with stage II(46.73%),217 with stage III(10.50%),and 8 with stage IV(0.39%).Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls(P<0.001).Elevated serum SEMA4C levels had AUC of 0.920(95%confidence interval[CI]:0.900–0.941)and 0.932(95%CI:0.911–0.953)for breast cancer detection in the two validation cohorts.The AUCs for detecting early-stage breast cancer(n=366)and ductal carcinoma in situ(n=85)were 0.931(95%CI:0.916–0.946)and 0.879(95%CI:0.832–0.925),respectively.Serum SEMA4C levels significantly decreased after surgery,and the reduction was more striking after modified radical mastectomy,compared with mass excision(P<0.001).The positive rate of enhanced serum SEMA4C levels was 84.77%for breast cancer and below 20.75%for the other 14 solid tumors.Conclusions:Serum SEMA4C demonstrated promising potential as a candidate biomarker for breast cancer diagnosis.However,validation in prospective settings and by other study groups is warranted.展开更多
Given the continuous and growing demand for point of care(POC)diagnostic tests,attention has been shifted toward integration and miniaturization of laboratory protocols into“sample-in-answer-out”devices.Microfluidic...Given the continuous and growing demand for point of care(POC)diagnostic tests,attention has been shifted toward integration and miniaturization of laboratory protocols into“sample-in-answer-out”devices.Microfluidic technologies have been considered an ideal solution to address the requirements of POC diagnostics since many laboratory functions can be miniaturized and incorporated onto a single integrated chip.In this review,we summarize the advances of integrated microfluidic devices for POC diagnostics in the last 3 years.Particularly,we summarize current materials used for microfluidic chip fabrication,discuss the innovation of versatile integrated microfluidic devices,especially the strategies for simplifying sample preparation in manual or self-driven systems,and new detection methods of microfluidic chips.In addition,we describe new integrated microfluidic devices for POC diagnostics of protein-targeted immunodiagnostics,nucleic acid molecular tests,and small molecule metabolites analysis.We also provide future perspectives and current challenges for clinical translation and commercialization of these microfluidic technologies.展开更多
Single-cell RNA sequencing(sc RNA-seq)has become one of the most powerful tools to understand the heterogeneity of biological systems.While barcoding strategies have revolutionized the field of high-throughput sc RNA-...Single-cell RNA sequencing(sc RNA-seq)has become one of the most powerful tools to understand the heterogeneity of biological systems.While barcoding strategies have revolutionized the field of high-throughput sc RNA-seq,it is still challenging to achieve highly efficient,direct and universal cell barcoding with cost-effectiveness and minimal sample loss.Herein,a single micro-particle dispenser approach for rapid single barcode bead/cell manipulation and pairing,enabling highly efficient cell barcoding for sc RNA-seq(Dispen-Seq)was developed.Notably,Dispen-Seq provides a versatile platform which can enrich cell subgroups of interest while unlimited by input sample amounts,and can respond to changes in sample composition with high resolution and reproducibility.It is anticipated that Dispen-Seq will increase the scope of sc RNA-seq from academic research to practical applications.展开更多
Multicellular systems rely on the interactions between cells to coordinate cell signaling and regulate cell functions [1]. Understanding the mechanism of cell–cell interactions (CCIs) is critical to many physiologica...Multicellular systems rely on the interactions between cells to coordinate cell signaling and regulate cell functions [1]. Understanding the mechanism of cell–cell interactions (CCIs) is critical to many physiological and pathological processes, such as embryogenesis,differentiation, cancer metastasis, and immunological interactions.展开更多
基金This work was financially supported by the National Natural Science Foundation of China(Nos.U2102212,51871138,and 51821001)the Shanghai Rising-Star Program(No.21QA1403200)the Shanghai Engineering Research Center for Metal Parts Green Remanufacture(No.19DZ2252900)from Shanghai Engineering Research Center Construction Project.
文摘As-cast Al-Si alloys always face low ductility because of coarseα-Al grains and large lamellar eutectic Si.Although B-containing refiners and Sr modifiers could refine theα-Al grains and eutectic Si respec-tively,simultaneous addition leads to an invalid effect of Sr because B-containing refiner has a poison-ing effect(PE)on Sr modifier in the Al-10Si-B-Sr alloys.The present work achieves both refinement ofα-Al grains and modification of Si merely by the addition of 500 ppm La in Al-10Si-0.02B-0.015Sr alloy,which greatly enhances the ductility and tensile strength.Sr-B interaction in the Al-10Si-0.02B-0.015Sr melt results in a consumption of Sr by forming Sr-B intermetallic compound.CALPHAD-type calculations reveal that Sr concentration in liquid before eutectic reaction becomes a key parameter to estimate the alloying modification effect.The addition of La forms LaB 6 and thereby releases Sr to protect the Sr modification effect.First-principles calculations illustrate that both Sr and La are benefi-cial to the formation of twin boundaries in Si particles due to their negative formation energy of twin boundaries.The formed LaB 6 has a semicoherent interface withα-Al with the orientation relationship of[110]_(LaB6)//[110]_(Al) and(111)_(LaB6)//(111)_(Al),demonstrating that LaB 6 is an efficient nucleation site forα-Al,which contributes to the refinement ofα-Al in the Al-10Si-0.05La-0.02B-0.015Sr alloy.Our findings re-veal the micro-mechanism of refinement during the solidification process and develop an effective and simple way to obtain high-performance Al alloys.
基金National Science and Technology Major Sub-Project,Grant/Award Number:2018ZX10301402-002National Natural Science Foundation of China,Grant/Award Numbers:81772787,81902653,82072889+2 种基金Technical Innovation Special Project of Hubei Province,Grant/Award Number:2018ACA138Fundamental Research Funds for the Central Universities,Grant/Award Number:2019kfyXMBZ024Municipal Health Commission Project ofWuhan,Grant/Award Number:WX18Q16。
文摘Background:To date,there is no approved blood-based biomarker for breast cancer detection.Herein,we aimed to assess semaphorin 4C(SEMA4C),a pivotal protein involved in breast cancer progression,as a serum diagnostic biomarker.Methods:We included 6,213 consecutive inpatients from Tongji Hospital,Qilu Hospital,and Hubei Cancer Hospital.Training cohort and two validation cohorts were introduced for diagnostic exploration and validation.A pan-cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid tumors.Breast cancer patients who underwent mass excision prior to modified radical mastectomy were also analyzed.We hypothesized that increased pretreatment serum SEMA4C levels,measured using optimized in-house enzymelinked immunosorbent assay kits,could detect breast cancer.The endpoints were diagnostic performance,including area under the receiver operating characteristic curve(AUC),sensitivity,and specificity.Post-surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification.There was no restriction on disease stage for eligibilities.Results:We included 2667 inpatients with breast lesions,2378 patients with other solid tumors,and 1168 healthy participants.Specifically,118 patients with breast cancer were diagnosed with stage 0(5.71%),620 with stage I(30.00%),966 with stage II(46.73%),217 with stage III(10.50%),and 8 with stage IV(0.39%).Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls(P<0.001).Elevated serum SEMA4C levels had AUC of 0.920(95%confidence interval[CI]:0.900–0.941)and 0.932(95%CI:0.911–0.953)for breast cancer detection in the two validation cohorts.The AUCs for detecting early-stage breast cancer(n=366)and ductal carcinoma in situ(n=85)were 0.931(95%CI:0.916–0.946)and 0.879(95%CI:0.832–0.925),respectively.Serum SEMA4C levels significantly decreased after surgery,and the reduction was more striking after modified radical mastectomy,compared with mass excision(P<0.001).The positive rate of enhanced serum SEMA4C levels was 84.77%for breast cancer and below 20.75%for the other 14 solid tumors.Conclusions:Serum SEMA4C demonstrated promising potential as a candidate biomarker for breast cancer diagnosis.However,validation in prospective settings and by other study groups is warranted.
基金Fundamental Research Funds for the Central Universities,Grant/Award Number:ZQN-818State Key Laboratory of Chemo/Biosensing and Chemometrics,Grant/Award Number:2019006+1 种基金Natural Science Foundation of Fujian Province,China,Grant/Award Number:2021J01310National Natural Science Foundation of China,Grant/Award Numbers:21775128,21804022。
文摘Given the continuous and growing demand for point of care(POC)diagnostic tests,attention has been shifted toward integration and miniaturization of laboratory protocols into“sample-in-answer-out”devices.Microfluidic technologies have been considered an ideal solution to address the requirements of POC diagnostics since many laboratory functions can be miniaturized and incorporated onto a single integrated chip.In this review,we summarize the advances of integrated microfluidic devices for POC diagnostics in the last 3 years.Particularly,we summarize current materials used for microfluidic chip fabrication,discuss the innovation of versatile integrated microfluidic devices,especially the strategies for simplifying sample preparation in manual or self-driven systems,and new detection methods of microfluidic chips.In addition,we describe new integrated microfluidic devices for POC diagnostics of protein-targeted immunodiagnostics,nucleic acid molecular tests,and small molecule metabolites analysis.We also provide future perspectives and current challenges for clinical translation and commercialization of these microfluidic technologies.
基金supported by the National Key R&D Program of China(2018YFC1602900)the National Natural Science Foundation of China(21927806,21735004,222022409,21874089,21705024,21775128)the Program for Changjiang Scholars and Innovative Research Team in University(IRT13036)。
文摘Single-cell RNA sequencing(sc RNA-seq)has become one of the most powerful tools to understand the heterogeneity of biological systems.While barcoding strategies have revolutionized the field of high-throughput sc RNA-seq,it is still challenging to achieve highly efficient,direct and universal cell barcoding with cost-effectiveness and minimal sample loss.Herein,a single micro-particle dispenser approach for rapid single barcode bead/cell manipulation and pairing,enabling highly efficient cell barcoding for sc RNA-seq(Dispen-Seq)was developed.Notably,Dispen-Seq provides a versatile platform which can enrich cell subgroups of interest while unlimited by input sample amounts,and can respond to changes in sample composition with high resolution and reproducibility.It is anticipated that Dispen-Seq will increase the scope of sc RNA-seq from academic research to practical applications.
基金supported by the National Natural Science Foundation of China (22325404, 21974113, and 21927806)the National Key R&D Program of China (2021YFA0909400)Fundamental Research Funds for the Central Universities (20720210001 and 20720220005)。
文摘Multicellular systems rely on the interactions between cells to coordinate cell signaling and regulate cell functions [1]. Understanding the mechanism of cell–cell interactions (CCIs) is critical to many physiological and pathological processes, such as embryogenesis,differentiation, cancer metastasis, and immunological interactions.