Scanning transmission electron microscopy and atom probe tomography analysis of non-stoichiometry long-period-stacking-ordered structures in Mg-Ni-Y/Sm alloys

The long-period-stacking-ordered(LPSO)structure affects the mechanical,corrosion and hydrolysis properties of Mg alloys.The current work employs high angle annular dark field-scanning transmission electron microscopy(HAADF-STEM)and atom probe tomography(APT)to investigate the structural and local chemical information of LPSO phases formed in Mg-Ni-Y/Sm ternary alloys after extended isothermal annealing.Depending on the alloying elements and their concentrations,Mg-Ni-Y/Sm develops a two-phase LPSO+α-Mg structure in which the LPSO phase contains defects,hybrid LPSO structure,and Mg insertions.HAADF-STEM and APT indicate non-stoichiometric LPSO with incomplete Ni_(6)(Y/Sm)_(8) clusters.In addition,the APT quantitatively determines the local composition of LPSO and confirms the presence of Ni within the Mg bonding layers.These results provide insight into a better understanding of the structure and hydrolysis properties of LPSO-Mg alloys.

Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer

Objective:The choice of chemotherapeutic regimen for triple-negative breast cancer(TNBC)remains controversial.Homologous recombination deficiency(HRD)has attracted increasing attention in informing chemotherapy treatment.This study was aimed at investigating the feasibility of HRD as a clinically actionable biomarker for platinum-containing and platinum-free therapy.Methods:Chinese patients with TNBC who received chemotherapy between May 1,2008 and March 31,2020 were retrospectively analyzed with a customized 3D-HRD panel.HRD positivity was defined by an HRD score≥30 or deleterious BRCA1/2 mutation.A total of 386 chemotherapy-treated patients with TNBC were screened from a surgical cohort(NCT01150513)and a metastatic cohort,and 189 patients with available clinical and tumor sequencing data were included.Results:In the entire cohort,49.2%(93/189)of patients were identified as HRD positive(40 with deleterious BRCA1/2 mutations and 53 with BRCA1/2 intact with an HRD score of≥30).In the first-line metastatic setting,platinum therapy was associated with longer median progression-free survival(mPFS)than platinum-free therapy[9.1 vs.3.0 months;hazard ratio(HR),0.43;95%confidence interval 0.22–0.84;P=0.01].Among HRD-positive patients,the mPFS was significantly longer in those treated with platinum rather than platinum-free therapy(13.6 vs.2.0 months;HR,0.11;P=0.001).Among patients administered a platinum-free regimen,HRD-negative patients showed a PFS significantly superior to that of HRD-positive patients(P=0.02;treatment-biomarker P-interaction=0.001).Similar results were observed in the BRCA1/2-intact subset.In the adjuvant setting,HRD-positive patients tended to benefit more from platinum chemotherapy than from platinum-free chemotherapy(P=0.05,P-interaction=0.02).Conclusions:HRD characterization may guide decision-making regarding the use of platinum treatment in patients with TNBC in both adjuvant and metastatic settings.

Temporal and Spatial Distribution Characteristics of Tornadoes in Liaoning Province and Countermeasures

Based on the data of tornadoes in Liaoning Province from 1951 to 2005,the spatial and temporal distribution characteristics of tornadoes were analyzed by means of moving average,Daniel trend test and other methods.The results show that the frequency of tornadoes in coastal areas was obviously higher than that in land.Tornadoes mainly occurred in the central plains,the coastal areas of Liaodong Peninsula and the junction of plain and sea.The frequency of tornadoes was the highest in the 1980s and the lowest in the 1990s,and suddenly increased in 2005.The occurrence of tornadoes had an obvious seasonal change.They mainly happened in summer,peaking in September.During a day,most of them appeared from 13:00 to 21:00,and lasted for only a few minutes to dozens of minutes.The frequency of tornadoes showed a significant downward trend during 1991-2000 and a significant upward trend during 1961-1970 and 2001-2005.There were eight serious tornadoes in the 55 years,among which the tornado occurring in 1988 was the severest,and the number of deaths caused by the tornado in 1969 was the largest.

A real-world study of immune checkpoint inhibitors in advanced triple-negative breast cancer

Background:Triple-negative breast cancer(TNBC)is the most aggressive type of breast cancer.Immune checkpoint inhibitors(ICIs)have been widely used to treat various tumors and have changed the landscape of tumor management,but the data from real-world studies of ICIs for TNBC treatment remain limited.The aim of this study was to evaluate the efficacy of ICIs in the treatment of patients with advanced TNBC in a real-world setting and to explore possible correlates.Methods:The clinical data of advanced TNBC patients who received ICI treatment in the Chinese People's Liberation Army(PLA)General Hospital were collected.Treatment responses,outcomes and adverse events(AEs)were assessed.Results:Eighty-one patients were included in the study.The confirmed objective response rate(ORR)was 32.1%,and the disease control rate(DCR)was 64.2%.The median progression-free survival(PFS)was 4.2 months,and the median overall survival(OS)was 11.0 months.PFS and OS were longer in patients who achieved clinical benefit from ICIs and shorter in patients who received later-line ICIs and higher levels of inflammation;specifically,patients with higher TILs had longer PFS.Overall AEs were tolerable.Conclusions:ICIs are effective in the treatment of advanced TNBC,and the adverse reactions are tolerable.A panel of biomarkers including LDH,ALP,and bNLR were identified to predict the efficacies of ICIs in TNBC treatment.

Exosomal transfer of microRNA-590-3p between renal tubular epithelial cells after renal ischemia-reperfusion injury regulates autophagy by targeting TRAF6

Background:Acute kidney injury(AKI)is a common complication in patients,especially elderly patients,who undergo cardiac surgery with cardiopulmonary bypass.Studies have indicated a protective role of autophagy in AKI.However,the mechanisms underlying the regulatory effect of autophagy in AKI among patients undergoing cardiac surgeries are poorly understood.In this study,we aimed to test the hypothesis that exosomal microRNAs(miRNAs)regulate autophagy in tubular epithelial cells after AKI.Methods:Plasma exosomal RNA was extracted from young and elderly AKI patients undergoing cardiac surgery,and the miRNAs expression during the perioperative period were analyzed using next-generation sequencing.The screened miRNAs and their target genes were subjected to gene oncology function and Kyoto Encyclopedia of Genes and Genome enrichment analyses.Renal tubular epithelial cell line(HK-2 cells)was cultured and hypoxia/reoxygenation(H/R)model was established,which is an in vitro renal ischemia/reperfusion(I/R)model.We used Western blot analysis,cell viability assay,transfection,luciferase assay to investigate the mechanisms underlying the observed increases in the levels of renal I/R injury-mediated exosomal miRNAs and their roles in regulating HK-2 cells autophagy.Results:miR-590-3p was highly enriched in the plasma exosomes of young AKI patients after cardiac surgery.Increased levels of miR-590-3p led to the increases in the expression of autophagy marker proteins,including Beclin-1 and microtubule associated protein 1 light chain 3 beta(LC3II),and prolonged the autophagic response in HK-2 cells after H/R treatment.These effects were achieved mainly via increases in the exosomal miR-590-3p levels,and the tumor necrosis factor receptor-associated factor 6 protein was shown to play a key role in I/R injury-mediated autophagy induction.Conclusion:Exosomes released from HK-2 cells after renal I/R injury regulate autophagy by transferring miR-590-3p in a paracrine manner,which suggests that increasing the miR-590-3p levels in HK-2 cell-derived exosomes may increase autophagy and protect against kidney injury after renal I/R injury.

Objective assessment of bradykinesia in Parkinson’s disease using evolutionary algorithms:clinical validation

Background:There is an urgent need for developing objective,effective and convenient measurements to help clinicians accurately identify bradykinesia.The purpose of this study is to evaluate the accuracy of an objective approach assessing bradykinesia in finger tapping(FT)that uses evolutionary algorithms(EAs)and explore whether it can be used to identify early stage Parkinson’s disease(PD).Methods:One hundred and seven PD,41 essential tremor(ET)patients and 49 normal controls(NC)were recruited.Participants performed a standard FT task with two electromagnetic tracking sensors attached to the thumb and index finger.Readings from the sensors were transmitted to a tablet computer and subsequently analyzed by using EAs.The output from the device(referred to as"PD-Monitor")scaled from−1 to+1(where higher scores indicate greater severity of bradykinesia).Meanwhile,the bradykinesia was rated clinically using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale(MDS-UPDRS)FT item.Results:With an increasing MDS-UPDRS FT score,the PD-Monitor score from the same hand side increased correspondingly.PD-Monitor score correlated well with MDS-UPDRS FT score(right side:r=0.819,P=0.000;left side:r=0.783,P=0.000).Moreover,PD-Monitor scores in 97 PD patients with MDS-UPDRS FT bradykinesia and each PD subgroup(FT bradykinesia scored from 1 to 3)were all higher than that in NC.Receiver operating characteristic(ROC)curves revealed that PD-Monitor FT scores could detect different severity of bradykinesia with high accuracy(≥89.7%)in the right dominant hand.Furthermore,PD-Monitor scores could discriminate early stage PD from NC,with area under the ROC curve greater than or equal to 0.899.Additionally,ET without bradykinesia could be differentiated from PD by PD-Monitor scores.A positive correlation of PD-Monitor scores with modified Hoehn and Yahr stage was found in the left hand sides.Conclusions:Our study demonstrated that a simple to use device employing classifiers derived from EAs could not only be used to accurately measure different severity of bradykinesia in PD,but also had the potential to differentiate early stage PD from normality.

Extraction of tight binding parameters from in-situ ARPES on the continuously doped surface of cuprates

Recently we developed a technique of ozone/vacuum annealing to continuously change the doping level of the surface of Bi_2Sr_2CaCu_2O_(8+)and measured a nearly whole superconducting dome on one surface by in-situ angle-resolved photoemission spectroscopy [arXiv: 1805.06450]. Here we study the evolution of the electronic structures of Bi_2Sr_2CaCu_2O_(8+)xusing this technique together with tight binding fits. The tight binding parameters are extracted to study their evolution with doping.