纸上得来终觉浅,绝知此事要躬行——“树叶电镀”科普实验的实践与反思

介绍了作为2023年中国科学技术大学科技周化学与材料学院科普点的志愿者,在准备“树叶电镀”科普实验时,如何经历重重失败,克服种种困难,最终顺利完成“树叶电镀”项目的经历,以及在此经历中的感悟与收获。“树叶电镀”实验是受艺术性的树叶书签之启发,主要利用化学镀与电镀原理,目的在树叶表面均匀镀上一层铜的科普实验。通过该实验,观众可初步了解氧化还原反应及电化学的初步知识,激发小朋友们对于化学的兴趣。

Genetic variation of circHIBADH enhances prostate cancer risk through regulating HNRNPA1-related RNA splicing

The current study aimed to investigate associations of circRNAs and related genetic variants with the risk of prostate cancer(PCa)as well as to elucidate biological mechanisms underlying the associations.We first compared expression levels of circRNAs between 25 paired PCa and adjacent normal tissues to identify riskassociated circRNAs by using the MiOncoCirc database.We then used logistic regression models to evaluate associations between genetic variants in candidate circRNAs and PCa risk among 4662 prostate cancer patients and 3114 healthy controls,and identified circHIBADH rs11973492 T>C as a significant risk-associated variant(odds ratio=1.20,95%confidence interval:1.08-1.34,P=7.06×10^(-4))in a dominant genetic model,which altered the secondary structure of the corresponding RNA chain.In the in silico analysis,we found that circHIBADH sponged and silenced 21 RNA-binding proteins(RBPs)enriched in the RNA splicing pathway,among which HNRNPA1 was identified and validated as a hub RBP using an external RNA-sequencing data as well as the in-house(four tissue samples)and publicly available single-cell transcriptomes.Additionally,we demonstrated that HNRNPA1 influenced hallmarks including MYC target,DNA repair,and E2F target signaling pathways,thereby promoting carcinogenesis.In conclusion,genetic variants in circHIBADH may act as sponges and inhibitors of RNA splicing-associated RBPs including HNRNPA1,playing an oncogenic role in PCa.

Genetic variant in a BaP-activated super-enhancer increases prostate cancer risk by promoting AhR-mediated FAM227A expression

Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.

Donor-Derived CD19-Targeted T Cell Infusion Eliminates B Cell Acute Lymphoblastic Leukemia Minimal Residual Disease with No Response to Donor Lymphocytes after Allogeneic Hematopoietic Stem Cell Transplantation

Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.

Comparison of clinical features of nephrotic syndrome after haploidentical and matched donor hematopoietic stem cell transplantation

To the Editor:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is one of the most effective options for hematological diseases.However,allo-HSCT treatment can cause serious complications.Post-transplant kidney damage is an important complication.In this study,we retrospectively analyzed the frequency of nephrotic syndrome(NS)after allo-HSCT and compared the frequency and clinical characteristics of NS between haploidentical donor(HID)and matched donor(MD)HSCT(including matched sibling donors[MSD]and unrelated donors[URD]).

Bridging chimeric antigen receptor T-cell before transplantation improves prognosis of relapsed/refractory B-cell acute lymphoblastic leukemia

To the Editor:For recipients with relapsed/refractory(R/R)B-cell acute lymphoblastic leukemia(B-ALL),allogeneic hematopoietic stem cell transplantation(allo-HSCT)often fails to provide them with a satisfactory prognosis.The chimeric antigen receptor T(CAR-T)cells are proven to be safe and effective for these patients.[1]But there are few published studies assessing the advantages of CAR-T compared to traditional chemotherapy as a bridging treatment followed by HSCT.Consequently,we conducted this study to confirm whether children and young adult R/R B-ALL patients with CAR-T therapy could expect a better post-HSCT prognosis,compared to R/R patients only receiving traditional chemotherapy before transplantation.

Accelerating local SGD for non-IID data using variance reduction

Distributed stochastic gradient descent and its variants have been widely adopted in the training of machine learning models,which apply multiple workers in parallel.Among them,local-based algorithms,including Local SGD and FedAvg,have gained much attention due to their superior properties,such as low communication cost and privacypreserving.Nevertheless,when the data distribution on workers is non-identical,local-based algorithms would encounter a significant degradation in the convergence rate.In this paper,we propose Variance Reduced Local SGD(VRL-SGD)to deal with the heterogeneous data.Without extra communication cost,VRL-SGD can reduce the gradient variance among workers caused by the heterogeneous data,and thus it prevents local-based algorithms from slow convergence rate.Moreover,we present VRL-SGD-W with an effectivewarm-up mechanism for the scenarios,where the data among workers are quite diverse.Benefiting from eliminating the impact of such heterogeneous data,we theoretically prove that VRL-SGD achieves a linear iteration speedup with lower communication complexity even if workers access non-identical datasets.We conduct experiments on three machine learning tasks.The experimental results demonstrate that VRL-SGD performs impressively better than Local SGD for the heterogeneous data and VRL-SGD-W is much robust under high data variance among workers.