Effect of Stereotactic Body Radiation Therapy on Diverse Organ Lesions in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors

Objective The combination of stereotactic body radiation therapy(SBRT)and immune checkpoint inhibitors(ICIs)is actively being explored in advanced non-small-cell lung cancer(NSCLC)patients.However,little is known about the optimal fractionation and radiotherapy target lesions in this scenario.This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs.Methods The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec.2015 to Sep.2021.Patients were grouped according to radiation sites.Progression-free survival(PFS)and overall survival(OS)were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank(Mantel-Cox)test.Results A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study.Radiation sites included lung lesions(lung group,n=43),bone metastases(bone group,n=24),and brain metastases(brain group,n=57).Compared with the brain group,the mean PFS(mPFS)in the lung group was significantly prolonged by 13.3 months(8.5 months vs.21.8 months,HR=0.51,95%CI:0.28–0.92,P=0.0195),and that in the bone group prolonged by 9.5 months with a 43%reduction in the risk of disease progression(8.5 months vs.18.0 months,HR=0.57,95%CI:0.29–1.13,P=0.1095).The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group.The mean OS(mOS)in the lung and bone groups was longer than that of the brain group,and the risk of death decreased by up to 60%in the lung and bone groups as compared with that of the brain group.When SBRT was concurrently given with ICIs,the mPFS in the lung and brain groups were significantly longer than that of the bone group(29.6 months vs.16.5 months vs.12.1 months).When SBRT with 8–12 Gy per fraction was combined with ICIs,the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups(25.4 months vs.15.2 months vs.12.0 months).Among patients receiving SBRT on lung lesions and brain metastases,the mPFS in the concurrent group was longer than that of the SBRT→ICIs group(29.6 months vs.11.4 months,P=0.0003 and 12.1 months vs.8.9 months,P=0.2559).Among patients receiving SBRT with<8 Gy and 8–12 Gy per fraction,the mPFS in the concurrent group was also longer than that of the SBRT→ICIs group(20.1 months vs.5.3 months,P=0.0033 and 24.0 months vs.13.4 months,P=0.1311).The disease control rates of the lung,bone,and brain groups were 90.7%,83.3%,and 70.1%,respectively.Conclusion The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients.This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens.Dose fractionation regimens of 8–12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT.

Neuroprotective effects of long noncoding RNAs involved in ischemic postconditioning after ischemic stroke

During acute reperfusion,the expression profiles of long noncoding RNAs in adult rats with focal cerebral ischemia undergo broad changes.However,whether long noncoding RNAs are involved in neuroprotective effects following focal ischemic stroke in rats remains unclear.In this study,RNA isolation and library preparation was performed for long noncoding RNA sequencing,followed by determining the coding potential of identified long noncoding RNAs and target gene prediction.Differential expression analysis,long noncoding RNA functional enrichment analysis,and co-expression network analysis were performed comparing ischemic rats with and without ischemic postconditioning rats.Rats were subjected to ischemic postconditioning via the brief and repeated occlusion of the middle cerebral artery or femoral artery.Quantitative real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of differentially expressed long noncoding RNAs after ischemic postconditioning in a rat model of ischemic stroke.The results showed that ischemic postconditioning greatly affected the expression profile of long noncoding RNAs and mRNAs in the brains of rats that underwent ischemic stroke.The predicted target genes of some of the identified long noncoding RNAs(cis targets)were related to the cellular response to ischemia and stress,cytokine signal transduction,inflammation,and apoptosis signal transduction pathways.In addition,15 significantly differentially expressed long noncoding RNAs were identified in the brains of rats subjected to ischemic postconditioning.Nine candidate long noncoding RNAs that may be related to ischemic postconditioning were identified by a long noncoding RNA expression profile and long noncoding RNA-mRNA co-expression network analysis.Expression levels were verified by quantitative real-time reverse transcription-polymerase chain reaction.These results suggested that the identified long noncoding RNAs may be involved in the neuroprotective effects associated with ischemic postconditioning following ischemic stroke.The experimental animal procedures were approved by the Animal Experiment Ethics Committee of Kunming Medical University(approval No.KMMU2018018)in January 2018.

Superconductivity in Topological Semimetal θ-TaN at High Pressure

Recently,θ-TaN was proposed to be a topological semimetal with a new type of triply degenerate nodal points.Here,we report studies of pressure dependence of transport,Raman spectroscopy and synchrotron x-ray diffraction on θ-TaN up to 61 GPa.We find that θ-TaN becomes superconductive above 24.6 GPa with Tc at 3.1 K.The θ-TaN is of n-type carrier nature with carrier density about 1.1 × 1020/cm3 at 1.2 GPa and 20 K, while the carrier density increases with the pressure and saturates at about 40 GPa in the measured range.However,there is no crystal structure transition with pressure up to 39 GPa,suggesting the topological nature of the pressure induced superconductivity.

Influence of Different Quality Sperm on Early Embryo Morphokinetic Parameters and Cleavage Patterns:A Retrospective Time-lapse Study

To investigate whether sperm with low concentration and motility can impact preimplantation embryos and to analyze how the effects present under a time-lapse incubation system,2905 oocytes were collected from 219 couples between January 2014 and December 2015.Patients were divided into three groups according to sperm quality.Morphokinetic parameters and six cleavage patterns in the initial three cleavages were evaluated using the Primo Vision system.Embryo quality and clinic outcomes such as implantation rate,pregnancy rate and live birth rate were measured.The results showed that the concentration and motility of sperm correlated strongly with the rate of 2PN embryos,good-quality embryos on D3,blastocysts on D5/6 and good quality embryos on D5/6.The time-lapse system recordings showed that compromised sperm quality could result in a significant delay in cc l and a decrease in cc2,and impact embryo developmental potential mainly through large fragments or/and blastomere fragmentation in the initial three cleavages.In conclusion,sperm with low concentration and motility can have paternal effects on preimplantation embryos.These paternal effects present both as changes in morphokinetic parameters and cleavage patterns,which occur as early as fertilization and may cause severe damage to the preimplantation embryos.

Federated Learning on Multimodal Data:A Comprehensive Survey

With the growing awareness of data privacy,federated learning(FL)has gained increasing attention in recent years as a major paradigm for training models with privacy protection in mind,which allows building models in a collaborative but private way without exchanging data.However,most FL clients are currently unimodal.With the rise of edge computing,various types of sensors and wearable devices generate a large amount of data from different modalities,which has inspired research efforts in multimodal federated learning(MMFL).In this survey,we explore the area of MMFL to address the fundamental challenges of FL on multimodal data.First,we analyse the key motivations for MMFL.Second,the currently proposed MMFL methods are technically classified according to the modality distributions and modality annotations in MMFL.Then,we discuss the datasets and application scenarios of MMFL.Finally,we highlight the limitations and challenges of MMFL and provide insights and methods for future research.

Affection of Single-Nucleotide Polymorphisms in miR-27a, miR-124a, and miR-146a on Susceptibility to Type 2 Diabetes Mellitus in Chinese Han People

Background：Polymorphisms of microRNA （miRNA）,as a novel mechanism,are closely associated with disease states by interfering with miRNA function.Direct correlations have been identified between single-nucleotide polymorphisms （SNPs） in miRNA,but the effect on type 2 diabetes mellitus （T2DM） onset among Chinese population remains unclear.Therefore,the aim of this study was to identify correlations between common SNPs in miR-27a,miR-146a,and miR-124a with T2DM among a Chinese population,as well as to explore diabetic pathological mechanisms and the impact of environmental factors.Methods：SNPscan technology was used to genotype 995 patients newly diagnosed with T2DM and 967 controls.Logistic regression analysis was performed to compare mutation frequencies between cases and controls.Results：We found no significant correlations between all genotypes of these miRNAs and T2DM in our research.However,stratification analysis identified a lower risk of T2DM associated with the rs531564GC genotype among younger subjects （age ＜ 45 years） （adjusted P =0.043; odds ratio [OR] =0.73; 95％ confidence interval [CI] =0.54-0.99）.Furthermore,the rs895819CC genotype in overweight people （24 ＜ body mass index [BMI] ＜ 28） was significantly associated with an increased risk of T2DM （adjusted P =0.042; OR =1.73; 95％ CI =1.02-2.94）,while the rs2910164 genotype in miR-146a was not significantly correlated with T2DM.The genetic risk score was calculated based on the number of risk alleles of the three SNPs and was found to be correlated to total cholesterol （adjusted P =0.021）.Conclusions：The rs531564GC genotype acted as a protective factor to decrease the risk of T2DM in younger subjects （age ＜ 45 years）,while the presence of the rs895819CC genotype increased the risk of illness among overweight subjects （24 ＜ BMI ＜ 28 kg/m2）.The presence of SNPs in miRNA might promote disease by affecting miRNA expression and gene function.Thus,miRNA mimics or inhibitors that directly regulate miRNA expression present novel and promising therapeutic targets.

Relationship between Modulator Recognition Factor 2/AT-rich Interaction Domain 5B Gene Variations and Type 2 Diabetes Mellitus or Lipid Metabolism in a Northern Chinese Population

Background： Four single nucleotide polymorphisms （SNPs） in the modulator recognition factor 2/AT-rich interaction domain 5B （MRF2/ARID5B） gene located at chromosome 10q21,2 have been shown to be associated with both type 2 diabetes mellitus （T2DM） and coronary artery disease in a Japanese cohort. This study aimed to investigate the relationship between these SNPs （rs2893880, rs10740055, rs7087507, rs10761600） and new-onset T2DM and lipid metabolism in a Northern Chinese population. Methods： This was a case-control study. The rs2893880, rs10740055, rs7087507, and rs10761600 genetic variants were genotyped by SNPscan and analyzed in relation to T2DM susceptibility in 2000 individuals （090 with newly diagnosed T2DM and 1001 controls without diabetes mellitus）. Associations between the MRF2/ARID5B genetic models and T2DM were determined by multivariate logistic regression. Results： Regarding the rs 10740055 SNP, AA was associated with a higher risk of T2DM compared with codominant-type CC （adjusted by sex, age, and body mass index [BMI], P = 0.041, odds ratio [OR] = 1.421, 95% confidence interval [C1 ] 1.014-1.991）. Meanwhile, AA individuals were at increased risk of presenting with T2DM compared with individuals with CC or a single C （adjusted by sex, age, and BMI, P = 0.034, OR = 1.366, 95% CI 1.023-1.824）. With respect to rsl0761600, AT contributed to a higher risk of T2DM compared with AA （adjusted by sex, age, and BMI, P = 0.013, OR = 1.585, 95% CI 1.101-2.282）, while TT also increased the risk of presenting with T2DM compared with AA or A （adjusted by sex, age, and BMI, P = 0.004, OR = 1.632, 95% CI 1.166-2.284）. High-density lipoprotein cholesterol （HDL-C） levels were significantly different among the three genotypes of rs7087507 in the controls （P = 0.048） （GG〉GA）. Conclusions： The present results identified MRF2/AR1D5B as a potential susceptibility gene for new-onset T2DM in a Northern Chinese population, while the rs7087507 SNP was associated with HDL-C levels. Further larger studies are required to validate these findings.

Strong,Removable,and Photoluminescent Hyperbranched Polyamide-amine Hot Melt Adhesive

The development of adhesive technology is gaining increasing attention in machinery,electronics,aviation,and other fields.However,traditional adhesives are difficult to be peeled and removed after cross-linking and curing due to the limited solubility in common solvents,which causes pollution and damage to the surface of the adherend.In this work,we synthesized random hyperbranched polyamide-amine hot melt adhesives through Michael addition of 1,8-octanediamine and N,N’-methylene diacrylamide(ODA-RHP HMA).Owing to the presence of various polar groups,ODA-RHP HMA exhibited robust lap shear strength to different substrates,including glass(6.6 MPa),ceramics(10.3 MPa),steel(11.5 MPa),and aluminum(11.8 MPa).Due to the hydrogen bonds in ODA-RHP,the HMA demonstrated intrinsic self-healing ability,which can be used repeatedly when being subjected to cyclic heating and cooling.Since ODA-RHP HMA can be swollen or dissolved in ethanol,the adhesives can be easily removed through erasing.In addition,ODA-RHP exhibited aggregation-induced luminescence due to the tertiary amine structure in the molecular structure of ODA-RHP,which can be used in the field of cultural relics restoration.

Facile preparation of Nb_(2)O_(5) microspheres and their excellent electrochemical performance in aqueous zinc-ion hybrid supercapacitors

The aqueous solution-based zinc-ion hybrid supercapacitors(ZHSCs)have attracted immense attention as they are characterized by high power and energy densities.Electrode materials with high performance should be developed for ZHSCs to resolve power imbalances between capacitor-and battery-type electrode materials.To address this issue,Nb_(2)O_(5) microspheres(with the structure like sweet dumplings with exposed stuffing)were produced following a hydrothermal process which was followed by a high-temperature calcination process.The specific capacity of the as-synthesized Nb_(2)O_(5) microspheres was up to 324 F·g^(-1) when the current density was 0.1 A·g^(-1),and the long-term capacity retention was 85%at the end of 5000 cycles.The results revealed that the nanospheres could be used as battery-type electrode materials for the fabrication of ZHSCs.Nb_(2)O_(5)//AC ZHSCs were fabricated with Nb_(2)O_(5) microspheres as the negative electrode materials,and activated carbon(AC)was used as the positive electrode material.As a result,a specific capacity of 108 F·g^(-1) was achieved when the current density was 0.1 A·g^(-1).The power density was high(8020 W·kg^(-1))at 28 Wh·kg^(-1),and the energy density was high(60 Wh·kg^(-1))at 100 W·kg^(-1).The structurally novel Nb_(2)O_(5) microspheres can be potentially used for the development of the next-generation ZHSCs that exhibit excellent performance.

The Use of Goal Attainment Scaling in the Acupuncture of Children with Intellectual Disability

Objective: The therapeutic effect of acupuncture is often evaluated based on the experience and judgment of acupuncturists and the subjective feelings of patients. Thus, we investigated the suitability of goal attainment scaling(GAS), an objective outcome measurements, to evaluate the responsiveness of children with intellectual disability to acupuncture therapy. Methods: This is an assessor-blinded, single-group cohort study that included 17 children with intellectual disabilities. The therapeutic effect of acupuncture was assessed by the T scores of GAS at four time points during the 3-month treatment. The responsiveness of GAS to acupuncture therapy was measured using the standardized response mean(SRM). Results: Compared with control, the 4-, 8-, and 12-week scores improved significantly after treatment(P < 0.01, P≤0.001,P≤0.001), with significant differences between each month(P < 0.01, P≤0.001, P≤0.001). Furthermore, all periods assessed GAS(to measure the therapeutic effect of acupuncture) showed marked responsiveness(SRMs >0.8). Conclusion: GAS is responsive in evaluating individual changes in the acupuncture treatment of children with intellectual disabilities. It is a feasible tool to match both the needs of children with intellectual disabilities and the clinical characteristics of acupuncture.