Genetic algorithm-optimized backpropagation neural network establishes a diagnostic prediction model for diabetic nephropathy:Combined machine learning and experimental validation in mice

Background:Diabetic nephropathy(DN)is the most common complication of type 2 diabetes mellitus and the main cause of end-stage renal disease worldwide.Diagnostic biomarkers may allow early diagnosis and treatment of DN to reduce the prevalence and delay the development of DN.Kidney biopsy is the gold standard for diagnosing DN;however,its invasive character is its primary limitation.The machine learning approach provides a non-invasive and specific criterion for diagnosing DN,although traditional machine learning algorithms need to be improved to enhance diagnostic performance.Methods:We applied high-throughput RNA sequencing to obtain the genes related to DN tubular tissues and normal tubular tissues of mice.Then machine learning algorithms,random forest,LASSO logistic regression,and principal component analysis were used to identify key genes(CES1G,CYP4A14,NDUFA4,ABCC4,ACE).Then,the genetic algorithm-optimized backpropagation neural network(GA-BPNN)was used to improve the DN diagnostic model.Results:The AUC value of the GA-BPNN model in the training dataset was 0.83,and the AUC value of the model in the validation dataset was 0.81,while the AUC values of the SVM model in the training dataset and external validation dataset were 0.756 and 0.650,respectively.Thus,this GA-BPNN gave better values than the traditional SVM model.This diagnosis model may aim for personalized diagnosis and treatment of patients with DN.Immunohistochemical staining further confirmed that the tissue and cell expression of NADH dehydrogenase(ubiquinone)1 alpha subcomplex,4-like 2(NDUFA4L2)in tubular tissue in DN mice were decreased.Conclusion:The GA-BPNN model has better accuracy than the traditional SVM model and may provide an effective tool for diagnosing DN.

Green and Effective Ammonium Carbonate-assisted Process for Drying Hemicellulose Obtained through Alkali Extraction of Bleached Bamboo Kraft Pulp

Hemicellulose has a wide range of applications,including that as an emulsifier for the food industry and raw material for the synthesis of bioethanol/biochemicals and biodegradable films.Hemicellulose is usually present as a spent liquor,such as the prehydrolysis liquor of the prehydrolysis kraft dissolving pulp production process and the alkali extraction liquor of the cold caustic extraction of pulp fibers.Due to its dilute nature,hemicellulose needs to be dried for practical utilization,and this is challenging.In this study,cellulose and hemicellulose in a bleached bamboo kraft pulp were separated using an alkali extraction process.Hemicellulose obtained from the extraction liquor was dried by an ammonium carbonate-assisted drying process.The effects of drying time and drying temperature were determined.Structure of the hemicellulose obtained by the ammonium carbonate-assisted drying process was similar to that of original hemicellulose,as revealed by detailed Fourier transform infrared and X-ray diffraction analyses.The novel drying method was more energy efficient and required a shorter drying time than the conventional freeze drying method,and the excellent solubility in alkaline solutions favored the chemical modification of hemicellulose.The dried hemicellulose can be used as a renewable raw material for the preparation of hydrogels and other substances such as bioethanol/biochemicals and biodegradable films.

An integrated bioinformatics analysis and experimental study identified key biomarkers CD300A or CXCL1,pathways and immune infiltration in diabetic nephropathy mice

Diabetic nephropathy(DN)is a common microvascular complication that easily leads to end-stage renal disease.It is important to explore the key biomarkers andmolecular mechanisms relevant to diabetic nephropathy(DN).We used highthroughput RNA sequencing to obtain the genes related to DN glomerular tissues and healthy glomerular tissues of mice.Then we used LIMMA to analyze differentially expressed genes(DEGs)between DN and non-diabetic glomerular samples.And we performed KEGG,gene ontology functional(GO)enrichment,and gene set enrichment analysis to reveal the signaling pathway of the disease.The CIBERSORT algorithm based on support vector machine was used to determine the immune infiltration score.Random forest algorithm and Cytoscape obtained hub genes.Finally,we applied co-staining,immunohistochemical staining,RT-qPCR and western blotting to validate the protein and mRNA expression of both hub genes.We obtained 913 DEGs mainly related to inflammatory factors and immunity.GSEA results showed that differential genes were mainly enriched in IL-17 signaling pathway,lipid and atherosclerosis,rheumatoid arthritis,TNF signaling pathway,neutrophil extracellular trap formation,Staphylococcus aureus infection and other pathways.The intersection of the random forest algorithm and Cytoscape revealed both hub genes of CD300A and CXCL1.Experiments have shown that the both key genes of CD300A and CXCL1 shown increased expression in glomerular podocytes,and are related to the inflammation of diabetic nephropathy.And immunohistochemical staining and RT-qPCR further confirmed that the protein and mRNA expression level of CD300A or CXCL1 in glomeruli tissue in DN mice were increased.The expression levels of CD300A and CXCL1 increased significantly under HG(high glucose)stimulation,further confirming that diabetes can lead to increased levels of CD300A and CXCL1 at the cellular level.Through bioinformatics analysis,machine learning algorithms,and experimental research,CD300A and CXCL1 are confirmed as both potential biomarkers in diabetic nephropathy.And we further revealed the main pathways of differential genes and the differentially distributed immune infiltrating cells in diabetic nephropathy.

Redox-responsive phenyl-functionalized polylactide micelles for enhancing Ru complexes delivery and phototherapy

Poly(ethylene glycol)-poly(lactic acid)block copolymer(PEG-PLA)is one of the most widely used biomedical polymers in clinical drug delivery owing to its biocompatibility and biodegradability.However,endowing PEG-PLA micelles with high drug loading,self-assembly stability and fast intracellular drug release is still challenging.Redox-responsive diblock copolymers(MPEG-SS-PMLA)of poly(ethylene glycol)and phenyl-functionalized poly(lactic acid)with disulfide bond as the linker are synthesized to prepare PLA-based micelles that demonstrate excellent colloidal stability and high Ru loading.Notably,MPEGSS-PMLA achieved a remarkably high Ru loading efficiency of 84.3%due to the existence of strongπ-πstacking between phenyl and Ru complex.MPEG-SS-PMLA exhibited good colloidal stability in physiological condition but quickly destabilized by reductive tumor microenvironment.Interestingly,about 74%of Ru complex was released under 10 mmol/L GSH concentration.Ru-loaded MEPG-SS-PMLA showed efficient delivery and release of Ru complex into MCF-7 cancer cells,achieving enhanced in vitro and in vivo antitumor activity of photodynamic therapy.This feasible functionalization method of MPEG-PLA has appeared to be a clinically viable platform for controlled delivery therapeutic agents and enhanced phototherapy.

Realizing n-type CdSb with promising thermoelectric performance

Realizing high performance in both n-type and p-type materials is essential for designing efficient ther-moelectric devices.However,the doping bottleneck is often encountered,i.e.,only one type of conduction can be realized.As one example,p-type CdSb with high thermoelectric performance has been discovered for several decades,while its n-type counterpart has rarely been reported.In this work,the calculated band structure of CdSb demonstrates that the valley degeneracy is as large as ten for the conduction band,and it is only two for the valence band.Therefore,the n-type CdSb can potentially realize an ex-ceptional thermoelectric performance.Experimentally,the n-type conduction has been successfully real-ized by tuning the stoichiometry of CdSb.By further doping indium at the Cd site,an improved room-temperature electron concentration has been achieved.Band modeling predicts an optimal electron con-centration of∼2.0×1019 cm−3,which is higher than the current experimental values.Therefore,future optimization of the n-type CdSb should mainly focus on identifying practical approaches to optimize the electron concentration.

Balancing the anionic framework polarity for enhanced thermoelectric performance in YbMg_(2)Sb_(2) Zintl compounds

1-2-2-type Zintl phase compound has aroused great interest for potential thermoelectric applications.However,YbMg_(2)Sb_(2) is seldom studied due to the very low electrical conductivity resulting from the large difference in the electronegativity between Mg and Sb.In this paper,we adjust the covalently bonded network of MgeSb by replacing part of the Mg with Zn which has the electronegativity closer to that of Sb.The decreased polarity in the anionic framework offers more free distance for electrons for the enhanced Hall mobility and electrical conductivity.Together with the increased point defect and the decreased lattice thermal conductivity by introduction of Zn,the maximum ZT value of ~0.8 at 773 K is achieved in YbMg_(0.9)Zn_(1.1)Sb_(2) which is~100% enhancement compared with that of YbMg_(2)Sb_(2).

Phase Boundary Mapping in ZrNiSn Half-Heusler for Enhanced Thermoelectric Performance

The solubility range of interstitial Ni in the ZrNi1+xSn half-Heusler phase is a controversial issue,but it has an impact on the thermoelectric properties.In this study,two isothermal section phase diagrams of the Zr-Ni-Sn ternary system at 973K and 1173 K were experimentally constructed based on the binary phase diagrams of Zr-Ni,Zr-Sn,and Ni-Sn.The thermodynamic equilibrium phases were obtained after a long time of heating treatment on the raw alloys prepared by levitation melting.Solubilities of x<0:07 at 973 K and x<0:13 at 1173 K were clearly indicated.An intermediate-Heusler phase with a partly filled Ni void was observed,which is believed to be beneficial to the lowered lattice thermal conductivity.The highest ZT value~0:71 at 973 K was obtained for ZrNi_(1.11)Sn_(1.04).The phase boundary mapping provides an important instruction for the further optimization of ZrNiSn-based materials and other systems.

Dual phase equal-atomic NbTaTiZr high-entropy alloy with ultra-fine grain and excellent mechanical properties fabricated by spark plasma sintering

Super-high strength NbTaTiZr high-entropy alloys(NbTaTiZr HEAs)have been successfully fabricated by the mechanical alloying(MA)with spark plasma sintering(SPS)technology,which is 2-fold compared with that of NbTaTiZr HEAs prepared by vacuum arc melting(VAM).After the SPS process,the bulk NbTaTiZr alloy samples are provided with dual-phase body-centered cubic(BCC)structure and nanoscale grain size about 500 nm that is obviously smaller than that of NbTaTiZr HEA fabricated by VAM.When the sintering temperature is 800℃,the compressive fracture strength is the highest reaching at 2511±78 MPa.When the sintering temperature is 1000℃,the fracture strain is the highest reaching at 12.8%,and compressive fracture strength and yield strength also reach at 2274±91 MPa and 2172±47 MPa,respectively.The excellent mechanical properties of bulk NbTaTiZr alloy samples are attributed to the merits of MA and SPS,and the collaboration effect of ultra-fine grains strengthening,solid solution strengthening and interstitial solid solution strengthening.

利用点缺陷策略提高Zintl相BaAgSb的热电性能

Zintl相化合物由于其独特的"声子玻璃-电子晶体"(PGEC)结构在热电领域具有广泛的应用前景.本文报道了Zintl相热电材料BaAgSb的热电性质.通过引入Ba空位,可以提高p型BaAgSb的载流子浓度,抑制其本征激发,Ba_(0.98)AgSb的ZT值在773 K达到了~0.56.此外,在Ba位进一步合金化Eu,不仅能够引入点缺陷散射降低晶格热导率,而且由于载流子迁移率的提高使其电输运性质也得到了改善.最终,Ba_(0.78)Eu_(0.2)AgSb的ZT值在773 K达到~0.73.

Enhanced thermoelectric performance in Ti(Fe, Co, Ni)Sb pseudoternary Half-Heusler alloys

TiFe0.5Ni0.5Sb-based half-Heusler compounds have the intrinsic low lattice thermal conductivity and the adjustable band structure.Inspired by the previously reports to achieve both p-and n-type components by tuning the ratio of Fe and Ni based on the same parent TiFe0.5Ni0.5Sb,we selected Co as the amphoteric dopants to prepare both n-type and p-type pseudo-ternary Ti(Fe,Co,Ni)Sb-based halfHeusler alloys.The carrier concentration,as well as the density of states effective mass was significantly increased by Co doping,contributing to the enhanced power factor of 1.80 mW m^(-1) K^(-2) for n-type TiFe0.3Co_(0.2)Ni_(0.5)Sb and 2.21 mW m^(-1) K^(-2) for p-type TiFe_(0.5)Co_(0.15)Ni_(0.35)Sb at 973 K.Combined with the further decreased lattice thermal conductivity due to the strain field and mass fluctuation scattering induced by alloying Hf on the Ti site,peak ZTs of 0.65 in n-type Ti0.8Hf_(0.2)Fe_(0.3)Co_(0.2)Ni_(0.5)Sb and 0.85 in ptype Ti0.8Hf_(0.2)Fe_(0.5)Co_(0.15)Ni_(0.35)Sb were achieved at 973 K,which is of great significance for the thermoelectric power generation applications.