Development of a clinical prediction model for diabetic kidney disease with glucose and lipid metabolism disorders based on machine learning and bioinformatics technology.

OBJECTIVE: In this study, we investigated the internal relationship between the pathogenesis of diabetic kidney disease (DKD) and abnormal glucose and lipid metabolism to identify potential biomarkers for diagnosis and treatment and investigated the role of the immune microenvironment of glucose and lipid metabolism disorders in the occurrence and progression of DKD. MATERIALS AND METHODS: The chip datasets GSE104948 and GSE96804 from the Gene Expression Common Database (GEO) were merged using the "lima" and "sva" software packages in R Software (4.2.3), and the merged dataset was used as the validation set. The intersection between the differential genes of DKD and the glucose and lipid metabolism genes in the MSigDB database was identified, and a nomogram of the incidence risk of DKD was built using three machine learning methods, namely LASSO regression, support vector machine (SVM), and random forest (RF), to validate the accuracy of the prediction model. Immune scores were conducted using the unsupervised clustering method, and patients were divided into two subgroups. The two subgroups were screened for differential genes for enrichment analysis. The differential genes of patients diagnosed with DKD were clustered into two gene subgroups for co-expression analysis. In this study, we utilized the Cytoscape software to construct a network of interactions among key genes. RESULTS: Using machine learning, a diagnostic model was developed with G6PC and HSD17B14 as key factors. Enrichment analysis and immune scoring demonstrated that the development of DKD was related to the imbalance in the microenvironment brought about by glucose lipid metabolism disorders. CONCLUSIONS: G6PC and HSD17B14 may be potential biomarkers for DKD, and the established predictive model is more helpful in predicting the incidence of DKD.

[Clinicopathological features of early gastric cancer after Helicobacter pylori eradication].

Objective: To investigate the clinicopathological features of early gastric cancers after Helicobacter pylori (H. pylori) eradication. Methods: The clinical data of 26 cases of gastric cancer that were diagnosed after H. pylori eradication and 45 cases without H. pylori eradication in the 989 Hospital of the Joint Logistics Support Force of the People's Liberation Army (the former 152 Hospital), Pingdingshan, China from 2013 to 2021 were collected. The histological, immunophenotypic and clinical characteristics of the two groups were compared, and discussed with review of the related literature. Results: Among the gastric cancer patients with H. pylori eradication, there were 20 males and 6 females with a median age of 65 years (range 53 to 77 years). The cancer involved the upper part of the stomach in 12 cases, the middle part of the stomach in 4 cases, and the lower part of the stomach in 10 cases. The median diameter of the tumors was 12 mm (range 4-29 mm). According to the Paris Classification, 4 cases were 0-Ⅱa, 4 cases were 0-Ⅱb, 18 cases were 0-Ⅱc. White light endoscopy showed that the lesions were reddish to yellowish. The lesion boundary was clear in 12 cases and was unclear or gastritis-like changes in 14 cases, while the irregular microvascular structure and microsurface structure, as well as the relatively visible spinous boundary, were visible under narrow-band imaging. There were 20 cases of well-differentiated tubular adenocarcinoma, 4 cases of highly to moderately differentiated tubular adenocarcinoma, and 2 cases of well-differentiated tubular adenocarcinoma with papillary adenocarcinoma. Compared with gastric cancers without H. pylori eradication, gastric cancers diagnosed after H. pylori eradication was associated with lower nucleus-cytoplasm ratio (<50%), normal epithelial coverage on the cancer surface, mild atypical epithelial coverage on the cancer surface, elongation of non-cancerous glands in the cancer tissue and subepithelial progression of cancerous glands were higher (P<0.05). The cellular immunophenotypes were gastric type in 6 cases, intestinal type in 4 cases and gastrointestinal mixed type in 16 cases. Conclusions: The early gastric cancers diagnosed after H. pylori eradication are more subtle clinically and mostly well-differentiated tubular adenocarcinoma. The important morphological features of gastric cancer diagnosed after H. pylori eradication are decreased cytological atypia and overlying normal epithelium or mildly atypical epithelium of the cancer. Understanding and recognizing these morphological features are helpful to make correct endoscopic and pathological diagnoses.

A 63-bp insertion in exon 2 of the porcine KIF21A gene is associated with arthrogryposis multiplex congenita.

A recessive form of arthrogryposis multiplex congenita (AMC) was detected 20 years ago in the Swiss Large White (SLW) pig population. A diagnostic marker test enabled the identification of carrier animals, but the underlying causal mutation remains unknown. To identify the mutation underlying AMC, we collected SNP chip genotyping data for 11 affected piglets and 23 healthy pigs. Association testing using 47 829 SNPs confirmed that AMC maps to SSC5 (P = 9.4 × 10-13 ). Subsequent autozygosity mapping revealed a common 6.06 Mb region (from 66 757 970 to 72 815 151 bp) of extended homozygosity in 11 piglets affected by AMC. Using WGS data, we detected a 63-bp insertion compatible with the recessive inheritance of AMC in the second exon of KIF21A gene encoding Kinesin Family Member 21A. The 63-bp insertion is predicted to introduce a premature stop codon in KIF21A gene (p.Val41_Phe42insTer) that truncates 1614 amino acids (~97%) from the protein. We found that this deleterious allele still segregates at a frequency of 0.1% in the SLW pig population. Carrier animals can now be detected unambiguously and excluded from breeding.

Genome-wide association study for αS1- and αS2-casein phosphorylation in Dutch Holstein Friesian.

Phosphorylation of caseins (CN) is a crucial post-translational modification that allows caseins to form colloid particles known as casein micelles. Both αS1- and αS2-CN show varying degrees of phosphorylation (isoforms) in cow milk and were suggested to be more relevant for stabilizing internal micellar structure than ß- and κ-CN. However, little is known about the genetic background of individual αS2-CN phosphorylation isoforms and the phosphorylation degrees of αS1- and αS2-CN (αS1-CN PD and αS2-CN PD), defined as the proportion of isoforms with higher degrees of phosphorylation in total αS1- and αS2-CN, respectively. We aimed to identify genomic regions associated with these traits using 50K single nucleotide polymorphisms for 1,857 Dutch Holstein Friesian cows. A total of 10 quantitative trait loci (QTL) regions were identified for all studied traits on 10 Bos taurus autosomes (BTA1, 2, 6, 9, 11, 14, 15, 18, 24, and 28). Regions associated with multiple traits were found on BTA1, 6, 11, and 14. We showed 2 QTL regions on BTA1, one affecting αS2-CN production and the other harboring the SLC37A1 gene, which encodes a phosphorus antiporter and affects αS1- and αS2-CN PD. The QTL on BTA6 harbors the casein gene cluster and affects individual αS2-CN phosphorylation isoforms. The QTL on BTA11 harbors the PAEP gene that encodes for ß-lactoglobulin and affects relative concentrations of αS2-CN-10P and αS2-CN-11P as well as αS1-CN PD and αS2-CN PD. The QTL on BTA14 harbors the DGAT1 gene and affects relative concentrations of αS2-CN-10P and αS2-CN-11P as well as αS1-CN PD and αS2-CN PD. Our results suggest that effects of identified genomic regions on phosphorylation of αS1- and αS2-CN are related to changes in milk synthesis and phosphorus secretion in milk. The actual roles of SLC37A1, PAEP, and DGAT1 in αS1- and αS2-CN phosphorylation in Dutch Holstein Friesian require further investigation.

Elliptically bent crystal x-ray spectrometer for time-resolved laser plasma experiments.

Measuring time-resolved spectra is crucial in inertial confinement fusion and radiation source development experiments. An elliptically bent crystal spectrometer is designed to measure X-rays in the range of 2.5-11.0 keV, which was achieved using four different lattice spacings of 0.8512, 0.6687, 0.4246, and 0.2749 nm with spectral resolution E/δE of ∼500. The X-rays emitted from a source at one focus of the ellipse undergo Bragg reflection off a crystal and pass through the second focus of the ellipse to a streak camera slit with 18-mm length and 80-µm width to generate a time-resolved spectrum. An alignment method for the time-resolved spectrometer was developed with the straight line connecting the centers of the two small holes on the fabricated substrate being the axis of the ellipse, thus allowing the spacing between the source and the elliptical crystal to be tuned to couple with the streak camera. The time-resolved spectrometer's performance was experimentally tested at the Shenguang II laser facility. The results indicate that its performance is close to that predicted theoretically.

[Analysis of occupational chronic carbon disulfide poisoning: a study of 372 cases].

Objective: To investigate the clinical features of occupational chronic carbon disulfide(CS(2)) poisoning. Methods: A total of 372 patients with occupational chronic CS(2) poisoning were selected from a chemical fiber factory, and their clinical features were summarized and analyzed. Results: Major clinical manifestations of the 372 patients with occupational chronic CS(2) poisoning included sleep disorders, dizziness, headache, and numbness of limbs, and the detection rates of these manifestations were 84.7%, 84.4%, 79.8%, and 72.8%, respectively. Electroneuromyography showed peripheral nerve injuries. Conclusion: Occupational chronic CS(2) poisoning can affect the central and peripheral nervous system.

Genetic parameters for αS1-casein and αS2-casein phosphorylation isoforms in Dutch Holstein Friesian.

Relative concentrations of αS1-casein and αS2-casein (αS1-CN and αS2-CN) phosphorylation isoforms vary considerably among milk of individual cows. We estimated heritabilities for αS2-CN phosphorylation isoforms, determined by capillary zone electrophoresis from 1,857 morning milk samples, and genetic correlations among αS2-CN phosphorylation isoforms in Dutch Holstein Friesian. To investigate if phosphorylation of αS1-CN and αS2-CN are due to the same genetic mechanism, we also estimated genetic correlations between αS1-CN and αS2-CN phosphorylation isoforms as well as the genetic correlations between the phosphorylation degrees (PD) of αS1-CN and αS2-CN defined as the proportion of isoforms with higher degrees of phosphorylation in total αS1-CN and αS2-CN, respectively. The intra-herd heritabilities for the relative concentrations of αS2-CN phosphorylation isoforms were high and ranged from 0.54 for αS2-CN-10P to 0.89 for αS2-CN-12P. Furthermore, the high intra-herd heritabilities of αS1-CN PD and αS2-CN PD imply a strong genetic control of the phosphorylation process, which is independent of casein production. The genetic correlations between αS2-CN phosphorylation isoforms are positive and moderate to high (0.33-0.90). Furthermore, the strong positive genetic correlation (0.94) between αS1-CN PD and αS2-CN PD suggests that the phosphorylation processes of αS1-CN and αS2-CN are related. This study shows the possibility of breeding for specific αS1-CN and αS2-CN phosphorylation isoforms, and relations between the phosphorylation degrees of αS1-CN and αS2-CN and technological properties of milk need to be further investigated to identify potential benefits for the dairy industry.

A pinhole camera for ultrahigh-intensity laser plasma experiments.

A pinhole camera is an important instrument for the detection of radiation in laser plasmas. It can monitor the laser focus directly and assist in the analysis of the experimental data. However, conventional pinhole cameras are difficult to use when the target is irradiated by an ultrahigh-power laser because of the high background of hard X-ray emission generated in the laser/target region. Therefore, an improved pinhole camera has been developed that uses a grazing-incidence mirror that enables soft X-ray imaging while avoiding the effect of hard X-ray from hot dense plasmas.

Genetic and nongenetic factors contributing to differences in αS-casein phosphorylation isoforms and other major milk proteins.

Relative concentrations of αS-casein (αS-CN) phosphorylation isoforms vary considerably among milk of individual cows. We aimed to explore to what extent genetic and other factors contribute to the variation in relative concentrations of αS-CN phosphorylation isoforms and the phosphorylation degree of αS-CN defined as the proportion of isoforms with higher degrees of phosphorylation. We also investigated the associations of genetic variants of milk proteins and casein haplotypes with relative concentrations of αS-CN phosphorylation isoforms and with the phosphorylation degree of αS-CN in French Montbéliarde cattle from the cheese production area of Franche-Comté. Detailed milk protein composition was determined by liquid chromatography coupled with electrospray ionization mass spectrometry from 531 test-day morning milk samples. Parity, lactation stage, and genetic variation of cows contributed to the phenotypic variation in relative concentrations of individual αS-CN phosphorylation isoforms and in the phosphorylation degree of αS-CN. As lactation progressed, we observed a significant increase for relative concentrations of αS-CN isoforms with higher degrees of phosphorylation (αS1-CN-9P, αS2-CN-13P, and αS2-CN-14P) as well as for the phosphorylation degree of both αS1-CN and αS2-CN. Furthermore, the ß-CN I variant was associated with a greater proportion of isoforms with lower degrees of phosphorylation (αS1-CN-8P, αS2-CN-10P, and αS2-CN-11P); the ß-CN B variant was associated with a greater proportion of isoforms with higher degrees of phosphorylation (αS1-CN-9P, αS2-CN-12P to αS2-CN-14P). The heritability estimates were low to moderate for relative concentrations of αS2-CN phosphorylation isoforms (0.07 to 0.32), high for relative concentrations of αS1-CN-8P (0.84) and αS1-CN-9P (0.56), and moderate for phosphorylation degrees of αS1-CN (0.37) and αS2-CN (0.23). Future studies investigating relations between the phosphorylation degree of αS-CN and technological properties of milk will be beneficial for the dairy industry.

[A clinical study of serum protein markers in patients with 1-bromopropane poisoning].

Objective: To investigate the changes in protein expression in patients with 1-bromopropane (1-BP) poisoning using high-throughput proteomic technique and to screen out protein markers. Methods: Serum samples were collected from 3 patients with 1-BP poisoning and 15 controls. The label-free proteomic tech-nique was used for the quantitation and identification of proteins expressed in these samples, and the results were compared between the patients with 1-BP poisoning and the control population. The bioinformatics tools were used to analyze the function of differentially expressed proteins. Results: Compared with the control popula-tion, the patients with 1-BP poisoning had >2-fold upregulation of 38 proteins and >2-fold downregulation of 68 proteins. The differentially expressed proteins were mainly involved in immune response, signal transduction, and stress response. Conclusion: The proteins screened out may be potential protein markers for 1-BP poison-ing, which provides reliable and precise methods and thoughts for the diagnosis of 1-BP poisoning.

Slowing down light using a dendritic cell cluster metasurface waveguide.

Slowing down or even stopping light is the first task to realising optical information transmission and storage. Theoretical studies have revealed that metamaterials can slow down or even stop light; however, the difficulty of preparing metamaterials that operate in visible light hinders progress in the research of slowing or stopping light. Metasurfaces provide a new opportunity to make progress in such research. In this paper, we propose a dendritic cell cluster metasurface consisting of dendritic structures. The simulation results show that dendritic structure can realise abnormal reflection and refraction effects. Single- and double-layer dendritic metasurfaces that respond in visible light were prepared by electrochemical deposition. Abnormal Goos-Hänchen (GH) shifts were experimentally obtained. The rainbow trapping effect was observed in a waveguide constructed using the dendritic metasurface sample. The incident white light was separated into seven colours ranging from blue to red light. The measured transmission energy in the waveguide showed that the energy escaping from the waveguide was zero at the resonant frequency of the sample under a certain amount of incident light. The proposed metasurface has a simple preparation process, functions in visible light, and can be readily extended to the infrared band and communication wavelengths.

The relationships among bovine αS-casein phosphorylation isoforms suggest different phosphorylation pathways.

Casein (CN) phosphorylation is an important posttranslational modification and is one of the key factors responsible for constructing and stabilizing casein micelles. Variation in phosphorylation degree of αS-CN is of great interest because it is suggested to affect milk technological properties. This study aimed to investigate the variation in phosphorylation degree of αS-CN among milk of individual cows and to explore relationships among different phosphorylation isoforms of αS-CN. For this purpose, we analyzed morning milk samples from 529 French Montbéliarde cows using liquid chromatography coupled with electrospray ionization mass spectrometry. We detected 3 new phosphorylation isoforms: αS2-CN-9P, αS2-CN-14P, and αS2-CN-15P in bovine milk, in addition to the known isoforms αS1-CN-8P, αS1-CN-9P, αS2-CN-10P, αS2-CN-11P, αS2-CN-12P, and αS2-CN-13P. The relative concentrations of each αS-CN phosphorylation isoform varied considerably among individual cows. Furthermore, the phenotypic correlations and hierarchical clustering suggest at least 2 regulatory systems for phosphorylation of αS-CN: one responsible for isoforms with lower levels of phosphorylation (αS1-CN-8P, αS2-CN-10P, and αS2-CN-11P), and another responsible for isoforms with higher levels of phosphorylation (αS1-CN-9P, αS2-CN-12P, αS2-CN-13P, and αS2-CN-14P). Identifying all phosphorylation sites of αS2-CN and investigating the genetic background of different αS2-CN phosphorylation isoforms may provide further insight into the phosphorylation mechanism of caseins.

CD44+/CD24+ cervical cancer cells resist radiotherapy and exhibit properties of cancer stem cells.

OBJECTIVE: The aim of the study is to investigate the radiosensitivity of CD44+/CD24+ cervical cancer cells and to explore its mechanism of radiotherapy resistance. Moreover, we further to test whether the CD44+/CD24+ cervical cancer cells had the characteristics of stem cells. MATERIALS AND METHODS: The human squamous cell carcinoma SiHa cells were cultured in vitro, and CD44+/CD24+ SiHa cells were sorted by FACS analysis. CD44+/CD24+ SiHa cells and the parental SiHa cells were given several fractionated irradiation at a cumulative dose of 8 Gy, 16 Gy, 30 Gy, respectively. Survival curves were obtained and fitted using clonogenic assays, and the radiosensitivity of tumor cells was compared according to the radiobiological parameters, including Do, Dq, N and SF 2. Morphological changes of cell apoptosis were determined using Hoechst 33258 fluorescence staining. The ultrastructural changes in cells with apoptosis were observed by transmission electron microscopy. Cell apoptosis rate was determined by FCAS analysis. DNA "ladder" in apoptotic cells was detected by gel electrophoresis. The mRNA levels of cell apoptosis-related genes were detected by RT-PCR assay. Balling capacities of CD44+/CD24+ SiHa cells and parental SiHa cells were detected by suspension culture without FBS. The in vivo tumorigenicity was detected by inoculating CD44+/CD24+ SiHa and parental SiHa cells into nude mice. RESULTS: The FACS analysis results demonstrated that there was a concomitant increase in the percentage of CD44+/CD24+ cells as the increasing irradiation doses. Colony formation assay results showed that the colony formation rate of CD44+/CD24+ SiHa cells was significantly higher than that of parental SiHa cells (p < 0.05). Moreover, the data from Hoechst 33258 staining, DNA fragment gel electrophoresis, transmission electron microscopy and FACS analysis showed that CD44+/CD24+ SiHa cells had no cell apoptosis after irradiation treatment. RT-PCR results showed that the mRNA levels of bcl-2, surviving and OCT4 were significantly higher in CD44+/CD24+ SiHa cells than that of parental SiHa cells (p < 0.01). CD44+/CD24+ SiHa cells could form more compact cell spheres with a larger volume than that of parental SiHa cells (p < 0.05). CD44+/CD24+ cervical cancer cells had more potent tumorigenicity than that of parental cervical cancer cells. CONCLUSIONS: CD44+/CD24+ cervical cancer resist cell apoptosis induced by irradiation therapy and possessed the characteristics of stem cells.

[The research of proteome profiling change of 1-bromopropane poisoning cases].

Objective: This study was mainly focused on styudy on he proteome profile change between exposure to 1-Bromopropane (1-BP) and 1-BP poisoning. Methods: The samples of serums from exposure to 1-BP and 1-BP poisoning were collected and analyzed through Label free proteome technology platform. The differently expressed proteins between the two groups were quantified and identified, followed by function analysis by bioinformatics. Results: 127 proteins over 2 fold-change were selected, in which 39 proteins were up-regulated and 88 proteins were down-regulated. These different-ly expressed proteins were mainly involved in the process of enzyme active regulation, inflammatory reaction, protein modification, stress response, coagulation, transport. Conclusion: The differently expressed proteins provided the potential protein biomarkers for the early diagnosis of 1-BP poisoning and was beneficial for clinical diagnosis of 1-BP and understanding of the mechanism of 1-BP poisoning.

Genome-wide identification of aberrantly methylated promoter associated CpG islands in acute lymphocytic leukemia.

We performed a genome-wide analysis of promoter associated CpG island methylation using methylated CpG island amplification (MCA) coupled to representational differential analysis (RDA) or a DNA promoter microarray in acute lymphoblastic leukemia (ALL). We identified 65 potential targets of methylation with the MCA/RDA approach, and 404 with the MCA/array. Thirty-six (77%) of the genes identified by MCA/RDA were shared by the MCA/array approach. Chromosomal location of these genes was evenly distributed in all autosomes. Functionally, 303 of these genes clustered in 18 molecular pathways. Of the 36 shared genes, 31 were validated and 26 were confirmed as being hypermethylated in leukemia cell lines. Expression analysis of eight of these genes was epigenetically modulated by hypomethylating agents and/or HDAC inhibitors in leukemia cell lines. Subsequently, DNA methylation of 15 of these genes (GIPC2, RSPO1, MAGI1, CAST1, ADCY5, HSPA4L, OCLN, EFNA5, MSX2, GFPT2, GNA14, SALL1, MYO5B, ZNF382 and MN1) was validated in primary ALL samples. Patients with methylation of multiple CpG islands had a worse overall survival. This is the largest published list of potential methylation target genes in human leukemia offering the possibility of performing rational unbiased methylation studies in ALL.

G-CSF-mobilized peripheral blood mononuclear cells from diabetic patients augment neovascularization in ischemic limbs but with impaired capability.

BACKGROUND: Autologous transplantation of mobilized peripheral blood mononuclear cells (M-PBMNCs) is a novel approach to improve critical limb ischemia (CLI) in diabetes. However, endothelial progenitor cells (EPCs) from diabetes are dysfunctional and impaired in ischemia-induced neovascularization. OBJECTIVE: This study aimed to confirm the compromised efficiency of diabetic M-PBMNCs in therapeutic neovascularization, and to determine the underlying mechanisms of this impairment. METHODS: Diabetic M-PBMNCs from 17 diabetic patients or healthy controls, or phosphate-buffered saline (PBS) were injected into the ischemic limbs of streptozotocin-induced diabetic nude mice. The limb blood perfusion, ambulatory score, ischemia damage, capillary/fiber ratio, arteriole density, collateral vessel formation, and pericytes recruitment were evaluated between these three groups. Non-invasive real time image and histopathology were used to detect the in vivo role of transplanted M-PBMNCs. Proliferation and adhesion of EPCs were assayed. In vitro vascular network incorporation and matrigel plug assay were used to test the pro-neovascularization role of M-PBMNCs. RESULTS: Transplantation of diabetic M-PBMNCs also improved neovascularization, but to a lesser extent from that observed with non-diabetic ones. This was associated with the impairment of diabetic M-PBMNCs capacity to differentiate into EPCs, to incorporate into vessel-like tubules in vitro, to participate in vascular-like structure formation in a subcutaneous matrigel plug, and to stimulate the recruitment of pericytes/smooth muscle cells. In addition, there was impairment in vasculogenesis, which was related to the reduced adhesion ability of EPCs from diabetic M-PBMNCs. CONCLUSIONS: Diabetes reduced the capacity of M-PBMNCs to augment neovascularization in ischemia.

The transcription factor E2F: a crucial switch in the control of homeostasis and tumorigenesis.

The transcription factor E2F plays a crucial role in governing cell proliferation through manipulation of the expression of many genes required for cell cycle progression. As studies are exploring in depth, E2F has grown into a multimember family and has been required for the regulation of a large number of genes involved in various cellular processes. The expanding E2F membership and biological function provide us some new insights relating to the evolution of E2F. One of them is to understand the exact mechanisms by which E2F executes in these different cellular processes during ontogenesis. This review summarizes recent advances in this field, with an emphasis on a notion that E2F acts as a molecular switch in the control of both normal cell and tumor development.

ATM induction insufficiency in a radiosensitive breast-cancer patient.

The ataxia telangiectasia (A-T) gene (ATM) is a dominant breast cancer gene with tumour suppressor activity. ATM also regulates cellular sensitivity to ionising radiation (IR) presumably through its role as a facilitator of DNA repair. In normal cells and tissues the ATM protein is rapidly induced by IR to threshold/maximum levels. The kinase function of the ATM protein is also rapidly activated in response to IR. The fact that women carriers of ATM mutations can have an increased risk of developing breast cancer and that many sporadic breast tumours have reduced levels of the ATM protein broadens the scope of ATM's tumour suppressor within the breast. This report describes the downregulation of ATM protein levels in a radiosensitive breast cancer patient. Postinduction ATM levels were up to tenfold lower in the patient's fresh tissues compared to normal controls. These results might indicate a much broader role for ATM anomalies in breast cancer aetiology.