Robust poor man's Majorana zero modes using Yu-Shiba-Rusinov states.

Kitaev chains in quantum dot-superconductor arrays are a promising platform for the realization of topological superconductivity. As recently demonstrated, even a two-site chain can host Majorana zero modes known as "poor man's Majorana". Harnessing the potential of these states for quantum information processing, however, requires increasing their robustness to external perturbations. Here, we form a two-site Kitaev chain using Yu-Shiba-Rusinov states in proximitized quantum dots. By deterministically tuning the hybridization between the quantum dots and the superconductor, we observe poor man's Majorana states with a gap larger than 70 µeV. The sensitivity to charge fluctuations is also greatly reduced compared to Kitaev chains made with non-proximitized dots. The systematic control and improved energy scales of poor man's Majorana states realized with Yu-Shiba-Rusinov states will benefit the realization of longer Kitaev chains, parity qubits, and the demonstration of non-Abelian physics.

Discovery of a Series of 4-Amide-thiophene-2-carboxyl Derivatives as Highly Potent P2Y14 Receptor Antagonists for Inflammatory Bowel Disease Treatment.

The P2Y14 receptor has been proven to be a potential target for IBD. Herein, we designed and synthesized a series of 4-amide-thiophene-2-carboxyl derivatives as novel potent P2Y14 receptor antagonists based on the scaffold hopping strategy. The optimized compound 39 (5-((5-fluoropyridin-2-yl)oxy)-4-(4-methylbenzamido)thiophene-2-carboxylic acid) exhibited subnanomolar antagonistic activity (IC50: 0.40 nM). Moreover, compound 39 demonstrated notably improved solubility, liver microsomal stability, and oral bioavailability. Fluorescent ligand binding assay confirmed that 39 has the binding ability to the P2Y14 receptor, and molecular dynamics (MD) simulations revealed the formation of a unique intramolecular hydrogen bond (IMHB) in the binding conformation. In the experimental colitis mouse model, compound 39 showed a remarkable anti-IBD effect even at low doses. Compound 39, with a potent anti-IBD effect and favorable druggability, can be a promising candidate for further research. In addition, this work lays a strong foundation for the development of P2Y14 receptor antagonists and the therapeutic strategy for IBD.

A two-site Kitaev chain in a two-dimensional electron gas.

Artificial Kitaev chains can be used to engineer Majorana bound states (MBSs) in superconductor-semiconductor hybrids1-4. In this work, we realize a two-site Kitaev chain in a two-dimensional electron gas by coupling two quantum dots through a region proximitized by a superconductor. We demonstrate systematic control over inter-dot couplings through in-plane rotations of the magnetic field and via electrostatic gating of the proximitized region. This allows us to tune the system to sweet spots in parameter space, where robust correlated zero-bias conductance peaks are observed in tunnelling spectroscopy. To study the extent of hybridization between localized MBSs, we probe the evolution of the energy spectrum with magnetic field and estimate the Majorana polarization, an important metric for Majorana-based qubits5,6. The implementation of a Kitaev chain on a scalable and flexible two-dimensional platform provides a realistic path towards more advanced experiments that require manipulation and readout of multiple MBSs.

Retracted: Marchantin M Induces Apoptosis of Prostate Cancer Cells Through Endoplasmic Reticulum Stress.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Tian-Wei Zhang, Li Xing, Jun-Long Tang, Jing-Xiao Lu, Chun-Xiao Liu. Marchantin M Induces Apoptosis of Prostate Cancer Cells Through Endoplasmic Reticulum Stress. Med Sci Monit, 2015; 21: 3570-3576. DOI: 10.12659/MSM.894476.

Realization of a minimal Kitaev chain in coupled quantum dots.

Majorana bound states constitute one of the simplest examples of emergent non-Abelian excitations in condensed matter physics. A toy model proposed by Kitaev shows that such states can arise at the ends of a spinless p-wave superconducting chain1. Practical proposals for its realization2,3 require coupling neighbouring quantum dots (QDs) in a chain through both electron tunnelling and crossed Andreev reflection4. Although both processes have been observed in semiconducting nanowires and carbon nanotubes5-8, crossed-Andreev interaction was neither easily tunable nor strong enough to induce coherent hybridization of dot states. Here we demonstrate the simultaneous presence of all necessary ingredients for an artificial Kitaev chain: two spin-polarized QDs in an InSb nanowire strongly coupled by both elastic co-tunnelling (ECT) and crossed Andreev reflection (CAR). We fine-tune this system to a sweet spot where a pair of poor man's Majorana states is predicted to appear. At this sweet spot, the transport characteristics satisfy the theoretical predictions for such a system, including pairwise correlation, zero charge and stability against local perturbations. Although the simple system presented here can be scaled to simulate a full Kitaev chain with an emergent topological order, it can also be used imminently to explore relevant physics related to non-Abelian anyons.

[Transurethral bipolar isokinetic anatomical enucleation for giant (> 300 g) prostatic hyperplasia: Report of 5 cases and review of the literature].

OBJECTIVE: To explore the application prospect and clinical efficacy of transurethral plasmakinetic enucleation of the Giant prostatic hyperplasia. METHODS: The clinical data of 5 patients with Giant prostatic hyperplasia treated by transurethral plasmakinetic enucleation in our department from december 2021 to january 2023 were retrospectively analyzed. RESULTS: All 5 patients successfully completed the operation, aged 69－80 years (73.2±4.32),PSA level was 8.07～42.90ng/ml (22.81±13.97), prostate volume was 321.05－534.26g (388.34±84.26), enucleation time was 120－240 min (174±61.48), Gland processing time 40－120 min（63±32.71). There were 1 case of perforation of prostate capsule and severe hematuria，3 cases of blood transfusion. 2 cases of transient urinary incontinence were improved after 2 weeks and 4 months postoperative respectively. International Prostate Symptom Score (IPSS),and quality of life score (QoL) and Maximum urine flow rate(Qmax) were significantly improved compared with preoperative parameters. CONCLUSION: It is safe and effective to treat GPH with plasma enucleation through urethra with skilled plasma enucleation technique.

Singlet and triplet Cooper pair splitting in hybrid superconducting nanowires.

In most naturally occurring superconductors, electrons with opposite spins form Cooper pairs. This includes both conventional s-wave superconductors such as aluminium, as well as high-transition-temperature, d-wave superconductors. Materials with intrinsic p-wave superconductivity, hosting Cooper pairs made of equal-spin electrons, have not been conclusively identified, nor synthesized, despite promising progress1-3. Instead, engineered platforms where s-wave superconductors are brought into contact with magnetic materials have shown convincing signatures of equal-spin pairing4-6. Here we directly measure equal-spin pairing between spin-polarized quantum dots. This pairing is proximity-induced from an s-wave superconductor into a semiconducting nanowire with strong spin-orbit interaction. We demonstrate such pairing by showing that breaking a Cooper pair can result in two electrons with equal spin polarization. Our results demonstrate controllable detection of singlet and triplet pairing between the quantum dots. Achieving such triplet pairing in a sequence of quantum dots will be required for realizing an artificial Kitaev chain7-9.

Discovery of a Series of 5-Amide-1H-pyrazole-3-carboxyl Derivatives as Potent P2Y14R Antagonists with Anti-Inflammatory Characters.

UDPG/P2Y14R signaling pathway has been considered as a potential therapeutic target for innate immune system diseases. Based on the scaffold hopping strategy, a series of pyrazole analogues were designed and synthesized as novel P2Y14R antagonists with improved physicochemical properties, together with potential anti-inflammatory activities. Additionally, we designed and synthesized a fluorescent probe based on highly selective and potent PPTN to study the affinity of synthesized compounds. The optimized compound 16 (1-(4-fluorobenzyl)-5-(4-methylbenzamido)-1H-pyrazole-3-carboxylic acid, P2Y14R IC50 = 1.93 nM) showed strong binding ability to P2Y14R, high selectivity, notably improved solubility, and more favorable pharmacokinetic profiles. Moreover, compound 16 possessed extremely low cytotoxicity and anti-inflammatory effect in vitro. In an acute peritonitis model, compound 16 could effectively reduce the levels of inflammatory factor IL-6, IL-1ß, and TNF-α of mice induced by LPS. Compound 16, with potent in vitro and in vivo efficacy and favorable druggability, can be a promising candidate for further research.

Association of RDW, NLR, and PLR with Atrial Fibrillation in Critical Care Patients: A Retrospective Study Based on Propensity Score Matching.

Objective: Previous studies have shown inconsistent results in relation to the red cell distribution width (RDW), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) of atrial fibrillation (AF). This retrospective study is aimed at detecting the association of RDW, NLR, and PLR with AF. Methods: A total of 4717 critical care patients were screened from the Medical Information Mart for Intensive Care- (MIMIC-) III database. The patients were separated into the non-AF and AF groups. The imbalances between the groups were reduced using propensity score matching (PSM). ROC curves were generated to detect the diagnostic value of RDW, NLR, and PLR. Logistic regression analysis was used to detect the risk factors for AF. Results: A total of 991 non-AF patients paired with 991 AF patients were included after PSM in this study. The RDW level in the AF group was significantly higher than that in the non-AF group (15.09 ± 1.93vs. 14.89 ± 1.91, P = 0.017). Neither NLR nor PLR showed any significant difference between the two groups (P > 0.05 for each). According to ROC curve, RDW showed a very low diagnostic value of AF (AUC = 0.5341), and the best cutoff of RDW was 14.1 (ACU = 0.5257, sensitivity = 0.658, specificity = 0.395). Logistic regression analysis showed that an elevated RDW level increased 1.308-fold (95%CI = 1.077-1.588, P = 0.007) risk of AF. Neither elevated NLR nor elevated PLR was a significant risk factor for AF (OR = 0.993, 95%CI = 0.802-1.228, P = 0.945 for NLR; OR = 0.945, 95%CI = 0.763-1.170, P = 0.603 for PLR). Conclusions: Elevated RDW level but not NLR or PLR levels is associated with AF. RDW > 14.1 is a risk factor for AF, but its diagnostic capacity for AF is not of great value.

EHBP1, TUBB, and WWOX SNPs, Gene-Gene and Gene-Environment Interactions on Coronary Artery Disease and Ischemic Stroke.

The associations among the EH domain-binding protein 1 (EHBP1), tubulin beta class I (TUBB), and WW domain-containing oxidoreductase (WWOX) single nucleotide polymorphisms (SNPs) and coronary artery disease (CAD) and ischemic stroke (IS) are not yet understood. This study aimed to detect the associations of these SNPs, gene-gene and gene-environment interactions and CAD and IS in the Guangxi Han population. A total of 1853 unrelated subjects were recruited into normal control (n = 638), CAD (n = 622), and IS (n = 593) groups. Related genotypes were determined by high-throughput sequencing. The genotypic and minor allelic frequencies of rs2278075 were different between the CAD and control groups, and those of rs2710642, rs3130685, and rs2278075 were also different between the IS and control groups. The rs2278075T allele, rs3130685-rs2222896-rs2278075, rs3130685-rs2222896-diabetes, rs3130685-rs2222896-drinking, and haplotype rs2710642A-rs10496099C-diabetes interactions were associated with increased risk, while G-T-G-C-G-A and G-T-T-T-G-T-drinking were associated with reduced risk of CAD. The rs2278075T and rs2710642G alleles, rs2710642G-rs10496099C haplotype, rs3130685-rs2278075-rs2222896, and rs2710642-rs2278075-hypertension interactions aggravated the association with IS, whereas the rs3130685T allele, rs2710642A-rs10496099C haplotype and the interactions of H1 (s2710642A-rs10496099C)-H2 (rs2710642G-rs10496099C)-drinking and I1 (A-C-G-C-A-A)-I3 (A-C-G-T-A-A)-I4 (A-C-G-T-G-A)-I5 (G-T-G-C-G-A) diminished the association with IS. Carrying WWOX rs2278075T was strongly associated with CAD or IS, while EHBP1 rs2710642 and TUBB rs3130685 might alter the association of IS by modifying the serum lipid profile. This study demonstrates that the EHBP1, TUBB, and WWOX SNPs, gene-gene and gene-environment interactions are associated with the risk of CAD and IS in the Guangxi Han population.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition).

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Tunable Superconducting Coupling of Quantum Dots via Andreev Bound States in Semiconductor-Superconductor Nanowires.

Semiconductor quantum dots have proven to be a useful platform for quantum simulation in the solid state. However, implementing a superconducting coupling between quantum dots mediated by a Cooper pair has so far suffered from limited tunability and strong suppression. This has limited applications such as Cooper pair splitting and quantum dot simulation of topological Kitaev chains. In this Letter, we propose how to mediate tunable effective couplings via Andreev bound states in a semiconductor-superconductor nanowire connecting two quantum dots. We show that in this way it is possible to individually control both the coupling mediated by Cooper pairs and by single electrons by changing the properties of the Andreev bound states with easily accessible experimental parameters. In addition, the problem of coupling suppression is greatly mitigated. We also propose how to experimentally extract the coupling strengths from resonant current in a three-terminal junction. Our proposal will enable future experiments that have not been possible so far.

CYP17A1-ATP2B1 SNPs and Gene-Gene and Gene-Environment Interactions on Essential Hypertension.

Background: The association between the CYP17A1 and ATP2B1 SNPs and essential hypertension (referred to as hypertension) is far from being consistent. In addition to the heterogeneity of hypertension resulting in inconsistent results, gene-gene and gene-environment interactions may play a major role in the pathogenesis of hypertension rather than a single gene or environmental factor. Methods: A case-control study consisting of 1,652 individuals (hypertension, 816; control, 836) was conducted in Maonan ethnic minority of China. Genotyping of the four SNPs was performed by the next-generation sequencing technology. Results: The frequencies of minor alleles and genotypes of four SNPs were different between the two groups (p < 0.001). According to genetic dominance model analysis, three (rs1004467, rs11191548, and rs17249754) SNPs and two haplotypes (CYP17A1 rs1004467G-rs11191548C and ATP2B1 rs1401982G-rs17249754A) were negatively correlated, whereas rs1401982 SNP and the other two haplotypes (CYP17A1 rs1004467A-rs11191548T and ATP2B1 rs1401982A-rs17249754G) were positively associated with hypertension risk (p ≤ 0.002 for all). Two best significant two-locus models were screened out by GMDR software involving SNP-environment (rs11191548 and BMI ≥ 24 kg/m2) and haplotype-environment (CYP17A1 rs1004467G-rs11191548C and BMI ≥ 24 kg/m2) interactions (p ≤ 0.01). The subjects carrying some genotypes increased the hypertension risk. Conclusions: Our outcomes implied that the rs1004467, rs11191548, and rs17249754 SNPs and CYP17A1 rs1004467G-rs11191548C and ATP2B1 rs1401982G-rs17249754A haplotypes have protective effects, whereas the rs1401982 SNP and CYP17A1 rs1004467A-rs11191548T and ATP2B1 rs1401982A-rs17249754G haplotypes showed adverse effect on the prevalence of hypertension. Several SNP-environment interactions were also detected.

Optical planar and ridge waveguides formed in Er3+-doped germanate glass by ion implantation and precise diamond blade dicing.

In this work, we report on the preparation and characterization of the planar and ridge optical waveguides in the Er3+-doped germanate glass by combining hydrogen ion implantation and precise diamond blade dicing. The nuclear energy loss and the implantation depth were calculated by the SRIM 2013 software. The refractive index profile was obtained by the reflectivity calculation method. The dark-mode spectrum and the near-field intensity distribution were measured by the prism coupling system and end-face coupling technique, respectively. This work has important reference significance for the development of Er3+-doped germanate glass active devices in the optical communication field.

SYTL3-SLC22A3 Single-Nucleotide Polymorphisms and Gene-Gene/Environment Interactions on the Risk of Hyperlipidemia.

The current study aims to further delineate the associations between the synaptotagmin-like 3 (SYTL3) and solute carrier family 22 member 3 (SLC22A3) single-nucleotide polymorphisms (SNPs) and their haplotypes and gene-gene (G × G)/environment (G × E) interactions on the risk of hyperlipidemia (HLP) in the Maonan and Han ethnic groups. Genotype distribution among the SYTL3-SLC22A3 SNPs in 2,829 individual patients bearing no relationship to each other (Han, 1,436; Maonan, 1,393) was analyzed utilizing next-generation sequencing techniques. The genotype frequencies of the rs6455600, rs2129209, and rs446809 SNPs were varied between the two ethnic groups (P < 0.05-0.001). Various SNPs were correlated with serum levels of triglyceride (TG; rs446809), total cholesterol (TC; rs6455600, rs2129209, and rs539298), and low-density lipoprotein cholesterol (LDL-C; rs446809) among the Han population, whereas various SNPs were also correlated with TC (rs6455600 and rs539298), TG (rs446809), and LDL-C (rs446809) levels in the Maonan ethnic group (P < 0.008-0.001). One part of haplotypes resulted in worsened HLP-related morbidity in the Han (SYTL3 A-C-A-A; SLC22A3 A-A and A-G; and SYTL3-SLC22A3 A-C-A-A-A-A and A-C-A-A-A-G) and Maonan (SYTL3 A-C-A-A; SLC22A3 A-A and A-G; and SYTL3-SLC22A3 A-C-A-A-A-A, G-T-C-A-A-A, and G-T-C-A-C-A) ethnic groups, whereas another part of haplotypes lowered HLP-related health risks in the Han (SLC22A3 C-A and C-G and SYTL3-SLC22A3 A-C-A-A-C-A, A-C-A-A-C-G, and G-T-C-A-C-A) and Maonan (SLC22A3 C-G and SYTL3-SLC22A3 A-C-A-A-C-G) ethnic groups. We discovered that the SYTL3-SLC22A3 SNPs and their haplotypes were associated with serum lipid levels and the risk of HLP in our studied populations.

Associations between TUBB-WWOX SNPs, their haplotypes, gene-gene, and gene-environment interactions and dyslipidemia.

In this study, we investigated associations between single nucleotide polymorphisms (SNPs) in the tubulin beta class I (TUBB) and WW domain-containing oxidoreductase (WWOX) genes, gene-gene interactions, and gene-environment interactions and dyslipidemia in the Chinese Maonan ethnic group. Four SNPs (rs3132584, rs3130685, rs2222896, and rs2548861) were genotyped in unrelated subjects with normal lipid levels (864) or dyslipidemia (1129). While 5.0% of Maonan subjects carried the rs3132584TT genotype, none of the Chinese Han in Beijing subjects did. Allele and genotype frequencies differed between the normal and dyslipidemia groups for three SNPs (rs3132584, rs3130685, and rs2222896). rs2222896G allele carriers in the normal group had higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol levels. The rs3132584GG, rs3130685CC+TT, and rs2222896GG genotypes as well as the rs2222896G-rs2548861G and rs2222896G-rs2548861T haplotypes were associated with an elevated risk of dyslipidemia; the rs2222896A-rs2548861T and rs2222896A-rs2548861G haplotypes were associated with a reduced risk of dyslipidemia. Among the thirteen TUBB-WWOX interaction types identified, rs3132584T-rs3130685T-rs2222896G-rs2548861T increased the risk of dyslipidemia 1.371-fold. Fourteen two- to four-locus optimal interactive models for SNP-SNP, haplotype-haplotype, gene-gene, and gene-environment interactions exhibited synergistic or contrasting effects on dyslipidemia. Finally, the interaction between rs3132584 and rs2222896 increased the risk of dyslipidemia 2.548-fold and predicted hypertension.

Silencing of Gasdermin D by siRNA-Loaded PEI-Chol Lipopolymers Potently Relieves Acute Gouty Arthritis through Inhibiting Pyroptosis.

Gasdermin D (GSDMD) plays a causal role in NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis eruption, which has been regarded as a potential therapeutic target for pyroptosis-related diseases including acute gouty arthritis. In the present study, the synthesized PEI-Chol (cholesterol grafted polyethylenimine) was assembled with GSDMD small interfering RNA (siRNA) to form PEI-Chol/siGSDMD polyplexes, which provided high transfection efficiency for siRNA-mediated GSDMD knockdown. Then we evaluated the effect of GSDMD siRNA-loaded PEI-Chol on inflammatory cascades in bone-marrow-derived macrophages (BMDMs) and acute gouty arthritis animal models under MSU exposure. When accompanied by pyroptosis blockade and decreased release of interleukin-1 beta (IL-1ß), NLRP3 inflammasome activation was also suppressed by GSDMD knockdown in vivo and in vitro. Moreover, in MSU-induced acute gouty arthritis mice, blocking GSDMD with siRNA significantly improved ankle swelling and inflammatory infiltration observed in histopathological analysis. Furthermore, investigation using a mouse air pouch model verified the effect of siGSDMD-loaded PEI-Chol on pyroptosis of recruited macrophages and related signaling pathways in response to MSU. These novel findings exhibited that GSDMD knockdown relieved acute gouty arthritis through inhibiting pyroptosis, providing a possible therapeutic approach for MSU-induced acute gouty arthritis molecular therapy using PEI-Chol as a nucleic acid delivery carrier.

Association between SLC44A4-NOTCH4 SNPs and serum lipid levels in the Chinese Han and Maonan ethnic groups.

BACKGROUND: The current research was to assess the relationship of the solute carrier family 44 member 4 (SLC44A4) rs577272, notch receptor 4 (NOTCH4) rs3134931 SNPs and serum lipid levels in the Han and Maonan ethnic groups. METHODS: The genetic makeup of the SLC44A4 rs577272 and NOTCH4 rs3134931 SNPs in 2467 unrelated subjects (Han, 1254; Maonan,1213) was obtained by using polymerase chain reaction and restriction fragment length polymorphism technique, combined with gel electrophoresis, and confirmed by direct sequencing. RESULTS: The genotype frequencies of SLC44A4 rs577272 and NOTCH4 rs3134931 SNPs were different between Han and Maonan populations (P < 0.05); respectively. The SLC44A4 rs577272 SNP was associated with total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels in Maonan group. The NOTCH4 rs3134931 SNP was associated with triglyceride (TG) in Han; and TG and low-density lipoprotein cholesterol (LDL-C) levels in Maonan groups (P < 0.025-0.001). Stratified analysis according to gender showed that the SLC44A4 rs577272 SNP was associated with TC and HDL-C in Han and Maonan females; TC in Maonan males, meanwhile, the NOTCH4 rs3134931 SNP was associated with TG and HDL-C in Han males; TG in Han females; TG and LDL-C in Maonan males; and TG, HDL-C and LDL-C in Maonan females. Linkage disequilibrium analysis showed that the most common haplotype was rs577272G-rs3134931A (> 50%) in both Han and Maonan groups. The haplotype of rs577272G-rs3134931A was associated with TG and HDL-C in Han; and TC, TG and HDL-C in Maonan ethnic groups. CONCLUSIONS: These results suggest that the relationship among SLC44A4 rs577272, NOTCH4 rs3134931 SNPs and serum lipid parameters may vary depending on the gender and/or ethnicity/race in some populations. Haplotypes could explain more changes in serum lipid parameters than any single SNP alone particularly for TC, TG and HDL-C.

Potential Molecular Mechanism of the NPPB Gene in Postischemic Heart Failure with and without T2DM.

BACKGROUND: This study is aimed at investigating natriuretic peptide B (NPPB) coexpression genes and their pathways involved in heart failure (HF) among patients both with and without type 2 diabetes mellitus (T2DM). METHODS: The microarray dataset GSE26887, containing 19 postischemic HF patients' peripheral blood samples (7 with T2DM and 12 without T2DM), was examined to detect the genes coexpressed with NPPB using the corr.test function in the R packet. Furthermore, using online analytical tools, we determined the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, Gene Ontology (GO) annotation, and protein-protein interaction (PPI) network of the coexpression genes. The modules and hub genes of the PPI network were then identified using the Cytoscape software. RESULTS: In patients with T2DM, a total of 41 biological processes (BP), 20 cellular components (CC), 13 molecular functions (MF), and 41 pathways were identified. Furthermore, a total of 61 BPs, 16 CCs, 13 MFs, and 22 pathways in patients without T2DM were identified. In both groups of patients, 17 BPs, 10 CCs, 6 MFs, and 13 pathways were enriched. We also identified 173 intersectional coexpression genes (63 positively, 106 negatively, and 4 differently coexpressed in patients with and without T2DM, respectively) in both types of patients, which were enriched in 16 BPs, 8 CCs, 3 MFs, and 8 KEGG pathways. Moreover, the PPI network (containing 237 edges and 170 nodes) with the top module significantly enriched in 4 BPs (tricarboxylic acid metabolic process, citrate metabolic process, tricarboxylic acid cycle, and aerobic respiration) and 3 pathways (citrate cycle, malaria parasite metabolic pathway, and AGE-RAGE signaling pathway in diabetic complications) was constructed. DECR1, BGN, TIMP1, VCAN, and CTCF are the top hub genes. CONCLUSIONS: Our findings may elucidate the functions and roles of the NPPB gene in patients with postischemic HF and facilitate HF management.