Transient interactions modulate the affinity of NF-κB transcription factors for DNA.

The dimeric nuclear factor kappa B (NF-κB) transcription factors (TFs) regulate gene expression by binding to a variety of κB DNA elements with conserved G:C-rich flanking sequences enclosing a degenerate central region. Toward defining mechanistic principles of affinity regulated by degeneracy, we observed an unusual dependence of the affinity of RelA on the identity of the central base pair, which appears to be noncontacted in the complex crystal structures. The affinity of κB sites with A or T at the central position is ~10-fold higher than with G or C. The crystal structures of neither the complexes nor the free κB DNAs could explain the differences in affinity. Interestingly, differential dynamics of several residues were revealed in molecular dynamics simulation studies, where simulation replicates totaling 148 µs were performed on NF-κB:DNA complexes and free κB DNAs. Notably, Arg187 and Arg124 exhibited selectivity in transient interactions that orchestrated a complex interplay among several DNA-interacting residues in the central region. Binding and simulation studies with mutants supported these observations of transient interactions dictating specificity. In combination with published reports, this work provides insights into the nuanced mechanisms governing the discriminatory binding of NF-κB family TFs to κB DNA elements and sheds light on cancer pathogenesis of cRel, a close homolog of RelA.

Integrated bulk and scRNA sequence identified anoikis-related diagnostic biomarkers and potential association with immune infiltration in type A aortic dissection.

Type-A aortic dissection (TAAD) is common life-threatening cardiovascular diseases with high-morbidity and mortality but the concrete etiology of disease remains unclear, which might disturb or delay the early diagnosis for TAAD. Anoikis is a special form of programmed cell-death (PCD) induced by detachment of anchorage-dependent cells from the extracellular matrix (ECM) or neighboring cells, and has been widely applied to identify anoikis-related biomarkers for the prediction and prognosis in oncological fields. However, the specific roles of anoikis-related genes (ARGs) in TAAD remain unclear. In this study, we first identified and validated eight diagnostic ARGs for TAAD based on multiple RNA-sequence datasets, including CHEK2, HIF1A, HK2, HMGA1, SERPINA1, PTPN1, SLC2A1 and VEGFA. The comprehensive functional annotation was evaluated by the integrated functional enrichments analysis. We identified the activation of inflammatory-related pathways, metabolic reprogramming and angiogenesis, and the inhibition of cardiovascular development pathways in TAAD. Immune cell infiltration (ICI) analysis further demonstrated that innate immune-cells were more dominant than adaptive immune-cells in TAAD tissues, especially in macrophages, monocytes, activated-DC, NKT cells and CD56+dim NK cells. The cellular landscape was further validated by single-cell RNA sequence technology with significant associations with anoikis in TAAD patients. Four vital ARGs (HIF1A, HMGA1, SERPINA1 and VEGFA) were ultimately identified along with the changes of differentiation trajectory, and major expressions were conformably concentrated on Macro1-3, Mono1-2 and Mono4 subtypes. These findings provide a promising diagnostic biomarker for the accurately diagnosing the disease and would be helpful to further explore the potential pathogenesis with anoikis process for TAAD.

METTL3-induced FGD5-AS1 contributes to the tumorigenesis and PD-1/PD-L1 checkpoint to enhance the resistance to paclitaxel of endometrial carcinoma.

Endometrial cancer (EC), a widely occurring cancer in the uterus, is among the top four most frequent malignancies in women. To improve approaches for combating this disease, it is essential to gain a more comprehensive comprehension of the intricate causes of EC. Accumulating evidence highlight the essential role of long non-coding RNA (LncRNA) in EC progression, while its biological and mechanical function has not been fully revealed. In this study, a LncRNA microarray analysis was performed using four pairs of paclitaxel (PTX) resistant EC cells, FGD5-AS1 was identified as a significantly upregulated gene. Biologically, it was found that FGD5-AS1 enhances chemoresistance of EC cells to PTX treatment and blocking immune escape via PD-1/PD-L1 checkpoint. Furthermore, FGD5-AS1 exerted an oncogene role in EC cells via promoting cell proliferation and migration. Mechanically, METTL3 could upregulate FGD5-AS1 expression via N6-methyladenosine (m6A) modification. The biological roles of METTL3 were exerted via modulating FGD5-AS1 expression in EC. Collectively, our research has shed light on the involvement of the METTL3/FGD5-AS1 axis in the development of PTX resistance in EC. This finding offers a new avenue for further exploration of the underlying mechanisms of chemoresistance in EC and provides valuable insights for the development of potential therapeutic targets in the treatment of EC.

Radiotherapy plus immune checkpoint inhibitor in prostate cancer.

The immune checkpoint inhibitor (ICI) is a promising strategy for treating cancer. However, the efficiency of ICI monotherapy is limited, which could be mainly attributed to the tumor microenvironment of the "cold" tumor. Prostate cancer, a type of "cold" cancer, is the most common cancer affecting men's health. Radiotherapy is regarded as one of the most effective prostate cancer treatments. In the era of immune therapy, the enhanced antigen presentation and immune cell infiltration caused by radiotherapy might boost the therapeutic efficacy of ICI. Here, the rationale of radiotherapy combined with ICI was reviewed. Also, the scheme of radiotherapy combined with immune checkpoint blockades was suggested as a potential option to improve the outcome of patients with prostate cancer.

Characteristics of Adenosine-to-Inosine RNA editing-based subtypes and novel risk score for the prognosis and drug sensitivity in stomach adenocarcinoma.

Stomach adenocarcinoma (STAD) is always characterized by high mortality and poor prognosis with drug resistance and recrudescence due to individual genetic heterogeneity. Adenosine-to-Inosine RNA editing (ATIRE) has been reported associated with multiple tumors but the potential connection between ATIRE-related signatures and STAD remains unclear. In this study, we comprehensively elevated the genetic characteristics of ATIRE in STAD patients and first screened five vital survival-related ATIRE sites to identify a novel ATIRE-Risk score. Based on the risk scores, we further divided the patients into two different subtypes with diverse clinical characteristics and immune landscapes including immune cell infiltration (ICI), tumor microenvironment (TME), and immune checkpoint expression analysis. The low-risk subgroups, associated with better survival prognosis, were characterized by activated immune-cells, higher immune scores in TME, and down-expression of immunotherapy checkpoints. Moreover, different expressional genes (DEGs) between the above subtypes were further identified and the activation of immune-related pathways were found in low-risk patients. The stratified survival analysis further indicated patients with low-risk and high-tumor mutation burden (TMB) exhibited the best prognosis outcomes, implying the role of TMB and ATIRE-Risk scores was synergistic for the prognosis of STAD. Interestingly, anti-tumor chemotherapeutic drugs all exhibited lower IC50 values in low-risk subgroups, suggesting these patients might obtain a better curative response from the combined chemotherapy of STAD. Finally, combined with classical clinical features and ATIRE-Risk scores, we successfully established a promising nomogram system to accurately predict the 1/3/5-years survival ratio of STAD and this model was also estimated with high diagnostic efficiency and stable C-index with calibration curves. These significant ATIRE sites are promising to be further explored and might serve as a novel therapeutic target for STAD treatment.

Necroptosis-Related miRNA Biomarkers for Predicting Overall Survival Outcomes for Endometrial Cancer.

Endometrial cancer (EC) is the gynecological tumor with the highest incidence. In recent years, it has been proved that necroptosis is a method of cell death related to EC. However, the expression of necroptosis-related miRNA in EC and its correlation with prognosis still ill-defined. Use the Cancer Genome Atlas (TCGA) cohort to obtain prognostic data and related clinical data for ECs and normal endometrium tissues. In this study, we identified three necroptotic regulatory miRNAs that are necroptosis-related and survival-related miRNAs (DENSMs) between normal endometrium tissues and EC from 13 necroptosis-related miRNAs. The three DENSMs signature was built to develop prognostic model and classified all EC patients into a high or low risk group. EC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (p = 0.0242), and the risk score was found to be an independent prognosis factor for predicting the OS of EC patients (p = 0.0254) in multivariate Cox regression. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed dephosphorylation, microtubule, protein serine/threonine kinase activity, PI3K-Akt signaling pathway and MAPK signaling pathway are closely related to it. In conclusion, the risk prediction model based on necroptosis-related miRNAs can effectively predict the prognosis of EC patients.

How to synchronously slow down starch digestion and retrogradation: A structural analysis study.

Digestibility and retrogradation properties of starch are important for the nutrition and quality of starch-based foods. In this study, a new idea on the synchronous delay the starch digestion and retrogradation was proposed, and the regulation mechanism was explored from perspectives of structural evolution using 13C NMR, XRD and SAXS techniques as well as the molecular dynamics simulations. Results showed that the chestnut starch treated with hot extrusion and 8% catechins (HE-8% CA)## could reach highest anti-retrogradation rate (AR 76.63%) and lowest rapidly digestible starch content (RDS 64.55%) at day 24. The starch digestion was slowed down by increasing single/double helix, V-type crystallinity and compactness of aggregates, while retrogradation process was suppressed by inhibiting the packing of short-range ordered structure into long-range ordered structure. The hydrogen bonding and van der Waals forces were the main driving force for the interactions between flavonoid polyphenols and starch molecules. Overall, this study is instructive for further investigations on the synchronous modulation of functional properties of starch.

Exosomal long noncoding RNA HOXD-AS1 promotes prostate cancer metastasis via miR-361-5p/FOXM1 axis.

Development of distant metastasis is the main cause of deaths in prostate cancer (PCa) patients. Understanding the mechanism of PCa metastasis is of utmost importance to improve its prognosis. The role of exosomal long noncoding RNA (lncRNA) has been reported not yet fully understood in the metastasis of PCa. Here, we discovered an exosomal lncRNA HOXD-AS1 is upregulated in castration resistant prostate cancer (CRPC) cell line derived exosomes and serum exosomes from metastatic PCa patients, which correlated with its tissue expression. Further investigation confirmed exosomal HOXD-AS1 promotes prostate cancer cell metastasis in vitro and in vivo by inducing metastasis associated phenotype. Mechanistically exosomal HOXD-AS1 was internalized directly by PCa cells, acting as competing endogenous RNA (ceRNA) to modulate the miR-361-5p/FOXM1 axis, therefore promoting PCa metastasis. In addition, we found that serum exosomal HOXD-AS1 was upregulated in metastatic PCa patients, especially those with high volume disease. And it is correlated closely with Gleason Score, distant and nodal metastasis, Prostatic specific antigen (PSA) recurrence free survival, and progression free survival (PFS). This sheds a new insight into the regulation of PCa distant metastasis by exosomal HOXD-AS1 mediated miR-361-5p/FOXM1 axis, and provided a promising liquid biopsy biomarker to guide the detection and treatment of metastatic PCa.

Actinomycin D causes oocyte maturation failure by inhibiting chromosome separation and spindle assembly†.

Actinomycin D (ActD) has been considered as one of the most effective and safe chemotherapeutic medications for treating a number of cancers. Although ActD has been used in the treatment of gynecological tumors and pediatric tumors for more than 50 years, the toxic effects of ActD on mammalian oocytes remain unknown. In this study, the influence of ActD on mouse and human oocyte maturation and the possible mechanisms were investigated. Notably, ActD inhibited oocyte maturation and arrested oocytes at the metaphase I (MI) stage in a dose-dependent manner. In addition, ActD arrested oocyte maturation when the oocytes were treated at different successive stages, including the germinal vesicle (GV), germinal vesicle breakdown, and MI stages. In ActD-treated oocytes, disordered chromosome condensation and irregular spindle assembly occurred, resulting in incomplete chromosome segregation and oocytes arresting at the MI phase; these results possibly occurred because ActD triggered the formation of reactive oxygen species, resulting in DNA damage and decreased ATP in mouse GV oocytes. Besides, in vivo treatment with ActD also inhibited mouse oocyte maturation. Similar effects were seen in human oocytes. Collectively, our results indicated that ActD exposure disrupted oocyte maturation by increasing DNA damage, which is a finding that might help with optimizing future methods for female fertility preservation before undergoing chemotherapy.

Fusion peptide engineered "statically-versatile" titanium implant simultaneously enhancing anti-infection, vascularization and osseointegration.

Although antimicrobial titanium implants can prevent biomaterial-associated infection (BAI) in orthopedics, they display cytotoxicity and delayed osseointegration. Therefore, versatile implants are desirable for simultaneously inhibiting BAI and promoting osseointegration, especially "statically-versatile" ones with nonessential external stimulations for facilitating applications. Herein, we develop a "statically-versatile" titanium implant by immobilizing an innovative fusion peptide (FP) containing HHC36 antimicrobial sequence and QK angiogenic sequence via sodium borohydride reduction promoted Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC-SB), which shows higher immobilization efficiency than traditional CuAAC with sodium ascorbate reduction (CuAAC-SA). The FP-engineered implant exhibits over 96.8% antimicrobial activity against four types of clinical bacteria (S. aureus, E. coli, P. aeruginosa and methicillin-resistant S. aureus), being stronger than that modified with mixed peptides. This can be mechanistically attributed to the larger bacterial accessible surface area of HHC36 sequence. Notably, the implant can simultaneously enhance cellular proliferation, up-regulate expressions of angiogenesis-related genes/proteins (VEGF and VEGFR-2) of HUVECs and osteogenesis-related genes/proteins (ALP, COL-1, RUNX-2, OPN and OCN) of hBMSCs. In vivo assay with infection and non-infection bone-defect model reveals that the FP-engineered implant can kill 99.63% of S. aureus, and simultaneously promote vascularization and osseointegration. It is believed that this study presents an excellent strategy for developing "statically-versatile" orthopedic implants.

Increased Expression of KISS1 and KISS1 Receptor in Human Granulosa Lutein Cells-Potential Pathogenesis of Polycystic Ovary Syndrome.

Kisspeptins are a family of neuropeptides that are essential for fertility. Recent experimental data suggest a putative role of kisspeptin signaling in the direct control of ovarian function. To explore the expression of KISS1 and KISS1 receptor (KISS1R) in human granulosa lutein cells and the potential role of KISS1/KISS1R system in the pathogenesis of polycystic ovary syndrome (PCOS), we measured the concentration of KISS1 in follicular fluid, the expression of KISS1 and KISS1R in granulosa lutein cells, and the circulating hormones. The expression levels of KISS1 and KISS1R were significantly upregulated in human granulosa lutein cells obtained from women with PCOS. The expression levels of KISS1 in human granulosa lutein cells highly correlated with those of KISS1R in non-PCOS patients, but not in patients with PCOS, most likely due to the divergent expression patterns in women with PCOS. Additionally, the expression levels of KISS1 highly correlated with the serum levels of anti-Müllerian hormone (AMH). The expression levels of KISS1 and KISS1R, as well as the follicular fluid levels of KISS1, were not significantly different between the pregnant and nonpregnant patients in both PCOS and non-PCOS groups. In conclusion, the increased expression of KISS1 and KISS1R in human granulosa lutein cells may contribute to the pathogenesis of PCOS. The expression levels of KISS1 highly correlated with the serum levels of AMH. The KISS1 and KISS1R system in the ovary may not have a remarkable role in predicting the in vitro fertilization (IVF) outcome.

The correlation between osteopontin adsorption and cell adhesion to mixed self-assembled monolayers of varying charges and wettability.

Osteopontin (OPN) is a key mediator of cell interactions with biomaterials. However, few studies have been dedicated to studying cell adhesion on OPN-adsorbed substrates with controlled charge and wettability. Here, amino-carboxyl (NH2/COOH) and hydroxyl-methyl (OH/CH3) mixed self-assembled monolayers (SAMs) of varying charges and wettability, respectively, were used as controllable model surfaces to study OPN adsorption and subsequent mesenchymal stem cell (MSC) adhesion. The amount of OPN adsorbed onto the NH2/COOH mixed SAMs appeared to monotonically depend on the surface charge, whereas only a moderately hydrophilic surface was conducive to OPN adsorption on OH/CH3 mixed SAMs. The results correlated well with cell spreading on OPN-coated surfaces in a serum-free medium culture. In addition, the OH/CH3 mixed SAMs with moderate wettability tended to promote ß1, ß3, αv and α5 integrins, indicating that wettability may guide cell adhesion by mediating the integrins signaling pathway. This work will have reference value for designing biologically responsive substrate surfaces.

Epigenetic regulation of an adverse metabolic phenotype in polycystic ovary syndrome: the impact of the leukocyte methylation of PPARGC1A promoter.

OBJECTIVE: To investigate PPARGC1A promoter methylation and mitochondria DNA (mtDNA) content in the leukocytes of women with polycystic ovary syndrome (PCOS) and analyze the relationship between these indices and metabolic risk for women with PCOS. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENT(S): A total of 175 women with PCOS and 127 healthy controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Women with and without PCOS classified using the typical metabolic risk criteria of the National Cholesterol Education Program's Adult Treatment Panel III report (ATPIII), methylation of PPARGC1A promoter tested by methylation-specific polymerase chain reaction, and mtDNA content confirmed by quantitative polymerase chain reaction (PCR). RESULT(S): PPARGC1A promoter methylation was specifically increased, but mtDNA content was specifically decreased in women with PCOS compared with the control women after adjustment for body mass index. Moreover, in women with PCOS who have increased metabolic risk, the differences in PPARGC1A promoter methylation and mitochondrial content were aggravated. CONCLUSION(S): In conclusion, PPARGC1A promoter methylation and mitochondrial content were found to be potential biomarkers for the prediction of metabolic risk in women with PCOS.

Surface chemistry from wettability and charge for the control of mesenchymal stem cell fate through self-assembled monolayers.

Self-assembled monolayers (SAMs) of alkanethiols on gold are highly controllable model substrates and have been employed to mimic the extracellular matrix for cell-related studies. This study aims to systematically explore how surface chemistry influences the adhesion, morphology, proliferation and osteogenic differentiation of mouse mesenchymal stem cells (mMSCs) using various functional groups (-OEG, -CH3, -PO3H2, -OH, -NH2 and -COOH). Surface analysis demonstrated that these functional groups produced a wide range of wettability and charge: -OEG (hydrophilic and moderate iso-electric point (IEP)), -CH3 (strongly hydrophobic and low IEP), -PO3H2 (moderate wettability and low IEP), -OH (hydrophilic and moderate IEP), -NH2 (moderate wettability and high IEP) and -COOH (hydrophilic and low IEP). In terms of cell responses, the effect of wettability may be more influential than charge for these groups. Moreover, compared to -OEG and -CH3 groups, -PO3H2, -OH, -NH2 and -COOH functionalities tended to promote not only cell adhesion, proliferation and osteogenic differentiation but also the expression of αv and ß1 integrins. This finding indicates that the surface chemistry may guide mMSC activities through αv and ß1 integrin signaling pathways. Model surfaces with controllable chemistry may provide insight into biological responses to substrate surfaces that would be useful for the design of biomaterial surfaces.

miR-29b-Loaded Gold Nanoparticles Targeting to the Endoplasmic Reticulum for Synergistic Promotion of Osteogenic Differentiation.

Precise control of stem cells, such as human bone marrow-derived mesenchymal stem cells (hMSCs), is critical for the development of effective cellular therapies for tissue engineering and regeneration medicine. Emerging evidence suggests that several miRNAs act as key regulators of diverse biological processes, including differentiation of various stem cells. In this study, we have described a delivery system for miR-29b using PEI-capped gold nanoparticles (AuNPs) to synergistically promote osteoblastic differentiation. The cell proliferation assay revealed that AuNPs and AuNPs/miR-29b exert negligible cytotoxicity to hMSCs and MC3T3-E1 cells. With the assistance of AuNPs as a delivery vector, miR-29b could efficiently enter the cytoplasm and regulate osteogenesis. AuNPs/miR-29b more effectively promoted osteoblast differentiation and mineralization through induced the expression of osteogenesis genes (RUNX2, OPN, OCN, ALP) for the long-term, compared to the widely used commercial transfection reagent, Lipofectamine. With no obvious cytotoxicity, PEI-capped AuNPs showed great potential as an adequate miRNA vector for osteogenesis differentiation. Interestingly, we observed loading of AuNPs as well as AuNPs/miR-29b into the lumen of the endoplasmic reticulum (ER). Our findings collectively suggest that AuNPs, together with miR-29b, exert a synergistic promotory effect on osteogenic differentiation of hMSCs and MC3T3-E1 cells.

Subarray coherence based postfilter for eigenspace based minimum variance beamformer in ultrasound plane-wave imaging.

This paper introduces a new beamformer, which combines the eigenspace based minimum variance (ESBMV) beamformer with a subarray coherence based postfilter (SCBP), for improving the quality of ultrasound plane-wave imaging. The ESBMV beamformer has been validated in improving the imaging contrast, but the difficulty in dividing the signal subspace limits the usage of it in the low signal-to-noise ratio (SNR) scenarios. Coherence factor (CF) based methods could optimize the output of a distortionless beamformer to reduce sidelobes, but the influence by the subarray decorrelation technique on the postfilter design has not attracted enough concern before. Accordingly, an ESBMV-SCBP beamformer was proposed in this paper, which used the coherence of the subarray signal to compute an SCBP to optimize the ESBMV results. Simulated and experimental data were used to evaluate the performance of the proposed method. The results showed that the ESBMV-SCBP method achieved an improved imaging quality compared with the ESBMV beamformer. In the simulation study, the contrast ratio (CR) for an anechoic cyst was improved by 9.88 dB and the contrast-to-noise ratio (CNR) was improved by 0.97 over the ESBMV. In the experimental study, the CR improvements for two anechoic cysts were 7.32 dB and 9.45 dB, while the CNRs were improved by 1.27 and 0.66, respectively. The ESBMV-SCBP also showed advantages over the ESBMV-Wiener beamformer in preserving a less grainy speckle, which is closer to that of distortionless beamformers and benefits the imaging contrast. With a relatively small extra computational load, the proposed method has potential to enhance the quality of the ultrasound plane-wave imaging.

Metabolism alteration in follicular niche: The nexus among intermediary metabolism, mitochondrial function, and classic polycystic ovary syndrome.

Classic polycystic ovary syndrome (PCOS) is a high-risk phenotype accompanied by increased risks of reproductive and metabolic abnormalities; however, the local metabolism characteristics of the ovaries and their effects on germ cell development are unclear. The present study used targeted metabolomics to detect alterations in the intermediate metabolites of follicular fluid from classic PCOS patients, and the results indicated that hyperandrogenism but not obesity induced the changed intermediate metabolites in classic PCOS patients. Regarding the direct contact, we identified mitochondrial function, redox potential, and oxidative stress in cumulus cells which were necessary to support oocyte growth before fertilization, and suggested dysfunction of mitochondria, imbalanced redox potential, and increased oxidative stress in cumulus cells of classic PCOS patients. Follicular fluid intermediary metabolic profiles provide signatures of classic PCOS ovary local metabolism and establish a close link with mitochondria dysfunction of cumulus cells, highlighting the role of metabolic signal and mitochondrial cross talk involved in the pathogenesis of classic PCOS.

[Analysis of the deafness gene screening results from newborns in Shijiazhuang].

OBJECTIVE: To build information repository of the carrying rate of neonatal deafness gene in Shijiazhuang. METHOD: Blood samples were collected from the heel in 3-days neonates. Mutations of the deafness related genes were detected by the method of fluorescent PCR. Neonates received the detection of 6 mutation sites from 3 genes, including GJB2 (235delC, 299-300delAT), SLC26A4 (IVS7-2A> G, 2168A> G), mitochondrial DNA12S rRNA(1494C>T,1555A>G). RESULT: There were 384 neonates who carried mutations among 421 subjects and the carrying rate was 4.08%, 158 (1.68%) newborns carried heterozygous mutations and 1 (0.01%) case carried homogeneous mutation of GJB2 (235 delC), 55 (0.58%) neonates carried heterozygous mutations of GJB2 (299-300delAT); 133 (1.41%) neonates carried heterozygous mutations and 1 (0.01%) homogeneous of SLC26A4(IVS7-2A>G),19 (0.20%) newborns carried heterozygous mutations of SLC26A4 (2168A>G). The numbers of neonates who carried homogeneous and heterogeneous mutation of mitochondrial 12S rRNA gene were 14 and 3 with carring rates of 0.15% and 0.03%. Two newborns were found to carry more than one mutation. One carried 235delC, IVS7-2A>G and 1555A>G and another carried 235delC and IVS7-2A>G. CONCLUSION: The main mutational patterns were 235delC from GJB2 gene and IVS7-2A>G from SLC26A4 gene in Shijiazhuang newborns. The carrying rate information repository of neonatal deafness gene has been built preliminarily.

Assessment of ocular biomechanics using dynamic ultra high-speed Scheimpflug imaging in keratoconic and normal eyes.

PURPOSE: To introduce several new ocular biomechanical parameters for comparison between keratoconic and normal eyes using an analysis method based on corneal dynamic deformation video recorded by corneal visualization Scheimpflug technology (Corvis ST; Oculus Optikgeräte GmbH, Wetzlar, Germany). METHODS: This comparative study comprised 52 keratoconic eyes of 43 patients with keratoconus and 52 normal eyes of 52 controls. An analysis method (PolyU [Labview 2009; National Instrument, Austin, TX]) was developed to introduce several new ocular biomechanical parameters and to compare the difference between keratoconic and normal eyes. The repeatability of the new parameters measurement was evaluated and compared with the Corvis ST measurement. Receiver operating characteristic curves were used to establish a cutoff value for the new biomechanical parameters. RESULTS: Intraclass correlation coefficients of the deformation amplitude, peak distance, corneal concave radius of curvature, maximum deformation area, maximum corneal inward velocity and outward velocity (Vin, max and Vout, max) were high in both the keratoconic and normal eyes (all intraclass correlation coefficients > 0.75). The measurement agreement of the PolyU analysis method and Corvis ST was good. Most of the biomechanical parameters of patients with keratoconus were significantly different from those of the controls. In the receiver operating characteristic analysis, the Vin, max was the best predictive parameter with an area under the curve of 0.79. CONCLUSIONS: The corneal deformation video recorded by the Corvis ST provides useful information for the study of ocular biomechanics. Most of the new ocular biomechanical parameters were significantly different between keratoconic and normal eyes. Further research is needed to develop more comprehensive clinical applications with these new ocular biomechanical parameters.

Association analyses between the genetic polymorphisms of HNF4A and FOXO1 genes and Chinese Han patients with type 2 diabetes.

The hepatocyte nuclear factor 4-alpha (HNF4A) and human forkhead box O1 (FOXO1) genes have been discovered to be associated with type 2 diabetes (T2D) in different populations. This study aimed to evaluate the association between HNF4A and FOXO1 genetic polymorphisms and type 2 diabetes in the Chinese Han population. Five hundred and seventy-seven patients with type 2 diabetes and 462 normal controls were enrolled in this study. Six single-nucleotide polymorphisms (SNPs) in HNF4A and seven in FOXO1 were selected and genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan(®) technology. Single-locus analyses indicated that the C allele of rs11574736 from HNF4A had a lower frequency in the case group compared with the control group (P = 0.005, OR = 0.74, 95% CI = 0.59-0.92). The genotype distributions of rs11574736 also differed between the two groups (P = 0.02). However, none of the FOXO1 SNPs showed any association with type 2 diabetes in the Chinese Han population. Further analysis suggested the two genes interact with each other (rs3908773/rs717247/rs6031587/rs11574736: P < 0.0001, testing accuracy = 0.55, CV consistency = 6/10). In conclusion, this study shows an association between the HNF4A gene and type 2 diabetes in the Chinese Han population. Moreover, the authors confirmed the results of previous studies for the interaction between HNF4A and FOXO1 in the pathogenesis of type 2 diabetes.