Electrical Transport and Dynamics of Confined DNA through Highly Conductive 2D Graphene Nanochannels.

Confining DNA in nanochannels is an important approach to studying its structure and transportation dynamics. Graphene nanochannels are particularly attractive for studying DNA confinement due to their atomic flatness, precise height control, and excellent mechanical strength. Here, using femtosecond laser etching and wetting transfer, we fabricate graphene nanochannels down to less than 4.3 nm in height, with the length-to-height ratios up to 103. These channels exhibit high stability, low noise, and self-cleaning ability during the long-term ionic current recording. We report a clear linear relationship between DNA length and the residence time in the channel and further utilize this relationship to differentiate DNA fragments based on their lengths, ranging widely from 200 bps to 48.5 kbps. The graphene nanochannel presented here provides a potential platform for label-free analyses and reveals fundamental insights into the conformational dynamics of DNA and proteins in confined space.

MdPRX34L, a class III peroxidase gene, activates the immune response in apple to the fungal pathogen Botryosphaeria dothidea.

MAIN CONCLUSION: MdPRX34L enhanced resistance to Botryosphaeria dothidea by increasing salicylic acid (SA) and abscisic acid (ABA) content as well as the expression of related defense genes. The class III peroxidase (PRX) multigene family is involved in complex biological processes. However, the molecular mechanism of PRXs in the pathogen defense of plants against Botryosphaeria dothidea (B. dothidea) remains unclear. Here, we cloned the PRX gene MdPRX34L, which was identified as a positive regulator of the defense response to B. dothidea, from the apple cultivar 'Royal Gala.' Overexpression of MdPRX34L in apple calli decreased sensitivity to salicylic acid (SA) and abscisic acid（ABA). Subsequently, overexpression of MdPRX34L in apple calli increased resistance to B. dothidea infection. In addition, SA contents and the expression levels of genes related to SA synthesis and signaling in apple calli overexpressing MdPRX34L were higher than those in the control after inoculation, suggesting that MdPRX34L enhances resistance to B. dothidea via the SA pathway. Interestingly, infections in apple calli by B. dothidea caused an increase in endogenous levels of ABA followed by induction of ABA-related genes expression. These findings suggest a potential mechanism by which MdPRX34L enhances plant-pathogen defense against B. dothidea by regulating the SA and ABA pathways.

Changes in liver and kidney function, red blood cell count and hemoglobin levels 1 day after ultrasound-guided percutaneous microwave ablation for uterine fibroids.

OBJECTIVE: To investigate the changes in liver and kidney function, red blood cell (RBC) count and hemoglobin (HGB) levels in patients undergoing ultrasound-guided percutaneous microwave ablation (UPMWA) for uterine fibroids on postoperative day 1. METHODS: The changes in liver and kidney function, RBC count and HGB levels in 181 patients who underwent selective UPMWA in the Second Affiliated Hospital of Shantou University Medical College, China, between August 2017 and January 2023 were retrospectively analyzed. RESULTS: All patients underwent UPMWA for uterine fibroids; 179 patients had multiple uterine fibroids and 2 patients had single uterine fibroids. The maximum fibroid diameter ranged from 18 to 140 mm, with an average of 68.3 mm. Ultrasound imaging was used to confirm that the blood flow signal within the mass had disappeared in all patients, indicating that the ablation was effective. Within 24 h, compared with before UPMWA, levels of total bilirubin, direct bilirubin, indirect bilirubin and aspartate aminotransferase had significantly increased (p < 0.01), whereas levels of total protein, albumin, globulin, alanine aminotransferase, creatinine and urea had significantly decreased (p < 0.01). Acute kidney injury (AKI) occurred in 1 of the 181 patients. The RBC count and HGB levels decreased significantly after UPMWA (p < 0.01). CONCLUSION: Ultrasound-guided percutaneous microwave ablation for uterine fibroids can impose a higher detoxification load on the liver and cause thermal damage to and the destruction of RBCs within local circulation, potentially leading to AKI. Protein levels significantly decreased after UPMWA. Therefore, perioperative organ function protection measures and treatment should be actively integrated into clinical practice to improve prognosis and enhance recovery.

Down-regulation of kappa opioid receptor promotes ESCC proliferation, invasion and metastasis via the PDK1-AKT signaling pathway.

BACKGROUND: As a class of the opioid receptors, the kappa opioid receptor (KOR) has been verified to be a potential biomarker and therapeutic target for human malignant tumors. However, a thorough understanding of whether KOR affects progression of esophageal squamous cell carcinoma (ESCC) is still lacking. This study focused on exploring the effect of knocking down KOR in ESCC and its underlying mechanism. METHODS: Bioinformatics analysis was used to compare the different expression level of OPRK1 (KOR gene) in tumor and adjacent normal tissues, and predict the relationship between KOR expression and overall survival. RNA-sequence analysis was performed to detect the altered functions and mechanisms after down regulating KOR. The in vitro and in vivo assays were used to detect the effects of down-regulated KOR on cell proliferation, migration and invasion. Substrate gel zymography and 3D cell culture assays were used to find the effect of KOR knockdown on the degradation of extracellular matrix (ECM), and immunefluorescence was performed to detect the altered cytoskeleton. Western blotting and immunohistochemistry were used to explore the underlying mechanism pathway. RESULTS: Bioinformatics analysis revealed that the expression of OPRK1 was lower in tumor tissue than that in adjacent normal tissues, and lowered expression of KOR was associated with poorer overall survival. The in vitro assays demonstrated that down-regulation of KOR enhanced ESCC proliferation, metastasis and invasion. Western blotting revealed that down-regulation of KOR could activate PDK1-AKT signaling pathway, which actively regulated the cancer progression. Down-regulation of KOR enhanced the formation of invadopodia, secretion of matrix metalloproteinase-2 (MMP2) and rearrangement of cytoskeleton, which were positively related with the invasion of ESCC. KOR knockdown enhanced the tumor invasion and elevated the AKT phosphorylation in nude mice. The AKT kinase inhibition could reverse the effect of down-regulation of KOR. CONCLUSION: KOR might act as a tumor suppressor in ESCC and down-regulation of KOR could enhance the ESCC tumor phenotype. Video Abstract.

Parecoxib inhibits esophageal squamous cell carcinoma progression via the PDK1-AKT pathway.

BACKGROUND: Parecoxib plays an important role in inhibition of human cancer. However, the effect of parecoxib on esophageal squamous cell carcinoma (ESCC) is still not well known. The purpose of this study was to investigate the effect of parecoxib on ESCC and its underlying mechanism. METHODS: RNA-sequence analysis was performed to identify functional alterations and mechanisms. Cell cycle, proliferation, invasion, and migration were assessed using flow cytometry, CCK-8 assay, colony formation, transwell, and wound healing assays. Extracellular matrix (ECM) degradation was detected by substrate gel zymography and 3D cell culture assay. Western blotting was used to detect parecoxib-dependent mechanisms involving cell cycle, proliferation, invasion, and migration. Tumor formation in vivo was detected by mouse assay. RESULTS: Functional experiments indicated that parecoxib induced ESCC cell cycle arrest in G2 phase, and inhibited cell proliferation, invasion, and migration in vitro. Western blotting revealed that parecoxib downregulated the phosphorylation levels of AKT and PDK1, as well as the expression of the mutant p53, cyclin B1, and CDK1, while upregulating p21waf1. Parecoxib inhibited matrix metalloproteinase-2 (MMP2) secretion and invadopodia formation, which were related to ECM degradation. Furthermore, we found that parecoxib suppressed ESCC growth in heterotopic tumor models. CONCLUSION: Parecoxib inhibits ESCC progression, including cell cycle, proliferation, invasion, and migration, via the PDK1-AKT signaling pathway.

Nakamurella leprariae sp. nov., isolated from a lichen sample.

A novel actinobacterium, YIM 132084T, was isolated from Lepraria sp. lichen collected from Yunnan province, south-west PR China and identified by a polyphasic taxonomic approach. The strain was Gram-stain-positive, aerobic, catalase-positive, oxidase-negative, non-motile and coccus-shaped. Colonies were round, convex, smooth and light orange yellow in color. It grew at 10-40 °C (optimum 28 °C), at pH 6.0-11.0 (optimum pH 7.0) and in the presence of 0-4% NaCl (optimum 0%). Strain YIM 132084T comprised diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol as the major polar lipids, MK-8(H4) as the predominant menaquinone, and anteiso-C15:0, anteiso-C17:0, iso-C15:0 and iso-C16:0 as major fatty acids. Strain YIM 132084T had meso-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan, and mannose, ribose, glucose and rhamnose as whole-cell sugars. The 16S rRNA gene sequence showed high level of similarity with Nakamurella flavida KCTC 19127T (97.7%) and Nakamurella flava CGMCC 4.7524T (97.7%). The G + C content of the genomic DNA was 72.4 mol%. Based on draft genome sequences, strain YIM 132084T showed an average nucleotide identity value of 76.1% and 74.9%, a digital DNA-DNA hybridization value of 20.9% and 20.6% with the reference strains Nakamurella flavida and Nakamurella flava, respectively. The results of the phenotypic, chemotaxonomic and phylogenetic analyses showed that strain YIM 132084T represents a novel species of the genus Nakamurella, for which the name Nakamurella leprariae sp. nov. is proposed. The type strain is YIM 132084T (= CGMCC 4.7667T = NBRC 114280T = KCTC 49367T).

The oncogenic effects of HES1 on salivary adenoid cystic carcinoma cell growth and metastasis.

BACKGROUND: Our previous study demonstrated a close relationship between NOTCH signaling pathway and salivary adenoid cystic carcinoma (SACC). HES1 is a well-known target gene of NOTCH signaling pathway. The purpose of the present study was to further explore the molecular mechanism of HES1 in SACC. METHODS: Comparative transcriptome analyses by RNA-Sequencing (RNA-Seq) were employed to reveal NOTCH1 downstream gene in SACC cells. Immunohistochemical staining was used to detect the expression of HES1 in clinical samples. After HES1-siRNA transfected into SACC LM cells, the cell proliferation and cell apoptosis were tested by suitable methods; animal model was established to detect the change of growth ability of tumor. Transwell and wound healing assays were used to evaluate cell metastasis and invasion. RESULTS: We found that HES1 was strongly linked to NOTCH signaling pathway in SACC cells. The immunohistochemical results implied the high expression of HES1 in cancerous tissues. The growth of SACC LM cells transfected with HES1-siRNAs was significantly suppressed in vitro and tumorigenicity in vivo by inducing cell apoptosis. After HES1 expression was silenced, the SACC LM cell metastasis and invasion ability was suppressed. CONCLUSIONS: The results of this study demonstrate that HES1 is a specific downstream gene of NOTCH1 and that it contributes to SACC proliferation, apoptosis and metastasis. Our findings serve as evidence indicating that HES1 may be useful as a clinical target in the treatment of SACC.

Notch2 signaling contributes to cell growth, invasion, and migration in salivary adenoid cystic carcinoma.

Many studies have explored whether the Notch signaling pathway has a tumor-suppressive or an oncogenic role in various tumors; however, the role of the Notch signaling pathway in salivary adenoid cystic carcinoma (SACC) is still unknown. In this study, we attempt to define the role of Notch2 signaling in cell growth, invasion, and migration in SACC. We compared Notch2 expression in clinical SACC samples with that of normal samples by using immunohistochemical staining. Then, we down-regulated Notch2 expression to observe the effect of Notch2 on proliferation, invasion, migration, and the expression of known target genes of Notch signal pathway. According to our results, Notch2 expression was higher in SACC tissues compared with normal tissues. Knockdown of Notch2 inhibited cell proliferation, invasion, and migration in vitro and down-regulated the expression of HEY2 and CCND1. The results of this study suggest that Notch2 has an essential role in the cell growth, invasion, and migration of SACC. Notch2 may therefore be a potential target gene for the treatment of SACC by interfering with cell growth and metastasis.

Optimization of apple fruit flavor by MdVHP1-2 via modulation of soluble sugar and organic acid accumulation.

For fleshy fruits, the content and ratio of organic acids and soluble sugars are key factors for their flavor. Therefore, a better understanding of soluble sugar and organic acid accumulation in vacuoles is essential to the improvement of fruit quality. Vacuolar-type inorganic pyrophosphatase (V-PPase) has been found in various plants with crucial functions based on the hydrolysis of PPi. However, the effects of V-PPase on the soluble sugar and organic acid accumulation in apple fruit remain unclear. In this study, MdVHP1-2, a V-PPase protein in the vacuolar membrane, was identified. The results showed a positive correlation between the expression of MdVHP1-2 and the sugar/acid ratio during ripening of apple fruits. A series of transgenic analyses showed that overexpression of MdVHP1-2 significantly elevated the contents of soluble sugars and organic acids as well as the sugar/acid ratio in apple fruits and calli. Additionally, transient interference induced by MdVHP1-2 expression inhibited the accumulation of soluble sugars and organic acids in apple fruits. In summary, this study provides insight into the mechanisms by which MdVHP1-2 modulates fruit flavor through mediation of soluble sugar and organic acid accumulation, thereby facilitating improvement of the overall quality of apple and other fruits.

Prognostic Value of Preoperative MRI-derived 3D Quantitative Tumor Arterial Burden in Patients with Hepatocellular Carcinoma Receiving Transarterial Chemoembolization.

Purpose To investigate the association of tumor arterial burden (TAB) on preoperative MRI with transarterial chemoembolization refractoriness (TACER) and progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC). Materials and Methods This retrospective study included patients with HCC who underwent repeated transarterial chemoembolization (TACE) treatments between January 2013 and December 2020. HCC was confirmed with pathology or imaging, and patients with other tumors, lost follow-up, or with a combination of other treatments were excluded. TACER was defined as viable lesions of more than 50% or increase in tumor number after two or more consecutive TACE treatments, continuous elevation of tumor markers, extrahepatic spread, or vascular invasion. TAB assessed with preoperative MRI was divided into high and low groups according to the median. A Cox proportional hazards model was used to determine the predictors of TACER and PFS. Results A total of 355 patients (median age, 61 years [IQR, 54-67]; 306 [86.2%] men, 49 [13.8%] women) were included. During a median follow-up of 32.7 months, the high TAB group had significantly faster TACER and decreased PFS than the low TAB group (all log-rank P < .001). High TAB was the strongest independent predictor of TACER and PFS in multivariable Cox regression analyses (hazard ratio [HR], 2.23 [95% CI: 1.51, 3.29]; HR, 2.30 [95% CI: 1.61, 3.27], respectively), especially in patients with Barcelona Clinic Liver Cancer stage A or a single tumor. The restricted cubic spline plot demonstrated that the HR of TACER and PFS continuously increased with increasing TAB. Conclusion High preoperative TAB at MRI was a risk factor for faster refractoriness and progression in patients with HCC treated with TACE. Keywords: Interventional-Vascular, MR Angiography, Hepatocellular Carcinoma, Transarterial Chemoembolization, Progression-free Survival, MRI Supplemental material is available for this article. © RSNA, 2024.

Mechanism of Guigan Longmu Decoction in the Treatment of Arrhythmias Based on Network Pharmacology and Untargeted Metabolomics Assays.

BACKGROUND: Guigan longmu decoction (GGLM), a traditional Chinese medicine compound, has demonstrated efficacy in treating rapid arrhythmia clinically. Nevertheless, its mechanism of action remains elusive. This study aims to elucidate the molecular mechanism underlying the efficacy of GGLM in treating arrhythmia utilizing non-targeted metabolomics, widely-targeted metabolomics, and network pharmacology, subsequently validated through animal experiments. METHODS: Initially, network pharmacology analysis and widely-targeted metabolomics were performed on GGLM. Subsequent to that, rats were administered GGLM intervention, and nontargeted metabolomics assays were utilized to identify metabolites in rat plasma postadministration. The primary signaling pathways, core targets, and key active ingredients of GGLM influencing arrhythmia were identified. Additionally, to validate the therapeutic efficacy of GGLM on arrhythmia rat models, a rat model of rapid arrhythmia was induced via subcutaneous injection of isoproterenol, and alterations in pertinent pathogenic pathways and proteins in the rat model were assessed through qRT-PCR and Western blot following GGLM administration. RESULTS: The results of network pharmacology showed that 99 active ingredients in GGLM acted on 249 targets and 201 signaling pathways, which may be key to treating arrhythmia. Widelytargeted metabolic quantification analysis detected a total of 448 active ingredients in GGLM, while non-targeted metabolomics identified 279 different metabolites and 10 major metabolic pathways in rats. A comprehensive analysis of the above results revealed that the core key active ingredients of GGLM in treating arrhythmia include calycosin, licochalcone B, glabridin, naringenin, medicarpin, formononetin, quercetin, isoliquiritigenin, and resveratrol. These active ingredients mainly act on the relevant molecules and proteins upstream and downstream of the MAPK pathway to delay the onset of arrhythmia. Animal experimental results showed that the heart rate of rats in the model group increased significantly, and the mRNA and protein expression of p38, MAPK, JNK, ERK, NF-kb, IL-1ß, and IL-12 in myocardial tissue also increased significantly. However, after intervention with GGLM, the heart rate of rats in the drug group decreased significantly, while the mRNA and protein expression of p38 MAPK, JNK, ERK1, NF-kb, IL-1ß, and IL-12 in myocardial tissue decreased significantly. CONCLUSION: GGLM, as an adjunctive therapy in traditional Chinese medicine, exhibits favorable therapeutic efficacy against arrhythmia. This can be attributed to the abundant presence of bioactive compounds in the formulation, including verminin, glycyrrhizin B, glabridine, naringenin, ononin, quercetin, isorhamnetin, and kaempferol. The metabolites derived from these active ingredients have the potential to mitigate myocardial inflammation and decelerate heart rate by modulating the expression of proteins associated with the MAPK signaling pathway in vivo.

Multi-matrices factorization with application to missing sensor data imputation.

We formulate a multi-matrices factorization model (MMF) for the missing sensor data estimation problem. The estimation problem is adequately transformed into a matrix completion one. With MMF, an n-by-t real matrix, R, is adopted to represent the data collected by mobile sensors from n areas at the time, T1, T2, ..., Tt, where the entry, Rij, is the aggregate value of the data collected in the ith area at Tj. We propose to approximate R by seeking a family of d-by-n probabilistic spatial feature matrices, U(1), U(2), ..., U(t), and a probabilistic temporal feature matrix, [formula in text]. We also present a solution algorithm to the proposed model. We evaluate MMF with synthetic data and a real-world sensor dataset extensively. Experimental results demonstrate that our approach outperforms the state-of-the-art comparison algorithms.

[Effect of carbon disulfide on mitochondrial respiratory chain in spermatogenic cells in male rats].

OBJECTIVE: To investigate the effect of carbon disulfide (CS(2)) on the mitochondrial respiratory chain in testicular spermatogenic cells in male rats and to explore the possible mechanism of reproductive system damage caused by CS(2) in male rats. METHODS: Twenty-four male Sprague-Dawley rats (clean grade) were randomly divided into four groups: three CS(2) exposure groups (CS(2) concentrations: 50, 250, and 1250 mg/m(3)) and a control group. The rats in CS(2) exposure groups were exposed to CS(2) by static inhalation for 10 weeks (2 h/d, 5 d/w), while the rats in control group were exposed to air. Then, all rats were sacrificed by decapitation; testicular tissues were collected, and mitochondrial protein in spermatogenic cells were extracted; the levels of mitochondrial respiratory chain enzyme complex I∼V were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, all CS(2) exposure groups had significantly increased levels of mitochondrial respiratory chain enzyme complex I∼V in spermatogenic cells (P < 0.05). There were no significant differences in the levels of respiratory chain enzyme complex I∼IV between the CS(2) exposure groups (P < 0.05), but the level of respiratory chain enzyme complex V rose significantly as the concentration of CS(2) increased (P<0.05). CONCLUSION: Various levels of CS(2) exposure may increase the levels of mitochondrial respiratory chain enzyme complex in testicular spermatogenic cells among male rats, thus affecting the normal oxidative phosphorylation in mitochondria.

[Effect of carbon disulfide on mitochondrial apoptosis-related proteins in cytoplasm of testicular tissue among male rats].

OBJECTIVE: To investigate the role of mitochondrial pathway in the apoptosis of spermatogenic cells induced by inhalation of carbon disulfide in male rats. METHODS: Twenty-four male Sprague-Dawley rats (clean grade) were divided into four groups according to their body weights: three CS(2) exposure groups (CS(2) concentrations: 50, 250, and 1250 mg/m(3)) and a control group. The rats in CS(2) exposure groups were exposed to CS(2) by static inhalation for 10 weeks (2 h/d, 5 d/w), while the rats in control group were exposed to air. Then, all rats were sacrificed by decapitation; testicular tissues were collected, and cytoplasmic proteins were extracted; the levels of apoptosis-inducing factor (AIF), cytochrome c (cyto c), Bcl-2, Bax, procaspase-9, and procaspase-3 were measured by Western blot, and the activities of caspase-9 and caspase-3 were measured using a test kit. RESULTS: Compared with the control group, all CS(2) exposure groups had significantly increased levels of cyto c in the cytoplasm of testicular tissue (P<0.05); in the 250 mg/m(3) CS(2) exposure group, the Bax/Bcl-2 ratio and activities of caspase-9 and caspase-3 increased significantly (P<0.05), and the content of procaspase-9 and procaspase-3 decreased significantly (P<0.05); in the 1250 mg/m(3) CS(2) exposure group, the relative expression levels of Bax and AIF in cytoplasm increased significantly (P<0.05), and the expression level of Bcl-2 decreased significantly (P<0.05). CONCLUSION: Mitochondrial pathway plays an important role in the CS(2)-induced apoptosis of spermatogenic cells in testicular tissue among male rats.

Regulation of a vacuolar proton-pumping P-ATPase MdPH5 by MdMYB73 and its role in malate accumulation and vacuolar acidification.

As the main organic acid in fruits, malate is produced in the cytoplasm and is then transported into the vacuole. It accumulates by vacuolar proton pumps, transporters, and channels, affecting the taste and flavor of fruits. Among the three types of proton pumps (V-ATPases, V-PPases, and P-ATPases), the P-ATPases play an important role in the transport of malate into vacuoles. In this study, the transcriptome data, collected at different stages after blooming and during storage, were analyzed and the results demonstrated that the expression of MdPH5, a vacuolar proton-pumping P-ATPase, was associated with both pre- and post-harvest malate contents. Moreover, MdPH5 is localized at the tonoplast and regulates malate accumulation and vacuolar pH. In addition, MdMYB73, an upstream MYB transcription factor of MdPH5, directly binds to its promoter, thereby transcriptionally activating its expression and enhancing its activity. In this way, MdMYB73 can also affect malate accumulation and vacuolar pH. Overall, this study clarifies how MdMYB73 and MdPH5 act to regulate vacuolar malate transport systems, thereby affecting malate accumulation and vacuolar pH. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00115-7.

Compressive Strength Prediction of Rubber Concrete Based on Artificial Neural Network Model with Hybrid Particle Swarm Optimization Algorithm.

Conventional neural networks tend to fall into local extremum on large datasets, while the research on the strength of rubber concrete using intelligent algorithms to optimize artificial neural networks is limited. Therefore, to improve the prediction accuracy of rubber concrete strength, an artificial neural network model with hybrid algorithm optimization was developed in this study. The main strategy is to mix the simulated annealing (SA) algorithm with the particle swarm optimization (PSO) algorithm, using the SA algorithm to compensate for the weak global search capability of the PSO algorithm at a later stage while changing the inertia factor of the PSO algorithm to an adaptive state. For this purpose, data were first collected from the published literature to create a database. Next, ANN and PSO-ANN models are also built for comparison while four evaluation metrics, MSE, RMSE, MAE, and R2, were used to assess the model performance. Finally, compared with empirical formulations and other neural network models, the result shows that the proposed optimized artificial neural network model successfully improves the accuracy of predicting the strength of rubber concrete. This provides a new option for predicting the strength of rubber concrete.

Identification of genetic variants in five chinese families with keratoconus: Pathogenicity analysis and characteristics of parental corneal topography.

Purpose: The study aims to identify genetic variants in five Chinese families with Keratoconus (KC) and describe the characteristics of parental corneal topography. Methods: Fifteen participants, including five probands and ten parents from five Chinese families with KC, were recruited for genetic and clinical analyses. Targeted next-generation sequencing using a custom-designed panel for KC was applied on the probands for variant identification. Sanger sequencing and cosegregation analysis of the suspected pathogenic variants were performed on the family members. The pathogenicities of variants were evaluated according to the American College of Medical Genetics and Genomics guidelines (ACMG). Pentacam 3D anterior segment analysis system was applied for keratectasia detection and the Corvis ST for corneal biomechanics measurement. Fifteen parameters were recorded, including nine keratectasia indicators (BAD-D, TP, Kmax, Df, Db, Dp, Dt, Da, ARTH), six corneal biomechanical indicators (CBI, DA ratio, SP-A1, IR, bIOP, TBI). Results: A total of six novel variants, including five missense variants and one frameshift variant, were detected in the HMX1, SLC4A11, TGFBI, PIKFYVE, and ZEB1 genes in five probands, all of which showed co-segregation of genotype and clinical phenotype and were determined to be pathogenic. The genetic model was autosomal dominant (AD) in four families and autosomal recessive (AR) in 1 family. The analysis of keratectasia and corneal biomechanical indicators of the proband's parents (first-generation relatives) in AD families revealed that there were several abnormal indexes in BAD-D, TP, Kmax, Df, Db, Dp, Dt, Da, CBI, DA ratio, SP-A1, IR, bIOP and TBI test indexes, showing clinical characteristics of incipient KC. Conclusion: Our study shows that variants in HMX1, SLC4A11, TGFBI, PIKFYVE, and ZEB1 were associated with KC. Our study extends the gene spectrum associated with KC, provides novel insights into KC phenotypic assessments, and contributes to early diagnosis for these patients.

Sex Differences in Characteristics, Treatments, and In-hospital Outcomes of Patients Undergoing Coronary Angiography or Intervention.

Background: Whether women have a higher risk of adverse events compared with men following coronary angiography (CAG) and percutaneous coronary intervention (PCI) remains controversial. We aimed to investigate the sex differences in characteristics, treatments and outcomes among patients undergoing CAG and PCI in a large Chinese cohort. Methods: We analyzed patients undergoing CAG and/or PCI in this multi-center registry cohort study Cardiorenal ImprovemeNt II (CIN-II) in 5 Chinese tertiary hospitals from 2007 to 2020. Clinical characteristics, treatment (discharge medication and PCI) and in-hospital outcomes (mortality and major bleeding) were compared between women and men. Results: Totally 141,459 patients underwent CAG (44,362 [31.4%] women), of which 69,345 patients underwent PCI (15,376 [22.2%] women). Women were older (64.4 vs. 60.8 years), had more chronic comorbidities and lower PCI rate for stable coronary artery disease (CAD) than men (52.8 vs. 64.2%). Women received less CAG and PCI procedures. Among women undergoing PCI they received similar discharge medication treatment. In addition, women undergoing PCI had mildly lower rate of major bleeding (0.2 vs. 0.3%, P = 0.033) but higher in-hospital mortality (1.2 vs. 0.8%, P < 0.001). After adjustment, women had a higher risk in the major bleeding (adjusted odds ratio, 2.04 [95% CI: 1.07 to 3.62]), and the in-hospital mortality (adjusted odds ratio, 1.87 [95% CI: 1.36 to 2.56]). Conclusion: Among our Chinese cohort, women are older with more chronic comorbidities, receiving less PCI procedure and similar discharge medication treatment. Women have nearly 90% higher risk of in-hospital mortality and over 1-fold increased risk of major bleeding after PCI compared with men.