Metal Nanoparticles Assisted Ultrafast Laser Plasmonic Microwelding of Oxide-Semiconductor Interconnects.

Integration of wafer-scale oxide and semiconductor materials meets the difficulties of residual stress and materials incompatibility. In this work, Ag NPs thin film is contributed as an energy confinement layer between oxide (Sapphire) and semiconductor (Si) wafers to localize the materials interaction during ultrafast laser irradiation. Due to the plasmonic effects generated within constructed dielectric-metal-dielectric structures (i.e., Sapphire-Ag-Si), thermal diffusion and chemical reaction between Ag and its neighboring materials facilitate the microwelding of Sapphire and Si wafers. Ag NPs can be totally sintered within the junction area to bridge oxide and semiconductor, while Al─O─Ag bond and Ag─Si bond are formed at Ag-Sapphire and Ag─Si interfaces, respectively. As-received heterogeneous joint exhibits a high shear strength up to 5.4 MPa, with the fracture occurring inside Si wafer. Meanwhile, insertion of metal nanolayer can greatly relieve the residual stress-induced microcracking inside the brittle materials. Such wafer-scale Sapphire and Si interconnects thus show robust strength and excellent impermeability even after thermal shocking (-40 °C to 120 °C) for 200 cycles. This metal NPs layer-assisted plasmonic microwelding technology can extend to broad materials integration, which is promising for high-performance microdevices development in MEMS, MOEMS, or microfluidics.

Rapid and sensitive detection of Mycoplasma synoviae using RPA combined with Pyrococcus furiosus Argonaute.

Mycoplasma synoviae (MS) is an important pathogen in laying hens and causes serious economic losses in poultry production. Rapid, accurate and specific detection is important for the prevention and control of MS. Argonaute from Pyrococcus furiosus (PfAgo) is emerging as a nucleic acid detector that works via "dual-step" sequence-specific cleavage. In this study, an MS detection method combining recombinase polymerase amplification (RPA) and PfAgo was established. Through elaborate design and screening of RPA primers and PfAgo gDNA and condition optimization, amplification and detection procedures can be completed within 40 min, whereas the results were superficially interpreted under UV and blue light. The sensitivity for MS detection was 2 copies/µL, and the specificity results showed no cross reaction with other pathogens. For the detection of 31 clinical samples, the results of this method and qPCR were completely consistent. This method provides a reliable and convenient method for the on-site detection of MS that is easy to operate without complex instruments and equipment.

Carrier screening for spinal muscular atrophy in 22913 Chinese reproductive age women.

BACKGROUND: To determine the carrier frequency of, and evaluate a carrier screening program for, spinal muscular atrophy (SMA) in reproductive age women in Shenzhen area. METHODS: A staged screening procedure was used to perform carrier screening for SMA in 22,913 Chinese reproductive age women between 2019 and 2022 in Shenzhen area of China. First, the copy number of exon 7 in the SMN1 gene were detected in women of reproductive age using real-time quantitative polymerase chain reaction. If SMA carriers were detected, their spouses were then recommended to test. Prenatal diagnosis was carried out in couples who were both carriers. RESULTS: A total of 389 women were found to be SMA carriers (1.70%, 95% CI: 1.53%-1.87%), indicating the carrier prevalence was approximately 1:59. Despite the proportion of nonpregnant women increased from 37.96% in 2019 to 58.18% in 2022 (p < 0.05) among the 22,913 reproductive age women, the recall rate of spouses was still not high (62.21%, 95% CI: 57.39%-67.03%). Eight partners were found to be SMA carriers and two fetuses were determined to have SMA with no copies of the SMN1 gene. CONCLUSION: Although the acceptability and awareness of SMA carrier screening in Chinese population has increased in recent years, it still fails to reach the ideal expectation. Our experience may provide a basis for and facilitate the popularization of SMA carrier screening in Shenzhen area.

Application of non-invasive prenatal testing in screening chromosomal aberrations in pregnancies with different nuchal translucency cutoffs.

OBJECTIVE: To investigate the efficiency of non-invasive prenatal testing (NIPT) in cases with different cutoffs of nuchal translucency (NT). METHODS: The study retrospectively analyses pregnancies with NT ≥ 2.5 mm who underwent NIPT. Results of NT, NIPT, chromosomal diagnostic and pregnancy outcomes were collected. RESULTS: Study group was composed of 1470 single pregnancies, including 864 with NT 2.5-2.9 mm, 350 with NT 3.0-3.4 mm and 256 with NT ≥ 3.5 mm. Non-significant differences were found in the positive predictive value (PPV) of NIPT between different cutoffs of NT. There was one false positive case with NT 4.3 mm, screening for 47,XYY in NIPT showed normal in diagnostic testing. For cases with normal NIPT results, the residual risk is 1:20 (5%, 95%CI: 0.1-10.1%) in fetuses with NT 3.0-3.4 mm and 1:15 (6.5%, 95%CI: 1.4%-11.5%) in fetuses with NT ≥ 3.5 mm. These false negative cases included one trisomy 21, seven pathogenic CNVs, one uniparental disomy and one single gene disorders. CONCLUSION: Our findings demonstrated that the PPV of NIPT for screening chromosomal aberrations were similarly in different NT cutoffs, while false positive case does exist. After normal in NIPT, risk for chromosomal aberrations remained, especially pathogenic CNV and even common trisomy. Therefore, prenatal diagnosis was recommended and CMA was suggested to apply in pregnancies with NT ≥ 3.0 mm.

Knockdown of TXNDC5 alleviates CCL4-induced hepatic fibrosis in mice by enhancing endoplasmic reticulum stress.

BACKGROUND: Hepatic fibrosis is a common pathological process in many chronic liver diseases. TXNDC5 has been shown to be involved in the progression of renal and pulmonary fibrosis. However, the role of TXNDC5 in hepatic fibrosis is unknown. The purpose of this study is to explore the role and mechanism of TXNDC5 in hepatic fibrosis. METHODS: We used TGF-ß1 to activate LX-2 cells and reduced TXNDC5 expression by short hairpin RNA. Cell viability was assessed by CCK-8 assay. Cell apoptosis was analyzed by flow cytometry or Tunel assay. The fibrosis-related proteins and endoplasmic reticulum stress (ERs)-related proteins were measured by western blot. ELISA was performed to detect COL1AL levels and MMP2/9 activities in cell medium. A mouse model of hepatic fibrosis was constructed by intraperitoneal injection of CCL4. HE and Masson staining were performed to assess fibrosis in mouse liver tissue. RESULTS: The results show that TXNDC5 was up-regulated in activated LX-2 cells and CCL4-induced hepatic fibrosis mice. Knockdown of TXNDC5 inhibited the viability of activated LX-2 cells and the production of collagen COL1A1. Knockdown of TXNDC5 promoted apoptosis of activated LX-2 cells. Mechanically, inhibition of TXNDC5 enhanced ERs, and the ERs inhibitor 4-Phenylbutyric acid (4-PBA) reversed the effect of TXNDC5 on activated LX-2 cells. More importantly, knockdown of TXNDC5 alleviated CCl4-induced hepatic fibrosis in mice. CONCLUSIONS: Knockdown of TXNDC5 may reduce hepatic fibrosis by regulating ERs, and targeting TXNDC5 seems to be a candidate treatment for hepatic fibrosis.

Dynamic changes in macrophage subtypes during lung cancer progression and metastasis at single-cell resolution.

Background: Lung cancer remains a major global health challenge. Macrophages (Macs) are one important component of tumor microenvironments (TMEs); however, their prognostic relevance to lung cancer is currently unknown due to the complexity of their phenotypes. Methods: In the present study, reanalysis and atlas reconstruction of downloaded single-cell RNA sequencing (scRNAseq) data were used to systematically compare the component and transcriptional changes in Mac subtypes across different stages of lung cancer. Results: We found that with the progression of lung cancer, the proportion of alveolar macrophages (aMacs) gradually decreased, while the proportions of Macs and monocytes (Monos) gradually increased, suggesting a chemotaxis process followed by a Mono-Mac differentiation process. Meanwhile, through ligand-receptor (LR) screening, we identified 9 Mac-specific interactions that were enriched during the progression and metastasis of lung cancer, which could potential promote M2 polarization or the infiltration of M2 Macs. Moreover, we found that the expression of SPP1 in Macs increased with lung cancer progression, and identified 9 genes that were correlated with the expression of SPP1 in Macs, which might also contribute to the immunosuppression process in lung cancer. Conclusions: Our results revealed detailed changes in Macs at different stages of lung cancer progression and metastasis and provided potential therapeutic targets that could be used in future lung cancer treatments.

Establishment and Validation of a Nomogram Prediction Model for the Severe Acute Pancreatitis.

Background: Severe acute pancreatitis (SAP) can progress to lung and kidney dysfunction, and blood clotting within 48 hours of its onset, and is associated with a high mortality rate. The aim of this study was to establish a reliable diagnostic prediction model for the early stage of severe pancreatitis. Methods: The clinical data of patients diagnosed with acute pancreatitis from October 2017 to June 2022 at the Shangluo Central Hospital were collected. The risk factors were screened by least absolute shrinkage and selection operator (LASSO) regression analysis. A novel nomogram model was then established by multivariable logistic regression analysis. Results: The data of 436 patients with acute pancreatitis, 45 (10.3%) patients had progressed to SAP. Through univariate and LASSO regression analyses, the neutrophils (P <0.001), albumin (P < 0.001), blood glucose (P < 0.001), serum calcium (P < 0.001), serum creatinine (P < 0.001), blood urea nitrogen (P < 0.001) and procalcitonin (P = 0.005) were identified as independent predictive factors for SAP. The nomogram built on the basis of these factors predicted SAP with sensitivity of 0.733, specificity of 0.9, positive predictive value of 0.458 and negative predictive value of 0.967. Furthermore, the concordance index of the nomogram reached 0.889 (95% CI, 0.837-0.941), and the area under the curve (AUC) in receiver operating characteristic curve (ROC) analysis was significantly higher than that of the APACHEII and ABISAP scoring systems. The established model was validated by plotting the clinical decision curve analysis (DCA) and clinical impact curve (CIC). Conclusion: We established a nomogram to predict the progression of early acute pancreatitis to SAP with high discrimination and accuracy.

A mouse model for X-linked Alport syndrome induced by Del-ATGG in the Col4a5 gene.

Alport syndrome (AS) is an inherited glomerular basement membrane (GBM) disease leading to end-stage renal disease (ESRD). X-linked AS (XLAS) is caused by pathogenic variants in the COL4A5 gene. Many pathogenic variants causing AS have been detected, but the genetic modifications and pathological alterations leading to ESRD have not been fully characterized. In this study, a novel frameshift variant c.980_983del ATGG in the exon 17 of the COL4A5 gene detected in a patient with XLAS was introduced into a mouse model in by CRISPR/Cas9 system. Through biochemical urinalysis, histopathology, immunofluorescence, and transmission electron microscopy (TEM) detection, the clinical manifestations and pathological alterations of Del-ATGG mice were characterized. From 16 weeks of age, obvious proteinuria was observed and TEM showed typical alterations of XLAS. The pathological changes included glomerular atrophy, increased monocytes in renal interstitial, and the absence of type IV collagen α5. The expression of Col4a5 was significantly decreased in Del-ATGG mouse model. Transcriptomic analysis showed that differentially expressed genes (DEGs) accounted for 17.45% (4,188/24003) of all genes. GO terms indicated that the functions of identified DEGs were associated with cell adhesion, migration, and proliferation, while KEGG terms found enhanced the degradation of ECM, amino acid metabolism, helper T-cell differentiation, various receptor interactions, and several important pathways such as chemokine signaling pathway, NF-kappa B signaling pathway, JAK-STAT signaling pathway. In conclusion, a mouse model with a frameshift variant in the Col4a5 gene has been generated to demonstrate the biochemical, histological, and pathogenic alterations related to AS. Further gene expression profiling and transcriptomic analysis revealed DEGs and enriched pathways potentially related to the disease progression of AS. This Del-ATGG mouse model could be used to further define the genetic modifiers and potential therapeutic targets for XLAS treatment.

Computational Drug Discovery in Ankylosing Spondylitis-Induced Osteoporosis Based on Data Mining and Bioinformatics Analysis.

BACKGROUND: Ankylosing spondylitis (AS) and osteoporosis (OP) are both prevalent illnesses in spine surgery, with OP being a possible consequence of AS. However, the mechanism of AS-induced OP (AS-OP) remains unknown, limiting etiologic research and therapy of the illness. To mine targetable medicine for the prevention and treatment of AS-OP, this study analyzes public data sets using bioinformatics to identify genes and biological pathways relevant to AS-OP. METHODS: First, text mining was used to identify common genes associated with AS and OP, after which functional analysis was carried out. The STRING database and Cytoscape software were used to create protein-protein interaction networks. Hub genes and potential drugs were discovered using drug-gene interaction analysis and transcription factors-gene interaction analysis. RESULTS: The results of text mining showed 241 genes common to AS and OP, from which 115 key symbols were sorted out by functional analysis. As options for treating AS-OP, protein-protein interaction analysis yielded 20 genes, which may be targeted by 13 medications. CONCLUSIONS: Carlumab, bermekimab, rilonacept, rilotumumab, and ficlatuzumab were first identified as the potential drugs for the treatment of AS-OP, proving the value of text mining and pathway analysis in drug discovery.

Prenatal and postnatal diagnosis of Phelan-McDermid syndrome: A report of 21 cases from a medical center and review of the literature.

Background: Phelan-McDermid syndrome (PMS), caused by deletions at 22q13.3 and pathogenic variants in the SHANK3 gene, is a rare developmental disorder characterized by hypotonia, developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD), dysmorphic features, absence of or delayed language, and other features. Methods: Conventional karyotyping, chromosomal microarray analysis (CMA), and whole exome sequencing (WES) have been used to detect genetic defects causing PMS. We summarized the genetic and clinical findings from prenatal to postnatal stages of detected cases of PMS and mapped potential candidate haploinsufficient genes for deletions of 22q13. This study aimed to summarize the laboratory findings, genetic defects, and genotype-phenotype correlations for Chinese patients with PMS. Results: Seven prenatal cases and fourteen postnatal cases were diagnosed with PMS in our center. Thirteen cases had a deletion ranging in size from 69 to 9.06 Mb at 22q13.2-q13.33, and five cases had a pathogenic variant or an intragenic deletion in the SHANK3 gene. Three familial cases with a parental carrier of a balanced translocation were noted. A review of the literature noted another case series of 29 cases and a report of five cases of PMS in China. Genotype-phenotype correlations confirmed haploinsufficiency of the SHANK3 gene for PMS and suggested other candidate haploinsufficient genes TNFRSFI3C and NFAM1 genes for immunological features and TCF20, SULT4A1, PARVB, SCO2, and UPK3A genes for intellectual impairment and behavioral abnormality, neurological features, macrocephaly/hypotonia, oculopathy, and renal adysplasia, respectively. Conclusion: Indications for prenatal diagnosis of PMS are not specific, and approximately 85% prenatally diagnosed PMS elected termination of pregnancies after genetic counseling. For postnatal cases, 62.5% were caused by a deletion at 22q13 and 37.5% were caused by a pathogenic variant or an intragenic deletion in the SHANK3 gene. Approximately 6.7% of cases with a deletion were familial, and almost all pathogenic variants were de novo. Combined karyotype, CMA, and WES should be performed to increase the diagnostic yield. The identification of other candidate haploinsufficient genes in deletions of 22q13.2-q13.33 could relate to more severe dysmorphic features, neurologic defects, and immune deficiency. These results provided evidence for diagnostic interpretation, genetic counseling, and clinical management for the Chinese cases of PMS.

Drug discovery in spinal cord injury-induced osteoporosis: a text mining-based study.

Background: Spinal cord injury (SCI) and osteoporosis (OP) are common diseases in spine surgery, and OP could be the complication of SCI. However, SCI-induced OP is a complex pathologic process and drug discovery is limited, which restricts the study in the mechanism and treatment of the disease. This study aims to identify the genes and molecular pathways related to SCI-induced OP through computational tools and public datasets, and to explore drug targeting therapy, ultimately preventing the occurrence of OP after SCI. Methods: In this study, common genes related to SCI and OP were obtained by text mining, then which conducted the functional analysis. Protein-protein interaction (PPI) networks were constructed by STRING online and Cytoscape software. Finally, core genes and potential drugs were performed after undergoing drug-gene interaction analysis which also completed functional analysis. Results: A total of 371 genes common to 'SCI' and 'OP' were identified by text mining. After functional analysis, 207 significant genes were screened out. Subsequently, PPI analysis yielded 23 genes targetable by 13 drugs which were the candidate to treat SCI-induced OP. Conclusions: Taken together, siltuximab, olokizumab, clazakizumab and BAN2401 were first discovered to become the potential drugs for the treatment of SCI-induced OP. Drug discovery using text mining and pathway analysis is a significant way to investigate the pathomechanism of the disease while exploring existing drugs to treat the disease.

Inhibition of IL1R1 or CASP4 attenuates spinal cord injury through ameliorating NLRP3 inflammasome-induced pyroptosis.

Spinal cord injury (SCI) is a devastating trauma characterized by serious neuroinflammation and permanent neurological dysfunction. However, the molecular mechanism of SCI remains unclear, and few effective medical therapies are available at present. In this study, multiple bioinformatics methods were used to screen out novel targets for SCI, and the mechanism of these candidates during the progression of neuroinflammation as well as the therapeutic effects were both verified in a rat model of traumatic SCI. As a result, CASP4, IGSF6 and IL1R1 were identified as the potential diagnostic and therapeutic targets for SCI by computational analysis, which were enriched in NF-κB and IL6-JAK-STATA3 signaling pathways. In the injured spinal cord, these three signatures were up-regulated and closely correlated with NLRP3 inflammasome formation and gasdermin D (GSDMD) -induced pyroptosis. Intrathecal injection of inhibitors of IL1R1 or CASP4 improved the functional recovery of SCI rats and decreased the expression of these targets and inflammasome component proteins, such as NLRP3 and GSDMD. This treatment also inhibited the pp65 activation into the nucleus and apoptosis progression. In conclusion, our findings of the three targets shed new light on the pathogenesis of SCI, and the use of immunosuppressive agents targeting these proteins exerted anti-inflammatory effects against spinal cord inflammation by inhibiting NF-kB and NLRP3 inflammasome activation, thus blocking GSDMD -induced pyroptosis and immune activation.

Autophagy activation by dietary piceatannol enhances the efficacy of immunogenic chemotherapy.

Immunogenic cell death (ICD) promotes the immune antitumor response via releasing damage-associated molecular patterns (DAMPs) from dying tumor cells. The induction of autophagy improves the efficacy of multiple immunogenic chemotherapies. Here, we show that piceatannol, a dietary phenolic compound that is widely distributed in multiple fruits and vegetables such as grapes, blueberries, and mushrooms, induces autophagy and enhances oxaliplatin (OXA)-induced anticancer immune response. Specifically, piceatannol enhanced OXA-induced release of DAMPs, several key hallmarks of ICD including ATP release, cell surface exposure of calreticulin, and high-mobility group box 1 (HMGB1) release. Mechanistically, piceatannol promoted autophagy via activating TFEB/TFE3, two key transcription factors of the autophagy-lysosome pathway, and inhibiting autophagy attenuated piceatannol plus OXA-induced ATP release. Furthermore, piceatannol induced endoplasmic reticulum stress, which is critical for its role in enhancing OXA-induced cell surface exposure of calreticulin, another key hallmark of ICD. Consistently, the combination of piceatannol with OXA promoted the anticancer effects in immunocompetent mice. Taken together, our results indicate the importance and great potential of dietary piceatannol in cancer immunotherapy. Therefore, piceatannol may be used as an ICD enhancer that improves the efficacy of chemotherapeutics such as OXA in cancer treatment with minimized toxicity.

Drug Discovery in Spinal Cord Injury With Ankylosing Spondylitis Identified by Text Mining and Biomedical Databases.

Spinal cord injury (SCI) and ankylosing spondylitis (AS) are common inflammatory diseases in spine surgery. However, it is a project where the relationship between the two diseases is ambiguous and the efficiency of drug discovery is limited. Therefore, the study aimed to investigate new drug therapies for SCI and AS. First, text mining was used to obtain the interacting genes related to SCI and AS, and then, the functional analysis was conducted. Protein-protein interaction (PPI) networks were constructed by STRING online and Cytoscape software to identify hub genes. Last, hub genes and potential drugs were performed after undergoing drug-gene interaction analysis, and MicroRNA and transcription factors regulatory networks were also analyzed. Two hundred five genes common to "SCI" and "AS" identified by text mining were enriched in inflammatory responses. PPI network analysis showed that 30 genes constructed two significant modules. Ultimately, nine (SST, VWF, IL1B, IL6, CXCR4, VEGFA, SERPINE1, FN1, and PROS1) out of 30 genes could be targetable by a total of 13 drugs. In conclusion, the novel core genes contribute to a novel insight for latent functional mechanisms and present potential prognostic indicators and therapeutic targets in SCI and AS.

[Laparoscopic management of persistent Müllerian duct syndrome: A case report and pedigree investigation].

OBJECTIVE: To investigate the clinical characteristics, diagnosis, treatment and etiology of persistent Müllerian duct syndrome (PMDS). METHODS: A 3-year-old boy was diagnosed with PMDS according to the clinical manifestations and the results of ultrasonography, laboratory examinations and earlier surgical examination. We performed genetic tests for the patient and his family members, removed the infantile uterus by laparoscopic wedge hysterectomy, biopsied and descended the bilateral testes, and ligated the bilateral internal rings, followed by a retrospective analysis and review of relevant literature. RESULTS: The operation was successful. Gonad biopsy revealed testis tissue, and PMDS was confirmed by intraoperative findings and related examinations. Good bilateral testicular blood supply was found during the 6-month follow-up after surgery. Medical exome sequencing showed the AMHR2 gene c.1499G > A (p.Cys500Tyr) mutant homozygote (A/A) in the patient and his sister and mutant heterozygote (G/A) in his parents. CONCLUSIONS: Laparoscopy is definitely effective for the treatment of PMDS. In surgery, the infantile uterus should be removed in case of good blood supply to the testis, and so were the bilateral testes if they cannot be descended. The homozygous mutation in the AMHR2 gene c. 1499G > A (p. Cys500Tyr) can lead to male PMDS. Pedigree investigation may provide some evidence for possible fertility in PMDS patients.

Theoretical Studies on the Structures of Metal String Complexes Crn(L)4Cl2 (n = 3, 5, 7; L = Oligo-α-Pyridylamide) under the Effect of an Electric Field.

To study the electronic structures and properties of [Crn(L)4Cl2] (n = 3, L = dpa: di(2-pyridyl)amido; n = 5, L = tpda: tripyridyldiamido; n = 7, L = teptra: tetrapyridyltriamine) metal string complexes, the BP86 method was used by considering the influence of the electric field (EF) applied parallel to the metal axis. As the EF increases, the migration of more positively charged Crodd is more significant than that of Creven, which results in alternating long-short Cr-Cr bonds. This happens because of the natural charges on the Crodd of 1-3, which are more electropositive than those on Creven. The electrons are pulled to the Cr and Cl(r) atoms at the high-potential side from Cl(l) at the low-potential side by the EF, which leads to asymmetrical FMOs. After the critical electric field (Ec), the configuration turns into a remarkably asymmetric one with alternating Cr-Cr quadruple bonds and weak interactions. The electrons are transferred from equatorial ligands (L) to metal chains. In the meantime, the asymmetry of the FMOs increases and the delocalization is further reduced, which affects the conductivity. Especially for [Cr7(teptra)4Cl2], the delocalized electrons of HOMO are completely transformed into a localized model after the critical electric field. It is observed that this supports the electric switching phenomenon ascribed to the conformations of delocalized and localized electrons. In addition, the longer the length of the metal chain, the smaller the Ec and the easier is for the complexes to be polarized by the EF.

Combining the Fecal Immunochemical Test with a Logistic Regression Model for Screening Colorectal Neoplasia.

Background: The fecal immunochemical test (FIT) is a widely used strategy for colorectal cancer (CRC) screening with moderate sensitivity. To further increase the sensitivity of FIT in identifying colorectal neoplasia, in this study, we established a classifier model by combining FIT result and other demographic and clinical features. Methods: A total of 4,477 participants were examined with FIT and those who tested positive (over 100 ng/ml) were followed up by a colonoscopy examination. Demographic and clinical information of participants including four domains (basic information, clinical history, diet habits and life styles) that consist of 15 features were retrieved from questionnaire surveys. A mean decrease accuracy (MDA) score was used to select features that are mostly related to CRC. Five different algorithms including logistic regression (LR), classification and regression tree (CART), support vector machine (SVM), artificial neural network (ANN) and random forest (RF) were used to generate a classifier model, through a 10X cross validation process. Area under curve (AUC) and normalized mean squared error (NMSE) were used in the evaluation of the performance of the model. Results: The top six features that are mostly related to CRC include age, gender, history of intestinal adenoma or polyposis, smoking history, gastrointestinal discomfort symptom and fruit eating habit were selected. LR algorithm was used in the generation of the model. An AUC score of 0.92 and an NMSE score of 0.076 were obtained by the final classifier model in separating normal individuals from participants with colorectal neoplasia. Conclusion: Our results provide a new "Funnel" strategy in colorectal neoplasia screening via adding a classifier model filtering step between FIT and colonoscopy examination. This strategy minimizes the need of colonoscopy examination while increases the sensitivity of FIT-based CRC screening.

[Clinical characterization and genetic analysis of a newborn with chromosome 8q21.11 deletion syndrome].

OBJECTIVE: To explore the genetic etiology for a newborn with corneal opacity. METHODS: The neonate and her parents were subjected to routine G-banding chromosomal karyotyping analysis. Copy number variation (CNV) was analyzed with low-coverage whole-genome sequencing (WGS) and single nucleotide polymorphism microarray (SNP array). RESULTS: No karyotypic abnormality was found in the newborn and her parents. Low-coverage WGS has identified a de novo 5.5 Mb microdeletion at chromosome 8q21.11-q21.13 in the neonate, which encompassed the ZFHX4 and PEX2 genes. The result was confirmed by SNP array-based CNV analysis. CONCLUSION: The newborn was diagnosed with chromosome 8q21.11 deletion syndrome. ZFHX4 may be one of the key genes underlying this syndrome.

Identification of Hub Genes as Potential Prognostic Biomarkers in Cervical Cancer Using Comprehensive Bioinformatics Analysis and Validation Studies.

BACKGROUND: Cervical cancer belongs to one of the most common female cancers; yet, the exact underlying mechanisms are still elusive. Recently, microarray and sequencing technologies have been widely used for screening biomarkers and molecular mechanism discovery in cancer studies. In this study, we aimed to analyse the microarray datasets using comprehensive bioinformatics tools and identified novel biomarkers associated with the prognosis of patients with cervical cancer. METHODS: The differentially expressed genes (DEGs) from Gene Expression Omnibus (GEO) datasets including GSE138080, GSE113942 and GSE63514 were analysed using GEO2R tool. The functional enrichment analysis was performed using g:Profiler tool. The protein-protein interaction (PPI) network construction and hub genes identification were performed using the STRING database and Cytoscape software, respectively. The hub genes were subjected to expression and survival analysis in the cervical cancer. The EdU incorporation and Cell Counting Kit-8 assays were performed to evaluate the effects of hub gene knockdown on the proliferation of cervical cancer cells. RESULTS: A total of 89 overlapping DEGs (63 up-regulated and 26 down-regulated genes) were identified in the microarray datasets. The functional enrichment analysis indicated that the overlapping DEGs were mainly associated with "DNA replication" and "cell cycle". Furthermore, the PPI network analysis revealed that the network contains 87 nodes and 309 edges. Sub-module analysis using the Molecular Complex Detection tool identified 21 hub genes from the PPI network. The expression levels of the 21 hub genes were all up-regulated in the cervical cancer tissues when compared to normal cervical tissues as analysed by GEPIA tool. The survival analysis showed that the low expression of cell division cycle 45 (CDC45), GINS complex subunit 2 (GINS2), minichromosome maintenance complex component 2 (MCM2) and proliferating cell nuclear antigen (PCNA) was significantly correlated with the shorter overall survival of patients with cervical cancer. Moreover, the protein expression levels of GINS2, MCM2 and PCNA, but not CDC45, were significantly up-regulated in the cervical cancer tissues when compared to normal cervical tissues. Finally, knockdown of MCM2 significantly suppressed the proliferation of HeLa and SiHa cells. CONCLUSION: In conclusion, we screened a total of 89 overlapping DEGs from the GEO datasets, and further analysis identified four hub genes (CDC45, GINS2, MCM2 and PCNA) that were likely associated with the prognosis of patients with cervical cancer. MCM2 knockdown repressed the cervical cancer cell proliferation. The current findings may provide novel insights into understanding the pathophysiology of cervical cancer and develop therapeutic targets for patients with cervical cancer.