In Vitro Functional Analysis Can Aid Precision Diagnostics of HNF1B-MODY.

Precision medicine relies on accurate and consistent classification of sequence variants. A correct diagnosis of hepatocyte nuclear factor (HNF) 1B maturity-onset diabetes of the young, caused by pathogenic variants in the HNF1B gene, is important for optimal disease management and prognosis, and it has implications for genetic counseling and follow-up of at-risk family members. We hypothesized that the functional characterization could provide valuable information to assist the interpretation of pathogenicity of HNF1B variants. Using different in vitro functional assays, variants identified among 313 individuals, suspected to have monogenic diabetes with or without kidney disease, were characterized. The data from the functional assays were subsequently conjugated with obtained clinical, biochemical, and in silico data. Two variants (p.A167P, p.H336Pfs∗22) showed severe loss of function due to impaired transactivation, reduced DNA binding (p.A167P), and mRNA instability (p.A167P). Although both these variant carriers were diagnosed with diabetes, the p.H336Pfs∗22 carrier also had congenital absence of a kidney, which is a characteristic trait for HNF1B maturity-onset diabetes of the young. Functional analysis of the p.A167P variant revealed damaging effects on HNF-1B protein function, which may warrant imaging of the kidneys and/or pancreas. In addition, the current study has generated important data, including evidence supporting the benign functional impact of five variants (p.D82N, p.T88A, p.N394D, p.V458G, and p.T544A), and piloting new approaches that will prove critical for the growth of HNF1B-diabetes diagnosis.

Transcriptomic and proteomic strategies to reveal the mechanism of Gymnocypris przewalskii scale development.

BACKGROUND: Fish scales are typical products of biomineralization and play an important role in the adaptation of fish to their environment. The Gymnocypris przewalskii scales are highly specialized, with scales embedded in only specific parts of the dermis, such as the areas around the anal fin and branchiostegite, making G. przewalskii an ideal material for biomineralization research. In this study, we aimed to unveil genes and pathways controlling scale formation through an integrated analysis of both transcriptome and proteome, of which G. przewalskii tissues of the dorsal skin (no scales) and the rump side skin (with scales) were sequenced. The sequencing results were further combined with cellular experiments to clarify the relationship between genes and signaling pathways. RESULTS: The results indicated the following: (1) a total of 4,904 differentially expressed genes were screened out, including 3,294 upregulated genes and 1,610 downregulated genes (with a filtering threshold of |log2Fold-Change|> 1 and p-adjust < 0.05). The identified differentially expressed genes contained family members such as FGF, EDAR, Wnt10, and bmp. (2) A total of 535 differentially expressed proteins (DEPs) were filtered out from the proteome, with 204 DEPs downregulated and 331 DEPs upregulated (with a filtering threshold of |Fold-Change|> 1.5 and p < 0.05). (3) Integrated analyses of transcriptome and proteome revealed that emefp1, col1a1, col6a2, col16a1, krt8, and krt18 were important genes contributing to scale development and that PI3K-AKT was the most important signaling pathway involved. (4) With the use of the constructed G. przewalskii fibroblast cell line, emefp1, col1a1, col6a2, col16a1, krt8, and krt18 were confirmed to be positively regulated by the PI3K-AKT signaling pathway. CONCLUSION: This study provides experimental evidence for PI3K-AKT controlled scale development in G. przewalskii and would benefit further study on stress adaptation, scale biomineralization, and the development of skin appendages.

Partial GCK gene deletion mutations causing maturity-onset diabetes of the young.

AIMS: Maturity-onset diabetes of the young (MODY) is an autosomal dominant monogenic form of diabetes, and glucokinase-maturity-onset diabetes of the young (GCK-MODY), or MODY 2, being the most prevalent type. However, the presence of copy number variants (CNVs) may lead to misdiagnoses, as genetic testing for MODY is typically reliant on sequencing techniques. This study aimed to describe the process of diagnosis in a Chinese pedigree with an exon 8-10 deletion of the GCK gene. METHODS: This study collected clinical data and medical history through direct interviews with the patient and reviewing relevant medical records. Sanger sequencing and whole exome sequencing (WES) were conducted over years of follow up. WES-based CNV sequencing technology was used to detect CNVs and the results were validated by multiplex ligation-dependent amplification dosage assay (MLPA). Additionally, we reviewed the previously reported cases caused by heterozygous exon deletion of the GCK gene. RESULTS: WES-based CNV detection revealed a heterozygous exon 8-10 deletion in the GCK gene within this particular pedigree after Sanger sequencing and WES failed to find causal variants in single nucleotide variations (SNVs) and small indels. The deletion was considered pathogenic according to ACMG/AMP and ClinGen guidelines. Most of the previously reported cases caused by heterozygous exon deletion or whole gene deletion of the GCK gene present similarly to GCK-MODY caused by SNVs and small indels. CONCLUSIONS: This study contributed to progress in our comprehension of the mutation spectrum of the GCK gene and underscored the significance of CNV detection in the genetic testing of MODY.

Thermobacterium salinum gen. nov., sp. nov., a novel member of the family Flavobacteriaceae isolated from a hydrothermal zone.

A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterial strain, designated as strain TK19130T, was isolated from the Lonqi hydrothermal zone in the Southwest Indian Ridge. Growth occurred with 1-12 % (w/v) NaCl (optimum, 2-4 %), at 10-40 °C (optimum, 30-35 °C) and at pH 6.0-9.0 (optimum, pH 7.0-8.0). The genome of strain TK19130T was 3.15 Mb, with a DNA G+C content of 41.35 %. Based on the results of 16S rRNA gene sequence analysis, strain TK19130T was affiliated with the family Flavobacteriaceae, in which the highest similarity was 90.54 % to Aureisphaera salina A6D-50T, under the genus demarcation boundary (94.50 %). Average nucleotide identity values between strain TK19130T and adjacent strains were 67.17-72.00 %, lower than the recommended threshold of 73.98 % for genus delineation. The predominant respiratory quinone of strain TK19130T was menaquinone 6. Major polar lipids were phosphatidylethanolamine, three aminolipids and one unidentified polar lipid. Major fatty acids were detected as iso-C15 : 1 G, iso-C15 : 0 and iso-C17 : 0 3-OH. Based on the polyphasic taxonomic evidence presented above, strain TK19130T formed an independent branch representing a new species of a novel genus within the family Flavobacteriaceae, for which the name Thermobacterium salinum gen. nov., sp. nov. is proposed. The type strain is TK19130T (=CGMCC 1.18993T=JCM 35842T=MCCC M28200T).

Radiotherapy dosimetry and radiotherapy related complications of immediate implant-based reconstruction after breast cancer surgery.

Backgrounds: The impact of immediate implant-based breast reconstruction (IBBR) on the delivery of radiotherapy plans remains controversial. This study aimed to compare the differences in radiotherapy dosimetry, complications of radiotherapy, and quality of life in patients who underwent modified radical mastectomy combined with or without IBBR. Methods: We retrospectively collected 104 patients with breast cancer who underwent intensity-modulated radiation therapy after modified radical mastectomy with IBBR (n =46) or not (n =58) from January 2017 to December 2021. The dosimetric differences in radiotherapy of planning target volume (PTV) and organs at risk and the differences in complications of radiotherapy between the two groups were compared. We also applied the functional assessment of cancer therapy-breast cancer (FACT-B) score to compare the difference in quality of life. The chi-square test and independent samples t-test were used to analyze the above data. Results: IBBR group was associated with higher PTV volumes, PTV D98, V95, and lower PTV Dmean, D2 compared with the non-reconstruction group (P<0.05). IBBR group also had lower radiotherapy dosimetric parameters in the ipsilateral lung and the heart of left breast cancer patients. The differences in the rates of radiation pneumonia (RP) and radiation dermatitis (RD) between the two groups were not statistically significant (P > 0.05). Moreover, FACT-B scores at 6 months after radiotherapy in patients with IBBR were higher than those without reconstruction (P < 0.05). Conclusion: Patients with IBBR achieved better radiation dosimetry distribution and higher quality of life without more complications of radiotherapy.

Bacterial communities associated with mushrooms in the Qinghai-Tibet Plateau are shaped by soil parameters / Las comunidades bacterianas asociadas con los hongos en la meseta de Qinghai-Tíbet están formadas por parámetros del suelo

Fungi capable of producing fruit bodies are essential food and medicine resources. Despite recent advances in the study of microbial communities in mycorrhizospheres, little is known about the bacterial communities contained in fruit bodies. Using high-throughput sequencing, we investigated the bacterial communities in four species of mushrooms located on the alpine meadow and saline-alkali soil of the Qinghai-Tibet Plateau (QTP). Proteobacteria (51.7% on average) and Actinobacteria (28.2% on average) were the dominant phyla in all of the sampled fairy ring fruit bodies, and Acidobacteria (27.5% on average) and Proteobacteria (25.7% on average) dominated their adjacent soils. For the Agria. Bitorquis, Actinobacteria was the dominant phylum in its fruit body (67.5% on average) and adjacent soils (65.9% on average). The alpha diversity (i.e., Chao1, Shannon, Richness, and Simpson indexes) of the bacterial communities in the fruit bodies were significantly lower than those in the soil samples. All of the fungi shared more than half of their bacterial phyla and 16.2% of their total operational taxonomic units (OTUs) with their adjacent soil. Moreover, NH4+ and pH were the key factors associated with bacterial communities in the fruit bodies and soils, respectively. These results indicate that the fungi tend to create a unique niche that selects for specific members of the bacterial community. Using culture-dependent methods, we also isolated 27 bacterial species belonging to three phyla and five classes from fruit bodies and soils. The strains isolated will be useful for future research on interactions between mushroom-forming fungi and their bacterial endosymbionts.(AU)

A Chinese family with cat eye syndrome and abnormality of eye movement: First case report.

Background: Cat eye syndrome (CES) is a rare disease with a wide spectrum of phenotypic variability that is observed in 1:150,000 newborns. CES is characterized clinically by the combination of iris coloboma, anal atresia, and preauricular tags and/or pits. Many eye malformations have been reported to be associated with CES, such as iris and chorioretinal coloboma. However, an abnormality of eye movement has not been previously reported. Case presentation: We report on a Chinese family carrying a 22q11.1-q11.21 duplication of 1.7Mb tetrasomy (chr22:16,500,000-18,200,000, hg38) in two generations. Based on the proband and her father's clinical manifestations, including ophthalmological examination, cytogenetic analysis, FISH, CNV-seq, and WES, the diagnosis of CES with an abnormality of eye movement was made. Conclusion: Our findings broadened the symptom spectrum of CES syndrome and laid the foundation for pathogenesis, diagnostic targets, and drug research on the abnormality of eye movement, and were helpful for early diagnosis and intervention of CES.

Fabricating Well-Dispersed Poly(Vinylidene Fluoride)/Expanded Graphite Composites with High Thermal Conductivity by Melt Mixing with Maleic Anhydride Directly.

Maleic anhydride (MA) is introduced to fabricate poly(vinylidene fluoride)/expanded graphite (PVDF/EG) composites via one-step melt mixing. SEM micrographs and WAXD results have demonstrated that the addition of MA helps to exfoliate and disperse the EG well in the PVDF matrix by promoting the mobility of PVDF molecular chains and enhancing the interfacial adhesion between the EG layers and the PVDF. Thus, much higher thermal conductivities are obtained for the PVDF/MA/EG composites compared to the PVDF/EG composites that are lacking MA. For instance, The PVDF/MA/EG composite prepared with a mass ratio of 93:14:7 exhibits a high thermal conductivity of up to 0.73 W/mK. It is 32.7% higher than the thermal conductivity of the PVDF/EG composite that is prepared with a mass ratio of 93:7. Moreover, the introduction of MA leads to an increased melting peak temperature and crystallinity due to an increased nucleation site provided by the uniformly dispersed EG in the PVDF matrix. This study provides an efficient preparation method for PVDF/EG composites with a high thermal conductivity.

Phase Change Composite Microcapsules with Low-Dimensional Thermally Conductive Nanofillers: Preparation, Performance, and Applications.

Phase change materials (PCMs) have been extensively utilized in latent thermal energy storage (TES) and thermal management systems to bridge the gap between thermal energy supply and demand in time and space, which have received unprecedented attention in the past few years. To effectively address the undesirable inherent defects of pristine PCMs such as leakage, low thermal conductivity, supercooling, and corrosion, enormous efforts have been dedicated to developing various advanced microencapsulated PCMs (MEPCMs). In particular, the low-dimensional thermally conductive nanofillers with tailorable properties promise numerous opportunities for the preparation of high-performance MEPCMs. In this review, recent advances in this field are systematically summarized to deliver the readers a comprehensive understanding of the significant influence of low-dimensional nanofillers on the properties of various MEPCMs and thus provide meaningful enlightenment for the rational design and multifunction of advanced MEPCMs. The composition and preparation strategies of MEPCMs as well as their thermal management applications are also discussed. Finally, the future perspectives and challenges of low-dimensional thermally conductive nanofillers for constructing high performance MEPCMs are outlined.

Bacterial communities associated with mushrooms in the Qinghai-Tibet Plateau are shaped by soil parameters.

Fungi capable of producing fruit bodies are essential food and medicine resources. Despite recent advances in the study of microbial communities in mycorrhizospheres, little is known about the bacterial communities contained in fruit bodies. Using high-throughput sequencing, we investigated the bacterial communities in four species of mushrooms located on the alpine meadow and saline-alkali soil of the Qinghai-Tibet Plateau (QTP). Proteobacteria (51.7% on average) and Actinobacteria (28.2% on average) were the dominant phyla in all of the sampled fairy ring fruit bodies, and Acidobacteria (27.5% on average) and Proteobacteria (25.7% on average) dominated their adjacent soils. For the Agria. Bitorquis, Actinobacteria was the dominant phylum in its fruit body (67.5% on average) and adjacent soils (65.9% on average). The alpha diversity (i.e., Chao1, Shannon, Richness, and Simpson indexes) of the bacterial communities in the fruit bodies were significantly lower than those in the soil samples. All of the fungi shared more than half of their bacterial phyla and 16.2% of their total operational taxonomic units (OTUs) with their adjacent soil. Moreover, NH4+ and pH were the key factors associated with bacterial communities in the fruit bodies and soils, respectively. These results indicate that the fungi tend to create a unique niche that selects for specific members of the bacterial community. Using culture-dependent methods, we also isolated 27 bacterial species belonging to three phyla and five classes from fruit bodies and soils. The strains isolated will be useful for future research on interactions between mushroom-forming fungi and their bacterial endosymbionts.

Sensitization of cervical cancer cells to radiation by the cyclin-dependent kinase inhibitor dinaciclib.

Dinaciclib is a selective cyclin-dependent kinase inhibitor, but its radiosensitizing effect remains unclear. The aim of this study is to investigate the radiosensitizing effect of Dinaciclib on cervical cancer cells. Two cervical cancer cell lines, Hela and Siha, were selected, and the IC50 was determined by CCK8. The radiosensitizing effect of Dinaciclib was verified by plate cloning assay, and the G2/M phase arrest and apoptosis of IR cells were verified by flow cytometry. Immunofluorescence assay was used to verify the formation of γH2AX foci following DNA damage. Western blot was performed to detect cell cycle, apoptosis, autophagy, and DNA damage-related pathways. Dinaciclib increased the cell sensitivity to IR. IR induced G2/M phase arrest and apoptosis, and Dinaciclib enhanced this effect. Further, Dinaciclib delayed DNA repair, including non-homologous end joining repair and homologous recombination repair, and reduced the expression of DNA repair proteins Ku80 (SiHa cells), Ku70, and RAD51, as well as the expression of apoptotic marker Bcl-2. The expression of autophagy marker Beclin1 induced tumor cell death and increased the formation of DNA damage marker γH2AX foci. Dinaciclib improves the sensitivity of cervical cancer cells to IR by inducing cell cycle arrest, delaying DNA repair, and increasing apoptosis. However, further research is needed to unravel the complexity of DNA repair pathways.

Prevalence and associated factors of inappropriate hospital admissions and days of children in a secondary hospital in Shanghai, China.

BACKGROUND: Although the appropriateness of hospital utilization of adults and the elderly in China was audited by several studies, the appropriateness of hospital use by children in Shanghai remains to be determined. This study aims to assess the level of inappropriate hospital admissions and hospital days, to detect factors associated with inappropriateness, and to elucidate reasons for inappropriateness. METHODS: A retrospective review of the records of 291 admissions and 1449 hospital days of children inpatients from a secondary hospital in Shanghai was performed by two reviewers using the Chinese version Pediatric Appropriateness Evaluation Protocol (C-PAEP). Demographics, socio-economic characteristics, and other admission- or hospital stay-related information were collected and analyzed to determine factors associated with inappropriateness utilizing multivariate regression models. RESULTS: 38.5% (n = 112) of admissions and 9.5% (n = 137) of hospital days were categorized as inappropriate, according to the C-PAEP. Children who were non-Shanghai residents (p < 0.001), admitted through the emergency sector (p = 0.030), and/or received services in a surgical ward (p < 0.001) had a higher risk of being admitted inappropriately. Payment method (p = 0.006), service type (p < 0.001), comorbidity (p = 0.016), length of stay (p = 0.007), and appropriateness of admission (p < 0.001) were found to be associated with prevalence of inappropriate hospital days. Approximately three-fourths of the inappropriate admissions were premature admissions (75.9%, n = 85). The most frequent reasons for inappropriate hospital days were awaiting test results (34.3%, n = 47), awaiting surgery (19.7%, n = 27), awaiting test execution (10.9%, n = 15), and family unprepared for home care (10.9%, n = 15). CONCLUSIONS: Although the extent of inappropriate hospital days was moderate compared with that found by previous investigations, the prevalence of inappropriateness of admission was considerable. To enhance the appropriateness of hospital care for children, interventions could be implemented according to the associated factors and identified causes.

Levetiracetam alleviates cognitive decline in Alzheimer's disease animal model by ameliorating the dysfunction of the neuronal network.

Background: Patients with Alzheimer's disease (AD) have a significantly higher risk of seizures than other individuals in an age-matched population, suggesting a close association between epilepsy and AD. We aimed to examine the effects of levetiracetam (LEV)-a drug for treating seizures-on learning and memory and the neuropathological features of AD. Methods: We crossbred APP23 mice with microtubule-associated protein tau (MAPT) transgenic mice to generate APP23/MAPT mice. These mice were treated with different concentrations of LEV in the presence of kainic acid (KA) for 3 months. Results: Low doses of LEV alleviated the effects of KA on memory defects in APP23/MAPT mice. Mechanistic investigations showed that low concentrations of LEV decreased tau phosphorylation by reducing the activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3α/ß, thus rescuing neurons from synaptic dystrophy and apoptosis. Low doses of LEV inhibited the effects of KA (i.e., inducing neuroinflammation and impairing the autophagy of amyloid ß-peptide), thus improving cognitive decline. High concentrations of LEV decreased the production and deposition of amyloid ß-peptide (Aß) by reducing the expression of ß-site APP-cleaving enzyme 1 and presenilin 1. However, high concentrations of LEV also induced neuronal apoptosis, decreased movement ability in mice, and did not alleviate cognitive decline in AD mice. Conclusion: Our results support the hypothesis that aberrant network activity contributes to the synaptic and cognitive deficits in APP23/MAPT mice. A low concentration of LEV may help ameliorate abnormalities of AD; however, a high LEV concentration did not induce similar results.

A hierarchical system of covalent and dual non-covalent crosslinks promotes the toughness and self-healing properties of polymer hydrogels.

While it is challenging to simultaneously achieve both high mechanical performance and self-healing ability within one polymer hydrogel network, we, herein, synthesized a novel class of hydrogels based on a combination of chemical and dual non-covalent crosslinks via micellar polymerization of 3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate, end-capped by 2-hydroxyethyl methacrylate (IPDI-HEMA), with acrylamide (AM). The prepared hydrogels were demonstrated to possess a tensile elongation at a break of at least 1900%, a fracture energy of 138.4 kJ m-3, and remarkable self-healing behaviors (e.g., a strong self-healing ability achieved at ambient temperature without the need for any stimulus or healing agent). The multiple crosslinks developed in this study for one polymer hydrogel network are significant steps to construct the desired functional hydrogels with excellent self-healing and mechanical properties.

Model for Integration of Monogenic Diabetes Diagnosis Into Routine Care: The Personalized Diabetes Medicine Program.

OBJECTIVE: To implement, disseminate, and evaluate a sustainable method for identifying, diagnosing, and promoting individualized therapy for monogenic diabetes. RESEARCH DESIGN AND METHODS: Patients were recruited into the implementation study through a screening questionnaire completed in the waiting room or through the patient portal, physician recognition, or self-referral. Patients suspected of having monogenic diabetes based on the processing of their questionnaire and other data through an algorithm underwent next-generation sequencing for 40 genes implicated in monogenic diabetes and related conditions. RESULTS: Three hundred thirteen probands with suspected monogenic diabetes (but most diagnosed with type 2 diabetes) were enrolled from October 2014 to January 2019. Sequencing identified 38 individuals with monogenic diabetes, with most variants found in GCK or HNF1A. Positivity rates for ascertainment methods were 3.1% for clinic screening, 5.3% for electronic health record portal screening, 16.5% for physician recognition, and 32.4% for self-referral. The algorithmic criterion of non-type 1 diabetes before age 30 years had an overall positivity rate of 15.0%. CONCLUSIONS: We successfully modeled the efficient incorporation of monogenic diabetes diagnosis into the diabetes care setting, using multiple strategies to screen and identify a subpopulation with a 12.1% prevalence of monogenic diabetes by molecular testing. Self-referral was particularly efficient (32% prevalence), suggesting that educating the lay public in addition to clinicians may be the most effective way to increase the diagnosis rate in monogenic diabetes. Scaling up this model will assure access to diagnosis and customized treatment among those with monogenic diabetes and, more broadly, access to personalized medicine across disease areas.

PPARγ/LXRα axis mediated phenotypic plasticity of lung fibroblasts in silica-induced experimental silicosis.

Silicosis is a disease mainly caused by pulmonary interstitial fibrosis caused by long-term inhalation of dust with excessively high content of free SiO2. Transdifferentiation of lung fibroblasts into myofibroblasts is an important cellular basis for silicosis, but the key transcription factors (TFs) involved in this process are still unclear. In order to explore the biological regulation of transcription factor PPARγ/LXRα in silica-induced pulmonary fibrosis, this study explored the molecular mechanism of PPARγ/LXRα involved in regulating transcription factors related to SiO2-induced lung injury at the cellular level and in animal models. ChIP-qPCR detected that PPARγ directly regulated the transcriptional activity of the LXRα gene promoter, while the PPARγ agonist RSG increased the expression of LXRα. In addition, we demonstrated in the cell model that upregulation of LXRα can inhibit silica-mediated fibroblast transdifferentiation, accompanied by an increase in the expression of SREBF1, PLTP and ABCA1. The results of LXRα silencing experiment matched those of overexpression experiment. These studies explored the role of LXRα in plasticity and phenotypic transformation between lung fibroblasts and myofibroblasts. Therefore, inhibiting or reversing the transdifferentiation of lung fibroblasts to myofibroblasts by intervening PPARγ/LXRα may provide a new therapeutic target for the treatment of silicosis.

Identification of novel biomarkers in breast cancer via integrated bioinformatics analysis and experimental validation.

Breast cancer (BC), an extremely aggressive malignant tumor, causes a large number of deaths worldwide. In this study, we pooled profile datasets from three cohorts to illuminate the underlying key genes and pathways of BC. Expression profiles GSE42568, GSE45827, and GSE124646, including 244 BC tissues and 28 normal breast tissues, were integrated and analyzed. Differentially expressed genes (DEGs) were screened out based on these three datasets. Functional analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway were performed using The Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING) and Molecular Complex Detection (MCODE) plugin were utilized to visualize protein protein interaction (PPI) of these DEGs. The module with the highest connectivity of gene interactions was selected for further analysis. All of these hub genes had a significantly worse prognosis in BC by survival analysis. Additionally, four genes (CDK1, CDC20, AURKA, and MCM4) dramatically were enriched in oocyte meiosis and cell cycle pathways through re-analysis of DAVID. Moreover, the mRNA and protein levels of CDK1, CDC20, AURKA, and MCM4 were significantly increased in BC patients. In addition, knockdown of CDK1 and CDC20 by small interfering RNA remarkably suppressed cell migration and invasion in MCF-7 and MDA-MB-231 cells. In conclusion, our results suggested that CDK1, CDC20, AURKA, and MCM4 were reliable biomarkers of BC via bioinformatics analysis and experimental validation and may act as prospective targets for BC diagnosis and treatment.

Highly Enhancing Electrical, Thermal, and Mechanical Properties of Polypropylene/Graphite Intercalation Compound Composites by In Situ Expansion during Melt Mixing.

Polypropylene/graphite intercalation compound (PP/GIC) composites are prepared via melt mixing at three different temperatures (180, 200, and 220 °C). The dispersion of GICs in the composites is clearly improved due to the increased interlamellar spacing caused by in situ expansion of GICs at higher temperatures, which facilitates the intercalation of PP molecular chains into the GIC galleries. As a result, the PP/GIC composite with 10 wt% GICs prepared at 220 °C (PG220) presents a dielectric constant of about 1.3 × 108 at 103 Hz, which is about six orders higher than that of the composite prepared at 180 °C (PG180). Moreover, the thermal conductivity of the PG220 sample (0.63 Wm-1K-1) is 61.5% higher than that of the PG180 sample. The well-dispersed GICs accelerates the crystallization of PP by increasing the nucleation point and enhances the thermal stability of the composites. The PG220 sample shows a Young's modulus that is about 21.2% higher than that of the PG180 samples. The results provide an efficient approach for fabricating polymer/GIC composites without complex exfoliation and dispersion processes.

Monogenic Diabetes in Youth With Presumed Type 2 Diabetes: Results From the Progress in Diabetes Genetics in Youth (ProDiGY) Collaboration.

OBJECTIVE: Maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis may result in a change in clinical treatment and impacts prediction of complications and familial risk. In this study, we aimed to assess the prevalence of MODY in multiethnic youth under age 20 years with a clinical diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS: We evaluated whole-exome sequence data of youth with a clinical diagnosis of type 2 diabetes. We considered participants to have MODY if they carried a MODY gene variant classified as likely pathogenic (LP) or pathogenic (P) according to current guidelines. RESULTS: Of 3,333 participants, 93 (2.8%) carried an LP/P variant in HNF4A (16 participants), GCK (23), HNF1A (44), PDX1 (5), INS (4), and CEL (1). Compared with those with no LP/P variants, youth with MODY had a younger age at diagnosis (12.9 ± 2.5 vs. 13.6 ± 2.3 years, P = 0.002) and lower fasting C-peptide levels (3.0 ± 1.7 vs. 4.7 ± 3.5 ng/mL, P < 0.0001). Youth with MODY were less likely to have hypertension (6.9% vs. 19.5%, P = 0.007) and had higher HDL cholesterol (43.8 vs. 39.7 mg/dL, P = 0.006). CONCLUSIONS: By comprehensively sequencing the coding regions of all MODY genes, we identified MODY in 2.8% of youth with clinically diagnosed type 2 diabetes; importantly, in 89% (n = 83) the specific diagnosis would have changed clinical management. No clinical criterion reliably separated the two groups. New tools are needed to find ideal criteria for selection of individuals for genetic testing.