Research on a new multiple-screening method for laser-induced plasma spectroscopy utilizing Lorentz.

In the field of Laser Induced Breakdown Spectroscopy (LIBS) research, the screening and extraction of complex spectra play a crucial role in enhancing the accuracy of quantitative analysis. This paper introduces a novel approach for multiple screenings of LIBS spectra using Lorentz Screening and Sensitivity and Volatility Analysis. Initially, Create symmetrical sampling standards for Lorentz fitting. Then the Lorentz fitting is used to uniformly screen the collected spectral information on both sides in order to eliminate adjacent interference peaks. Subsequently, Sensitivity and Volatility Analysis is employed to further remove overlapping peaks and select spectra with low volatility and high sensitivity. Sensitivity and Volatility Analysis is a spectral discrimination method proposed on the premise of intensity's correlation with concentration. It utilizes a Z-score method that incorporates both deviation and standard deviation for effective analysis. Furthermore, it meticulously selects spectral lines with minimal interference and volatility, thereby augmenting the precision of quantitative analysis. The quantitative accuracy (R2) for Chromium (Cr) and Nickel (Ni) elements can reach 0.9919 and 0.9768, respectively. Their average errors can be reduced to 0.0566 % and 0.1024 %. The study demonstrates that Lorentz Screening and Sensitivity and Volatility Analysis can select high-quality characteristic spectral lines to improve the performance of the model.

A study of the spectral signal effect of self-holes in metal additive manufacturing components using laser-induced breakdown spectroscopy (LIBS).

Understanding the detection mechanism of hole defects in metal additive manufacturing (AM) components is of great significance for the detection of metal AM component defects using laser-induced breakdown spectroscopy (LIBS). In this work, the mapping relationship between the hole defects of metal AM components and the LIBS spectral signal was studied using the controlled variable method. The effect of hole defects mostly showed a suppression effect and peaked at a hole depth of 1.0 mm when the LIBS system was at its optimal excitation parameter. To explore the possible reasons behind the inhibitory effect of self-holes, the variation law of the plasma temperature with and without hole defects was further investigated. Our results showed that the plasma temperature change curve was similar to the spectral line intensity change trend. Finally, the linear relationship between the focal length effect and the hole effect, and the relationship between the constraint effect and the hole effect were studied. The minimum fitting R2 between the constraint effect and the hole effect was 0.979. We believed that the inhibition of the hole effect was mainly caused by the absorption and loss of energy in the plasma during the process of plasma radiation and shock wave reflection from the hole wall. By studying the detection mechanism of hole defects in metal additive manufacturing components excited by LIBS and finding the effective characteristics of hole defects in metal AM components, it is helpful to achieve higher precision and higher sensitivity defect detection.

[The modified Valsalva maneuver in hypopharynx CT scan].

Objective:To analyze the significance and factors influencing of CT scan under the modified Valsalva maneuver. Methods:Clinical data of 52 patients with hypopharyngeal carcinoma diagnosed from August 2021 to December 2022 were collected, all patients had calm breathing CT scan and modified Valsalva maneuver CT scan. Compare the exposure effect of the aryepiglottic fold, interarytenoid fold, postcricoid area, piriform fossa apex, posterior hypopharyngeal wall, and glottis with each CT scanning method. The effects of age, neck circumference, neck length, BMI, tumor site, and T stage on the exposure effect were analyzed. Results:In 52 patients, 50 patients（96.15%） completed CT scan at once time. The exposure effect of the CT scan under modified Valsalva maneuver in the aryepiglottic fold, interarytenoid fold, postcricoid area, piriform fossa apex, posterior hypopharyngeal wall was significantly better than CT scan under calm breathing（Z=-4.002, -8.026, -8.349, -7.781, -8.608, all P<0.01）, while CT scan under modified Valsalva maneuver was significantly worse in glottis than CT scan under calm breathing（Z=-3.625, P<0.01）. In the modified Valsalva CT scan, age had no obvious effect on the exposure effect. The exposure effect was better with long neck length, smaller neck circumference, smaller BMI and smaller T stage. The exposure of postcricoid carcinoma was better than pyriform sinus carcinoma and posterior hypopharyngeal wall carcinoma. But differences were not all statistically significant. Conclusion:The anatomical structure of the hypopharynx was clearly under CT scan with modified Valsalva maneuver, which clinical application is simple, but the effect of glottis was worse. The influence of age, neck circumference, neck length, BMI, and tumor T stage on the exposure effect still needs further investigation.

Identification of a novel MAP3K1 variant in a family with 46, XY DSD and partial growth hormone deficiency.

The 46, XY disorder of sex development (DSD) is the main cause of birth defects; however, as it is a group of highly heterogeneous diseases, >50% of cases are not accurately diagnosed. Identification of more cases will improve understanding of the relationship between genotype and phenotype for DSD. The present study conducted a systematic analysis of the clinical characteristics of a proband with 46, XY DSD, applied genetic analysis by whole­exome sequencing to this pedigree and performed bioinformatics analysis of the identified variant. The proband presented with a short penis, lack of testicles and partial growth hormone (GH) deficiency at 1 year old. Histopathological examination revealed there were oviduct, epididymis and fibrous vascular tissue on both sides of the abdomen. The last follow­up at 5 years of age revealed that the patient exhibited restricted growth, a 1.5­cm penis and lack of testicles. Notably, a novel pathogenic mitogen­activated protein kinase kinase kinase 1 (MAP3K1) variant (c.3020A>G) was identified in the proband, resulting in a change in the 1,007th amino acid (glutamine) of the encoded protein. This variant caused the uncharged neutral glutamine to be replaced by a positively charged basic arginine. p.Gln1007 in MAP3K1 was confirmed to be conserved across various species. Pathogenicity analysis using bioinformatics tools suggested that this MAP3K1 variant may cause functional defects. In conclusion, the present study identified a novel MAP3K1 variant that was the cause of 46, XY DSD and partial GH deficiency. The present findings extend the mutation spectrum of MAP3K1 and provide novel characteristics of 46, XY DSD.

Characteristics and possible mechanisms of 46, XY differences in sex development caused by novel compound variants in NR5A1 and MAP3K1.

BACKGROUND: Dozens of genes are involved in 46, XY differences in sex development (DSD). Notably, about 3/4 of patients cannot make a clear etiology diagnosis and single gene variant identified cannot fully explain the clinical heterogeneity of 46, XY DSD. MATERIALS AND METHODS: We conducted a systematic clinical analysis of a 46, XY DSD patient, and applied whole-exome sequencing for the genetic analysis of this pedigree. The identified variants were analyzed by bioinformatic analysis and in vitro studies were performed in human embryonic kidney 293T (HEK-293T) cells which were transiently transfected with wild type or variant NR5A1 and MAP3K1 plasmid. Furthermore, protein production of SRY-box transcription factor 9 (SOX9) was analyzed in cell lysates. RESULTS: A novel NR5A1 variant (c.929A > C, p. His310Pro) and a rare MAP3K1 variant (c.2282T > C, p. Ile761Thr) were identified in the proband, whereas the proband's mother and sister who only carry rare MAP3K1 variant have remained phenotypically healthy to the present. These two variants were predicted to be pathogenic by bioinformatic analysis. In vitro, NR5A1 variant decreased the SOX9 production by 82.11% compared to wild type NR5A1, while MAP3K1 variant had little effect on the SOX9 production compared to wild type MAP3K1. Compared to wild type NR5A1 transfection, the SOX9 production of cells transfected with both wild type plasmids decreased by about 17.40%. Compared to variant NR5A1 transfection, the SOX9 production of cells transfected with both variant plasmids increased by the 36.64%. CONCLUSIONS: Our findings suggested the novel compound variants of NR5A1 and MAP3K1 can alter the expression of SOX9 and ultimately lead to abnormality of sex development.

Nobiletin Attenuates Cell Proliferation by Modulating the Activating Protein-1 Signaling Pathway in 7,12-Dimethylbenz[a]anthracene-Induced Mammary Carcinogenesis.

Breast cancer is a widespread disease that affects women globally. Diagnostic processes and remedial approaches to breast carcinogenesis have improved in recent decades, but continuous survival of patients with breast carcinogenesis is still lacking due to increased cell proliferation. The aim of the present work is to explore the anticell proliferative effects of nobiletin (NOB) against 7,12-dimethylbenz[a]anthracene (DMBA)-treated mammary tumorigenesis in rats. We stimulate mammary carcinogenesis using oral gavage of DMBA (25 mg/kg body weight) mixed with olive oil (1 mL). This results in reduced body weight; increased liver marker enzymes such as alkaline phosphatase, acid phosphatase, aspartate aminotransferase, and alanine aminotransferase; and cell proliferative markers such as c-Jun, proliferating cell nuclear antigen, c-Fos, cyclin D1, and activating protein-1 (AP-1) in the DMBA-treated cancer-bearing animals. NOB administration improved body weight, significantly reduced hepatic marker enzymes, and altered histopathological changes. Furthermore, NOB efficiently reduced tumor cell proliferation markers in DMBA-induced mammary carcinogenesis. Overall, these results suggest that NOB has an anticell proliferative effect on DMBA-induced mammary cancer via modulation of the AP-1 signaling pathway.

Cardio-facio-cutaneous syndrome-associated pathogenic MAP2K1 variants activate autophagy.

MAP2K1 encodes mitogen-activated protein kinase 1 (MEK1). Mutations in MAP2K1 lead to continuous activation of MEK/ERK signaling pathway, giving rise to cardio-facio-cutaneous syndrome (CFCS). However, the molecular mechanisms of abnormal activation of MEK/ERK signaling pathway and the role of autophagy, if any, in manifesting CFCS in MAP2K mutants remain unclear. Here, we report three Chinese children with CFCS having MAP2K1 pathogenic variants, identified by exome sequencing. They presented with dysmorphic facial features, seizures, psychomotor retardation, and short stature. Additionally, the third child showed pulmonary valve stenosis, multiple skeletal deformities, and osteoporosis. Whole exome sequencing revealed two heterozygous missense mutations in exon 3 of MAP2K1 (c.383G>T; p.Gly128Val and c.389A>G; p.Tyr130Cys), as well as a novel heterozygous missense variant (c.170A>T; p.Lys57Met) in exon 2 of MAP2K1. In SH-SY5Y cells, we identified, for the first time, that MAP2K1 mutations can activate the p-ERK-dependent cell cycle progression and autophagy, and cause CFCS. Our results extended the mutational spectrum of MAP2K1, examined the role of MEK1 protein in nerve cell functions, and demonstrated, for the first time, that autophagy may mediate the altered MAP2K1 function, leading to CFCS phenotypes.

Identification of a novel mutation in the FGFR3 gene in a Chinese family with Hypochondroplasia.

BACKGROUND: Hypochondroplasia (HCH; OMIM 146000) is a common autosomal dominant skeletal dysplasia characterized by disproportionate short stature, short extremities, relative macrocephaly, and lumbar lordosis. Because of its clinical and genetic heterogeneity, gene mutational analysis is particularly important in diagnosis and the phenotypes may be ameliorated if diagnosed early. MATERIALS AND METHODS: In this study, we examined a Chinese family with HCH, performed an inductive analysis of their clinical features and radiographic results, and applied targeted exome sequencing (TES) technology to perform a molecular diagnosis. RESULTS: The proband and his mother all presented disproportionate short stature, short, stubby extremities, unchanged interpedicular distances from L1-L5, and short iliac bones, with a 'fish mouth-shaped' sciatic notch. The mother received induced abortion recently because an ultrasound showed short femur length of her fetus at 24-week gestation. Eventually, a novel heterozygous mutation (c.1145G>A) in FGFR3 was identified by TES in the proband, his mother, and her fetus; this causes the substitution of glycine with aspartic acid in codon 382. CONCLUSIONS: In this study, we diagnosed a Chinese pedigree with HCH based on clinical data, radiographic features, and genetic testing results. Our results extend the genetic mutation spectrum of FGFR3 and demonstrate that TES is an effective method for the diagnosis of skeletal dysplasia in clinical practices.