[Genetic analysis of a Chinese pedigree affected with Cowden syndrome due to variant of PTEN gene].

OBJECTIVE: To explore the clinical features and genetic etiology of a Chinese pedigree affected with Cowden syndrome (CS). METHODS: A CS pedigree diagnosed in November 2022 at the Ningde Municipal Hospital Affiliated to Ningde Normal University was selected as the study subject. Clinical data were collected, and genetic testing was carried out for available members. Pathogenicity analysis was carried out for the candidate variant. RESULTS: The proband, a 7-year-old male, was found to have autism and intellectual disability. Whole exome sequencing revealed that he has harbored a c.462_463del (p.F154Lfs25) variant of the PTEN gene. The proband's 35-year-old mother, who was diagnosed with pulmonary hamartomas at our hospital, has manifested with lipomas, nodular goiter, and adenomas. Sanger sequencing confirmed that she was also heterozygous for the c.462_463del (p.F154Lfs25) variant of the PTEN gene. No other family members has carried the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+PM2_Supporting+PM6). CONCLUSION: The newly discovered c.462_463del (p.F154Lfs*25) variant of the PTEN gene probably underlay the CS in this pedigree. CS patients have higher risk for developing malignant tumors. Clinicians should be aware of this condition and emphasize follow-up of the patients.

Developing a class of dual atom materials for multifunctional catalytic reactions.

Dual atom catalysts, bridging single atom and metal/alloy nanoparticle catalysts, offer more opportunities to enhance the kinetics and multifunctional performance of oxygen reduction/evolution and hydrogen evolution reactions. However, the rational design of efficient multifunctional dual atom catalysts remains a blind area and is challenging. In this study, we achieved controllable regulation from Co nanoparticles to CoN4 single atoms to Co2N5 dual atoms using an atomization and sintering strategy via an N-stripping and thermal-migrating process. More importantly, this strategy could be extended to the fabrication of 22 distinct dual atom catalysts. In particular, the Co2N5 dual atom with tailored spin states could achieve ideally balanced adsorption/desorption of intermediates, thus realizing superior multifunctional activity. In addition, it endows Zn-air batteries with long-term stability for 800 h, allows water splitting to continuously operate for 1000 h, and can enable solar-powered water splitting systems with uninterrupted large-scale hydrogen production throughout day and night. This universal and scalable strategy provides opportunities for the controlled design of efficient multifunctional dual atom catalysts in energy conversion technologies.

Spin state modulation on dual Fe center by adjacent Ni sites enabling the boosted activities and ultra-long stability in Zn-air batteries.

Breakthrough in developing cost-effective Fe-based catalysts with superior oxygen reduction reaction (ORR) activities and ultra-long-term stability for application in Zn-air batteries (ZABs) remain a priority but still full of challenges. Herein, the neighboring NiN4 single-metal-atom and Fe2N5 dual-metal-atoms on the N-doped hollow carbon sphere (Fe/Ni-NHCS) were deliberately constructed as the efficient and robust ORR catalyst for ZABs. Both theory calculations and magnetic measurements demonstrate that the introduction of NiN4 provides a significant role on optimizing the electron spin state of Fe2N5 sites and reducing the energy barrier for the adsorption and conversion of the oxygen-containing intermediates, enabling the Fe/Ni-NHCS with excellent ORR performance and ultralow byproduct HO2- yield (0.5%). Impressively, the ZABs driven by Fe/Ni-NHCS exhibit unprecedented long-term rechargeable stability over 1200 h. This work paves a new venue to manipulate the spin state of active sites for simultaneously achieving superior catalytic activities and ultra-long-term stability in energy conversion technologies.

Asymmetric CoN3 P1 Trifunctional Catalyst with Tailored Electronic Structures Enabling Boosted Activities and Corrosion Resistance in an Uninterrupted Seawater Splitting System.

Employing seawater splitting systems to generate hydrogen can be economically advantageous but still remains challenging, particularly for designing efficient and high Cl- -corrosion resistant trifunctional catalysts toward the oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and hydrogen evolution reaction (HER). Herein, single CoNC catalysts with well-defined symmetric CoN4 sites are selected as atomic platforms for electronic structure tailoring. Density function theory reveals that P-doping into CoNC can lead to the formation of asymmetric CoN3 P1 sites with symmetry-breaking electronic structures, enabling the affinity of strong oxygen-containing intermediates, moderate H adsorption, and weak Cl- adsorption. Thus, ORR/OER/HER activities and stability are optimized simultaneously with high Cl- -corrosion resistance. The asymmetric CoN3 P1 structure based catalyst with boosted ORR/OER/HER performance endows seawater-based Zn-air batteries (S-ZABs) with superior long-term stability over 750 h and allows seawater splitting to operate continuously for 1000 h. A self-driven seawater splitting powered by S-ZABs gives ultrahigh H2 production rates of 497 µmol h-1 . This work is the first to advance the scientific understanding of the competitive adsorption mechanism between Cl- and reaction intermediates from the perspective of electronic structure, paving the way for synthesis of efficient trifunctional catalysts with high Cl- -corrosion resistance.

MiR-144-3p inhibits the proliferation and metastasis of lung cancer A549 cells via targeting HGF.

AIM: MicroRNAs have been confirmed as vital regulators in gene expression, which could affect multiple cancer cell biological behaviors. This study aims to elucidate the molecular mechanism of miR-144-3p in lung cancer cellular proliferation and metastasis. METHODS: MiR-144-3p expression in lung cancer tissues and cell lines was detected by qRT-PCR. HGF was predicted as the target gene of miR-144-3p using TargetScan and dual luciferase reporter assay. Immunohistochemistry and qRT-PCR were used to explore the impacts of HCF on lung cancer tissues and cell lines. Impacts of miR-144-3p and HGF on cancer cellular proliferation, migration and invasion were elucidated by CCK-8, Flow cytometry, Transwell invasion and Wound-healing assay. Moreover, nude mouse xenograft model was established to evaluate the effects of miR-144-3p on lung cancer cells. RESULTS: MiR-144-3p exhibited a reduction in both lung cancer tissues and cell lines. HGF was a direct target of miR-144-3p. In contrast to the miR-144-3p expression level, HGF showed a higher level in lung cancer tissues and cell lines. Overexpression miR-144-3p suppressed A549 and NCI-H1299 cell proliferation and metastasis, whereas this was reversed by HGF. MiR-144-3p exhibited an inhibitory effect on A549 cell-induced tumor growth of nude mice. CONCLUSIONS: This study reveals miR-144-3p/HGF axis may be involved in the suppression of lung cancer cellular proliferation and development, and miR-144-3p may function as a potential therapeutic target in lung cancer treatment in the future.

The effect of some trace elements on the expression of telomerase gene in lung cancer.

Lung cancer is a disorder that begins due to genetic and epigenetic changes. These changes cause the activation of oncogenes and the inactivation of tumor suppressor genes. Various factors influence the expression of these genes. In this research, we investigated the relationship between the number of trace elements zinc and copper and the ratio of these two in serum with the expression of the telomerase enzyme gene in lung cancer. For this purpose, we included 50 people with lung cancer in the study as the case group and 20 patients with non-tumor lung diseases as the control group. The TRAP assay method measured the telomerase activity in biopsy samples of lung tumor tissue. Also, serum copper and zinc were measured by atomic absorption spectrometry. The results showed that the mean serum concentration of copper and the ratio of copper to zinc in patients were significantly higher than in the controls (120.8 ± 5.7 versus 107.2 ± 6.5µg/dL)(P<0.05). However, there is no significant difference in the mean serum concentration of zinc between the two groups (p > 0.05). The patients' mean ratio of copper to zinc is significantly higher than the control group (1.6 ± 0.4 versus 1.1 ± 0.2)(p < 0.05). The average level of telomerase enzyme activity of patients showed a significant difference from the control group 32.8 ± 16.1 vs. zero percent) (p < 0.01). There is a direct and significant correlation between the serum level of copper and the level of telomerase enzyme activity in patients (r = 0.36 and p < 0.05). A positive correlation was observed between total serum copper concentration and the increasing age of patients (r = 0.39 and p < 0.01). The correlation between the ratio of copper to zinc and the serum copper concentration of the patients was positive and significant (r = 0.36 and p < 0.05), but the correlation between the amount of serum zinc and the ratio of copper to zinc was negative and significant (r = -0/ 72 and p < 0.01). The average copper serum concentration of people with small cell carcinoma (123.7 ± 2.8 µg/dL) compared to non-small cell carcinoma (117.6 ± 4.8 µg/dL) is high and significant (P< 0.05). Patients with small cell carcinoma had a high mean telomerase concentration (112 ± 0.57%) and significantly compared to non-small cell carcinomas (6.4 ± 2.5%)(P < 0.05). This situation regarding the zinc element and the ratio of copper to zinc in non-small cell carcinomas compared to small cell carcinomas were evaluated as non-significant (P>0.05). Based on the obtained results, it can be assumed that determining the amount of zinc and copper and the telomerase enzyme activity in lung cancer can have a biological role in the initiation and progression of tumor tissue, which requires more studies.

[Clinical investigation on the related factors for the application of systemic glucocorticoids in patients with acute exacerbation of chronic obstructive pulmonary disease with carbon dioxide retention].

OBJECTIVE: To investigate the factors affecting the application of systemic glucocorticoids in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with carbon dioxide (CO2) retention, and to guide the formulation of a strategy to reduce systemic glucocorticoid exposure. METHODS: The AECOPD patients with CO2 retention admitted to the Ningde Municipal Hospital of Fujian Medical University from January 2017 to December 2019 were enrolled. The general information, past history, times of acute exacerbations within 1 year, pneumonia on admission, causes of COPD, heart failure, blood gas analysis, eosinophil count (EOS), albumin (Alb) and apolipoprotein E (ApoE) levels, exhaled nitric oxide (FeNO) level, inhaled glucocorticoid and non-invasive mechanical ventilation treatment at acute exacerbation were collected. The patients were divided into recommended dosage group (exposure levels in the recommended dosage range, cumulative prednisone dosage ≤ 200 mg) and exceeded group (exposure levels exceeded the recommended dose, cumulative prednisone dosage > 200 mg) according to cumulative systemic glucocorticoid exposure dosage of the patients during hospitalization. The clinical data of patients between the two groups were compared, and possible factors with P < 0.1 in univariate analysis were included in multivariate Logistic regression analysis to screen the related factors of systemic glucocorticoid exposure level in AECOPD patients with CO2 retention. RESULTS: According to the order of hospitalization, 151 AECOPD patients with CO2 retention were enrolled, 8 patients were excluded, and 143 patients were enrolled in the analysis. Of the 143 patients, 68 received the recommended dose of systemic glucocorticoid, and 75 received excessive systemic glucocorticoid. Age, percentage of forced expiratory volume in 1 second (FEV1%) at stable phase, frequency of acute exacerbation within 1 year, heart failure ratio, oxygen index (PaO2/FiO2), arterial partial pressure of carbon dioxide (PaCO2), serum EOS and ApoE levels at admission, the ratio of aerosolized inhaled glucocorticoids and non-invasive mechanical ventilation showed statistical differences between the two groups. Multivariate Logistic regression analysis showed that related factors affecting systemic glucocorticoid exposure levels of AECOPD patients with CO2 retention were FEV1% at stable phase [odds ratio (OR) = 0.957, 95% confidence interval (95%CI) was 0.921-0.994, P = 0.023], acute exacerbation frequency within 1 year (OR = 1.530, 95%CI was 1.121-2.088, P = 0.007), heart failure (OR = 3.022, 95%CI was 1.263-7.231, P = 0.013), PaCO2 (OR = 1.062, 95%CI was 1.010-1.115, P = 0.018) and EOS at admission (OR = 0.103, 95%CI was 0.016-0.684, P = 0.019), aerosolized inhaled glucocorticoids (OR = 0.337, 95%CI was 0.145-0.783, P = 0.011) and non-invasive mechanical ventilation at acute exacerbation (OR = 0.422, 95%CI was 0.188-0.948, P = 0.037), of which high FEV1% at stable phase, high EOS at admission, aerosolized inhaled glucocorticoid and non-invasive mechanical ventilation at acute exacerbation were protective factors, while high frequency of acute exacerbation within 1 year, heart failure and high PaCO2 were risk factors. CONCLUSIONS: For AECOPD patients with CO2 retention, high FEV1% at stable phase, high EOS level at admission, aerosolized inhaled glucocorticoid and non-invasive mechanical ventilation at acute exacerbation can reduce systemic glucocorticoid exposure. In addition, high frequency of acute exacerbation within 1 year, heart failure, and high PaCO2 can increase systemic glucocorticoid exposure.

The value of apolipoprotein E in distinguishing benign and malignant unilateral pleural effusions.

Pleural effusion (PE) remains insurmountable challenge and public health problem, requiring novel noninvasive biomarkers for accurate diagnosis. The aim of this study was to assess the clinical significance of apolipoprotein E (Apo-E) in PE, in order to determine its potential use as a diagnostic biomarker for malignant PE (MPE).PE samples were obtained from 127 patients and the etiology of PE was determined by multiple diagnostic techniques. Apo-E levels were then measured in the pleural fluid samples.58 PE patients were diagnosed with tumors, while 69 were tumor-free. Apo-E levels in MPE patients were significantly higher than those with benign PE (BPE) (P < .05). An Apo-E cut-off of 69.96 ng/mL yielded sensitivity and specificity of 79.31% and 73.91% respectively for MPE detection. The area under the curve for Apo-E was 0.793 (95% confidence interval: 0.712 to 0.860), which was smaller than that of carcinoembryonic antigen (CEA) (Z = 2.081, P<.05). In addition, the combination of Apo-E and CEA detection yielded a higher sensitivity of 87.90% and specificity of 95.65% in diagnosing MPE.In conclusion, Apo-E levels in PE may be a potential biomarker for the detection of MPE. The combined detection of Apo-E and CEA could improve the diagnostic sensitivity and specificity for MPE. These findings provide a simple and convenient method for clinical screening and detection of PE.