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Incorporating outstanding flame retardancy and electromagnetic interference shielding effectiveness (EMI SE) into polymers is a pressing requirement for practical utilization. In this study, we first employed the principles of microencapsulation and electrostatic interaction-driven self-assembly to encapsulate polyethyleneimine (PEI) molecules and Ti3C2Tx nanosheets on the surface of ammonium polyphosphate (APP), forming a double-layer-encapsulated structure of ammonium polyphosphate (APP@PEI@Ti3C2Tx). Subsequently, flame-retardant thermoplastic polyurethane (TPU) composites were fabricated by melting the flame-retardant agent with TPU. Afterwards, by using air-assisted thermocompression technology, we combined a reduced graphene oxide (rGO) film with flame-retardant TPU composites to fabricate hierarchical TPU/APP@PEI@Ti3C2Tx/rGO composites. We systematically studied the combustion behavior, flame retardancy, and smoke-suppression performance of these composite materials, as well as the flame-retardant mechanism of the expansion system. The results indicated a significant improvement in the interface interaction between APP@PEI@Ti3C2Tx and the TPU matrix. Compared to pure TPU, the TPU/10APP@PEI@1TC composite exhibited reductions of 84.1%, 43.2%, 62.4%, and 85.2% in peak heat release rate, total heat release, total smoke release, and total carbon dioxide yield, respectively. The averaged EMI SE of hierarchical TPU/5APP@PEI@1TC/rGO also reached 15.53 dB in the X-band.

Associative learning of pure tones is known to cause tonotopic map expansion in the auditory cortex (ACx), but the function this plasticity sub-serves is unclear. We developed an automated training platform called the “Educage,” which was used to train mice on a go/no-go auditory discrimination task to their perceptual limits, for difficult discriminations among pure tones or natural sounds. Spiking responses of excitatory and inhibitory parvalbumin (PV+) L2/3 neurons in mouse ACx revealed learning-induced overrepresentation of the learned frequencies, as expected from previous literature. The coordinated plasticity of excitatory and inhibitory neurons supports a role for PV+ neurons in homeostatic maintenance of excitation–inhibition balance within the circuit. Using a novel computational model to study auditory tuning curves, we show that overrepresentation of the learned tones does not necessarily improve discrimination performance of the network to these tones. In a separate set of experiments, we trained mice to discriminate among natural sounds. Perceptual learning of natural sounds induced “sparsening” and decorrelation of the neural response, consequently improving discrimination of these complex sounds. This signature of plasticity in A1 highlights its role in coding natural sounds.

In order to explore highly efficient flame-retardant rigid polyurethane foam (RPUF), phosphorus/nitrogen compounds and expandable graphite (EG) were successfully incorporated into RPUF by a free one-spot method. The combustion results showed that the fire safety of the RPUF samples was remarkably improved by the addition of phosphoric/nitrogen compounds and EG. With the incorporation of 22.4 wt.% phosphorus/nitrogen compounds and 3.2 wt.% EG, the RPUF composites achieved UL-94 V-0 rating. Besides, the total heat release and total smoke release of RPUF composites were reduced by 29.6% and 32.4% respectively, compared to those of the pure RPUF sample. PO• and PO2• together with nonflammable gaseous products were evolved from phosphoric/nitrogen compounds in the gas phase, which quenched the flammable free radicals in the matrix and diluted the concentration of combustible gaseous products generated from PRUF during combustion. The compact char residues which acted as excellent physical barriers were formed by catalysis of EG and phosphoric/nitrogen compounds in the condense phase. The fire hazard of RPUF was significantly reduced by the synergistic effect of phosphorus-nitrogen compounds and EG. This work provides a promising strategy to enhance the fire safety of RPUF.

A disaster emergency consists of many unfavorable factors, such as different disaster areas, the limited capacity of the rescue centers, and complex rescue conditions. After taking into account the resources of the rescue centers, the ability of rescue teams, and the distance between the rescue centers and the disaster areas, this paper has established a complex model for multiple centers with limited capacity to dispatch teams for emergencies in different disaster areas. The model is solved by the genetic algorithm. Firstly, the paper takes the rescue task as the subunit to perform integer programming. Secondly, a rule is designed according to the symmetry of parents’ crossing. According to the rule, single parent crossover only allows two situations, (1) different rescue mission for the same rescue center and (2) different rescue centers under the same rescue mission. Finally, the performance of parent crossing and symmetric single parent crossing is compared. The results show that the two algorithms can converge to the optimal solution, but each of them has unique advantages in terms of convergence speed and stability. It is suggested that the strategy of the single-parent crossover should be used to deal with local emergency responses and that the two-parent crossover strategy is be used for more complicated global emergency responses.

A series of aluminum hypophosphite (AHPi)/graphite-like carbon nitride (g-C3N4) (designated as CAHPi) hybrids were prepared, followed by incorporation into thermoplastic polyurethane (TPU). The introduction of CAHPi hybrids into TPU led to a marked reduction in the peak of the heat release rate (pHRR), total heat release, weight loss rate, smoke production rate and total smoke production (TSP). For instance, pHRR and TSP decreased by 40% and 50% for TPU/CAHPi20. Furthermore, the increasing fire growth index and decreasing fire performance index were obtained for TPU/CAHPi systems, suggesting reduced fire hazards. It was found that improved fire safety of TPU nanocomposites was contributed by condensed phase and gas phase mechanisms. On one hand, g-C3N4 accelerated the thermal decomposition of AHPi for the formation of more char layers. On the other hand, g-C3N4 induced AHPi to generate more free radical capture agents when exposed to flame, besides protecting AHPi against thermal oxidation.

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac muscle disease characterized by clinical and genetic heterogeneity. Genetic testing can reveal the presence of disease-causing variants in genes encoding sarcomere proteins. However, it yields inconclusive or negative results in 40-60% of HCM cases, owing to, among other causes, technical limitations such as the inability to detect pathogenic intronic variants. Therefore, we aimed to increase the diagnostic yield of molecular analysis for HCM by improving the in-silico detection of intronic variants in MYBPC3 that may escape detection by algorithms normally used with tagged diagnostic panels. We included 142 HCM probands with negative results in Illumina TruSight Cardio panel analysis, including exonic regions of 174 cardiomyopathy genes. Raw data were re-analyzed using existing bioinformatics tools. The spliceogenic variant c.1224-80G>A was detected in three patients (2.1%), leading us to reconsider their molecular diagnosis. These patients showed late onset and mild symptoms, although no peculiar phenotypic characteristics were shared. Collectively, rare spliceogenic MYBPC3 variants may play a role in causing HCM, and their systematic detection should be performed to provide more comprehensive solutions in genetic testing using multigenic panels.

Objectives: Evaluate the prevalence of genetic factors in a large population of infertile subjects and define the seminological, hormonal, and ultrasonographic features for each alteration. Methods : This single-center retrospective study included male partners of infertile couples undergoing genetic investigations due to oligozoospermia or azoospermia evaluated from January 2012 to January 2022. The genetic investigations consist of karyotype, CFTR gene mutations plus variant of the IVS8-5T polymorphic trait, Y chromosome microdeletion, and Next Generation Sequencing panel to analyze genes implicated in congenital hypogonadotropic hypogonadism (CHH). Results : Overall, 15.4% (72/466) of patients received a diagnosis of genetic cause of infertility. Specifically, 23 patients (31.9%) harbor mutations in the CFTR gene, 22 (30.6%) have a 47, XXY karyotype, 14 (19.4%) patients show a Y chromosome microdeletion, 7 (9.7%) have structural chromosomal anomalies, and 6 (8.3%) have CHH. Overall, 80.6% of patients were azoospermic and 19.4% oligozoospermic (sperm concentration 3.5 ± 3.8 million/mL). Almost all patients presented hormonal alterations related to the specific genotype, while the main ultrasound alterations were testicular hypoplasia, calcifications/microcalcifications, and enlarged/hyperechoic epididymis. Conclusions : The prevalence of genetic abnormalities in males of infertile couples was 15.4% in our Center. CFTR gene disease-causing variants resulted in more frequent, with various clinical features, highlighting the complexity and heterogeneity of the presentation. Other investigations are needed to understand if conditions like ring chromosomes and other translocations are related to infertility or are incidental factors.

Germline pathogenic variants (PVs) in the Ataxia Telangiectasia mutated ( ATM ) gene (MIM* 607585) increase the risk for breast, pancreatic, gastric, and prostatic cancer and, to a reduced extent, ovarian and colon cancer and melanoma, with moderate penetrance and variable expressivity. We describe a family presenting early-onset gastric cancer and harboring a heterozygous pathogenic ATM variant. The proband had gastric cancer (age 45) and reported a sister deceased due to diffuse gastric cancer (age 30) and another sister who developed diffuse gastric cancer (age 52) and ovarian serous cancer. Next generation sequencing for cancer susceptibility genes ( APC , ATM , BRD1 , BRIP1 , CDH1 , CDK4 , CDKN2A , CHEK2 , EPCAM , MLH1 , MRE11 , MSH2 , MSH6 , MUTYH , NBN , PALB2 , PMS2 , PTEN , RAD50 , RAD51C , RAD51D , RECQL1 , SMAD4 , STK11 , and TP53 ) was performed. Molecular analysis identified the truncating c.5944C>T, p.(Gln1982*) variant in the ATM (NM_000051.3; NP_000042.3) in the proband. The variant had segregated in the living affected sister and in the unaffected daughter of the deceased affected sister. Familial early-onset gastric cancer is an unusual presentation for ATM -related malignancies. Individual variants may result in different specific risks. Genotype-phenotype correlations are challenging given the low penetrance and variable expressivity. Careful family history assessments are pivotal for prevention planning and are strengthened by the availability of molecular diagnoses.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease, characterized by the presence of unexplained left ventricular hypertrophy. This condition is often associated with electrocardiographic abnormalities including QTc prolongation occurring in 13% of patients. The main explanation for prolonged QTc in HCM is myocardial hypertrophy and the related structural damage. However, other mechanisms, including long QT syndrome (LQTS) genes mutations, may be involved. In the present study we explored the hypothesis of a distinct genetic basis underlying QTc prolongation in HCM by investigating the potential co-inheritance of pathogenic gene variants associated with LQTS and HCM. For this purpose, starting from a cohort of 150 HCM patients carrying pathogenic variants in sarcomere genes, we selected 25 patients carrying a QTc prolongation unexplained by any other cause. The QTc was considered prolonged if greater than 450 ms in males and greater than 470 ms in females. The NGS analysis was performed with Illumina TrueSight Cardio panel genes on Illumina MiniSeq platform. We identified pathogenic/likely pathogenic variants in the KCNQ1 in two patients (c.1781G > A, p. Arg594Gln; c.532G > A, p. Ala178Thr) (8%). Variants of uncertain significance were identified in SCN5A , KCNJ5 , AKAP9 and ANK2 in four patients (16%). Although the results are limited by the small number of patients included in the study, they highlight a minor contribution of LQTS genes for QTc prolongation in HCM patients. The screening for ion channel genes mutations may be considered in HCM patients with prolonged QTc unexplained by any other cause. This in-depth molecular diagnosis may contribute to improve risk stratification and treatment planning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Cava, Micolonghi, Musumeci, Petrucci, Savio, Fabiani, Tini, Germani, Libi, Rossi, Visco, Pizzuti, Volpe, Autore, Rubattu and Piane.)

Juvenile polyposis syndrome (JPS) is an autosomal dominant disorder characterized by hyperplastic polyps in the upper and lower gastrointestinal (GI) tract with a high risk of developing GI cancers. We have described a three-generation Italian family with all the spectrum of SMAD4 phenotype. A multigene panel test was performed on the genomic DNA of the proband by next-generation sequencing, including genes related to hereditary GI tumor syndromes. Molecular analysis revealed the presence of the c.1140-2A>G substitution in the SMAD4 gene, a novel splice variant that has never been described before. Our family is remarkable in that it illustrates the variable expressivity of the SMAD4 phenotype within the same family. The possibility of phenotype variability should also be considered within family members carrying the same mutation. In JPS, a timely genetic diagnosis allows clinicians to better manage patients and to provide early surveillance and intervention for their asymptomatic mutated relatives in the early decades of life.

The 5-10% of breast/ovarian cancers (BC and OC) are inherited, and germline pathogenic (P) variants in DNA damage repair (DDR) genes BRCA1 and BRCA2 explain only 10-20% of these cases. Currently, new DDR genes have been related to BC/OC and to pancreatic (PC) cancers, but the prevalence of P variants remains to be explored. The purpose of this study was to investigate the spectrum and the prevalence of pathogenic variants in DDR pathway genes other than BRCA1/2 and to correlate the genotype with the clinical phenotype. A cohort of 113 non- BRCA patients was analyzed by next-generation sequencing using a multigene panel of the 25 DDR pathways genes related to BC, OC, and PC. We found 43 unique variants in 18 of 25 analyzed genes, 14 classified as P/likely pathogenic (LP) and 28 as variants of uncertain significance (VUS). Deleterious variants were identified in 14% of index cases, whereas a VUS was identified in 20% of the probands. We observed a high incidence of deleterious variants in the CHEK2 gene, and a new pathogenic variant was detected in the RECQL gene. These results supported the clinical utility of multigene panel to increase the detection of P/LP carriers and to identify new actionable pathogenic gene variants useful for preventive and therapeutic approaches.

Molecular analysis of BRCA1 ( MIM # 604370) and BRCA2 ( MIM #600185) genes is essential for familial breast and ovarian cancer prevention and treatment. An efficient, rapid, cost-effective accurate strategy for the detection of pathogenic variants is crucial. Mutations detection of BRCA1/2 genes includes screening for single nucleotide variants (SNVs), small insertions or deletions (indels), and Copy Number Variations (CNVs). Sanger sequencing is unable to identify CNVs and therefore Multiplex Ligation Probe amplification (MLPA) or Multiplex Amplicon Quantification (MAQ) is used to complete the BRCA1/2 genes analysis. The rapid evolution of Next Generation Sequencing (NGS) technologies allows the search for point mutations and CNVs with a single platform and workflow. In this study we test the possibilities of NGS technology to simultaneously detect point mutations and CNVs in BRCA1/2 genes, using the Oncomine TM BRCA Research Assay on Personal Genome Machine (PGM) Platform with Ion Reporter Software for sequencing data analysis (Thermo Fisher Scientific). Comparison between the NGS-CNVs, MLPA and MAQ results shows how the NGS approach is the most complete and fast method for the simultaneous detection of all BRCA mutations, avoiding the usual time consuming multistep approach in the routine diagnostic testing of hereditary breast and ovarian cancers., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.

Primary effusion lymphomas (PELs) are invariably infected by human herpesvirus type 8 (HHV8) and often co-infected by Epstein-Barr virus (EBV). We found that expression of major histocompatibility complex class I (MHC-I) surface molecules was significantly decreased in PEL cells when compared with HHV8 negative lymphomas, irrespective of EBV infection. MHC-I downregulation rendered PEL cells sensitive to recognition and killing by natural killer (NK) cells. Intriguingly, analysis of MHC-I non-restricted cytotoxicity in two PEL patients indicated a reduced NK cell activity when compared with healthy individuals. These data suggest that PEL outgrowth may require an impaired NK cell function.

Kaposi's sarcoma (KS) develops upon reactivation of human herpesvirus 8 (HHV8) infection and virus dissemination to blood and tissue cells, including endothelial and KS spindle cells where the virus is mostly present in a latent form. However, this may likely require the presence of compromised host immune responses and/or the evasion of infected cells from the host immune response. In this regard, mechanisms of evasion of productively infected cells from both CTL and NK cell responses, and resistance of latently infected cells from specific CTL, have already been shown. Here we show that cells which are latently infected by HHV8 are indeed efficiently lysed by NK cells from individuals with a normal immune response. Notably, NK cell-mediated immunity was found to be significantly reduced in AIDS patients with progressing KS as compared to both HIV-negative patients with indolent classic KS or normal blood donors. However, it was restored after treatment with the highly active antiretroviral therapy (HAART) in AIDS-KS patients, that showed regression and clearance of HHV8 from PBMC. By contrast, AIDS-KS patients with a more aggressive disease and no clinical response had persistent HHV8 viremia associated with reduced NK cell cytotoxicity. These results suggest a key role for NK cells in the control of HHV8 latent infection, KS development, and in disease remission upon HAART.