IFIH1 variants are associated with generalised epilepsy preceded by febrile seizures.

BACKGROUND: IFIH1 variants have been reported to be associated with immune-related disorders with/without seizures. It is unknown whether IFIH1 variants are associated with common epilepsy without acquired causes and the mechanism underlying phenotypic variation remains elusive. METHODS: Trio-based whole-exome sequencing was performed on patients with febrile seizures or epilepsy with antecedent febrile seizures. Previously reported variants were systematically reviewed to investigate genotype-phenotype associations. RESULTS: Two de novo heterozygous and three biallelic missense variants were identified in five patients with generalised epilepsy with antecedent febrile seizures. The variants were predicted to be damaging by in silico tools and were associated with hydrogen bonding changes to neighbouring amino acids or decreased protein stability. Patients exhibited an early onset age and became seizure-free with favourable outcome. Further analysis revealed that de novo missense variants located in the Hel region resulted in seizures with multiple neurological abnormalities, while those in the pincer domain or C-terminal domain led to seizures with normal neurodevelopment, suggesting a sub-molecular effect. Biallelic missense variants, which were inherited from unaffected parents and presented low allele frequencies in general populations, were associated with seizures without neurological abnormalities. Truncation variants were related to refractory epilepsy and severe developmental delay, suggesting a genotype-phenotype correlation. IFIH1 is predominantly expressed in the neonatal stage and decreases dramatically in the adulthood, which is consistent with the early onset age and favourable outcome of the patients. CONCLUSIONS: IFIH1 variants are potentially associated with generalised epilepsy with antecedent febrile seizures. The sub-molecular implication and genotype-phenotype association help explain phenotype variations of IFIH1 variants.

Modulating the Activity and SO2 Resistance of α-Fe2O3 Catalysts for NH3-SCR of NOx via Crystal Facet Engineering.

The development of Fe-based catalysts for the selective catalytic reduction of NOx by NH3 (NH3-SCR of NOx) has garnered significant attention due to their exceptional SO2 resistance. However, the influence of different sulfur-containing species (e.g., ferric sulfates and ammonium sulfates) on the NH3-SCR activity of Fe-based catalysts as well as its dependence on exposed crystal facets of Fe2O3 has not been revealed. This work disclosed that nanorod-like α-Fe2O3 (Fe2O3-NR) predominantly exposing (110) facet performed better than nanosheet-like α-Fe2O3 (Fe2O3-NS) predominantly exposing (001) facet in NH3-SCR reaction, due to the advantages of Fe2O3-NR in redox properties and surface acidity. Furthermore, the results of the SO2/H2O resistance test at a critical temperature of 250 °C, catalytic performance evaluations on Fe2O3-NR and Fe2O3-NS sulfated by SO2 + O2 or deposited with NH4HSO4 (ABS), and systematic characterization revealed that the reactivity of ammonium sulfates on Fe2O3 catalysts to NO(+O2) contributed to their improved catalytic performance, while ferric sulfates showed enhancing and inhibiting effects on NH3-SCR activity on Fe2O3-NR and Fe2O3-NS, respectively; despite this, Fe2O3-NR showed higher affinity for SO2 + O2. This work set a milestone in understanding the NH3-SCR reaction on Fe2O3 catalysts in the presence of SO2 from the aspect of crystal facet engineering.

Mechanistic insights into poly(C)-binding protein hnRNP K resolving i-motif DNA secondary structures.

I-motifs are four-strand noncanonical secondary structures formed by cytosine (C)-rich sequences in living cells. The structural dynamics of i-motifs play essential roles in many cellular processes, such as telomerase inhibition, DNA replication, and transcriptional regulation. In cells, the structural dynamics of the i-motif can be modulated by the interaction of poly(C)-binding proteins (PCBPs), and the interaction is closely related to human health, through modulating the transcription of oncogenes and telomere stability. Therefore, the mechanisms of how PCBPs interact with i-motif structures are fundamentally important. However, the underlying mechanisms remain elusive. I-motif structures in the promoter of the c-MYC oncogene can be unfolded by heterogeneous nuclear ribonucleoprotein K (hnRNP K), a PCBP, to activate its transcription. Here, we selected this system as an example to comprehensively study the unfolding mechanisms. We found that the promoter sequence containing 5 C-runs preferred folding into type-1245 to type-1234 i-motif structures based on their folding stability, which was further confirmed by single-molecule FRET. In addition, we first revealed that the c-MYC i-motif structure was discretely resolved by hnRNP K through two intermediate states, which were assigned to the opposite hairpin and neighboring hairpin, as further confirmed by site mutations. Furthermore, we found all three KH (hnRNP K homology) domains of hnRNP K could unfold the c-MYC i-motif structure, and KH2 and KH3 were more active than KH1. In conclusion, this study may deepen our understanding of the interactions between i-motifs and PCBPs and may be helpful for drug development.

Insights into the structural dynamics and helicase-catalyzed unfolding of plant RNA G-quadruplexes.

RNA G-quadruplexes (rG4s) are noncanonical RNA secondary structures formed by guanine (G)-rich sequences. These complexes play important regulatory roles in both animals and plants through their structural dynamics and are closely related to human diseases and plant growth, development, and adaption. Thus, studying the structural dynamics of rG4s is fundamentally important; however, their folding pathways and their unfolding by specialized helicases are not well understood. In addition, no plant rG4-specialized helicases have been identified. Here, using single-molecule FRET, we experimentally elucidated for the first time the folding pathway and intermediates, including a G-hairpin and G-triplex. In addition, using proteomics screening and microscale thermophoresis, we identified and validated five rG4-specialized helicases in Arabidopsis thaliana. Furthermore, DExH1, the ortholog of the famous human rG4 helicase RHAU/DHX36, stood out for its robust rG4 unwinding ability. Taken together, these results shed light on the structural dynamics of plant rG4s.

A one-stop approach to diagnosing hereditary colorectal cancer in the Chinese population.

BACKGROUND AND AIM: The current procedure for identifying hereditary colorectal cancer (HCRC) is time consuming in clinical practice. This study aimed to develop a time-saving approach to diagnosing HCRC. METHODS: A total of 100 suspected HCRC patients were prospectively enrolled (cohort 1) and 116 colorectal cancer patients with DNA mismatch repair-deficient were retrospectively included (cohort 2). Next-generation sequencing (NGS) tests were performed on tumors and matched white blood cells (WBCs) or normal tissues. Using the conventional method upon WBC/normal tissue-based NGS data as a reference, the performance of the ColonCore method using tumor-only-based NGS data in predicting germline variants was explored in cohort 1 and validated in cohort 2. RESULTS: In cohort 1, the ColonCore method diagnosed 17 Lynch syndrome (LS) and 14 familial adenomatous polyposis (FAP); and by the conventional method, the cases were 16 and 10, respectively. The ColonCore method showed sensitivities of 100% in diagnosing LS (positive predictive value [PPV] 94.1%) and FAP (PPV 71.4%). Moreover, two of seven patients with multiple adenomas/polyps who did not meet existing clinical criteria for HCRC were predicted to harbor germline variants in APC and MUTYH. Additionally, the sensitivity of the ColonCore method in identifying LS patients from cohort 2 reached 85.7% with a PPV of 85.7%. CONCLUSION: The ColonCore method might be an acceptable tool for predicting germline variants associated with HCRC. Our work indicates the essentiality of NGS tests in CRC patients for precision diagnosis and treatment.

Aldosterone alleviates lipopolysaccharide-induced acute lung injury by regulating epithelial sodium channel through PI3K/Akt/SGK1 signaling pathway.

Reduced alveolar fluid clearance (AFC) is a major pathological feature of acute lung injury (ALI). Epithelial sodium channel (ENaC) plays a key role in regulating the transport of Na+ and clearing alveolar edema fluid effectively. ENaC has been reported to be regulated by aldosterone in the distal collecting tube of the kidney. We hypothesized whether aldosterone regulated ENaC in alveolar epithelium and correspondingly played a role in ALI. In this study we found that the expression of aldosterone synthesis encoding gene, CYP11B2, and ENaC were decreased in the lung tissue of LPS-induced ALI mice. Furthermore, aldosterone alleviated ALI by increasing the expression of ENaC-α and relieving pulmonary edema. Besides, we found that aldosterone upregulated ENaC-α through PI3K/Akt/SGK1 pathway. In conclusion, our study demonstrated that aldosterone attenuated pulmonary edema by upregulating ENaC-α through the PI3K/Akt/SGK1 pathway in LPS-induced ALI, indicating that aldosterone might be a promising adjuvant drug for ALI treatment.

Ultrasound elastography: a novel tool for the differential diagnosis of pleural effusion.

INTRODUCTION: Traditional thoracic ultrasound (TUS) is often the initial tool used to help diagnose malignant pleural effusion (MPE). Ultrasound elastography, a relatively new technique, has been used to differentiate malignant disease from benign disease by evaluating tissue "stiffness". However, no studies evaluating the efficacy of ultrasound elastography for diagnosing MPE are available. We assessed the value of ultrasound elsatography for diagnosing MPE prospectively. METHODS: All 244 enrolled patients were divided into a development set and a validation set in chronological order. The cut-off elasticity index was established using a receiver operating characteristic curve constructed from the continuous data of the patients in the development set. The diagnostic performance of ultrasound elastography was compared with that of TUS in the validation set. RESULTS: In the development set, the mean elasticity index (47.25 kPa) was the optimal cut-off. In the validation set, pleural ultrasound elastography had a sensitivity of 83.64%, a specificity of 90.67%, a positive predictive value of 86.79%, a negative predictive value of 88.31%, a positive likelihood ratio of 8.96 and a negative likelihood ratio of 0.18 for diagnosing MPE. The sensitivity of ultrasound elastography was significantly higher (p=0.006) than that of TUS (60%). CONCLUSION: Pleural ultrasound elastography is a better technique than TUS for differentiating MPE from benign pleural disease.

Negative pressure wound therapy reduces the motility of Pseudomonas aeruginosa and enhances wound healing in a rabbit ear biofilm infection model.

Pseudomonas aeruginosa motility, virulence factors and biofilms are known to be detrimental to wound healing. The efficacy of negative pressure wound therapy (NPWT) against P. aeruginosa has been little studied, either in vitro or in vivo. The present study evaluated the effect of negative pressure (NP) on P. aeruginosa motility in vitro, and the effect of NPWT on virulence factors and biofilms in vivo. P. aeruginosa motility was quantified under different levels of NP (atmospheric pressure, - 75, - 125, - 200 mmHg) using an in vitro model. Swimming, swarming and twitching motility were significantly inhibited by NP (- 125 and - 200 mmHg) compared with atmospheric pressure (p = 0.05). Virulence factors and biofilm components were quantified in NPWT and gauze treated groups using a rabbit ear biofilm model. Biofilm structure was studied with fluorescence microscopy and scanning electron microscopy. Additionally, viable bacterial counts and histological wound healing parameters were measured. Compared with the control, NPWT treatment resulted in a significant reduction in expression of all virulence factors assayed including exotoxin A, rhamnolipid and elastase (p = 0.01). A significant reduction of biofilm components (eDNA) (p = 0.01) was also observed in the NPWT group. The reduction of biofilm matrix was verified by fluorescence- and scanning electron-microscopy. NPWT lead to better histologic parameters (p = 0.01) and decreased bacterial counts (p = 0.05) compared with the control. NPWT treatment was demonstrated to be an effective strategy to reduce virulence factors and biofilm components, which may explain the increased wound healing observed.

Diagnostic Value of Cerebrospinal Fluid T-SPOT.TB for Tuberculousis Meningitis in China.

The aim of this study was to evaluate the diagnostic value of the cerebrospinal fluid (CSF) T-SPOT.TB test for the diagnosis of TB meningitis (TBM). A retrospective analysis of 96 patients with manifested meningitis was conducted; T-SPOT.TB test was performed for diagnosing TBM to determine the diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). A receiver operating characteristic (ROC) curve was also drawn to assess the diagnostic accuracy. The sensitivity, specificity, PPV, and NPV of CSF T-SPOT.TB test were 97.8%, 78.0%, 80.3%, and 97.5%, respectively, for 52 patients (54.2%) of the 96 enrolled patients. The area under the curve (AUC) was 0.910, and the sensitivities of CSF T-SPOT.TB for patients with stages I, II, and III of TBM were 96.7%, 97.2%, and 98.9%, respectively. CSF T-SPOT.TB test is a rapid and accurate diagnostic method with higher sensitivity and specificity for diagnosing TBM.

Loss of MyD88 leads to more aggressive TRAMP prostate cancer and influences tumor infiltrating lymphocytes.

BACKGROUND: The influence of pattern recognition receptor (PRR) signaling in the prostate tumor microenvironment remains unclear. Although there may be a role for PRR agonists as adjuvants to therapy, prior evidence suggests tumor promoting as well as tumor inhibiting mechanisms. The purpose of this study is to examine the role of the key Toll-like receptor (TLR) signaling adaptor protein myeloid differentiation primary response gene 88 (MyD88) in prostate cancer development. METHODS: MyD88(-/-) mice in a C57Bl6 background were crossed with transgenic adenocarcinomas of the mouse prostate (TRAMP) mice to create MyD88(-/-) TRAMP(Tg+/-) animals, which were compared to MyD88(+/+) TRAMP(Tg+/-) animals and their non-transgenic counterparts at 30 weeks. Prostates were examined histologically, by immunohistochemistry and immunofluorescence staining, and by qPCR, to characterize tumor-infiltrating immune populations as well as activation of the downstream NF-κB pathway and androgen receptor (AR) expression. Splenocytes were examined for development of distinct immune cell populations. RESULTS: Absence of MyD88 led to increased prostatic intraepithelial neoplasm (PIN) and areas of well-differentiated adenocarcinoma in TRAMP transgenic mice. Analysis of infiltrating immune populations revealed an increase in CD11b(+) Gr1(+) myeloid-derived suppressor cells (MDSCs), as evidenced by increased expression of prostatic arginase-1 and iNOS as well as the cytokine IL-10, and a deficiency in NK cells in prostates from MyD88(-/-) TRAMP(Tg+/-) compared to MyD88(+/+) TRAMP(Tg+/-) mice, whereas a decrease in splenocytic NK cell differentiation was observed in MyD88(-/-) mice. Prostate tumors revealed no significant differences in NF-κB or AR expression in MyD88(+/+) TRAMP(Tg+/-) compared to MyD88(-/-) TRAMP(Tg+/-) mice. CONCLUSIONS: During prostate cancer development in the TRAMP model, MyD88 may play a role in limiting prostate tumorigenesis by altering tumor-infiltrating immune populations. This suggests that in the context of specific cancers, distinct PRRs and signaling pathways of innate immune signaling may influence the tumor microenvironment and represent a novel therapeutic strategy.

Molecular cloning and sequence analysis of novel cytochrome P450 cDNA fragments from Dastarcus helophoroides.

The predatory beetle Dastarcus helophoroides (Fairmaire) (Coleoptera: Bothrideridae) is a natural enemy of many longhorned beetles and is mainly distributed in both China and Japan. To date, no research on D. helophoroides P450 enzymes has been reported. In our study, for the better understanding of P450 enzymes in D. helophoroides, 100 novel cDNA fragments encoding cytochrome P450 were amplified from the total RNA of adult D. helophoroides abdomens using five pairs of degenerate primers designed according to the conserved amino acid sequences of the CYP6 family genes in insects through RT-PCR. The obtained nucleotide sequences were 250 bp, 270 bp, and 420 bp in length depending on different primers. Ninety-six fragments were determined to represent CYP6 genes, mainly from CYP6BK, CYP6BQ, and CYP6BR subfamilies, and four fragments were determined to represent CYP9 genes. Twenty-two fragments, submitted to GenBank, were selected for further homologous analysis, which revealed that some fragments of different sizes might be parts of the same P450 gene.

Molecular cloning and characterization of a novel P450 gene encoding CYP6BK18 from Dastarcus helophoroides (Coleoptera: Bothrideridae).

A novel cDNA clone encoding a cytochrome P450 gene, named CYP6BK18 (GenBank KC683905), was isolated by reverse transcription PCR from Dastarcus helophoroides (Fairmaire) (Coleoptera: Bothrideridae), a natural enemy of beetles. The full-length cDNA sequence is 1,659 bp, containing a 1,533 bp open reading frame predicting a 510-amino acid protein possessing a transmembrane domain with a calculated molecular weight of 59.4 kDa and a theoretical pI of 8.94. The deduced amino acid sequence of CYP6BK18 showed a 59% identity with CYP6BK17 (GenBank XP_970481.1) from Tribolium castaneum. Phylogenetic analysis indicated that CYP6BK18 was most closely related to CYP6BK17 and CYP6BK14 (GenBank EFA05731.1) from T. castaneum. Expression patterns of CYP6BK18 in different tissues (head, oviduct, midgut, fat bodies, and Malpighian tubules), developmental stages (first- to sixth-instar larvae and adult) and 10 age groups of adult were analyzed by real-time quantitative PCR (RT-qPCR). The results showed that CYP6BK18 was highly expressed in adulthood. Also, RT-qPCR analysis among different age groups of adult showed that CYP6BK18 transcripts were abundant in the spawning period and peaked at the early stage of the adult development. Moreover, the tissue-specific expression levels of CYP6BK18 were in the order of midgut, Malpighian tubes and fatty body from high to low. These results suggest that cytochrome P450 CYP6BK18 may play a role in regulating the development and aging of D. helophoroides.

Evaluating the Performance of In silico Tools for PRRT2 Missense Variants.

BACKGROUND: Variants in the PRRT2 gene are associated with paroxysmal kinesigenic dyskinesia and other episodic disorders. With the employment of variant screening in patients with episodic dyskinesia, many PRRT2 variants have been discovered. Bioinformatics tools are becoming increasingly important for predicting the functional significance of variants. This study aimed to evaluate the performance of six in silico tools for PRRT2 missense variants. METHODS: Pathogenic PRRT2 variants were retrieved from the Human Gene Mutation Database (HGMD) and literature from the PubMed database. The benign set of non-deleterious variants was retrieved from the Genome Aggregation Database (gnomAD). The overall accuracy, sensitivity, specificity, positive predictive values, and negative predictive values of SIFT, PolyPhen2, MutationTaster, CADD, Fathmm, and Provean were analyzed. The MCC score and ROC curve were calculated. The GraphPad Prism 8.0 software was used to plot ROC curves for the six bioinformatics software. RESULTS: A total of 45 missense variants with confirmed pathogenicity were used as a positive set, and 222 missense variants were used as a negative set. The top three tools in accuracy are Fathmm, Provean, and MutationTaster. The top three predictors in sensitivity are SIFT, PolyPhen2, and CADD. Regarding specificity, the top three tools were Provean, Fathmm, and MutationTaster. In terms of the MCC and F-score, the highest degree was observed in Fathmm. Fathmm also had the highest AUC score. The cutoff values of Fathmm, CADD, PolyPhen2, and Provean were between the median prediction scores of the positive and negative sets. In contrast, the cutoff value of SIFT was below the median prediction score of the positive and negative sets. Fathmm had the highest accuracy. CONCLUSION: The prediction performance of six in silico tools differed among the parameters. Fathmm had the best prediction performance, with the highest accuracy and MCC/F-score for PRRT2 missense variants.

Clinical application of trio-based whole-exome sequencing in idiopathic generalized epilepsy.

PURPOSE: Idiopathic generalized epilepsies (IGEs) are a common group of genetic generalized epilepsies with high genetic heterogeneity and complex inheritance. However, the genetic basis is still largely unknown. This study aimed to explore the genetic etiologies in IGEs. METHODS: Trio-based whole-exome sequencing was performed in 60 cases with IGEs. The pathogenicity of candidate genetic variants was evaluated by the criteria of the American College of Medical Genetics and Genomics (ACMG), and the clinical causality was assessed by concordance between the observed phenotype and the reported phenotype. RESULTS: Seven candidate variants were detected in seven unrelated cases with IGE (11.7%, 7/60). According to ACMG, a de novo SLC2A1 (c.376C>T/p.Arg126Cys) variant identified in childhood absence epilepsy was evaluated as pathogenic with clinical concordance. Six variants were assessed to be uncertain significance by ACMG, but then considered causative after evaluation of clinical concordance. These variants included CLCN4 hemizygous variant (c.2044G>A/p.Glu682Lys) and IQSEC2 heterozygous variant (c.4315C>T/p.Pro1439Ser) in juvenile absence epilepsy, EFHC1 variant (c.1504C>T/p.Arg502Trp) and CACNA1H (c.589G>T/p.Ala197Ser) both with incomplete penetrance in juvenile myoclonic epilepsy, and GRIN2A variant (c.2011C>G/p.Gln671Glu) and GABRB1 variant (c.1075G>A/p.Val359Ile) both co-segregated with juvenile myoclonic epilepsy. Among them, GABRB1 was for the first time identified as potential novel causative gene for IGE. SIGNIFICANCE: Considering the genetic heterogeneity and complex inheritance of IGEs, a comprehensive evaluation combined the ACMG scoring and assessment of clinical concordance is suggested for the pathogenicity analysis of variants identified in clinical screening. GABRB1 is probably a novel causative gene for IGE, which warrants further studies.

The Roles of Non-coding RNA Targeting Astrocytes in Cerebral Ischemia.

Astrocytes are key targets for treating cerebral ischemia in the central nervous system. Non-coding RNAs (ncRNAs) participate in the pathological processes of astrocytes in cerebral ischemia. Recent reports suggest that ncRNAs ameliorate the outcome of cerebral ischemia by mediating astrocytes' inflammatory reaction, oxidative stress, excitotoxicity, autophagy, and apoptosis. Reconstructing cellular systems might offer a promising strategy for treating cerebral ischemia. This review briefly discusses the potential of ncRNAs as drug targets and explores the molecular regulatory mechanisms through which ncRNAs target astrocytes in cerebral ischemia. It provides an overview of the current research, discusses ncRNAs' implications as clinical markers for cerebral ischemia, and anticipates that ongoing research on ncRNAs may contribute to novel therapeutic approaches for treating this condition.

The influence of near-infrared therapy on arteriovenous fistula patency in haemodialysis patients: A multicentre, randomised, controlled clinical trial.

BACKGROUND: Arteriovenous fistula (AVF) is the preferred vascular access for patients undergoing haemodialysis (HD). AVF malfunction remains a major clinical problem and is a significant independent risk factor for death. Although far-infrared (FIR) therapy has been shown to reduce complications and improve the patency rate of AVFs in various studies, it has been cautiously recommended by the Kidney Disease Outcome Quality Initiative (KDOQI) guidelines for AVF care due to insufficient evidence. Therefore, it is necessary to identify more effective methods for preventing AVF dysfunction. Many in vitro studies and few clinical studies have examined the effects of near-infrared (NIR) therapy on the vasculature. This study will examine the effects of NIR therapy on AVF. METHODS: A randomised, controlled, open-label, multicentre trial will compare the effect of NIR on AVF patency after 1 year of therapy with that of a control group of patients with existing AVF. One group of patients received NIR treatment above their AVFs, whereas the control group received regular care. The primary outcome is the primary fistula patency rate within 12 months. In addition, acute changes in inflammatory, vasodilatory and haemodynamic parameters after a single treatment in the first 40 participants will be examined. This study was registered in the Clinical Trials Registry (ChiCTR2300071305) at https://register.clinicaltrials.gov/. DISCUSSIONS: This study will explore the long-term and acute effects of NIR on AVFs. The study findings will provide information that can be used to develop new technical support for the prevention of AVF dysfunction in patients undergoing haemodialysis.

Association of FAT1 with focal epilepsy and correlation between seizure relapse and gene expression stage.

PURPOSE: The FAT1 gene encodes FAT atypical cadherin 1, which is essential for foetal development, including brain development. This study aimed to investigate the relationship between FAT1 variants and epilepsy. METHODS: Trio-based whole-exome sequencing was performed on a cohort of 313 patients with epilepsy. Additional cases with FAT1 variants were collected from the China Epilepsy Gene V.1.0 Matching Platform. RESULTS: Four pairs of compound heterozygous missense FAT1 variants were identified in four unrelated patients with partial (focal) epilepsy and/or febrile seizures, but without intellectual disability/developmental abnormalities. These variants presented no/very low frequencies in the gnomAD database, and the aggregate frequencies in this cohort were significantly higher than those in controls. Two additional compound heterozygous missense variants were identified in two unrelated cases using the gene-matching platform. All patients experienced infrequent (yearly/monthly) complex partial seizures or secondary generalised tonic-clonic seizures. They responded well toantiseizure medication, but seizures relapsed in three cases when antiseizure medication were decreased or withdrawn after being seizure-free for three to six years, which correlated with the expression stage of FAT1. Genotype-phenotype analysis showed that epilepsy-associated FAT1 variants were missense, whereas non-epilepsy-associated variants were mainly truncated. The relationship between FAT1 and epilepsy was evaluated to be "Strong" by the Clinical Validity Framework of ClinGen. CONCLUSIONS: FAT1 is a potential causative gene of partial epilepsy and febrile seizures. Gene expression stage was suggested to be one of the considerations in determining the duration ofantiseizure medication. Genotype-phenotype correlation helps to explain the mechanisms underlying phenotypic variation.

Robust polymer hybrid and assembly materials from structure tailoring to efficient catalytic remediation of emerging pollutants.

A massive amount of toxic substances and harmful chemicals are released every day into the outer environment, imposing serious environmental impacts on both land and aquatic animals. To date, research is constantly in progress to determine the best catalytic material for the effective remediation of these harmful pollutants. Hybrid nanomaterials prepared by combining functional polymers with inorganic nanostructures got attention as a promising area of research owing to their remarkable multifunctional properties deriving from their entire nanocomposite structure. The versatility of the existing nanomaterials' design in polymer-inorganic hybrids, with respect to their structure, composition, and architecture, opens new prospects for catalytic applications in environmental remediation. This review article provides comprehensive detail on catalytic polymer nanocomposites and highlights how they might act as a catalyst in the remediation of toxic pollutants. Additionally, it provides a detailed clarification of the processing of design and synthetic ways for manufacturing polymer nanocomposites and explores further into the concepts of precise design methodologies. Polymer nanocomposites are used for treating pollutants (electrocatalytic, biocatalytic, catalytic, and redox degradation). The three catalytic techniques that are frequently used are thoroughly illustrated. Furthermore, significant improvements in the method through which the aforementioned catalytic process and pollutants are extensively discussed. The final section summarizes challenges in research and the potential of catalytic polymer nanocomposites for environmental remediation.

Surface Coordination Environment Engineering on PtxCu1-x Alloy Catalysts for the Efficient Photocatalytic Reduction of CO2 to CH4.

Alloy catalysts have been reported to be robust in catalyzing various heterogeneous reactions due to the synergistic effect between different metal atoms. In this work, aimed at understanding the effect of the coordination environment of surface atoms on the catalytic performance of alloy catalysts, a series of PtxCu1-x alloy model catalysts supported on anatase-phase TiO2 (PtxCu1-x/Ti, x = 0.4, 0.5, 0.6, 0.8) were developed and applied in the classic photocatalytic CO2 reduction reaction. According to the results of catalytic performance evaluation, it was found that the photocatalytic CO2 reduction activity on PtxCu1-x/Ti showed a volcanic change as a function of the Pt/Cu ratio, the highest CO2 conversion was achieved on Pt0.5Cu0.5/Ti, with CH4 as the main product. Further systematic characterizations and theoretical calculations revealed that the equimolar amounts of Pt and Cu in Pt0.5Cu0.5/Ti facilitated the generation of more Cu-Pt-paired sites (i.e., the higher coordination number of Pt-Cu), which would favor a bridge adsorption configuration of CO2 and facilitate the electron transfer, thus resulting in the highest photocatalytic CO2 reduction efficiency on Pt0.5Cu0.5/Ti. This work provided new insights into the design of excellent CO2 reduction photocatalysts with high CH4 selectivity from the perspective of surface coordination environment engineering on alloy catalysts.

Reprint of: Recessive APC2 missense variants associated with epilepsies without neurodevelopmental disorders.

OBJECTIVES: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy. METHODS: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations. RESULTS: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation. SIGNIFICANCE: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity.