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Defect-engineered carbon materials have been emerged as promising electrocatalysts for oxygen reduction reaction (ORR) in metal-air batteries. Developing a facile strategy for the preparation of highly active nanocarbon electrocatalysts remains challenging. Herein, a low-cost and simple route is developed to synthesize defective graphene by pyrolyzing the mixture of glucose and carbon nitride. Molecular dynamics simulations reveal that the graphene formation is ascribed to two-dimensional layered feature of carbon nitride, and high compatibility of carbon nitride/glucose systems. Structural measurements suggest that the graphene possesses rich edge and topological defects. The graphene catalyst exhibits higher power density than commercial Pt/C catalyst in a primary Zn-air battery. Combining experimental results and theoretical thermodynamic analysis, it is identified that graphitic nitrogen-modified topological defects at carbon framework edges are responsible for the decent ORR performance. The strategy presented in this work can be can be scaled up readily to fabricate defective carbon materials.

To investigate the occurrence of mosaicism in epilepsy probands and their parents using amplicon-based deep sequencing (ADS).Patients were recruited from the outpatient of Peking University First Hospital. Two hundred and sixty-four probands with pathogenic variants tested by next-generation sequencing (NGS) were enrolled.Mosaic variants were detected in seventeen disease-associated genes from 20 probands, 5 paternal, and 6 maternal parents. The frequency of mosaicism was 11.74% (31/264). Mosaicism in 11 genes was identified from 20 probands with the mutant allelic fractions (MAFs) of 12.95-38.00% in autosomal dominant genes. Five paternal mosaicisms were identified in genes with a MAF of 6.30-20.99%, and six maternal mosaic individuals with a MAF of 2.07-21.90%. Only four mosaic parents had milder seizure history. The affected sibling had the same phenotype consistent with that of the proband, who inherited the variant of SLC1A2 or STXBP1 from their unaffected mosaic mothers, respectively.Mosaic phenomenon is not rare in families with epilepsy. Phenotypes of mosaic parents were milder or normal. Mosaicism detection is helpful to identify the mutation origin and it provides a theoretical basis for prenatal diagnosis of family reproduction. ADS is a reliable way of mosaicism detection for clinical application.

Purpose The purpose of this paper is to develop high-performance Au-coated Ag alloy wires (ACAA wires) and demonstrate the effect of Au coating layers on the bonding performance and oxidation resistance for stable and reliable electronic packaging applications. Design/methodology/approach ACAA wire with a diameter of approximately 25 µm and Au layer thickness of approximately 100 nm were prepared by the continuous casting, plating and wire drawing method. The bonding performance of the ACAA wires were studied through bonding on 3,535 chips. The oxidation resistance of ACAA wires and Ag alloy wires (AA wires) were comparatively studied by means of chemical oxidation tests, accelerated life tests and electrochemical tests systematically. Findings ACAA wires could form axi-symmetrical spherical free air balls with controllable diameter of 1.5∼2.5 times of the wire diameter after electric flame-off process. The ball shear strength of ACAA wire was higher than that of AA wires. Most importantly, because of the surface Au coating layer, the oxidation resistance of ACAA wires was much enhanced. Research limitations/implications ACAA wires with different lengths of heat affected zone were not developed in this study, which limited their application with different loop height requirements. Practical implications With higher bonding strength and oxidation resistance, ACAA wires would be a better choice than previous reported AA wire in chip packaging which require high stability and reliability. Originality/value This paper provides a kind of novel ACAA wire, which possess the merits of high bonding strength and reliability, and show great potential in electronic packaging applications.

Background Programmed cell death receptor-1 (PD-1) monotherapy is a standard treatment for advanced cutaneous melanoma, but its efficacy and toxicity are defined in white populations and remain poorly characterized in other ethnic groups, such as East Asian, Hispanic and African. Objectives To determine the efficacy and toxicity of PD-1 monotherapy in different ethnic groups. Methods Clinical data for patients with unresectable or advanced melanoma treated with anti-PD-1 monotherapy between 2009 and 2019 were collected retrospectively from five independent institutions in the USA, Australia and China. Tumour response, survival and immune-related adverse events (irAEs) were compared by ethnicity (white vs. East Asian/Hispanic/African) across different melanoma subtypes: nonacral cutaneous (NAC)/unknown primary (UP) and acral/mucosal/uveal. Results In total, 1135 patients were included. White patients had significantly higher objective response rate (ORR) [54%, 95% confidence interval (CI) 50–57% vs. 20%, 95% CI 13–28%; adjusted P < 0·001] and longer progression-free survival (14·2 months, 95% CI 10·7–20·3 vs. 5·4 months, 95% CI 4·5–7·0; adjusted P < 0·001) than East Asian, Hispanic and African patients in the NAC and UP subtypes. White ethnicity remained independently associated with a higher ORR (odds ratio 4·10, 95% CI 2·48–6·81; adjusted P < 0·001) and longer PFS (hazard ratio 0·58, 95% CI 0·46–0·74; adjusted P < 0·001) in multivariate analyses after adjustment for age, sex, primary anatomical location, metastasis stage, baseline lactate dehydrogenase level, mutational status and prior systemic treatment. White and East Asian/Hispanic/African patients shared similar ORR and progression-free survival in acral/mucosal/uveal melanomas. Similar melanoma-subtype-specific ethnic discrepancies were observed in complete response rate and overall survival. White patients had higher rates of gastrointestinal irAEs but lower rates of endocrine, liver and other rare types of irAEs. These differences in irAEs by ethnicity were not attributable to varying melanoma subtypes. Conclusions Ethnic discrepancy in clinical benefit is specific to melanoma subtype, and East Asian, Hispanic and African patients with NAC and UP melanomas have poorer clinical benefits than previously recognized. The ethnic discrepancy in toxicity observed across different melanoma subtypes warrants an ethnicity-based irAE surveillance strategy. More research is needed to elucidate the molecular and immunological determinants of these differences. What is already known about this topic? There is a great difference in response to immunotherapy between different subtypes of melanoma (cutaneous, mucosal, acral and uveal) in patients with advanced disease. What does this study add? Our data show for the first time that there are differences between different ethnic groups in terms of both response and toxicity to immunotherapy beyond the well-appreciated discrepancies due to melanoma subtype.

Since tiny optical glass is the key component in various optical instruments, more and more researchers have paid attention to automatic defect detection on tiny optical glass in recent years. It remains a challenging problem, as the defects are extremely small. In this paper, we propose a video-based two-stage defect detection network to improve detection accuracy for small defects. Specifically, the detection process is carried out in a coarse-to-fine manner to improve the detection precision. First, the optical glass area is located on the down-sampled version of the input image, and then defects are detected only within the optical glass area with a higher resolution version, which can significantly reduce the false alarming rate. Since the defects may exist on any place of the optical glass, we fuse the results of multiple video frames captured from various perspectives to promote recall rates of the defects. Additionally, we propose an image quality evaluation module based on a clustering algorithm to select video frames with high quality for improving both detection recall and precision. We contribute a new dataset called OGD-DET for tiny-scale optical glass surface defect detection experiments. The datasets consist of 3415 images from 40 videos, and the size of the defect area ranges from 0.1 mm to 0.53 mm, 2 to 7 pixels on images with a resolution of 1536 × 1024 pixels. Extensive experiments show that the proposed method outperforms the state-of-the-art methods in terms of both accuracy and computation cost.

Senescent cells release a variety of cytokines, proteases, and growth factors collectively known as the senescence-associated secretory phenotype (SASP). Sustained SASP contributes to a pattern of chronic inflammation associated with aging and implicated in many age-related diseases. Here, we investigated the expression and function of the immunomodulatory cytokine BAFF (B-cell activating factor; encoded by the TNFSF13B gene), a SASP protein, in multiple senescence models. We first characterized BAFF production across different senescence paradigms, including senescent human diploid fibroblasts (WI-38, IMR-90) and monocytic leukemia cells (THP-1), and tissues of mice induced to undergo senescence. We then identified IRF1 (interferon regulatory factor 1) as a transcription factor required for promoting TNFSF13B mRNA transcription in senescence. We discovered that suppressing BAFF production decreased the senescent phenotype of both fibroblasts and monocyte-like cells, reducing IL6 secretion and SA-β-Gal staining. Importantly, however, the influence of BAFF on the senescence program was cell type-specific: in monocytes, BAFF promoted the early activation of NF-κB and general SASP secretion, while in fibroblasts, BAFF contributed to the production and function of TP53 (p53). We propose that BAFF is elevated across senescence models and is a potential target for senotherapy.

Senescence is a state of indefinite cell cycle arrest associated with aging, cancer, and age-related diseases. Here, using label-based mass spectrometry, ribosome profiling and nanopore direct RNA sequencing, we explore the coordinated interaction of translational and transcriptional programs of human cellular senescence. We find that translational deregulation and a corresponding maladaptive integrated stress response (ISR) is a hallmark of senescence that desensitizes senescent cells to stress. We show that senescent cells maintain high levels of eIF2α phosphorylation, typical of ISR activation, but translationally repress the stress response transcription factor 4 (ATF4) by ineffective bypass of the inhibitory upstream open reading frames. Surprisingly, ATF4 translation remains inhibited even after acute proteotoxic and amino acid starvation stressors, resulting in a highly diminished stress response. Furthermore, absent a response, stress exacerbates the senescence secretory phenotype and inflammatory pathways thus acting as a possible mechanistic link to disease. Our results reveal a novel mechanism that senescent cells exploit to evade an adaptive stress response and remain viable.

Supplementary Methods

PurposeAnkle fracture combined with deltoid ligament (DL) injury results in decreased stability of ankle mortise, reduced contact surface between tibial and talus, increased local stress, and increased postoperative complications. The purpose of this meta-analysis was to evaluate the postoperative effects of repairing ligaments in ankle fractures with DL rupture.MethodsAccording to the steps of the Cochrane systematic review, the related literatures from PubMed, Embase and the Cochrane Library Databases were retrieved as of September 1, 2021, and all relevant randomized controlled trials and retrospective studies were collected. The evaluation indicators include medial clear space (MCS), visual analogue scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS), complications rate. Meta-analysis was conducted by RevMan® 5.3 provided by the Cochrane collaboration.ResultsA total of 388 patients (195 patients in the ligament repair group and 193 patients in the non-repair group) were included in 7 clinical trials. Meta-analysis data showed there were no statistically significant differences between the ligament repair group and non-repair group in final follow-up VAS, final AOFAS and postoperative MCS (P = 0.50, P = 0.04, P = 0.14, P = 0.14, respectively). Final follow-up MCS and complications rate in ligament repair group were smaller than those in the non-repair group and were statistically significant (P P = 0.006, respectively).ConclusionAlthough there was no difference in in final follow-up VAS, final follow-up AOFAS and postoperative MCS between experimental group and control group, It's statistically significant in final follow-up MCS and complications rate. Ligament repair could reduce the width of MCS, restore ankle stability, reduce the incidence of complications and lead to a better prognosis.

This study aimed to investigate the influencing factors of frailty in elderly patients with multimorbidity and to develop a predictive risk model for frailty in elderly patients with multimorbidity.In total, 3836 elderly patients with multimorbidity who were admitted to the medical wards of five grade A tertiary hospitals in Sichuan Province from March 2020 to June 2021 were selected. Based on the general data of patients with multimorbidity, the independent risk factors for frailty were obtained using logistic analysis, and a risk prediction model of frailty was developed.Independent risk factors for frailty in patients with multimorbidity were age, types of medication, and comorbidity with chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD) and chronic cerebrovascular disease (CCVD); and the protective factors for frailty were body mass index (BMI), exercise and education level. The expression of the model was Z = -2.054 + 0.016 × age - 0.029 × BMI - 0.153 × education level-1.059 × exercise + 0.203 × types of medication + 0.788 × comorbidity with CHF + 0.950 × comorbidity with COPD + 0.363 × comorbidity with CCVD.Age, BMI, education level, exercise, types of medication, and comorbidity with CHF, COPD and CCVD can affect frailty risk in elderly patients with multimorbidity, which may be helpful to predict the frailty risk of elderly patients with multimorbidity. Geriatr Gerontol Int 2022; 22: 471-476.

Cutting is an imperative operation in the food-manufacturing factory, separating food into a predefined geometry. A broad range of solid foods, with various components, textures, and structures, pose enormous challenges to conventional cutting strategies. Additionally, the cutting performance is significantly impacted by the processing parameters, wherein trial-and-error or empirical methods are often used to select the parameters in source-wasting and time-consuming ways. Hence, there is a need to accelerate the development of advanced cutting techniques and novel modeling approaches in the food-manufacturing industry. Recently, advanced cutting techniques (ultrasonic vibration-assisted [UVA], laser, and waterjet cutting) are seen to be superior in processing foods of various textures, with the advantages of high cutting quality, low contamination, and easy operation. Compared with conventional cutting, advanced cutting techniques can dramatically reduce cutting force and energy consumption, resulting in high efficiency, energy-and-source saving, and low carbon footprint. Additionally, the finite element (FE) model does simulate the cutting process well, and artificial intelligence (AI) technology is competent to optimize the cutting parameters. This review is perhaps the first one focusing on the advanced cutting techniques applied in the food industry, serving as a summary of the cutting mechanisms, critical influence factors, and applications of conventional and advanced cutting techniques including UVA, laser, and waterjet cutting. In addition, the modeling approaches with respect to FE and AI models are emphasized. Finally, the challenges and future perspectives of advanced cutting techniques combined with modeling approaches are highlighted, and those approaches are promising in the future intelligent food-manufacturing industry. PRACTICAL APPLICATION: The review clearly demonstrates that advanced cutting techniques as having advantages such as high efficiency, energy-and-source saving, and low damages, thus exhibiting great potential in processing food of various textures with high cutting quality, low contamination, and easy operation. Additionally, the FE model does simulate the cutting process well and AI is competent in optimizing the cutting parameters, which possesses great potential in providing comprehensive cutting information and selecting the optimal combination of cutting parameters.

We report a novel strategy for the preparation of CsPbBr3 perovskite quantum dots by polyacrylic acid-b-polystyrene ligands, which demonstrated excellent optical properties and white LED performance.

A room-temperature self-healing polyurethane elastomer synthesised via optimized hierarchical H-bonding interactions ultimately exhibited a synchronous self-healing efficiency of more than 83% with tensile strength, elongation, and toughness.

The noises embedded in signals will degrade the signal processing quality. Traditional denoising algorithms might not work in practical systems since the statistical characteristics of noises might not be learned. To address this issue, we propose an efficient residual shrinkage convolutional neural network (RSCNN) aided denoiser based on the principle of the domain transformation, shrinking and inverse transforming operations conducted by the traditional denoiser. The proposed RSCNN is composed by the batch normalization layer, domain transformation layers, the shrinkage module and inverse transformation layers, wherein transformation layers consist of convolutional layers and the nonlinear activation function. Moreover, we propose a thresholds learning subnetwork to automatically determine the thresholds, so as to enhance noise suppressing performances. Furthermore, we compose the data set by preprocessing the received signals, and design the loss function according to different denoising requirements. To validate the efficiency and universality of the RSCNN aided denoiser, we apply the proposed RSCNN denoiser to three different application scenarios, including the modulation recognition, detection and decoding. After the offline training, at the online deployment stage, we utilize the RSCNN denoiser to reduce the noise power and improve the signal to noise ratios. Simulation results demonstrate that the proposed intelligent denoiser can efficiently improve the signal processing capabilities to achieve higher modulation recognition accuracy, better detection and decoding performances with lower complexity than benchmark schemes.

Autophagy plays a critical role in the physiology and pathophysiology of hepatocytes. High levels of homocysteine (Hcy) promote autophagy in hepatocytes, but the underlying mechanism is still unknown. Here, we investigated the relation between Hcy increased autophagy levels and the expression of nuclear transcription factor EB (TFEB). We demonstrate that Hcy increased autophagy levels is mediated by upregulation of TFEB. Silencing TFEB decreases the autophagy-related protein LC3BII/I and increases p62 expression levels in hepatocytes after exposure to Hcy. Moreover, the effect of Hcy on the expression of TFEB is regulated by hypomethylation of TFEB promoter catalyzed by DNA methyltransferase 3b (DNMT3b). In summary, this study shows that Hcy can activate autophagy by inhibiting DNMT3b-mediated DNA methylation and upregulating TFEB expression. These findings provide another new mechanism for Hcy-induced autophagy in hepatocytes.

Lobetyolin (LBT) is an important active ingredient in the traditional medicinal plant Codonopsis pilosula (Franch.) Nannf. However, the pharmacological targets and mechanisms of action of LBT against allergic rhinitis (AR) are not known. The aim of this study was to evaluate the possible functional role and potential mechanism of LBT as an anti-AR treatment through a combination of network pharmacology and molecular docking. The disease database and target screening database were used to find potential targets for screening LBT for the treatment of AR. Further network visualization analysis, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for potential targets. Finally, we performed some molecular docking with LBT and core targets to verify their relevant effects. The results revealed that a total of 64 target genes were obtained for LBT for AR. The top 10 targets with the highest enrichment scores were TNF, EGFR, MMP9, TLR4, ERBB2, JUN, CXCR4, HSP90AA1, KDR, and MMP2. GO and KEGG enrichment analysis showed that multiple signaling pathways are involved in LBT for AR. Molecular docking results showed that LBT binds strongly to the target proteins MMP2, MMP9, TNF, JUN, and EGFR through intermolecular forces. This study reveals for the first time the pharmacological targets and related pathways of LBT for the treatment of AR, indicating that LBT can intervene in the intrinsic molecular mechanism of AR through multiple targets and pathways.

Feature selection is an important data preprocessing approach that continues to be concerned in data mining . It has been extensively used to construct learning models and reduce storage and computing requirements. Fuzzy rough set is a useful theoretical tool for dealing with the mixed data with fuzziness and inconsistency. Hence, feature selection based on fuzzy rough sets has attracted much attention. However, most of the existing studies ignore the interaction between features, which leads to the loss of useful information. Motivated by this issue, we devise a Dynamic Interaction Feature Selection method based on Fuzzy Rough Set (DIFS_FRS). The method simultaneously considers the interactive relation between features, the relation between conditional features and decision classes, and the dynamic change of feature weights with the variation of feature subset. Firstly, the single-level dependency relevancy between features and classes is defined by the fuzzy dependency degree. Secondly, the multi-level joint interaction between features about classes is investigated. Correspondingly, the correlation evaluation index of features is constructed. Thereafter, a dynamic updating-feedback mechanism is established for a novel feature evaluation function. Finally, compared with the other six representative algorithms on eighteen data sets, the DIFS_FRS algorithm is demonstrated to have better performance.

In coexistent heterogeneous wireless networks, receivers have to process the signaling and the data following different specifications. With the aim to automatically and intelligently identify the received signal type and then recover the data, in this paper, we propose a unified intelligent channel decoder serially concatenated by a convolutional-neural-network-based classifier and a deep learning (DL)-aided decoder. The classifier mainly consists of the convolutional layer, the batch normalization layer, and the max-pooling layer, while the DL decoder is constituted by four full connection layers. At the training stage, the unified decoder is trained to learn the distinct characteristics of encoded codewords following different specifications. Then, at the deployment stage, the classifier will extract the distinct structural features and identify the coding pattern. Thus, the DL decoder could choose an appropriate set of neural network parameters for information recovery. Simulation results demonstrate that our proposed intelligent decoder achieves better reliability performances than benchmark schemes over both additive white Gaussian noise and Rayleigh fading channels.

Background As previous studies reported, gadolinium deposits in globus pallidus (GP) and dentate nucleus (DN) after repeated administrations of gadolinium-based contrast agents (GBCAs) and a signal intensity (SI) increase on T1-weighted images were related to linear GBCAs, not macrocyclic GBCAs. Purpose To identify whether quantitative susceptibility mapping (QSM) could measure a subtle increase in magnetic susceptibility in DN and GP in patients after repeated administrations of gadoteric acid meglumine (Gd-DOTA). Material and Methods In this study, 50 patients with cerebral tumors who had received at least three injections of Gd-DOTA (GBCA group) and 50 individuals without a history of GBCA injections (non-GBCA group) were included. The image data for QSM and T1-weighted images were reviewed. Spearman rank correlation was used to estimate the associations between the values (magnetic susceptibility of QSM and SI ratios of T1-weighted images) and the number of Gd-DOTA injections. Results The mean magnetic susceptibility of GP in GBCA group was 0.136 ± 0.031 ppm, which was significantly higher than that in control group (0.114 ± 0.030 ppm) ( P = 0.001). In the GBCA group (n = 50), we found a substantial positive correlation between magnetic susceptibility of GP and the number of Gd-DOTA injections according to Spearman rank correlation coefficient (ρ = 0.673, P = 0.0001). There was a modest but significant correlation between magnetic susceptibility of DN and the number of Gd-DOTA injections (ρ = 0.311, P = 0.028). Conclusion In comparison to the control group, the magnetic susceptibility of GP in the GBCA group was significantly higher and had a substantial positive association with the number of Gd-DOTA injections.

Hb variants prevalent in China are different from those in other countries. We aimed to assess the interference from Hb variants found in China on HbA1c measurement. All Hb variants were confirmed using Sanger sequencing. HbA1c was measured using a capillary electrophoresis method (Capillarys 3 OCTA), two cation-exchange high-performance liquid chromatography methods (ADAMS HA-8180V and HLC-723 G8 standard mode), an immunoassay (Cobas c501), and a boronate affinity chromatography method (Premier Hb9210). Premier Hb9210 was used as a comparative method. A total of 16 species of Hb variants were identified in 102 variant carriers. The most common variant was Hb E, followed by Hb Q-Thailand, Hb New York and Hb J-Bangkok. Clinically significant interference was observed for the Capillarys 3 OCTA (two Hb variants), ADAMS HA-8180V (seven Hb variants), HLC-723 G8 (14 Hb variants), and Cobas c501 (two Hb variants). The proportion of unacceptable HbA1c results was 13.7% for Capillarys 3 OCTA, 52.9% for HA-8180V, 83.3% for HLC-723 G8, and 3.9% for Cobas c501. Hb variants in China severely affect the accuracy of some commonly used HbA1c methods.

Post-intensive care syndrome (PICS) is the most common complication in patients discharged from intensive care unit (ICU), which seriously affects the life quality of the patients. At present, there is still lack of standardevaluation methods for PICS. Continuous and dynamic assessment can earlyidentify PICS, moreover, early identification and intervention of PICS can improve the life quality of patients those patients, which is critical to improve the long-term outcome of the patients. In this paper, we reviewed the current research states of evaluation timing, contents, tools and modalities of PICS domestic and abroad, analyzed the problems and prospects of the existing evaluation methods, aiming to provide a reference for clinical staff to effectively and comprehensively evaluate PICS.

The mammalian transcriptome comprises a vast family of long noncoding (lnc)RNAs implicated in physiologic processes such as myogenesis, through which muscle forms during embryonic development and regenerates in the adult. However, the specific molecular mechanisms by which lncRNAs regulate human myogenesis are poorly understood. Here, we identified a novel muscle-specific lncRNA, lncFAM71E1-2:2 (lncFAM), which increased robustly during early human myogenesis. Overexpression of lncFAM promoted differentiation of human myoblasts into myotubes, while silencing lncFAM suppressed this process. As lncFAM resides in the nucleus, chromatin isolation by RNA purification followed by mass spectrometry (ChIRP-MS) analysis was employed to identify the molecular mechanisms whereby it might promote myogenesis. Analysis of lncFAM-interacting proteins revealed that lncFAM recruited the RNA-binding protein HNRNPL to the promoter of MYBPC2, in turn increasing MYBPC2 mRNA transcription and enhancing production of the myogenic protein MYBPC2. These results highlight a mechanism whereby a novel ribonucleoprotein complex, lncFAM-HNRNPL, elevates MYBPC2 expression transcriptionally to promote myogenesis.

ObjectiveTo analyze the genotypes and phenotypes of mosaic male patients with PCDH19-related epilepsy (PCDH19-RE) and explore the correlation between genotype, variant allele frequency (VAF), and phenotypic severity.MethodsClinical data and peripheral blood samples of 11 male mosaic patients were collected and analyzed in our study. The VAF of the PCDH19 gene from peripheral blood was quantified using amplicon-based deep sequencing. Additional 20 mosaic male patients with PCDH19-RE were collected from the published literature, with 10 patients whose VAFs of the PCDH19 gene were available for analytic purposes.ResultsIn our cohort of 11 patients, 10 variants were identified, and four were novel. The VAF of the PCDH19 gene from peripheral blood ranged from 27 to 90%. The median seizure onset age was 6 months (range: 4–9 months). Clinical manifestations included cluster seizures (100%), fever sensitivity (73%), focal seizures (91%), developmental delay/intellectual disability (DD/ID, 82%), and autistic features (45%). Thirty-one mosaic male patients collected from our cohort and the literature developed seizures mostly (87%) within one year of age. Variant types included missense variants (42%), truncating variants (52%), splice variants (3%), and whole PCDH19 deletion (3%). Among 21 patients with a definite VAF from our cohort and the literature, nine had a low VAF ( ≤ 50%) and 12 had a high VAF (> 50%). Seventy-five percent of variants from the high VAF group were missense, whereas 89% of those from the low VAF group were truncations. The median seizure onset age was 6 months in the low VAF group and 9 months in the high VAF group (p = 0.018). Forty-four percent (4/9) of patients from the low VAF group achieved seizure-free for ≥1 year, whereas none of the 12 patients from the high VAF group did (p = 0.021). DD/ID was present in 83% (10/12) of the high VAF group and 56% (5/9) of the low VAF group (p = 0.331).ConclusionThe predominant variant types were truncating and missense variants. Missense variants tended to have higher VAFs. Patients with a high VAF were more likely to have a more severe epileptic phenotype. Our findings shed light on the phenotypic implications of VAF in mosaic males with PCDH19-RE.

This study aimed to comprehensively examine the genetic and phenotypic aspects of GABRB3-related epilepsy and to explore the potential prospects of personalized medicine. Genetic testing was conducted in all epilepsy patients without acquired factors for epilepsy. Through the collaboration of multicenter in China, we analyzed the genotype–phenotype correlation and antiepileptic therapy of 26 patients with GABRB3-related epilepsy. Thirteen GABRB3 variants were novel, and 25 were de novo. The seizure onset age ranged from 1 to 21 months (median age 3.75 months). Seizure types predominated including focal seizures (92.3%), generalized tonic–clonic seizures (23.1%), and epileptic spasms (15.4%). Clinical features included cluster seizures (80.8%), fever sensitivity (53.8%), and developmental delay (96.2%). Neuroimaging was abnormal in 10 patients, including dysplasia of the cerebral cortex, dysplasia of the frontal and temporal cortex, delayed myelination, and corpus callosum dysplasia. Eleven patients were diagnosed with developmental and epileptic encephalopathy (DEE), four with West syndrome, three with epilepsy of infancy with migrating focal seizures (EIMFS), one with epilepsy with myoclonic-atonic seizures (EMAS), one with Dravet syndrome, and one with febrile seizures plus (FS+). Seizures were controlled in 57.7% of patients by valproate, levetiracetam, or perampanel in the majority. The clinical features of GABRB3-related epilepsy included seizure onset in early infancy, cluster seizures and fever sensitivity. Most patients manifest severe epilepsy phenotypes. Valproate, levetiracetam and perampanel seem to have positive effects on seizure control for patients with GABRB3 variants.

Maternally inherited diabetes and deafness is a rare genetic disease mainly caused by a point mutation in mitochondrial deoxyribonucleic acid. Lipoprotein lipase gene mutations are associated with familial dyslipidemias, which are difficult to manage. We reported for the first time a case that had both maternally inherited diabetes and severe hyperlipidemia caused by lipoprotein lipase gene mutation (C.347(exon3)G>C) that was resistant to fenofibrate and atorvastatin. We were able to manage the patient’s hyperlipidemia with bezafibrate, and her diabetes was well controlled with insulin. In conclusion, genetic testing is helpful in identifying rare and interesting cases when clinicians suspect inheritable diseases. Additionally, when one fibrate drug is ineffective in treating hyperlipidemia, it might be worthwhile trying another fibrate.

In the field of super-resolution image reconstruction, as a learning-based method, deep plug-and-play super-resolution (DPSR) algorithm can be used to find the blur kernel by using the existing blind deblurring methods. However, DPSR is not flexible enough in processing images with high- and low-frequency information. Considering a channel attention mechanism can distinguish low-frequency information and features in low-resolution images, in this paper, we firstly introduce this mechanism and design a new residual channel attention networks (RCAN); then the RCAN is adopted to replace deep feature extraction part in DPSR to achieve the adaptive adjustment of channel characteristics. Through four test experiments based on Set5, Set14, Urban100 and BSD100 datasets, we find that, under different blur kernels and different scale factors, the average peak signal to noise ratio (PSNR) and structural similarity (SSIM) values of our proposed method increase by 0.31dB and 0.55%, respectively; under different noise levels, the average PSNR and SSIM values increase by 0.26dB and 0.51%, respectively.

Background Lycopene, one of the carotenoids, was increasingly attractive thanks to the significant nutritional and pharmaceutical value, causing the numerous demands of non-chemically synthesized lycopene. However, the insufficient lycopene production led to the high price. One potential way to ameliorate the situation was to elevate the extraction efficiency of lycopene by emerging technologies such as ultrasound-assisted extraction, microwave-assisted extraction. However, there is no comprehensive evaluation of these technologies. Therefore, this review is to comprehensively evaluate these technologies. Scope and approach The market investigations indicated the huge demands of lycopene. Rising challenges spawned many new assisted technologies to weaken the hindrances in lycopene extraction. This review mainly discussed the emerging technologies for natural lycopene extraction. In addition, the evaluation of various technologies was performed, including the influences on isomerization and degradation, economic analysis and sustainability analysis. Key findings and conclusions Hindrances of lycopene extraction from cells were illustrated. Besides, almost all the treatments could elevate the efficiency to different extents, which offered various ideas and pathways for lycopene extraction. And the summarization of advantages and disadvantages indicated the promising application potential. Many technologies could affect the isomerization and degradation of lycopene, indicating the necessity to control the extraction conditions. Statistical analysis presented comprehensive comparisons of key indicators (temperature, time, L/S and yield), and supported further evaluation. The economic analysis and sustainability analysis indicated that the cost and environmental effects varied with methods. In the future, methods with low cost, high efficiency and environment-friendly effects will be preferred.

Circular RNAs are abundant, covalently closed transcripts that arise in cells through back-splicing and display distinct expression patterns across cells and developmental stages. While their functions are largely unknown, their intrinsic stability has made them valuable biomarkers in many diseases. Here, we set out to examine circRNA patterns in amyotrophic lateral sclerosis (ALS). By RNA-sequencing analysis, we first identified circRNAs and linear RNAs that were differentially abundant in skeletal muscle biopsies from ALS compared to normal individuals. By RT-qPCR analysis, we confirmed that 8 circRNAs were significantly elevated and 10 were significantly reduced in ALS, while the linear mRNA counterparts, arising from shared precursor RNAs, generally did not change. Several of these circRNAs were also differentially abundant in motor neurons derived from human induced pluripotent stem cells (iPSCs) bearing ALS mutations, and across different disease stages in skeletal muscle from a mouse model of ALS (SOD1

To explore the phenotypic spectrum and refine the genotype-phenotype correlation of DYNC1H1-related epilepsy.The clinical data of 15 patients with epilepsy in our cohort and 50 patients with epilepsy from 24 published studies with the DYNC1H1 variants were evaluated.In our cohort, 13 variants were identified from 15 patients (seven males, eight females). Twelve variants were de novo and seven were new. Age at seizure onset ranged from 3 months to 4 years 5 months (median age 1 year). Common seizure types were epileptic spasms, focal seizures, tonic seizures, and myoclonic seizures. Mild-to-severe developmental delay was present in all patients. Six patients were diagnosed with West syndrome and one was diagnosed with epileptic encephalopathy with continuous spikes and waves during slow sleep (CSWS). Collectively, in our cohort and published studies, 17% had ophthalmic diseases, 31% of variants were located in the stalk domain, and 92% patients with epilepsy had a malformation of cortical development (MCD).The phenotypes of DYNC1H1-related epilepsy included multiple seizure types; the most common epileptic syndrome was West syndrome. CSWS is a new phenotype of DYNC1H1-related epilepsy. One-third of the variants in patients with epilepsy were located in the stalk domain. Most patients had a MCD and developmental delay.

Variations of blood pressure (BP) related to air temperature have been reported previously; however, no evidence is available regarding the association of hourly ambient temperature with ambulatory blood pressure.We conducted a longitudinal panel study among 1895 patients from an outpatient department who received repeated ambulatory blood pressure monitoring in Urumqi, China between July 2020 and December 2021. We obtained hourly ambient temperature from the nearest monitoring station to the residential address, and measured 4 ambulatory blood pressure indicators. Linear mixed-effect model combined with distributed lag models were applied to investigate the cumulative associations of hourly temperature with BP.A total of 97,466 valid blood pressure measurements were evaluated. We observed almost linear and monotonically decreasing relationships between temperature and blood pressure. The effects occurred in the same hour, attenuated thereafter and became insignificant approximately 36 h. A 10 °C decrease in temperature was significantly associated with increments of 0.84 mmHg in systolic blood pressure, 0.56 mmHg in diastolic blood pressure, 1.38 mmHg in mean arterial pressure, and 0.66 mmHg in pulse pressure over lag 0 to 36 h. Stronger associations were found among patients of female sex, age between 18 and 65 years, overweight or obesity, minority, less education or in the cold season, as well as those without hypertension or with coronary heart disease, or did not take anti-hypertension medication.Our study provides robust evidence that hourly ambient temperature is inversely associated with ambulatory blood pressure. It also highlights a linear relationship between decreased ambient temperature and elevated BP, which may have implications for the prevention and management of hypertension in susceptible populations.