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Abstract The RNA modification, 5‐methylcytosine (m5C), has recently gained prominence as a pivotal post‐transcriptional regulator of gene expression, intricately intertwined with various tumorigenic processes. However, the exact mechanisms governing m5C modifications during the onset and progression of colorectal cancer (CRC) remain unclear. Here, it is determined that the m5C methyltransferase NSUN2 exhibits significantly elevated expression and exerts an oncogenic function in CRC. Mechanistically, NSUN2 and YBX1 are identified as the “writer” and “reader” of ENO1, culminating in the reprogramming of the glucose metabolism and increased production of lactic acid in an m5C‐dependent manner. The accumulation of lactic acid derived from CRC cells, in turn, activates the transcription of NSUN2 through histone H3K18 lactylation (H3K18la), and induces the lactylation of NSUN2 at the Lys356 residue (K356), which is crucial for capturing target RNAs. Together, these findings reveal an intriguing positive feedback loop involving the NSUN2/YBX1/m5C‐ENO1 signaling axis, thereby bridging the connection between metabolic reprogramming and epigenetic remodeling, which may shed light on the therapeutic potential of combining an NSUN2 inhibitor with immunotherapy for CRC.

Abstract Background Tumors that resist anoikis, a programmed cell death triggered by detachment from the extracellular matrix, promote metastasis; however, the role of anoikis‐related genes (ARGs) in colorectal cancer (CRC) stratification, prognosis, and biological functions remains unclear. Methods We obtained transcriptomic profiles of CRC and 27 ARGs from The Cancer Genome Atlas, the Gene Expression Omnibus, and MSigDB databases, respectively. CRC tissue samples were classified into two clusters based on the expression pattern of ARGs, and their functional differences were explored. Hub genes were screened using weighted gene co‐expression network analysis, univariate analysis, and least absolute selection and shrinkage operator analysis, and validated in cell lines, tissues, or the Human Protein Atlas database. We constructed an ARG‐risk model and nomogram to predict prognosis in patients with CRC, which was validated using an external cohort. Multifaceted landscapes, including stemness, tumor microenvironment (TME), immune landscape, and drug sensitivity, between high‐ and low‐risk groups were examined. Results Patients with CRC were divided into C1 and C2 clusters. Cluster C1 exhibited higher TME scores, whereas cluster C2 had favorable outcomes and a higher stemness index. Eight upregulated hub ARGs (TIMP1, P3H1, SPP1, HAMP, IFI30, ADAM8, ITGAX, and APOC1) were utilized to construct the risk model. The qRT‐PCR, Western blotting, and immunohistochemistry results were consistent with those of the bioinformatics analysis. Patients with high risk exhibited worse overall survival (p

Abstract Cancer immunotherapy is arguably the most rapidly advancing realm of cancer treatment. Glutathione peroxidase 4 (GPX4) has emerged as the vital enzyme to prevent lipid peroxidation and maintain cellular redox homeostasis. However, the mechanism of GPX4 in the regulation of cancer immunotherapy of colon adenocarcinoma (COAD) are incompletely understood. In pan-cancer analysis, we found that GPX4 showed remarkably upregulated expression and exhibited significant association with overall survival in multiple cancer types, especially COAD. Furthermore, upregulated GPX4 expression was positively correlated with increased immune cells infiltration and enhanced expression of immunomodulators. Mechanistically, RBM15B- and IGFBP2-mediated N6-methyladenosine (m6A) modification and NSUN5-mediated 5-methylcytosine (m5C) modification of GPX4 facilitated anticancer immunity via activation of cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (STING) signaling by maintaining redox homeostasis in COAD. The risk model and nomogram model constructed based on the GPX4-derived genes further confirmed the prognostic and treatment-guiding value of GPX4. In all, our study demonstrated that m6A and m5C modification of GPX4 may be a promising target for cancer immunotherapy via activating the cGAS-STING signaling pathway in COAD.

Abstract Colorectal cancer (CRC) is one of the most common malignant cancers worldwide and seriously threatens human health. The clustered regulatory interspaced short palindromic repeat/CRISPR-associate nuclease 9 (CRISPR/Cas9) system is an adaptive immune system of bacteria or archaea. Since its introduction, research into various aspects of treatment approaches for CRC has been accelerated, including investigation of the oncogenes, tumor suppressor genes (TSGs), drug resistance genes, target genes, mouse model construction, and especially in genome-wide library screening. Furthermore, the CRISPR/Cas9 system can be utilized for gene therapy for CRC, specifically involving in the molecular targeted drug delivery or targeted knockout in vivo. In this review, we elucidate the mechanism of the CRISPR/Cas9 system and its comprehensive applications in CRC. Additionally, we discussed the issue of off-target effects associated with CRISPR/Cas9, which serves to restrict its practical application. Future research on CRC should in-depth and systematically utilize the CRISPR/Cas9 system thereby achieving clinical practice.

Abstract Real-time quantitative polymerase chain reaction (RT-qPCR) is the most common method to determine mRNA expression, and Minimum Information for Publication of RT-qPCR Experiments (MIQE) proposes that a panel of reference genes for RT-qPCR is conducive to obtaining accurate results. This study aimed to screen and verify the optimal panel of reference genes in colorectal cancer (CRC) and normal colonic cell lines. In the study, eight candidate reference genes (GAPDH, ACTB, 18S, PPIA, B2M, SDHA, GUSB, and YWHAZ) were selected for RT-qPCR to detect their expression in NCM460, HT29, HCT116, SW480, SW620, DLD-1, LOVO and RKO cell lines. The stability of reference genes and the optimal panel were evaluated by geNorm, NormFinder, and BestKeeper software. As results, the expression levels of candidate reference genes differed in the colonic epithelial cell lines, and the number of optimal panel of reference genes is two. B2M and YWHAZ were the two most stable reference genes for NCM460, HCT116, SW620, LOVO, and RKO cell lines, while only one of B2M and YWHAZ was most stable in HT29 and SW480 cells. In DLD-1 cells, the stability of B2M and YWHAZ ranked 3rd and 6th, PPIA and GUSB were the most stable two. Furthermore, the YWHZA + B2M performed smaller intragroup differences than other panel or single reference gene. In conclusion, this study indicates the optimal panel of reference genes is YWHZA + B2M for the NCM460, HCT116, SW620, LOVO, RKO, SW480, and HT29 cell lines, but it is PPIA + GUSB in DLD-1 cell lines.

Recent efforts for increasing the success in drug discovery focus on an early, massive, and routine mechanistic and/or kinetic characterization of drug-target engagement as part of a design-make-test-analyze strategy. From an experimental perspective, many mechanistic assays can be translated into a scalable format on automation platforms and thereby enable routine characterization of hundreds or thousands of compounds.However, now the limiting factor to achieve such in-depth characterization at high-throughput becomes the quality-driven data analysis, the sheer scale of which outweighs the time available to the scientific staff of most labs. Therefore, automated analytical workflows are needed to enable such experimental scale-up. We have implemented such a fully automated workflow in Genedata Screener for time-dependent ligand-target binding analysis to characterize non-equilibrium inhibitors. The workflow automates Quality Control (QC) / data modelling and decision-making process in a staged analysis: (1) quality control of raw input data—fluorescence signal-based progress curves — featuring automated rejection of unsuitable measurements; (2) automated model selection — one-step versus two-step binding model — using statistical methods and biological validity rules; (3) result visualization in specific plots and annotated result tables, enabling the scientist to review large result sets efficiently and, at the same time, to rapidly identify and focus on interesting or unusual results; (4) an interactive user interface for immediate adjustment of automated decisions, where necessary.Applying this workflow to first-pass, high-throughput kinetic studies on kinase projects has allowed us to surmount previously rate-limiting manual analysis steps and boost productivity; and is now routinely embedded in a biopharma discovery research process.

Abstract Circular RNAs (circRNAs) are a recently discovered kind of regulatory RNAs that have emerged as critical biomarkers of various types of cancers. Metabolic reprogramming has gradually been identified as a distinct hallmark of cancer cells. The pentose phosphate pathway (PPP) plays an indispensable role in satisfying the bioenergetic and biosynthetic demands of cancer cells. However, little is known about the role of circRNAs and PPP in colorectal cancer (CRC). The novel circ_0003215 was identified at low levels in CRC and was negatively correlated with larger tumor size, higher TNM stage, and lymph node metastasis. The decreased level of circ_0003215 was resulted from the RNA degradation by m6A writer protein YTHDF2. A series of functional assays demonstrated that circ_0003215 inhibited cell proliferation, migration, invasion, and CRC tumor metastasis in vivo and in vitro. Moreover, circ_0003215 regulated the expression of DLG4 via sponging miR-663b, thereby inducing the metabolic reprogramming in CRC. Mechanismly, DLG4 inhibited the PPP through the K48-linked ubiquitination of glucose-6-phosphate dehydrogenase (G6PD). Taken together, we have identified m6A-modified circ_0003215 as a novel regulator of metabolic glucose reprogramming that inhibited the PPP and the malignant phenotype of CRC via the miR-663b/DLG4/G6PD axis.

Background It is well-established that serum testosterone in men decreases with age, yet the underlying mechanism of this change remains elusive. Methods The expression patterns of Fancd2 opposite-strand (Fancd2os) in BALB/c male mice and testicular tissue derived cell lines (GC-1, GC-2, TM3, and TM4) were assessed using real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence. The Fancd2os-overexpressing or knockdown TM3 cells were constructed by infecting them with lentivirus particles and were used to evaluated the function of Fancd2os. The testosterone production was measured using enzyme linked immunosorbent assay (ELISA) and the steroidogenic enzymes such as steroidogenic acute regulatory protein (StAR), P450 cholesterol side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) were analysed using RT-PCR. The apoptosis of TM3 cells induced by ultraviolet light or testicular tissues was detected using flow cytometry, Western blot or dUTP-biotin nick end labeling (TUNEL) assays. Pearson correlation analysis was used to assess the correlation between the Fancd2os expression and TUNEL-positive staining in mouse testicular Leydig cells. Results The Fancd2os protein was predominantly expressed in mouse testicular Leydig cells and its expression increased with age. Fancd2os overexpression inhibited testosterone levels in TM3 Leydig cells, whereas knockdown of Fancd2os elevated testosterone production. Fancd2os overexpression downregulated the levels of StAR, P450scc and 3β-HSD, while Fancd2os knockdown reversed this effect. Fancd2os overexpression promoted ultraviolet light-induced apoptosis of TM3 cells. In contrast, Fancd2os knockdown restrained apoptosis in TM3 cells. In vivo assays revealed that higher Fancd2os levels and mouse age were associated with increased apoptosis in Leydig cells and decreased serum testosterone levels. Pearson correlation analysis exhibited a strong positive correlation between the expression of Fancd2os and TUNEL-positive staining in mouse testicular Leydig cells. Conclusion Our findings suggest that Fancd2os regulates testosterone synthesis via both steroidogenic enzymes and the apoptotic pathway.

Colorectal cancer (CRC) is a common malignancy worldwide, and the gut microbiota and metabolites play an important role in its initiation and progression. In this study, we constructed a mouse model of inflammation-induced colorectal tumors, with fixed doses of azoxymethane/dextran sulfate sodium (AOM/DSS). We found that colorectal tumors only formed in some mice treated with certain concentrations of AOM/DSS (tumor group), whereas other mice did not develop tumors (non-tumor group). 16S rDNA amplicon sequencing and liquid chromatography-mass spectrometry (LC-MS)/MS analyses were performed to investigate the microbes and metabolites in the fecal samples. As a result, 1189 operational taxonomic units (OTUs) were obtained from the fecal samples, and the non-tumor group had a relatively higher OTU richness and diversity. Moreover, 53 different microbes were identified at the phylum and genus levels, including Proteobacteria, Cyanobacteria, and Prevotella. Furthermore, four bacterial taxa were obviously enriched in the non-tumor group, according to linear discriminant analysis scores (log10) > 4. The untargeted metabolomics analysis revealed significant differences between the fecal samples and metabolic phenotypes. Further, the heatmaps and volcano plots revealed 53 and 19 dysregulated metabolites between the groups, in positive and negative ion modes, respectively. Styrene degradation and amino sugar-nucleotide sugar metabolism pathways were significantly different in positive and negative ion modes, respectively. Moreover, a correlation analysis between the metabolome and microbiome was further conducted, which revealed the key microbiota and metabolites. In conclusion, we successfully established a tumor model using a certain dose of AOM/DSS and identified the differential intestinal microbiota and characteristic metabolites that might modulate tumorigenesis, thereby providing new concepts for the prevention and treatment of CRC.

BackgroundThe RNA modification 5-methylcytosine (m5C) is one of the most prevalent post-transcriptional modifications, with increasing evidence demonstrating its extensive involvement in the tumorigenesis and progression of various cancers. Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related deaths worldwide. However, the role of m5C modulators in shaping tumor microenvironment (TME) heterogeneity and regulating immune cell infiltration in CRC requires further clarification.ResultsThe transcriptomic sequencing data of 18 m5C regulators and clinical data of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) and systematically evaluated. We found that 16 m5C regulators were differentially expressed between CRC and normal tissues. Unsupervised cluster analysis was then performed and revealed two distinct m5C modification patterns that yielded different clinical prognoses and biological functions in CRC. We demonstrated that the m5C score constructed from eight m5C-related genes showed excellent prognostic performance, with a subsequent independent analysis confirming its predictive ability in the CRC cohort. Then we developed a nomogram containing five clinical risk factors and the m5C risk score and found that the m5C score exhibited high prognostic prediction accuracy and favorable clinical applicability. Moreover, the CRC patients with low m5C score were characterized by “hot” TME exhibiting increased immune cell infiltration and higher immune checkpoint expression. These characteristics were highlighted as potential identifiers of suitable candidates for anticancer immunotherapy. Although the high m5C score represented the non-inflammatory phenotype, the CRC patients in this group exhibited high level of sensitivity to molecular-targeted therapy.ConclusionOur comprehensive analysis indicated that the novel m5C clusters and scoring system accurately reflected the distinct prognostic signature, clinicopathological characteristics, immunological phenotypes, and stratifying therapeutic opportunities of CRC. Our findings, therefore, offer valuable insights into factors that may be targeted in the development of precision medicine-based therapeutic strategies for CRC.

Effective and efficient provision and reuse of knowledge across a knowledge network in the global value chain still faces two challenges, namely the interpretability of model and the efficacy of construction. This research aims to address these challenges by proposing a novel representation model for design knowledge. First, a knowledge representation model based on the integration of the cognitive process theory and the Requirement-Function-Behavior-Structure model (C-RFBS model) is proposed to incorporate key elements from the cognitive process of designers to capture the rationale of deliberation and the context of decision-making, which the knowledge records created become more interpretable. Second, knowledge graph is employed to improve the productivity of knowledge records creation, storage and exploration. On this basis, we describe the creation of knowledge records using the C-RFBS model as well as the computational framework and methods for storing knowledge using knowledge graph. The proposed model and methods are implemented in a knowledge retrieval system on which we have conducted a fork design case study to evaluate and demonstrate the models and methods. As shown in the evaluation, the proposed model can effectively support knowledge elicitation and achieved improved performance in terms of knowledge retrieval through incorporating knowledge graph.

Abstract General plasmonic systems to realize plasmonically induced transparency (PIT) effect only exist one single PIT mainly because they only allow one single coupling pathway. In this study, we propose a distinct graphene resonator-based system, which is composed of graphene nanoribbons (GNRs) coupled with dielectric grating-loaded graphene layer resonators, to achieve two switchable PIT effects. By designing crossed directions of the resonators, the proposed system exists two different PIT effects characterized by different resonant positions and linewidths. These two PIT effects result from two separate and polarization-selective coupling pathways, allowing us to switch the PIT from one to the other by simply changing the polarization direction. Parametric studies are carried to demonstrate the coupling effects whereas the two-particle model is applied to explain the physical mechanism, finding excellent agreements between the numerical and theoretical results. Our proposal can be used to design switchable PIT-based plasmonic devices, such as tunable dual-band sensors and perfect absorbers.

Abstract A suspended monolayer graphene has only about 2.3% absorption rate in visible and infrared band, which limits its optoelectronic applications. To significantly increase graphene’s absorption efficiency, a tunable dual-band and polarization-insensitive coherent perfect absorber (CPA) is proposed in the mid-infrared regime, which contains the silicon array coupled in double-layers graphene waveguide. Based on the FDTD methods, dual-band perfect absorption peaks are achieved in 9611 nm and 9924 nm, respectively. Moreover, due to its center symmetric feature, the proposed absorber also demonstrates polarization-insensitive. Meanwhile, the coherent absorption peaks can be all-optically modulated by altering the relative phase between two reverse incident lights. Furthermore, by manipulating the Fermi energies of two graphene layers, two coherent absorption peaks can move over a wide spectrum range, and our designed CPA can also be changed from dual-band CPA to narrowband CPA. Thus, our results can find some potential applications in the field of developing nanophotonic devices with excellent performance working at the mid-infrared regime.

In this paper, we combine the dielectric metasurface with monolayer graphene to realize a high quality(Q)-factor quasi-BIC-based optical modulator, and the corresponding modulation performances are investigated by using the finite-difference time-domain (FDTD) method, which can be well fitting by the Fano formula based on the temporal couple-mode theory. The results demonstrate that bound states in the continuum (BIC) will turn into the quasi-BIC with high Q-factor by breaking the symmetry of every unit of the metasurface. Meanwhile, the amplitude and bandwidth of transmission based on the quasi-BIC mode can be efficiently adjusted by changing the Fermi energy (EF) of monolayer graphene, and the maximum difference in transmission up to 0.92 is achieved. Moreover, we also discuss the influence of the asymmetry degree to further investigate the modulation effect of graphene on the quasi-BIC mode.

Abstract The constructive interference of bright and dark plasmonic modes results in plasmon-induced absorption (PIA) effect. Here, we theoretically investigate PIA effect, which is realized by the constructive interference between a Fabry-Perot (F-P) resonance mode and a graphene quasi-guided mode. Numerical simulation reveals at least three advantages of our structure over previous ones. First, the extinction ratio can reach ~ 99.999%, resulting in the ultra-high figure of merit* (FOM*) as high as 106. Second, the intensity of this pronounced PIA effect can be optimized by adjusting the coupling distance. Third, the resonance frequency can be easily tunable by tuning the graphene Fermi level. This system may have potential applications in dynamically optical switching and biochemical sensing.

Objective To summarize the causes, treatment and prognosis of severe epistaxis after transnasal endoscopic skull base surgery. Methods and Results There were 12 patients with delayed severe epistaxis after transnasal endoscopic skull base surgery from February 2007 to January 2018. Surgical methods included endoscopic electrocoagulation hemostasis in 7 cases (7/12), DSA-assisted endoscopic electrocoagulation hemostasis in one case (1/12), DSA-assisted superselective arterial embolization in 3 cases (3/12), and DSA-assisted superselective arterial embolization combined with endoscopic electrocoagulation hemostasis in one case (1/12). Successful hemostasis occurred in 11 cases, and one case died. Patients were followed up for (17.21 ± 3.42) months without epistaxis recurrence. Conclusions Epistaxis mainly occurs over 7 to 14 d after transnasal endoscopic skull base surgery. The choice of operation methods is related to the location of bleeding and responsible artery. Endoscopic electrocoagulation hemostasis is an effective method without serious complications. Patients with internal carotid artery (ICA) pseudoaneurysms can be cured by endoscopic electrocoagulation hemostasis plus arterial embolization. DOI: 10.3969/j.issn.1672-6731.2019.04.009

Abstract A subwavelength terahertz plasmonic waveguide based on bulk Dirac semimetal (BDS)-insulator-metal (BIM) structure is investigated, which indicates that there is an optimized frequency range with the better confinement as well as lower loss. A broadband mode confinement up to λ 0/15 with a relatively low loss of 1.0 dB/λ 0 can be achieved. We also show that two silicon ribbons introduced into the BIM waveguide can form a dynamically tunable filter tailoring terahertz surface plasmon polaritons in deep-subwavelength scale, which can be further exploited for the design of ultra-compact THz plasmonic devices with dynamical tunability. Our results may also provide potential applications in optical filtering.

A broadband and polarization-insensitive optical absorber based on van der Waals (vdW) material h-BN is proposed in the mid-infrared regime. By utilizing the finite-difference time-domain (FDTD) simulation, the broadband absorption spectrum above 95% is achieved from 6490 to 7295 nm. Moreover, the proposed structure can maintain the excellent performance and broadband absorption in a wide range of incident angles. To illustrate the physical mechanism of proposed absorber, we investigate the magnetic field distributions in the each h-BN structural unit at different wavelengths, and comprehend it with the dispersion relation. Thus, we believe that our research can find some important applications for thermal emitters and photovoltaic devices with outstanding properties working at mid-infrared regime. Keyword: vdW material, Absorption, Mid-infrared regime

In this paper, we present an easy-to-implement metamaterial absorber based on bulk Dirac semimetal (BDS). The proposed device not only obtains an ultrahigh quality factor (Q-factor) of 4133 and dynamic adjustability at high absorption, but also exhibits an excellent sensing performance with a figure of merit (FOM) of 4125. These outstanding properties are explained by the surface lattice resonance, which allows us to improve the quality factor significantly and control resonance wavelength precisely by tuning the unit cell periods, Fermi energy of the BDS, and structural parameters. Our findings can provide high-performance applications in terahertz filtering, detection, and biochemical sensing.

Abstract We demonstrate the existence of Fano resonance spectral response in a system of nanoscale plasmonic resonant ring stacked by means of a half nanoring. Our proposed scheme exploits the stacked method under normal incidence to excite the subradiant mode. The nanostructure, which utilizes the combination of Fano resonance and polarization-resolved, has a new rotation mode and high tunability, providing a dynamic control of plasmonic spectral response. High-quality resonant line shapes corresponding to the different order modes of Fano structures are readily achieved at near-infrared wavelengths, which is a benefit to the application for nanosensor in highly integrated circuits.

Objective To investigate the imaging characteristics and nasal endoscopic repair surgery for delayed postoperative cerebrospinal fluid (CSF) rhinorrhea in patients with pituitary tumor. Methods From June 2009 to November 2014 there were 23 cases with delayed CSF rhinorrhea in our hospital, which occurred one year to 5 years after the operation for pituitary tumor. Pituitary hormone assay, head MRI, cisternal CT and nasal endoscopic examination were performed in all patients. After definite diagnosis the patients underwent nasal endoscopic repair surgery of CSF rhinorrhea. During the operation, large leakage orifices were packed with muscle, and then patched with xenogenic acellular dermal matrix, while the small ones were directly patched with xenogenic acellular dermal matrix after tumor resection, and the sphenoid sinus was packed with gelatin sponge and iodoform gauze. Results Patients were hospitalized for 3 to 5 weeks. Among them, 20 patients were successfully recured after one nasal endoscopic repair surgery, 2 underwent the second surgery, and one underwent the third surgery. Patients were followed up for 3 months to 5 years with no CSF rhinorrhea reoccurred. Conclusions Delayed postoperative CSF rhinorrhea in patients with pituitary tumor were likely due to residual tumor growth and postoperative radiotherapy. Pituitary tumor often occur in sella, thus nasal endoscopic resection and repair surgery is feasible in treatment. The surgery is safe and the success rate is high. DOI: 10.3969/j.issn.1672-6731.2017.09.012

A plasmon-induced transparency (PIT) spectral response in an ultracompact plasmonic structure composed of a metal–insulator–metal waveguide Bragg grating coupled with an air rectangle cavity is proposed, and the corresponding transmission characteristics are investigated theoretically and numerically. By using the transmission line theory (TLT), a remarkable PIT transmission can be proposed in this structure. Moreover, we study the transmission as a function of the coupling distance between the air cavity and insulator layer, and we also discuss the transmission as a function of the thickness of air cavity. To validate the correctness of the TLT results, we have compared them with the finite-difference time-domain method. Both of them agree well with each other. Thus, our results can offer a new possibility and important theory analysis for the designs of the optical switching devices, sensors, and slow light devices in highly integrated optical circuits.

An amendment to this paper has been published and can be accessed via the original article.

Metamaterial-based perfect absorbers have attracted considerable attention due to their potential for practical applications. The existing absorbers, however, are mostly polarization insensitive or only sensitive to one direction, which is inapplicable in some areas. Polarization tunable or high absorption in two orthogonal directions is very useful and necessary. Herein, we present a polarization tunable absorber formed by an asymmetric patch and a dielectric layer on top of a metallic board. With this structure, the frequency of the absorber can be tuned by merely changing the polarization of the incident. The tunable mechanism originates from the different length of the patch along the two orthogonal directions. The concept is rather general and applicable to various absorbers, as long as the asymmetric design is valid. The absorber can find practical applications in manipulation of the polarization of the light and detecting waves with specific polarization.

From June 2005 to October 2012, there were 135 cases with cerebrospinal fluid (CSF) rhinorrhea admitted in our hospital who underwent nasal endoscopic repair surgery, and intracranial infection happened in 3 cases after surgery, including intracranial mucormycosis in one case, brain abscess in one case and bacterial infection in one case. These 3 cases underwent surgery to clear up the focus of infection, supplemented by antifungal drugs or antibiotic therapy. Case 1 and Case 2 were followed up for 2 years without CSF rhinorrhea or intracranial infection; Case 3 died due to multiple organ failure. The intracranial complications after nasal endoscopic surgery for repairing CSF leakage are rare and need combined treatment of relevant departments. doi: 10.3969/j.issn.1672-6731.2014.08.016

Objective To explore the surgical management of second tracheotomy. Methods Retrospective analysis of 32 cases with recurrent cerebrovascular disease or pulmonary infection who under⁃went second tracheotomy in our hospital from 2008 to 2010. Results These 32 cases were operated successfully without complication. Among these cases, 6 patients occurred hemorrhage after operation and the hemostatic effect was good. Conclusion Second tracheotomy is difficult. It depends on the first tracheotomy condition and the trachea exposure to decide the operation mode and incision position. DOI：10.3969/j.issn.1672⁃6731.2012.01.017

Background The ZFHX3 gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between ZFHX3 variants and epilepsy. Methods Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A Drosophila Zfh2 knockdown model was used to validate the association between ZFHX3 and epilepsy. Results Compound heterozygous ZFHX3 variants were identified in eight unrelated cases. The burden of ZFHX3 variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In Zfh2 knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The Zfh2 knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that ZFHX3 orthologous were highly expressed in the embryonic stage and decreased dramatically after birth. Conclusion ZFHX3 is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness. [ABSTRACT FROM AUTHOR]

Purpose: To identify novel genetic causes of febrile seizures (FS) and epilepsy with febrile seizures plus (EFSC). Methods: We performed whole-exome sequencing in a cohort of 32 families, in which at least two individuals were affected by FS or EFSC. The probands, their parents, and available family members were recruited to ascertain whether the genetic variants were co-segregation. Genes with repetitively identified variants with segregations were selected for further studies to define the gene-disease association. Results: We identified two heterozygous ATP6V0C mutations (c.64G > A/p.Ala22Thr and c.361_373del/p.Thr121Profs_7) in two unrelated families with six individuals affected by FS or EFSC. The missense mutation was located in the proteolipid c-ring that cooperated with a-subunit forming the hemichannel for proton transferring. It also affected the hydrogen bonds with surround residues and the protein stability, implying a damaging effect. The frameshift mutation resulted in a loss of function by yielding a premature termination of 28 residues at the C-terminus of the protein. The frequencies of ATP6V0C mutations identified in this cohort were significantly higher than that in the control populations. All the six affected individuals suffered from their first FS at the age of 7-8 months. The two probands later manifested afebrile seizures including myoclonic seizures that responded well to lamotrigine. They all displayed favorable outcomes without intellectual or developmental abnormalities, although afebrile seizures or frequent seizures occurred. Conclusion: This study suggests that ATP6V0C is potentially a candidate pathogenic gene of FS and EFSC. Screening for ATP6V0C mutations would help differentiating patients with Dravet syndrome caused by SCN1A mutations, which presented similar clinical manifestation but different responses to antiepileptic treatment. [ABSTRACT FROM AUTHOR]

Background: The DLG3 gene encodes disks large membrane-associated guanylate kinase scaffold protein 3, which plays essential roles in the clustering of N-methyl-D-aspartate receptors (NMDARs) at excitatory synapses. Previously, DLG3 has been identified as the causative gene of X-linked intellectual developmental disorder--90 (XLID-90; OMIM# 300850). This study aims to explore the phenotypic spectrum of DLG3 and the genotype-phenotype correlation. Methods: Trios-based whole-exome sequencing was performed in patients with epilepsy of unknown causes. To analyze the genotype-phenotype correlations, previously reported DLG3 variants were systematically reviewed. Results: DLG3 variants were identified in seven unrelated cases with epilepsy. These variants had no hemizygous frequencies in controls. All variants were predicted to be damaging by silico tools and alter the hydrogen bonds with surrounding residues and/or protein stability. Four cases mainly presented with generalized seizures, including generalized tonic-clonic and myoclonic seizures, and the other three cases exhibited secondary generalized tonic-clonic seizures and focal seizures. Multifocal discharges were recorded in all cases during electroencephalography monitoring, including the four cases with generalized discharges initially but multifocal discharges after drug treating. Protein-protein interaction network analysis revealed that DLG3 interacts with 52 genes with high confidence, in which the majority of disease-causing genes were associated with a wide spectrum of neurodevelopmental disorder (NDD) and epilepsy. Three patients with variants locating outside functional domains all achieved seizure-free, while the four patients with variants locating in functional domains presented poor control of seizures. Analysis of previously reported cases revealed that patients with non-null variants presented higher percentages of epilepsy than those with null variants, suggesting a genotypephenotype correlation. Significance: This study suggested that DLG3 variants were associated with epilepsy with/without NDD, expanding the phenotypic spectrum of DLG3. The observed genotype-phenotype correlation potentially contributes to the understanding of the underlying mechanisms driving phenotypic variation. [ABSTRACT FROM AUTHOR]

Using measurement of overnight returns, this article documents that trading behaviors due to information shocks and investor sentiments contribute to distress anomaly. We find that stocks with the highest (lowest) overnight returns are accompanied with the greatest (smallest) distress risk premium, and accordingly, a conditional distress probability portfolio composed with double sort of overnight returns and distress probability would yield significant profitability. The regression outcomes demonstrate that probability of default significantly interacts with average overnight returns in explaining the future stock returns. The conventional distress anomaly is subsumed by the conditional distress factor, but not vice versa; and only profits of conventional distress-probability portfolios, not of the conditional portfolios, mainly come from stocks with characteristics that are associated with stock mispricing. The empirical results indicate that investors hold distressed stocks longer than expected because positive information shocks occur with high level of information supply and good information quality. [ABSTRACT FROM AUTHOR]