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Abstract. Background:. Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully understood. Methods:. We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells. In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin. Results:. Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxia-telangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin sensitivity. Conclusion:. In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.

Abstract Optical information transmission is vital in modern optics and photonics due to its concurrent and multi-dimensional nature, leading to tremendous applications such as optical microscopy, holography, and optical sensing. Conventional optical information transmission technologies suffer from bulky optical setup and information loss/crosstalk when meeting scatterers or obstacles in the light path. Here, we theoretically propose and experimentally realize the simultaneous manipulation of the coherence lengths and coherence structures of the light beams with the disordered metasurfaces. The ultra-robust optical information transmission and self-reconstruction can be realized by the generated partially coherent beam with modulated coherence structure even 93% of light is recklessly obstructed during light transmission, which brings new light to robust optical information transmission with a single metasurface. Our method provides a generic principle for the generalized coherence manipulation on the photonic platform and displays a variety of functionalities advancing capabilities in optical information transmission such as meta-holography and imaging in disordered and perturbative media.

Abstract Motivated by unique topological semimetals in condensed matter physics, we propose an effective Hamiltonian with four degrees of freedom to describe evolutions of photonic double Weyl nodal line semimetals in one-dimensional hyper-crystals, which supports the energy bands translating or rotating independently in the form of Weyl quasiparticles. Especially, owing to the unit cells without inversion symmetry, a pair of reflection-phase singularities carrying opposite topological charges emerge near each nodal line, and result in a unique bilateral drumhead surface state. After reducing radiation leakages and absorption losses, these two singularities gather together gradually, and form a quasi-bound state in the continuum (quasi-BIC) ring at the nodal line ultimately. Our work not only reports the first realization of controllable photonics Weyl nodal line semimetals, establishes a bridge between two independent topological concepts−BICs and Weyl semimetals, but also heralds new possibilities for unconventional device applications, such as dual-mode schemes for highly sensitive sensing and switching.

Abstract Background Circular RNAs (circRNAs) have been proved to play crucial roles in the development of various cancers. However, the molecular mechanism of circGLIS3 involved in gastric cancer (GC) tumorigenesis has not been elucidated. Methods The higher expression level of circGLIS3 was identified in GC through RNA sequencing and subsequent tissue verification using Quantitative real-time PCR (qRT-PCR). A series of functional experiments in vitro and in vivo were performed to evaluated the effects of circGLIS3 on tumor growth and metastasis in GC. The interaction and regulation of circGLIS3/miR-1343-3p/PGK1 axis was confirmed by RNA pulldown, western blot, and rescue experiments. RIP and western blot were performed to demonstrate the role of circGLIS3 in regulating phosphorylation of VIMENTIN. We then used qRT-PCR and co culture system to trace circGLIS3 transmission via exosomal communication and identify the effect of exosomal circGLIS3 on gastric cancer and macrophages. Finally, RIP experiments were used to determine that EIF4A3 regulates circGLIS3 expression. Results CircGLIS3(hsa_circ_0002874) was significantly upregulated in GC tissues and high circGLIS3 expression was associated with advanced TNM stage and lymph node metastasis in GC patients. We discovered that overexpression of circGLIS3 promoted GC cell proliferation, migration, invasion in vitro and in vivo, while suppression of circGLIS3 exhibited the opposite effect. Mechanistically, circGLIS3 could sponge miR-1343-3p and up-regulate the expression of PGK1 to promote GC tumorigenesis. We also found that circGLIS3 reduced the phosphorylation of VIMENTIN at ser 83 site by binding with VIMENTIN. Moreover, it was proven that exosomal circGLIS3 could promote gastric cancer metastasis and the M2 type polarization of macrophages. In the final step, the mechanism of EIF4A3 regulating the generation of circGLIS3 was determined. Conclusion Our findings demonstrate that circGLIS3 promotes GC progression through sponging miR-1343-3p and regulating VIMENTIN phosphorylation. CircGLIS3 is a potential therapeutic target for GC patients.

Abstract Objectives To summarize the clinical features of epilepsy related to DEPDC5, NPRL2, and NPRL3 genes encoding the GATOR1 complex in children and to evaluate the factors affecting the prognosis of these epilepsies. Methods In this retrospective study, we reviewed the clinical and genetic characteristics of children with epilepsy related to GATOR1 variants who were admitted to the Peking University First Hospital between January 2016 and December 2021. Potential prognostic factors were assessed by comparing children with and without ongoing seizures. Results Fifty probands, including 31 boys and 19 girls were recruited. The median age at onset of epilepsy was 4 months, and 64% of patients had early‐onset epilepsy (≤1 year). The most frequent epileptic seizure type was focal seizure (86%). Among the 50 patients, only six were with de novo variants. According to the novel classification framework for GATOR1 variants, 36 patients were with pathogenic variants and 14 with likely pathogenic variants. DEPDC5 variants were found in 37 patients, NPRL3 in 9, and NPRL2 in 4. The phenotype was similar among the probands, with variants in DEPDC5, NRPL2, or NPRL3. 76% (38/50) of epilepsy related to GATOR1 variants was neuroimaging positive, including brain MRI positive in 31 patients, and MRI combined F‐18‐fluorodeoxyglucose positron emission tomography positive in the other seven patients. Twenty‐seven patients underwent epilepsy surgery. In total, after initial antiseizure medications alone, 92% (46/50) of patients were drug‐resistant epilepsies, only 8% (4/50) of the probands became seizure‐free but seizure‐free (≥6 m) occurred in 92.6% (25/27) of patients with drug‐resistant epilepsy after epilepsy surgery at the last follow‐up. Patients undergoing epilepsy surgery had better epilepsy prognosis. Significance Epilepsy related to GATOR1 variants had high possibility to be drug‐resistant epilepsy and to have positive neuroimaging finding. Epilepsy surgery is the only favorable factor for better seizure prognosis in this kind epilepsy.

Abstract Background Adolescent depression is becoming one of the major public health concerns, because of its increased prevalence and risk of significant functional impairment and suicidality. Clinical depression commonly emerges in adolescence; therefore, the prevention and intervention of depression at this stage is crucial. Recent evidence supports the importance of the gut microbiota (GM) in the modulation of multiple functions associated with depression through the gut-brain axis (GBA). However, the underlying mechanisms remain poorly understood. Therefore, in the current study, we aimed to screen the microbiota out from healthy and depressive adolescents, delineate the association of the targeted microbiota and the adolescent depression, address the salutary effects of the targeted microbiota on anti-depressive behaviors in mice involving the metabolism of the tryptophan (Trp)-derived neurotransmitters along the GBA. Results Here, we found the gut microbiota from healthy adolescent volunteers, first diagnosis patients of adolescent depression, and sertraline interveners after first diagnosis displayed significant difference, the relative abundance of Faecalibacterium, Roseburia, Collinsella, Blautia, Phascolarctobacterium, Lachnospiraceae-unclassified decreased in adolescent depressive patients, while restored after sertraline treatment. Of note, the Roseburia abundance exhibited a high efficiency in predicting adolescent depression. Intriguingly, transplantation of the fecal microbiota from healthy adolescent volunteers to the chronic restraint stress (CRS)-induced adolescent depressed mice significantly ameliorated mouse depressive behaviors, in which the Roseburia exerted critical roles, since its effective colonization in the mouse colon resulted in remarkably increased 5-HT level and reciprocally decreased kynurenine (Kyn) toxic metabolites quinolinic acid (Quin) and 3-hydroxykynurenine (3-HK) levels in both the mouse brain and colon. The specific roles of the Roseburia were further validated by the target bacteria transplantation mouse model, Roseburia intestinalis (Ri.) was gavaged to mice and importantly, it dramatically ameliorated CRS-induced mouse depressive behaviors, increased 5-HT levels in the brain and colon via promoting tryptophan hydroxylase-2 (TPH2) or -1 (TPH1) expression. Reciprocally, Ri. markedly restrained the limit-step enzyme responsible for kynurenine (indoleamine2,3-dioxygenase 1, IDO1) and quinolinic acid (3-hydroxyanthranilic acid 3,4-dioxygenase, 3HAO) generation, thereby decreased Kyn and Quin levels. Additionally, Ri. administration exerted a pivotal role in the protection of CRS-induced synaptic loss, microglial activation, and astrocyte maintenance. Conclusions This study is the first to delineate the beneficial effects of Ri. on adolescent depression by balancing Trp-derived neurotransmitter metabolism and improving synaptogenesis and glial maintenance, which may yield novel insights into the microbial markers and therapeutic strategies of GBA in adolescent depression. Video Abstract

In electrified transportation systems, power system failures can lead to greater disasters. Therefore, the reliability of converters in transportation systems has been a concern. Fault-tolerant techniques are widely applied to ensure that converters can continue to supply loads under fault conditions. Fault diagnosis as a prerequisite for fault tolerance has also become a research hotspot. This paper proposes a fast method for fault diagnosis of high-frequency LLC converters. The proposed fault diagnosis method is based on the observation of the voltage across the resonant capacitor to determine and locate the faulty power switch, providing a basis for fault tolerance. This diagnosis method requires a voltage sensor, which is also necessary for some control methods. When applying these control methods, the proposed fault diagnosis method can be used without additional sensors, beneficial for cost reduction. A full-bridge LLC converter controlled by a digital signal processor was used as an experimental platform to verify the effectiveness and speed of the proposed diagnostic method. The results show that the proposed fault diagnosis method can achieve the fast diagnosis of high-frequency LLC converters in a short time and with only minimal computational resources.

Metasurfaces, whose electromagnetic (EM) responses can be artificially designed, are two-dimensional arrays composed of subwavelength nanostructures. Accompanied by various fascinating developments in the past decade, metasurfaces have been proved as a powerful platform for the implementation of EM wave manipulation. However, the planar monoatomic metasurfaces widely used in previous works have limited design freedoms, resulting in some disadvantages for the realization of high-performance and new functional EM wave control. The latest developments show that few-layer metasurfaces and polyatomic metasurfaces are good alternatives to overcome the drawbacks of planar monoatomic metasurfaces and realize high-efficient, multi-band and broadband EM functionalities. They provide additional degrees of design freedom via introducing multilayer layouts or combining multiple meta-atoms into a unit cell respectively. Here, recent advances of few-layer and polyatomic metasurfaces are reviewed. The design strategies, EM properties and main advantages of few-layer metasurfaces and polyatomic metasurfaces are overviewed firstly. Then, few-layer metasurfaces and polyatomic metasurfaces in recent progress for EM wave manipulation are classified and discussed from the viewpoint of their design strategy. At last, an outlook on future development trends and potential applications in these fast-developing research areas is presented.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Exosomes have great potential as liquid biopsy specimens due to their presence and stability in body fluids. However, the function and diagnostic values of exosomal genes in CRC are poorly understood. In the present study, exosomal data of CRC and healthy samples from the exoRBase 2.0 and Gene Expression Omnibus (GEO) databases were used, and 38 common exosomal genes were identified. Through the least absolute shrinkage and selection operator (Lasso) analysis, support vector machine recursive feature elimination (SVM-RFE) analysis, and logistic regression analysis, a diagnostic model of the training set was constructed based on 6 exosomal genes. The diagnostic model was internally validated in the test and exoRBase 2.0 database and externally validated in the GEO database. In addition, the co-expression analysis was used to cluster co-expression modules, and the enrichment analysis was performed on module genes. Then a protein–protein interaction and competing endogenous RNA network were constructed and 10 hub genes were identified using module genes. In conclusion, the results provided a comprehensive understanding of the functions of exosomal genes in CRC as well as a diagnostic model related to exosomal genes.

BackgroundExosome circRNAs (Exo-circRNAs) regulate cancer progression and intercellular crosstalk in the tumor microenvironment. However, their biological functions and potential clinical importance in colorectal cancer (CRC) remain unknown.MethodsWe used exoRBase 2.0 data to identify significant differentially expressed Exo-circRNAs (Exo-DEcircRNAs) in CRC patients and healthy individuals. The least absolute shrinkage and selector operation algorithm, support vector machine-recursive feature elimination, and multivariate Cox regression analyses were used to select candidate Exo-circRNAs and constructed a diagnostic model. Quantitative reverse transcription-polymerase chain reaction analysis was performed to confirm the expression of Exo-circRNAs in the serum samples of patients. Furthermore, we constructed an exosome circRNA-miRNA-mRNA network for CRC. Upregulated target mRNAs in the exosome competing endogenous RNA (Exo-ceRNA) network were used for functional and pathway enrichment analyses. We identified 22 immune cell types in CRC patients using CIBERSORT. Correlation analysis revealed the relationship between Exo-ceRNA networks and immune-infiltrating cells. The relationship between target mRNAs and immunotherapeutic response was also explored. Finally, using the Kaplan–Meier survival curve, a prognostic upregulated target mRNA was screened. We constructed a survival-related Exo-ceRNA subnetwork and explored the correlation between the Exo-ceRNA subnetwork and immune-infiltrating cells.ResultsThe constructed diagnostic model had a high area under the curve (AUC) value in both the training and validation sets (AUC = 0.744 and AUC = 0.741, respectively). qRT-PCR confirmed that the Exo-circRNAs were differentially expressed in CRC serum samples. We constructed Exo-ceRNA networks based on the interactions among seven upregulated Exo-DEcircRNAs, eight differentially expressed miRNAs, and twenty-two differentially expressed mRNAs in CRC. Functional enrichment analysis revealed that the upregulated target mRNAs were significantly enriched in cytoskeletal motor activity and the PI3K-Akt signaling pathway. Co-expression analysis showed a significant correlation between the Exo-ceRNA networks and immune cells. The significant correlation was observed between target mRNAs and the immunotherapeutic response. Additionally, based on the prognostic upregulated target gene (RGS2), we constructed a survival-related Exo-ceRNA subnetwork (Exosome hsa_circ_0050334-hsa_miR_182_5p-RGS2). CIBERSORT results revealed that the Exo-ceRNA subnetwork correlated with M2 macrophages (P = 4.6e-07, R = 0.31).ConclusionsOur study identified an Exo-diagnostic model, established Exo-ceRNA networks, and explored the correlation between Exo-ceRNA networks and immune cell infiltration in CRC. These findings elucidated the biological functions of Exo-circRNAs and their potential clinical implications.

Playing a significant role in electrochemical energy conversion and storage systems, heteroatom-doped transition metal oxides are key materials for oxygen-involving reactions. Herein, mesoporous surface-sulfurized Fe–Co3O4 nanosheets integrated with N/S co-doped graphene (Fe–Co3O4–S/NSG) were designed as composite bifunctional electrocatalysts for the oxygen evolution reaction (OER) and the oxygen reduction reaction (ORR). Compared with the Co3O4–S/NSG catalyst, it exhibited superior activity in the alkaline electrolytes by delivering an OER overpotential of 289 mV at 10 mA cm−2 and an ORR half-wave potential of 0.77 V vs. RHE. Additionally, Fe–Co3O4–S/NSG kept stable at 4.2 mA cm−2 for 12 h without significant attenuation to render robust durability. This work not only demonstrates the satisfactory effect of the transition-metal cationic modification represented by iron doping on the electrocatalytic performance of Co3O4, but it also provides a new insight on the design of OER/ORR bifunctional electrocatalysts for efficient energy conversion.

There is evidence suggesting that immune genes play pivotal roles in the development and progression of colorectal cancer (CRC). Colorectal carcinoma patient data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) were randomly classified into a training set, a test set, and an external validation set. Differentially expressed gene (DEG) analyses, univariate Cox regression, and the least absolute shrinkage and selection operator (LASSO) were used to identify survival-associated immune genes and develop a prognosis model. Receiver operating characteristic (ROC) analysis and principal component analysis (PCA) were used to evaluate the discrimination of the risk models. The model genes predicted were verified using the Human Protein Atlas (HPA) databases, colorectal cell lines, and fresh CRC and adjacent tissues. To understand the relationship between IRGs and immune invasion and the TME, we analyzed the content of immune cells and scored the TME using CIBERSORT and ESTIMATE algorithms. Finally, we predicted the potential sensitive chemotherapeutic drugs in different risk score groups by the Genomics of Drug Sensitivity in Cancer (GDSC). A total of 491 IRGs were screened, and 14 IRGs were identified to be significantly related to overall survival (OS) and applied to construct an immune-related gene (IRG) prognostic signature (IRGSig) for CRC patients. Calibration plots showed that nomograms have powerful predictive ability. PCA and ROC analysis further verified the predictive value of this fourteen-gene prognostic model in three independent databases. Furthermore, we discovered that the tumor microenvironment changed significantly during the tumor development process, from early to middle to late stage, which may be an essential factor for tumor deterioration. Finally, we selected six commonly used chemotherapeutic drugs that have the potential to be useful in the treatment of CRC. Altogether, immune genes were used to construct a prognosis model for CRC patients, and a variety of methods were used to test the accuracy of this model. In addition, we explored the immune mechanisms of CRC through immune cell infiltration and TME in CRC. Furthermore, we assessed the therapeutic sensitivity of many commonly used chemotherapeutic medicines in individuals with varying risk factors. Finally, the immune risk model and immune mechanism of CRC were thoroughly investigated in this paper.

Although research on the metabolism related to gastric cancer (GC) is gradually gaining increasing interest, there are few studies regarding metabolism-related genes in GC. Understanding the characteristic changes of metabolism-related genes at the transcriptional and protein levels in GC will help us to identify new biomarkers and novel therapeutic targets. We harvested six pairs of samples from GC patients and evaluated the differentially expressed proteins using mass spectrometry-based proteomics. RNA sequencing was conducted simultaneously to detect the corresponding expression of mRNAs, and bioinformatics analysis was used to reveal the correlation of significant differentially expressed genes. A total of 57 genes were observed to be dysregulated both in proteomics and transcriptomics. Bioinformatics analysis showed that these differentially expressed genes were significantly associated with regulating metabolic activity. Further, 14 metabolic genes were identified as potential targets for GC patients and were related to immune cell infiltration. Moreover, we found that dysregulation of branched-chain amino acid transaminase 2 (BCAT2), one of the 14 differentially expressed metabolism-related genes, was associated with the overall survival time in GC patients. We believe that this study provides comprehensive information to better understand the mechanism underlying the progression of GC metastasis and explores the potential therapeutic and prognostic metabolism-related targets for GC.

Background Although the appropriateness of hospital utilization of adults and the elderly in China was audited by several studies, the appropriateness of hospital use by children in Shanghai remains to be determined. This study aims to assess the level of inappropriate hospital admissions and hospital days, to detect factors associated with inappropriateness, and to elucidate reasons for inappropriateness. Methods A retrospective review of the records of 291 admissions and 1449 hospital days of children inpatients from a secondary hospital in Shanghai was performed by two reviewers using the Chinese version Pediatric Appropriateness Evaluation Protocol (C-PAEP). Demographics, socio-economic characteristics, and other admission- or hospital stay-related information were collected and analyzed to determine factors associated with inappropriateness utilizing multivariate regression models. Results 38.5% (n = 112) of admissions and 9.5% (n = 137) of hospital days were categorized as inappropriate, according to the C-PAEP. Children who were non-Shanghai residents (p < 0.001), admitted through the emergency sector (p = 0.030), and/or received services in a surgical ward (p < 0.001) had a higher risk of being admitted inappropriately. Payment method (p = 0.006), service type (p < 0.001), comorbidity (p = 0.016), length of stay (p = 0.007), and appropriateness of admission (p < 0.001) were found to be associated with prevalence of inappropriate hospital days. Approximately three-fourths of the inappropriate admissions were premature admissions (75.9%, n = 85). The most frequent reasons for inappropriate hospital days were awaiting test results (34.3%, n = 47), awaiting surgery (19.7%, n = 27), awaiting test execution (10.9%, n = 15), and family unprepared for home care (10.9%, n = 15). Conclusions Although the extent of inappropriate hospital days was moderate compared with that found by previous investigations, the prevalence of inappropriateness of admission was considerable. To enhance the appropriateness of hospital care for children, interventions could be implemented according to the associated factors and identified causes.

Longitudinal metagenomics has been widely studied in the recent decade to provide valuable insight for understanding microbial dynamics. The correlation within each subject can be observed across repeated measurements. However, previous methods that assume independent correlation may suffer from incorrect inferences. In addition, methods that do account for intra-sample correlation may not be applicable for count data. We proposed a distribution-free approach, namely CorrZIDF, which extends the current method to model correlated zero-inflated metagenomic count data, offering a powerful and accurate solution for detecting significance features. This method can handle different working correlation structures without specifying each margin distribution of the count data. Through simulation studies, we have shown the robustness of CorrZIDF when selecting a working correlation structure for repeated measures studies to enhance the efficiency of estimation. We also compared four methods using two real datasets, and the new proposed method identified more unique features that were reported previously on the relevant research.