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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.

Abstract Background In order to make optimal long-term care-related decisions, it is important to take a societal perspective. Shanghai is one of the pilot cities of social long-term care insurance in China. However, little knowledge exists about the economic value of the informal care provided to dependent elderly people in China. This paper aims to evaluate the economic value of informal caregiving in Shanghai using the contingent valuation method by their least-preferred care tasks, and identify the associated factors of willingness-to-pay (WTP) and willingness-to-accept (WTA) of the informal caregivers. Methods This study employed the contingent valuation method to elicit 371 informal caregivers’ WTP and WTA for 1 hour of reduction or increase of least-preferred caring tasks in Shanghai. Univariate and multivariate analyses were conducted to explore the associated factors with the WTP and WTA values. Results The average WTP and WTA were 25.31 CNY and 38.66 CNY, respectively. The associated factors with WTP include caregiver’s income and caregiver’s relationship to the recipient. Care recipient’s age, income, least-preferred task by the caregiver, and subscales of Caregiver Reaction Assessment were found to be associated with WTA. The non-responsiveness rates were 26.1 and 33.2% for WTP and WTA questions, respectively. Conclusions The findings of the current study demonstrated that decision-makers and researchers should take the economic valuation results of informal care into account to make more informed and effective long-term care-related policies and analyses.

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.

Emerging evidence suggests that the gut microbiota may interact with the host brain and play pivotal roles in the pathogenesis of neuropsychiatric disorders. However, the mechanism underlying reciprocal interactions along the microbiota-gut-brain axis in depression remains unclear. In this study, a murine model of chronic restraint stress (CRS) was established to investigate the metabolic signaling of tryptophan (Trp) neurotransmission at the intestinal and central levels in depression. The results showed that CRS mice displayed depression- and anxiety-like behaviors. Additionally, kynurenine (Kyn) and its metabolites, an important Trp metabolic pathway, were strongly activated in the brain. Intriguingly, the Kyn toxic signaling was exacerbated in the gut, especially in the colon. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme responsible for Kyn metabolic pathway initiation, was significantly upregulated in the brain and gut in CRS mice compared with control mice, promoting transfer of Trp metabolic pathway to Kyn signaling. Additionally, administration of IDO inhibitor, 1-methyl-tryptophan (1-MT), partially rescued CRS-induced depression- and anxiety-like changes. Moreover, the enhanced intestinal permeability mediated by CRS allowed toxic metabolites to “leak” into the bloodstream. The microbiome profiles of CRS mice displayed obviously altered taxonomic composition and negative correlations were observed between Enterorhabdus, Parabacteroides and Kyn levels in the brain. Reciprocal crosstalk between the brain and gut was further validated by citalopram treatment, IDO inhibitor and microbiota intervention, which counteracted depression-like behavior, Kyn metabolic signaling and microbiota composition in CRS mice. Meanwhile, Parabacteroides treatment affected Trp metabolism in mouse hippocampus, manifesting as elevated concentration of 5-HT as well as ratio of 5-HT to Trp. These results suggest that long-term stress disrupts Kyn metabolism and endocrine function along the gut-brain axis, accompanied by the disrupted homeostasis of certain microbiota, which collectively contribute to the development of depression-like behavior.

Summary: Optical metasurface as a booming research field has put forward profound progress in optics and photonics. Compared with metallic-based components, which suffer from significant thermal loss and low efficiency, high-index all-dielectric nanostructures can readily combine electric and magnetic Mie resonances together, leading to efficient manipulation of optical properties such as amplitude, phase, polarization, chirality, and anisotropy. These advances have enabled tremendous developments in practical photonic devices that can confine and guide light at the nanoscale. Here we review the recent development of local electromagnetic resonances such as Mie-type scattering, bound states in the continuum, Fano resonances, and anapole resonances in dielectric metasurfaces and summarize the fundamental principles of dielectric resonances. We discuss the recent research frontiers in dielectric metasurfaces including wavefront-shaping, metalenses, multifunctional and computational approaches. We review the strategies and methods to realize the dynamic tuning of dielectric metasurfaces. Finally, we conclude with an outlook on the challenges and prospects of dielectric metasurfaces.

Traditional optical lenses and the corresponding imaging systems, which are based on the optical paths when light propagates inside the bulky media, usually suffer from the bulky size, Abbe-Rayleigh diffraction restricted resolution, and limited responses to different kinds of incident light. Recently, the burgeoning development of metasurfaces comprised of artificial micro- or nano-structures at the subwavelength scale has drawn more and more attentions of the scientific community due to the intriguing abilities such as efficient light–matter interactions and multi-dimensional manipulation of optical waves, which provide profound potentials to realize functional metalens with an ultrahigh numerical aperture (NA) and with super-resolution focal spots on a compact size. Here, the research motivations, the broad outline and the recent advances of planar diffractive metalens are summarized, including the principles of metalens design, the basic components of metalens, and the development of metalens systems. Various approaches to remove the focusing aberrations are presented, which is the essential condition to realize metalens objectives and microscopy. Different types of novel metalenses are revealed, such as label-free sub-resolution metalens, nonlinear metalens, artificial intelligence-aided metalens, multifunctional metalens and reconfigurable metalens. Challenges and future goals are also presented at the end the review.

Background/Aims: Aortic dissection (AD) is also known as intramural hematoma. This study aimed to screen peripheral blood biomarkers of small molecule metabolites for AD using high-performance liquid chromatography-mass spectrometry (HPLC-MS). Methods: Sera from 25 healthy subjects, 25 patients with well-established AD, and 25 patients with well-established hypertension were investigated by HPLC-MS to detect metabolites, screen differentially expressed metabolites, and analyze metabolic pathways. Results: Twenty-six and four metabolites were significantly up- and down-regulated in the hypertensive patients compared with the healthy subjects; 165 metabolites were significantly up-regulated and 109 significantly down-regulated in the AD patients compared with the hypertensive patients. Of these metabolites, 35 were up-regulated and 105 down-regulated only in AD patients. The metabolites that were differentially expressed in AD are mainly involved in tryptophan, histidine, glycerophospholipid, ether lipid, and choline metabolic pathways. As AD alters the peripheral blood metabolome, analysis of peripheral blood metabolites can be used in auxiliary diagnosis of AD. Conclusion: Eight metabolites are potential biomarkers for AD, 3 of which were differentially expressed and can be used for auxiliary diagnosis of AD and evaluation of treatment effectiveness.

Abstract Chirality is a nearly ubiquitous natural phenomenon. Its minute presence in most naturally occurring materials makes it incredibly difficult to detect. Recent advances in metasurfaces indicate that they exhibit devisable chirality in novel forms; this finding offers an effective opening for studying chirality and its features in such nanostructures. These metasurfaces display vast possibilities for highly sensitive chirality discrimination in biological and chemical systems. Here, we show that two-layer metasurfaces based on twisted nanorods can generate giant spin-selective transmission and support engineered chirality in the near-infrared region. Two designed metasurfaces with opposite spin-selective transmission are proposed for treatment as enantiomers and can be used widely for spin selection and enhanced chiral sensing. Specifically, we demonstrate that the chirality in these proposed metasurfaces can be adjusted effectively by simply changing the orientation angle between the twisted nanorods. Our results offer simple and straightforward rules for chirality engineering in metasurfaces and suggest intriguing possibilities for the applications of such metasurfaces in spin optics and chiral sensing.

Background: China has implemented numerous pilots to shift its hospital payment mechanism from the traditional retrospective cost-based system to prospective diagnosis-related-group (DRG) -based system. This study investigated the impact of the DRG payment reform with global budget in Zhongshan, China. Methods: A total of 2895 patients diagnosed with acute myocardial infarction (AMI) were selected from local two largest tertiary hospitals, among which 727 were discharged prior to the payment reform and 2168 afterwards. Difference-in-difference (DID) regression models were used to evaluate the policy effects on patients’ percutaneous coronary intervention (PCI) use, hospital expenditures, in-hospital mortality, and readmission rates within 30 days after discharge. Results: Patients’ PCI use and hospital expenditures increased quickly after the payment reform. With patients with no local insurance scheme as reference, PCI use for local insured patients decreased significantly by 4.55 percent (95 percent confidence interval [CI]: 0.23, 0.72), meanwhile the total hospital expenses decreased significantly by US$986.10 (b=-0.15, P=0.0037) after reform. No changes were observed with patients’ hospital mortality and readmission rates in our study. Conclusion: The innovative DRG-based payment reform in Zhongshan suggested a positive effect on AMI patient’s cost containment but negative effect on encouraging resource use. It had no impacts on patients’ care quality. Cost shifting consequence from the insured to the uninsured was observed. More evidence of the impacts of the DRG-based payment in China’s health scenario is needed before it is generalized nationwide.

Particle–fluid flows are ubiquitous in nature and industry. Understanding the dynamic behaviour of these complex flows becomes a rapidly developing interdisciplinary research focus. In this work, a numerical modelling approach for complex particle–fluid flows using the discrete element method coupled with the lattice Boltzmann method (DEM-LBM) is presented. The discrete element method and the lattice Boltzmann method, as well as the coupling techniques, are discussed in detail. The DEM-LBM is thoroughly validated for typical benchmark cases: the single-phase Poiseuille flow, the gravitational settling and the drag force on a fixed particle. In order to demonstrate the potential and applicability of DEM-LBM, three case studies are performed, which include the inertial migration of dense particle suspensions, the agglomeration of adhesive particle flows in channel flow and the sedimentation of particles in cavity flow. It is shown that DEM-LBM is a robust numerical approach for analysing complex particle–fluid flows.

OBJECTIVES:Admission rates have increased in China, despite the fact that accessibility to primary care is improving. Hospital care could be cost-inefficient, and little is currently known about the appropriateness of admissions to tertiary hospitals in China. This study aims to measure the extent of inappropriate admissions in the cardiology and orthopedics departments of a tertiary hospital in Shanghai, to explore the factors associated with inappropriateness for each department, and to identify the causes of inappropriate admissions. METHODS:The records of inpatients discharged on randomly sampled two days each week during March 2013 to February 2014 from the two departments were extracted. Two reviewers were recruited to assess the records according to the Chinese version of the Appropriateness Evaluation Protocol (C-AEP). Demographic, socio-economic, and other admissions-related variables were collected. Logistic regression analysis was adopted to determine the associated factors of inappropriateness. RESULTS:35.0% (N = 120) of the 343 admissions and 38.7% (N = 179) of the 463 admissions of the cardiology and orthopedics departments were not justified by the C-AEP, respectively. Age (OR = 0.717), self-pay (OR = 3.752), admission via outpatient sector (OR = 5.332), and readmission (OR = 2.501) were identified as factors affecting the appropriateness of admissions in the cardiology department. Age (OR = 0.930), self-pay (OR = 2.597), admission during 12:00-17:59 (OR = 3.211), and admission via outpatient sector (OR = 7.060) were determined to be associated with appropriateness of admission in the orthopedics department. The main reason for inappropriateness was premature admission for both departments. CONCLUSIONS:The magnitude of inappropriate admissions was considerable in the departments. To improve appropriateness, the results suggest that further interventions should be focused on both external and internal factors.

The dynamic behaviors of the joint interfaces make a great difference in machine tools, especially in high-end numerical control machines. To provide an assessment of the normal dynamic parameters in contact deformation of elastoplastic solid joint interfaces theoretically, a dynamic model of joint interfaces was proposed and studied. Based on contact fractal theory and contact-mechanics theory, interfacial parameters, including normal damping dissipation factor, stiffness and damping have been investigated, while the influences of the elastic, elastoplastic and fully plastic deformations of contacting asperities are considered. Solution for the force-displacement relationship in the elastoplastic regime is done by the well supported assumptions: the microcontact area and microcontact normal load are enforcing continuity between the elastic and fully plastic regimes. Numerical calculation results reveal the complications of nonlinear relation between normal contact load and normal dynamic parameters, including the normal stiffness, damping dissipation factor and damping over joint interfaces. Furthermore, normal dynamic parameters and fractal parameters, including fractal dimension D and fractal roughness parameter G also present complicated relationships.

To adapt the Appropriateness Evaluation Protocol (AEP) to the specific settings of health care in China and to validate the Chinese version AEP (C-AEP).Forward and backward translations were carried out to the original criteria. Twenty experts participated in the consultancy to form a preliminary version of the C-AEP. To ensure applicability, tests of reliability and validity were performed on 350 admissions and 3,226 hospital days of acute myocardial infraction patients and total hip replacement patients in two tertiary hospitals by two C-AEP reviewers and two physician reviewers. Overall agreement, specific agreement, and Cohen's Kappa were calculated to compare the concordance of decisions between pairs of reviewers to test inter-rater reliability and convergent validity. The use of "overrides" and opinions of experts were recorded as measurements of content validity. Face validity was tested through collecting perspectives of nonprofessionals. Sensitivity, specificity, and predictive values were also reported.There are 14 admission and 24 days of care criteria in the initial version of C-AEP. Kappa coefficients indicate substantial agreement between reviewers: with regard to inter-rater reliability, Kappa (κ) coefficients are 0.746 (95% confidence interval [CI] 0.644-0.834) and 0.743 (95% CI 0.698-0.767) of admission and hospital days, respectively; for convergent validity, the κ statistics are 0.678 (95% CI 0.567-0.778) and 0.691 (95% CI 0.644-0.717), respectively. Overrides account for less than 2% of all judgments. Content validity and face validity were confirmed by experts and nonprofessionals, respectively. According to the C-AEP reviewers, 18.3% of admissions and 28.5% of inpatient days were deemed inappropriate.The C-AEP is a reliable and valid screening tool in China's tertiary hospitals. The prevalence of inappropriateness is substantial in our research. To reduce inappropriate utilization, further investigation is needed to elucidate the reasons and risk factors for this inappropriateness.

A transient lateral photovoltaic effect has been observed in Ag-doped ZnO thin films. Under the nonuniform irradiation of a 1064 nm pulsed laser, the photovoltaic response shows high sensitivity to the spot position on the film surface. The highest photovoltaic responsivity of 27.1 mV mJ−1 was observed, with a decline time of ∼1.5 ns and a full width at half-maximum (FWHM) of ∼4 ns. The photovoltaic position sensitivity can reach about 3.8 mV mJ−1 mm−1. This paper demonstrates the potential of Ag-doped ZnO films in the position-sensitive infrared detection