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Background Recently, many strategies have emerged to develop the conventional treatment of hepatocellular carcinoma (HCC). Previously, we have established an HCC targeting system of conditionally replicative adenovirus (CRAd) delivered by human umbilical cord-derived mesenchymal stem cells (HUMSCs). At present, the system needs to be developed for enhancing anti-tumor effect and overcoming limitation caused by alpha-fetoprotein (AFP) heterogeneity of HCC. Methods A bispecific T cell engager (BiTE) targeting programmed death ligand 1 (PD-L1) controlled by human telomerase reverse transcriptase (hTERT) promoter was armed on the CRAd of old system. A series of experiments in vitro such as ELISA, flow cytometry, electron microscope and so on were performed for identification of the novel system. Then the anti-tumor effect was explored on orthotopic transplantation model mice and AFP heterogeneous model mice by bioluminescent imaging and the side effects were assessed by levels of serum AST and ALT and HE staining for extrahepatic organs. The distributions of CRAd and BiTE in tumor tissue were detected using confocal microscope and the intratumoral T cell was analyzed by flow cytometry. Results Firstly, the characters of the new system including the selective killing activity of CRAd, the release of BiTE and the CRAd package and delivery by HUMSC were identified. And then the result on orthotopic transplantation model mice showed that the new system had better anti-tumor activity and less hepatotoxicity than the old. In the tumor tissue of model mice treated by the new system, the infiltration and activation of T cells were significantly enhanced. Lastly, the new system could eliminate the AFP negative cells in AFP heterogeneous tumor efficiently. Conclusions Comparing the old system, the new provides a more effective and safer strategy against HCC.

Background Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) genes play important roles in folliculogenesis. Altered expression of the two have been found among patients with poor ovarian response (POR). In this prospective cohort study, we have determined the expression of the GDF9 and BMP15 genes in follicle fluid (FF) and granulosa cells (GCs) derived from poor ovarian responders grouped by age, and explored its correlation with the outcome of in vitro fertilization and embryo transfer (IVF-ET) treatment. Methods A total of 196 patients with POR were enrolled from a tertiary teaching hospital. The patients were diagnosed by the Bologna criteria and sub-divided into group A ( 40 year old). A GnRH antagonist protocol was conducted for all patients, and FF and GCs were collected after oocyte retrieval. Expression of the GDF9 and BMP15 genes in the FF and GCs was determined with enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Results Compared with group C, groups A and B had significantly more two pronuclei (2PN) oocytes and transplantable embryos, in addition with higher rates of implantation and clinical pregnancy (P GDF9 and BMP15 genes in the FF and GCs differed significantly among the three groups (P P > 0.05). The relative levels of GDF9 and BMP15 proteins in GCs have correlated with the relative mRNA levels in GCs and protein concentrations in FF (P Conclusions For poor ovarian responders, in particular those over 40, the expression of GDF9 and BMP15 is declined along with increased age and in accompany with poorer oocyte quality and IVF outcome, whilst the ratio of GDF9/BMP15 mRNA levels remained relatively constant. Trial registration Chinese Clinical Trial Registry Center (ChiCTR1800016107). Registered on 11 May 2018.

CD20 is an effective immunotherapy target for CD20+ B-cell malignant cells. Monoclonal antibody, especially rituximab, has been a conventional strategy in the treatment of B-cell malignancies such ...

Cisplatin (DDP)-based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a huge challenge. In the present study, we aimed to explore the effects of SPP1 on the proliferation and apoptosis rate of the HeLa cervical cancer cell line with cisplatin (DDP) resistance. Microarray analysis was employed to select differentially expressed genes in cervical cancer tissues and adjacent tissues. Then, we established a DDP-resistant HeLa cell line (res-HeLa). Western blotting was used to detect SPP1 expression in both tissue and cells. After the transfection with si-SPP1 and pcDNA3.1-SPP1, colony formation and MTT assays were applied to detect cell proliferation changes. Flow cytometry was employed to detect the cell apoptosis rate. Western blotting was performed to verify the activation of PI3K/Akt signal pathway proteins related to DDP resistance. SPP1 was overexpressed in cervical cancer tissues and cell lines. Compared to normal HeLa cells, expression of SPP1 was significantly enhanced in res-HeLa cells. SPP1 knockdown resulted in repressed proliferation and enhanced apoptosis of res-HeLa cells, which could be reversed by SPP1 overexpression in HeLa cells. Additionally, downregulation of SPP1 improved the DDP sensitivity of HeLa by inhibiting the PI3K/Akt signaling pathway. SPP1 inhibition could suppress proliferation, induce apoptosis and increase the DDP chemo-sensitivity of HeLa cells.

Finding effective and objective biomarkers to inform the diagnosis of schizophrenia is of great importance yet remains challenging. However, there is relatively little work on multi-biological data for the diagnosis of schizophrenia. This was a cross-sectional study in which we extracted multiple features from three types of biological data including gut microbiota data, blood data, and electroencephalogram data. Then, an integrated framework of machine learning, consisting of five classifiers, three feature selection algorithms, and four cross-validation methods was used to discriminate patients with schizophrenia from healthy controls. Our results showed that the performance of the classifier using multi-biological data was better than that of the classifiers using single biological data, with 91.7% accuracy and 96.5% AUC. The most discriminative features (top 5%) for the classification include gut microbiota features (Lactobacillus, Haemophilus, and Prevotella), blood features (superoxide dismutase, monocyte-lymphocyte ratio, and neutrophil), and electroencephalogram features (nodal local efficiency, nodal efficiency, and nodal shortest path length in the temporal and frontal-parietal areas).The proposed integrated framework may be help in understanding the pathophysiology of schizophrenia and developing biomarkers for schizophrenia using multi-biological data.

Macrophages as components of the innate immune system play a critical role in antitumor responses. Strategies for targeting CD47 are becoming a hot spot for cancer therapy. The expression of CD47 is exercised by macrophages to make a distinction between “self” or “nonself.” Anti-CD47 antibodies block the interaction between macrophage signal regulatory protein-α (SIRPα) and tumor surface CD47. In this study, we report and assess a novel anti-CD47 blocking antibody named 2C8, which exhibits high affinity and tremendous anticancer effects. More concretely, 2C8 significantly induces macrophages, including protumorigenic subtype M2 macrophages killing tumor cells in vitro, and is revealed to be more effective than commercially available anti-CD47 mAb B6H12.2. In vivo, 2C8 controls tumor growth and extends survival of xenograft mice. The antitumor ability of 2C8 might be applicable to many other cancers. The generation of a novel CD47 antibody contributes to consolidating clinical interest in targeting macrophages for the treatment of malignancy and, moreover, as a supplement therapy when patients are resistant or refractory to other checkpoint therapies or relapse after such treatments.

Obesity is common comorbidity in patients with schizophrenia. Previous studies have reported that homocysteine (Hcy) is increased in schizophrenia. However, no study has reported the association between BMI and Hcy levels in schizophrenia. This cross-sectional naturalistic study aimed to evaluate the relationship between BMI, Hcy and clinical symptoms in Chinese Han patients with chronic schizophrenia. Clinical and anthropometric data as well as plasma Hcy level and glycolipid parameters were collected. Psychopathology was measured with the Positive and Negative Syndrome Scale (PANSS). Our results showed that compared with the low BMI group, the high BMI group had a higher PANSS general psychopathology subscore, higher levels of blood glucose, total cholesterol and high-density lipoprotein (HDL) cholesterol (all p p p

Background Oxidative stress (OS), defined as an imbalance between excessive reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) production and antioxidant insufficiency, has been suggested to be involved in the pathogenesis of poor ovarian response (POR). Growth hormone (GH) can reduce OS in some cell types. This study investigated whether GH can improve OS and the in vitro fertilization and embryo transfer (IVF-ET) outcomes of poor ovarian responders. Methods This study enrolled 105 patients with POR and 58 patients without POR (controls) who were diagnosed according to the Bologna criteria and underwent conventional IVF-ET. Poor ovarian responders were randomly assigned to two groups: the POR-GH group, which received pretreatment with GH 4 IU/d on day 2 of the previous menstrual cycle before IVF until the trigger day, and the POR-C group, which received no pretreatment. OS markers in follicular fluid (FF), ROS levels in granulosa cells (GCs), and the IVF outcomes of the groups were compared. Results Endometrial thickness on trigger day, the number of cleaved embryos, the number of higher-quality embryos, and the rates of embryo formation, higher-quality embryo formation, implantation and clinical pregnancy were significantly increased in the POR-GH group compared with the POR-C group (P P P Conclusions Pretreatment with GH alleviates OS and improves oocyte quality and IVF outcomes of poor ovarian responders. Trial registration Chinese Clinical Trial Registry. ChiCTR1900021269. Registered 8 February 2019, http://www.chictr.org.cn/edit.aspx?pid=35837&htm=4.

I read with interest the recent published article from Professor Robert L. Medcalf, entitled “Fibrinolysis and COVID‐19: a plasmin paradox” [1]. As an indirect marker of thrombin and plasmin activation, D‐dimer has been suggested to guide anticoagulant treat in COVID‐19 patients [2, 3]. However, D‐dimer may not be able to reflect accurate fibrinolysis status of COVID‐19 patients, and therefore can’t guide the possible antifibrinolysis or thrombolytic therapy in different stages of COVID‐19, as Professor Robert L. Medcalf discussed. Hence, we speculated that measuring direct markers of thrombin, plasmin and so on, may provide more therapeutic targets in COVID‐19 patients with coagulopathy.

The development of neuroimaging instrumentation has boosted neuroscience researches. Consequently, both the fineness and the cost of data acquisition have profoundly increased, leading to the main bottleneck of this field: limited sample size and high dimensionality of neuroimaging data. Therefore, the emphasis of ideas of data pooling and research collaboration has increased over the past decade. Collaborative analysis techniques emerge as the idea developed. In this paper, we present NEURO-LEARN, a solution for collaborative pattern analysis of neuroimaging data. Its collaboration scheme consists of four parts: projects, data, analysis, and reports. While data preparation workflows defined in projects reduce the high dimensionality of neuroimaging data by collaborative computation, pooling of derived data and sharing of pattern analysis workflows along with generated reports on the Web enlarge the sample size and ensure the reliability and reproducibility of pattern analysis. Incorporating this scheme, NEURO-LEARN provides an easy-to-use Web application that allows users from different sites to share projects and processed data, perform pattern analysis, and obtain result reports. We anticipate that this solution will help neuroscientists to enlarge sample size, conquer the curse of dimensionality and conduct reproducible studies on neuroimaging data with efficiency and validity.

Background: Growth differentiation factor 9 ( GDF9 ) and bone morphogenetic protein 15 ( BMP15 ) genes play important roles in folliculogenesis. Altered expression of the GDF9 and BMP15 genes have been found among patients with poor ovarian response (POR). In this prospective cohort study, we determined the expression of the GDF9 and BMP15 genes in follicle fluid (FF) and granulosa cells (GCs) from poor ovarian responders grouped by age, and explored its correlation with the outcome of in vitro fertilization and embryo transfer (IVF-ET) treatment. Methods: A total of 196 patients with POR were enrolled from a tertiary teaching hospital. The patients were diagnosed based on the Bologna criteria and sub-divided into different age groups: group A ( 40 year old). A GnRH antagonist protocol was conducted for all patients, and FF and GCs were collected after oocyte retrieval. Expression of GDF9 and BMP15 in the FF and GCs was determined with enzyme linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. Results: Compared with group C, groups A and B had significantly more transplantable embryos and higher rates of implantation and clinical pregnancy ( P < 0.05). Group A also had significantly more two pronuclei (2PN) oocytes ( P < 0.05). The expression level of GDF9 and BMP15 in the FF and GCs differed significantly among the three groups ( P < 0.05), showing a trend of decline with age. Conclusion: For poor ovarian responders, the expression of GDF9 and BMP15 is declined with increased age in accompany with poorer oocyte quality and IVF outcome, particularly for those over 40.

Background Oxidative stress (OS), defined as an imbalance between reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) excessive production and antioxidant insufficient, has been suggested to be involved in the pathogenesis of poor ovarian response (POR). Growth hormone (GH) can function reduce OS in some types of cells. This study investigated whether GH can significantly improve OS and in vitro fertilization and embryo transfer (IVF-ET) outcomes in patients with POR.Methods This study enrolled 105 and 58 patients with and without POR (controls), respectively, diagnosed according to the Bologna criteria, who underwent conventional IVF-ET. Patients with POR were randomly assigned to two groups: POR-GH group: pretreatment with GH 4IU/d on day 2 of the previous menstrual cycle before IVF till the trigger day; POR-C group: no pretreatment. The markers of OS in follicle fluid (FF),reactive oxygen species (ROS) levels in granulosa cells (GC), and IVF outcomes of the patients were compared between the three groups.Result(s) The endometrial thickness on trigger day, number of cleaved embryos, higher quality embryos, the rates of implantation and clinical pregnancy were significantly increased in POR-GH group compared with POR-C group (P

CW (continuous wave) coherent anti-Stoke Raman spectroscopy (CARS) of gases using a hollow-core photonic crystal fiber (HC-PCF) is demonstrated with gaseous CO2 as an example. Raman transition is pumped by a tunable dye laser. The seeding stokes light is provided by a home-made ECDL. Both lasers operate in single longitudinal mode. The output radiation from the fiber is filtered and coupled into an imaging spectrometer. Anti-stokes signal is observed with 10 mW pump power and 1 mW stokes power. The peak anti-Stokes signal of ν1 band of 6 atm CO2 is 59000 CCD counts with the exposure time set to 5 ms. The v1 and 2v2 components of the fermi dyad of CO2 is resolved.

A tunable external cavity diode laser (ECDL) system with narrow line-width emission at 410 nm is presented. Based on a commercially available laser diode and a Littrow arranged reflective holographic grating, a maximum output power over 500 mW with line-width of about 50 pm is achieved at the rated current. The power efficiency is over 85% and the threshold decreases over 20% compared to the free-running laser diode. Manual tuning range over 5 nm is achieved around threshold condition and over 2 nm at high injection currents up to 500 mA with side mode suppression ratio larger than 20 dB.

The objective of this study was to investigate the effects of 10 Hz repetitive transcranial magnetic stimulation (rTMS) in patients with schizophrenia using EEG microstates. Thirty-eight patients with chronic schizophrenia were included in a double-blind, randomized and sham-controlled trial (19 participants in the active group and 19 participants in the sham group) and received 10 Hz active or sham rTMS stimulation to the left dorsolateral prefrontal cortex (left DLPFC) 5 days per week over for 4 weeks. Four classical microstate classes (i.e., classes A, B, C and D) were identified by clustering, and the parameters (i.e., duration, occurrence and contribution) of each class were computed. Our results showed that (1) after stimulation, the positive and negative syndrome scale (PANSS) positive scores decreased significantly in the active group; (2) the duration of the microstate of class C derived from EEG data decreased significantly in the active group; and (3) the change of the duration of class D in the active group was significantly higher than that in the sham group. Our findings demonstrated that 10 Hz active rTMS stimulation was beneficial to improving the positive symptoms of patients with chronic schizophrenia, and the EEG microstate could be an effective indicator of symptom improvements.

Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction. First, we constructed the anti-CD3scfv gene driven by human α-fetoprotein (AFP) promoter into an adenoviral vector and the E1A gene into the lentiviral vector. Our results showed that anti-CD3scfv could specifically express on the surface of HCC cells and activate the lymphocytes to kill target cells effectively in vitro. HUMSC infected by AdCD3scfv followed by LentiR.E1A could support the adenoviral replication and packaging in vitro 36 h after LentiR.E1A infection. Using a subcutaneous HepG2 xenograft model, we confirmed that AdCD3scfv and LentiR.E1A co-transfected HUMSC could migrate selectively to the tumor site and produce considerable adenoviruses. The new generated AdCD3scfv infected and modified tumor cells successfully. Mice injected with the MSC.E1A.AdCD3scfv and lymphocytes significantly inhibited the tumor growth compared with control groups. Furthermore, 5-fluorouracil (5-FU) could sensitize adenovirus infection at low MOI resulting in improved lymphocytes cytotoxicity in vitro and in vivo. In summary, this study provides a promising strategy for solid tumor immunotherapy.

The 5-year survival rate of patients with B cell lymphoma is about 50% after initial diagnosis, mainly because of resistance to chemotherapy. Hence, it is necessary to understand the mechanism of chemo-resistance and to explore novel methods to circumvent multidrug resistance. Previously, we showed that an engineered cytotoxic fusion protein anti-CD19(Fab)-LDM (lidamycin), can induce apoptosis of B-lymphoma cells. Herein, we successfully established an adriamycin (ADR)-resistant B cell lymphoma cell line BJAB/ADR. The mRNA and protein level of ATP-binding cassette subfamily B member 1 (ABCB1) were significantly overexpressed in BJAB/ADR cells. Increased efflux function of ABCB1 was observed by analyzing intracellular accumulation and efflux of Rhodamine 123. The efflux of Rhodamine 123 could be significantly ameliorated by verapamil. Treatment with anti-CD19(Fab)-LDM at different concentrations induced cytotoxic response of BJAB/ADR cells similar to that of the sensitive cells. In vivo studies showed that anti-CD19(Fab)-LDM had better antitumor effect in BJAB and BJAB/ADR cell lymphoma xenografts compared with ADR or LDM treatment alone. Taken together, anti-CD19(Fab)-LDM can effectively inhibit the growth of BJAB/ADR cells both in vitro and in vivo. Anti-CD19(Fab)-LDM could be a promising molecule for the treatment of drug resistant cancers.

Background PD-1/PD-L1 blockade can confer durable benefits in the treatment of metastatic cancers, but the response rate remains modest and potential adverse effects occur sometimes. Concentrating immunotherapeutic agents at the site of disease was believed to break local immune tolerance and reduce systemic toxicity. E1A-engineered mesenchymal stromal cell (MSC.E1A) was an attractive transfer system that preferentially homing and treating cancer metastasis, through which the tumor cells were modified by locally replicated adenoviruses to release CD3-HAC, a bifunctional fusion protein that anti-CD3 scfv linked with high-affinity consensus (HAC) PD-1. Subsequently, CD3-HAC, wbich was bound on PD-L1-positive breast cancer cells, recruited T cells to exhibit a potent antitumor immunity incombination with immune checkpoint blockade. Methods We constructed the CD3-HAC gene driven by human telomerase reverse transcriptase (hTERT) promoter into an adenoviral vector and the E1A gene into the lentiviral vector. The homing property of MSCs in vivo was analyzed with firefly luciferase-labeled MSCs (MSC.Luc) by bioluminescent imaging (BLI). The cytotoxicity of T cells induced by CD3-HAC towards PD-L1-positive cells was detected in vitro and in vivo in combination with 5-FU. Results Our data suggest that CD3-HAC could specifically bind to PD-L1-positive tumor cells and induce lymphocyte-mediated lysis effectively both in vitro and in vivo. The intervention with HAC diminished the effects of PD-1/PD-L1 axis on T cells exposed to MDA-MB-231 cells and increased lymphocytes activation. MSCs infected by AdCD3-HAC followed by LentiR.E1A could specially migrate to metastasis of breast cancer and produce adenoviruses in the tumor sites. Furthermore, treatment with MSC.CD3-HAC.E1A in combination with 5-FU significantly inhibited the tumor growth in mice. Conclusions This adenovirus-loaded MSC.E1A system provides a promising strategy for the identification and elimination of metastasis with locally released immuno-modulator. Electronic supplementary material The online version of this article (10.1186/s13045-019-0723-8) contains supplementary material, which is available to authorized users.

Background The study purpose was to make investigation into the influence of XIST on cervical cancer progression and what’s more its potential mechanism. Methods The cervical cancer data sets (lncRNA, miRNA, and mRNA) obtained from TCGA were analyzed with the “mixOmics” R package. Then, the expression of XIST, miR-140-5p, and ORC1 were detected using qRT-PCR and western blot in both tissues and cervical cancer cell lines (Hela and C33A) to verify the bioinformatics analyses results. CCK-8 assay, 5-ethynyl-2′-deoxyuridine (EdU) assays, cell cycle assay and cell apoptosis assay were practiced. Besides, immunohistochemistry staining was operated for the detection of the Ki-67, E-cadherin and vimentin expression in cervical cancer tissues and the apoptosis-related proteins expression (c-caspase3, Bcl-2, total PARP and cleaved PARP) was verified through western blot. And in vivo experiments were implemented. Results MiR-140-5p was down-regulated but XIST and ORC1 were up-regulated in cervical cancer tissues and cell lines. Knocking down of the XIST or ORC1 memorably suppressed cell proliferation, blocked cell cycle, decreased the expression of Bcl-2 while increased the apoptosis rate and the expression of c-caspase3 and cleaved PARP in HeLa and C33A cells. Besides, the results of immunohistochemistry staining showed knocking down the expression of XIST improved the expression levels of E-cadherin and decreased Ki-67 and vimentin expression. And overexpression of miR-140-5p also could inhibit the progression and reverse the influence of XIST and ORC1 in HeLa and C33A cells. Conclusion Our study indicated the effects of XIST/miR-140-5p/ORC1 axis on the progression of cervical cancer which will shed new light on epigenetic diagnostics and therapeutics in cervical cancer.

Figure S1. Schematic representation of the therapeutic strategy. Figure S2. Schematic representation of lentiviral expression vector for E1A. Figure S3. Western blot analysis of CD3-HAC. Figure S4. Transduced MDA-MB-231 cells secreted CD3-HAC constantly. Figure S5. The expression of Perforin and Granzyme B of PBMC was measured in co-culture system. Figure S6. The expression of PD-1 on CD8+ cells was measured by flow cytometry after co-incubation with 231.CD3 for 3â days. Figure S7. The inhibitory curve of MDA-MB-231 cells treated with 5-FU. Figure S8. Intratumor injection of adenoviruses against the MDA-MB-231 cells xenograft tumors. Figure S9. Each fluorescence channel in Fig. 6a. Figure S10. Immunohistochemical analysis of the lung. Figure S11. Dual viruses infected MCSs causing no detectable side effects in vivo. Table S1. Primary antibodies. Table S2. Secondary antibodies. (DOCX 129760â kb)

Currently, it is a key challenge to remove the postsurgical residuals and metastasis of hepatocellular carcinoma (HCC). Oncolytic adenoviral virotherapy is an attractive treatment modality for cancer; however, the difficulty remains regarding its intravenous administration. The aim of this study was to develop a targeted therapeutic system which has great potential to overcome the postsurgical residuals and metastasis of HCC. In this system, we developed a conditionally replicative adenovirus (CRAd) loaded on human umbilical cord-derived mesenchymal stem cells (HUMSCs), in which the CRAd contained an adenovirus E1A gene dual regulated by α-fetoprotein promoter and microRNA-122 target sequence. When HUMSCs homed to the tumor sites and differentiated into hepatocyte-like cells within tumor microenvironment, the CRAds were packaged and released strictly to the local tumor. Subsequently, the CRAd lysed tumor cells selectively with the post-infection regulation. The study showed the specific oncolytic effect of the CRAd to HCC cells and the production of the CRAd by differentiated HUMSCs in vitro. Furthermore, we proved the hepatocyte-like transformation of HUMSC in the microenvironment of orthotopic or heterotopic hepatoma. Finally, this therapeutic system exhibited dramatic tumor inhibition on both orthotopic and subcutaneous hepatic xenograft tumor model mice with less toxicity on normal organs. The study results have demonstrated that this targeted therapeutic strategy is a promising method to resolve the problem of postsurgical residuals and metastasis of HCC.

A high performance plasmonic sensor based on a metal-insulator-metal (MIM) waveguide coupled with a double-cavity structure consisting of a side-coupled rectangular cavity and a disk cavity is proposed. The transmission characteristics of the rectangular cavity and disk cavity are analyzed theoretically and the improvements of performance for the double-cavity structure compared with a single cavity are studied. The influence of structural parameters on the transmission spectra and sensing performance are investigated in detail. A sensitivity of 1136 nm/RIU with a high figure of merit of 51,275 can be achieved at the resonant wavelength of 1148.5 nm. Due to the high performance and easy fabrication, the proposed structure may be applied in integrated optical circuits and on-chip nanosensors.

Background The gut microbiome and microbiome-gut-brain (MGB) axis have been receiving increasing attention for their role in the regulation of mental behavior and possible biological basis of psychiatric disorders. With the advance of next-generation sequencing technology, characterization of the gut microbiota in schizophrenia (SZ) patients can provide rich clues for the diagnosis and prevention of SZ. Methods In this study, we compared the differences in the fecal microbiota between 82 SZ patients and 80 demographically matched normal controls (NCs) by 16S rRNA sequencing and analyzed the correlations between altered gut microbiota and symptom severity. Results The alpha diversity showed no significant differences between the NC and SZ groups, but the beta diversity revealed significant community-level separation in microbiome composition between the two groups (pseudo-F =3.337, p < 0.001, uncorrected). At the phylum level, relatively more Actinobacteria and less Firmicutes (p < 0.05, FDR corrected) were found in the SZ group. At the genus level, the relative abundances of Collinsella, Lactobacillus, Succinivibrio, Mogibacterium, Corynebacterium, undefined Ruminococcus and undefined Eubacterium were significantly increased, whereas the abundances of Adlercreutzia, Anaerostipes, Ruminococcus and Faecalibacterium were decreased in the SZ group compared to the NC group (p < 0.05, FDR corrected). We performed PICRUSt analysis and found that several metabolic pathways differed significantly between the two groups, including the Polyketide sugar unit biosynthesis, Valine, Leucine and Isoleucine biosynthesis, Pantothenate and CoA biosynthesis, C5-Branched dibasic acid metabolism, Phenylpropanoid biosynthesis, Ascorbate and aldarate metabolism, Nucleotide metabolism and Propanoate metabolism pathways (p < 0.05, FDR corrected). Among the SZ group, the abundance of Succinivibrio was positively correlated with the total Positive and Negative Syndrome Scale (PANSS) scores (r = 0.24, p < 0.05, uncorrected) as well as the general PANSS scores (r = 0.22, p < 0.05, uncorrected); Corynebacterium was negatively related to the negative scores of PANSS (r = 0.22, p < 0.05, uncorrected). Conclusions Our findings provided evidence of altered gut microbial composition in SZ group. In addition, we found that Succinvibrio and Corynebacterium were associated with the severity of symptoms for the first time, which may provide some new biomarkers for the diagnosis of SZ.