Intestinal Piezo1 aggravates intestinal barrier dysfunction during sepsis by mediating Ca2+ influx.

INTRODUCTION: Intestinal barrier dysfunction is a pivotal factor in sepsis progression. The mechanosensitive ion channel Piezo1 is associated with barrier function; however, its role in sepsis-induced intestinal barrier dysfunction remains poorly understood. METHODS: The application of cecal ligation and puncture (CLP) modeling was performed on both mice of the wild-type (WT) variety and those with Villin-Piezo1flox/flox genetic makeup to assess the barrier function using in vivo FITC-dextran permeability measurements and immunofluorescence microscopy analysis of tight junctions (TJs) and apoptosis levels. In vitro, Caco-2 monolayers were subjected to TNF-α incubation. Moreover, to modulate Piezo1 activation, GsMTx4 was applied to inhibit Piezo1 activation. The barrier function, intracellular calcium levels, and mitochondrial function were monitored using calcium imaging and immunofluorescence techniques. RESULTS: In the intestinal tissues of CLP-induced septic mice, Piezo1 protein levels were notably elevated compared with those in normal mice. Piezo1 has been implicated in the sepsis-mediated disruption of TJs, apoptosis of intestinal epithelial cells, elevated intestinal mucosal permeability, and systemic inflammation in WT mice, whereas these effects were absent in Villin-Piezo1flox/flox CLP mice. In Caco-2 cells, TNF-α prompted calcium influx, an effect reversed by GsMTx4 treatment. Elevated calcium concentrations are correlated with increased accumulation of reactive oxygen species, diminished mitochondrial membrane potential, and TJ disruption. CONCLUSIONS: Thus, Piezo1 is a potential contributor to sepsis-induced intestinal barrier dysfunction, influencing apoptosis and TJ modification through calcium influx-mediated mitochondrial dysfunction.

Non-volatile 2 × 2 optical switch using multimode interference in an Sb2Se3-loaded waveguide.

We propose a non-volatile 2 × 2 photonic switch based on multimode interference in an Sb2Se3-loaded waveguide. The different modal symmetries of the TE0 and TE1 modes supported in the multimode region change their propagation constants distinctly upon the Sb2Se3 phase transition. Through careful optical design and FDTD optimization of the multimode waveguide dimensions, efficient switching is achieved despite the modest index contrast of Sb2Se3 relative to Ge2Sb2Te5. The fabricated optical switch demonstrates favorable characteristics, including low insertion loss of ∼1 dB, a compact length of ∼27 µm, and small cross talk below -15 dB across a 35 nm bandwidth. Such non-volatile and broadband components will be critical for future high-density programmable photonic-integrated circuits for optical communications and signal processing.

The active Fe chelator proline-2'-deoxymugineic acid enhances peanut yield by improving soil Fe availability and plant Fe status.

Iron (Fe) deficiency restricts crop yields in calcareous soil. Thus, a novel Fe chelator, proline-2'-deoxymugineic acid (PDMA), based on the natural phytosiderophore 2'-deoxymugineic acid (DMA), was developed to solve the Fe deficiency problem. However, the effects and mechanisms of PDMA relevant to the Fe nutrition and yield of dicots grown under field conditions require further exploration. In this study, pot and field experiments with calcareous soil were conducted to investigate the effects of PDMA on the Fe nutrition and yield of peanuts. The results demonstrated that PDMA could dissolve insoluble Fe in the rhizosphere and up-regulate the expression of the yellow stripe-like family gene AhYSL1 to improve the Fe nutrition of peanut plants. Moreover, the chlorosis and growth inhibition caused by Fe deficiency were significantly diminished. Notably, under field conditions, the peanut yield and kernel micronutrient contents were promoted by PDMA application. Our results indicate that PDMA promotes the dissolution of insoluble Fe and a rich supply of Fe in the rhizosphere, increasing yields through integrated improvements in soil-plant Fe nutrition at the molecular and ecological levels. In conclusion, the efficacy of PDMA for improving the Fe nutrition and yield of peanut indicates its outstanding potential for agricultural applications.

Compact nonvolatile polarization switch using an asymmetric Sb2Se3-loaded silicon waveguide.

We propose and simulate a compact (∼29.5 µm-long) nonvolatile polarization switch based on an asymmetric Sb2Se3-clad silicon photonic waveguide. The polarization state is switched between TM0 and TE0 mode by modifying the phase of nonvolatile Sb2Se3 between amorphous and crystalline. When the Sb2Se3 is amorphous, two-mode interference happens in the polarization-rotation section resulting in efficient TE0-TM0 conversion. On the other hand, when the material is in the crystalline state, there is little polarization conversion because the interference between the two hybridized modes is significantly suppressed, and both TE0 and TM0 modes go through the device without any change. The designed polarization switch has a high polarization extinction ratio of > 20 dB and an ultra-low excess loss of < 0.22 dB in the wavelength range of 1520-1585 nm for both TE0 and TM0 modes.

Predicting clinically significant prostate cancer with a deep learning approach: a multicentre retrospective study.

PURPOSE: This study aimed to develop deep learning (DL) models based on multicentre biparametric magnetic resonance imaging (bpMRI) for the diagnosis of clinically significant prostate cancer (csPCa) and compare the performance of these models with that of the Prostate Imaging and Reporting and Data System (PI-RADS) assessment by expert radiologists based on multiparametric MRI (mpMRI). METHODS: We included 1861 consecutive male patients who underwent radical prostatectomy or biopsy at seven hospitals with mpMRI. These patients were divided into the training (1216 patients in three hospitals) and external validation cohorts (645 patients in four hospitals). PI-RADS assessment was performed by expert radiologists. We developed DL models for the classification between benign and malignant lesions (DL-BM) and that between csPCa and non-csPCa (DL-CS). An integrated model combining PI-RADS and the DL-CS model, abbreviated as PIDL-CS, was developed. The performances of the DL models and PIDL-CS were compared with that of PI-RADS. RESULTS: In each external validation cohort, the area under the receiver operating characteristic curve (AUC) values of the DL-BM and DL-CS models were not significantly different from that of PI-RADS (P > 0.05), whereas the AUC of PIDL-CS was superior to that of PI-RADS (P < 0.05), except for one external validation cohort (P > 0.05). The specificity of PIDL-CS for the detection of csPCa was much higher than that of PI-RADS (P < 0.05). CONCLUSION: Our proposed DL models can be a potential non-invasive auxiliary tool for predicting csPCa. Furthermore, PIDL-CS greatly increased the specificity of csPCa detection compared with PI-RADS assessment by expert radiologists, greatly reducing unnecessary biopsies and helping radiologists achieve a precise diagnosis of csPCa.

Short-Chain Fatty Acids Reduce Oligodendrocyte Precursor Cells Loss by Inhibiting the Activation of Astrocytes via the SGK1/IL-6 Signalling Pathway.

Short-chain fatty acids (SCFAs) are known to be actively involved in neurological diseases, but their roles in hypoxic-ischaemic brain injury (HIBI) are unclear. In this study, a rat model of HIBI was established, and this study measured the changes in IL-6 and NOD-like receptor thermal protein domain associated protein 3 (NLRP3), in addition to proliferation and apoptosis indicators of oligodendrocyte precursor cells (OPCs). The mechanism of action of SCFA on astrocytes was also investigated. Astrocytes were subjected to hypoxia in vitro, and OPCs were treated with IL-6. The results showed that SCFAs significantly alleviated HIBI-induced activation of astrocytes and loss of OPCs. SCFA pretreatment (1) downregulated the expression of NLRP3, IL-6, CCL2, and IP-10; (2) had no effect on the proliferation of OPCs; (3) ameliorated the abnormal expression of Bax and Bcl-2; and (4) regulated IL-6 expression via the SGK1-related pathway in astrocytes. Our findings revealed that SCFAs alleviated the loss of OPCs by regulating astrocyte activation through the SGK1/IL-6 signalling pathway.

USF2 knockdown downregulates THBS1 to inhibit the TGF-ß signaling pathway and reduce pyroptosis in sepsis-induced acute kidney injury.

OBJECTIVE: Acute kidney injury (AKI) is a serious complication of sepsis. This study was performed to explore the mechanism that THBS1 mediated pyroptosis by regulating the TGF-ß signaling pathway in sepsis-induced AKI. METHODS: Gene expression microarray related to sepsis-induced AKI was obtained from the GEO database, and the mechanism in sepsis-induced AKI was predicted by bioinformatics analysis. qRT-PCR and ELISA were performed to detect expressions of THBS1, USF2, TNF-α, IL-1ß, and IL-18 in sepsis-induced AKI patients and healthy volunteers. The mouse model of sepsis-induced AKI was established, with serum creatinine, urea nitrogen, 24-h urine output measured, and renal tissue lesions observed by HE staining. The cell model of sepsis-induced AKI was cultured in vitro, with expressions of TNF-α, IL-1ß, and IL-18, pyroptosis, Caspase-1 and GSDMD-N, and activation of TGF-ß/Smad3 pathway detected. The upstream transcription factor USF2 was knocked down in cells to explore its effect on sepsis-induced AKI. RESULTS: THBS1 and USF2 were highly expressed in patients with sepsis-induced AKI. Silencing THBS1 protected mice against sepsis-induced AKI, and significantly decreased the expressions of NLRP3, Caspase-1, GSDMD-N, IL-1ß, and IL-18, increased cell viability, and decreased LDH activity, thus partially reversing the changes in cell morphology. Mechanistically, USF2 promoted oxidative stress responses by transcriptionally activating THBS1 to activate the TGF-ß/Smad3/NLRP3/Caspase-1 signaling pathway and stimulate pyroptosis, and finally exacerbated sepsis-induced AKI. CONCLUSION: USF2 knockdown downregulates THBS1 to inhibit the TGF-ß/Smad3 signaling pathway and reduce pyroptosis and further ameliorate sepsis-induced AKI.

Radiographic analysis of dynamic lumbar motion during the five-repetition sit-to-stand test in degenerative lumbar spondylolisthesis.

BACKGROUND: To investigate the mechanisms of low back pain triggered by the five-repetition sit-to-stand test (5R-STS test) in degenerative lumbar spondylolisthesis (DLS) from radiographic perspective, as well as to determine the most useful diagnostic modalities in the evaluation of segmental instability. METHODS: We retrospectively performed a study of 78 patients (23 men and 55 women) with symptomatic DLS at L4/5 in our institution between April 2020 and December 2021. Each patient was assessed by using the 5R-STS test and received a series of radiographs including the upright standing, normal sitting, standing flexion-extension radiographs, and supine sagittal MR images. Enrolled patients were divided into two groups based on the 5R-STS test score: severe group and mild group. Translational and angular motion was determined by comparing normal sitting radiograph (N) with upright standing radiograph (U) (Combined, NU), flexion/extension radiographs (FE) as well as normal sitting radiograph (N) with a supine sagittal MR image (sMR) (Combined, N-sMR). RESULTS: Overall, 78 patients were enrolled, and there were 31(39.7%) patients in group S and 47(60.3%) patients in group M, with an average age of 60.7 ± 8.4 years. The normal sitting radiograph demonstrated the maximum slip percentage (SP) and the highest kyphotic angle both in group S and group M. Compared with group M, group S revealed significantly higher SP in the normal sitting position (24.1 vs 19.6; p = 0.002). The lumbar slip angular in group S with a sitting position was significantly higher than that in group M (-5.2 vs -1.3; p < 0.001). All patients in group S had objective functional impairment (OFI) and 28 patients of them were diagnosed with lumbar instability by using the combination of normal sitting radiograph (N) and supine sagittal MR image (sMR) (Combined, N-sMR). CONCLUSION: DLS patients with positive sign of the 5R-STS test is a distinct subgroup associated with lumbar instability. The modality of the combination of normal sitting radiograph (N) and supine sagittal MR image (sMR) had a significant advantage in terms of the ability to identify segmental instability.

A Novel Adaptive Feature Fusion Strategy for Image Retrieval.

In the era of big data, it is challenging to efficiently retrieve the required images from the vast amount of data. Therefore, a content-based image retrieval system is an important research direction to address this problem. Furthermore, a multi-feature-based image retrieval system can compensate for the shortage of a single feature to a certain extent, which is essential for improving retrieval system performance. Feature selection and feature fusion strategies are critical in the study of multi-feature fusion image retrieval. This paper proposes a multi-feature fusion image retrieval strategy with adaptive features based on information entropy theory. Firstly, we extract the image features, construct the distance function to calculate the similarity using the information entropy proposed in this paper, and obtain the initial retrieval results. Then, we obtain the precision of single feature retrieval based on the correlation feedback as the retrieval trust and use the retrieval trust to select the effective features automatically. After that, we initialize the weights of selected features using the average weights, construct the probability transfer matrix, and use the PageRank algorithm to update the initialized feature weights to obtain the final weights. Finally, we calculate the comprehensive similarity based on the final weights and output the detection results. This has two advantages: (1) the proposed strategy uses multiple features for image retrieval, which has better performance and more substantial generalization than the retrieval strategy based on a single feature; (2) compared with the fixed-feature retrieval strategy, our method selects the best features for fusion in each query, which takes full advantages of each feature. The experimental results show that our proposed method outperforms other methods. In the datasets of Corel1k, UC Merced Land-Use, and RSSCN7, the top10 retrieval precision is 99.55%, 88.02%, and 88.28%, respectively. In the Holidays dataset, the mean average precision (mAP) was 92.46%.

The critical role of the hippocampal NLRP3 inflammasome in social isolation-induced cognitive impairment in male mice.

Early life stress exerts detrimental effects on cognitive function, but the mechanism by which this occurs is unknown. The NLRP3 inflammasome-mediated inflammatory response has emerged as a prominent contributor to cognitive impairment induced by chronic stress. In the present study, we showed that 8-week chronic social isolation (SI) led to cognitive impairment in mice, remarkably increasing expression of the hippocampal NLRP3 inflammasome. Furthermore, the 8-week SI procedure significantly increased the levels of hippocampal IL-1ß and IL-18 without significant alteration of the level of serum IL-1ß, suggesting a central mechanism for IL-1ß-related CNS inflammation. Moreover, inflammatory microglial and expression of AMPAR were reduced in the hippocampus of SI mice. Minocycline is an antibiotic that limits microglia responses, and previous study also showed that minocycline could prevent stress-induced pro-inflammatory cytokine expression in the brain. Our experiment found that minocycline improved cognitive behavior in SI mice. Minocycline also prevented expression of the hippocampal NLRP3 inflammasome, indicating that microglia might be the primary contributor to SI-induced hippocampal NLRP3 inflammasome activation. Furthermore, alterations in SI mice were also restored by chronic treatment with the NLRP3 inhibitor MCC950. These results indicate that the microglia-derived NLRP3 inflammasome may be primarily involved in the inflammatory response to social isolation and that specific NLRP3 inflammasome inhibition using MCC950 may represent a promising therapeutic approach for early stress induced cognitive impairment.

Safety awareness and use of child safety seats among parents after the legislation in Shanghai.

PURPOSE: To investigate the changes and underlying mechanisms in parents' safety awareness and the use of child safety seats after the mandatory legislation in Shanghai city, China. METHODS: This study was carried out by Shanghai Key Laboratory of Environment and Children's Health using a multi-stage, simple random sampling method. Volunteers with children aged 0-12 months were recruited. Child safety seats were sent to each volunteer's family. Telephone encounters and/or on-site visits were used to collect data from parents using a phased survey on children's safety during car use. RESULTS: Among all respondents, 91.2% had heard of motor vehicle accidents involving children, and 97.2% could describe the appropriate use of a safety seat to minimize the risk of child injury in a collision. Among 1078 families with newborns, awareness of child safety seats was 91.9%. There were 86% patients aware that new laws and regulations have been released regarding the use of child safety seats, and 98.5% of them plan to comply with the new laws. Moreover, 61% patients think that taxis should be routinely equipped with child safety seats. CONCLUSION: The parents in Shanghai obtained a high level of awareness of children's traffic safety after the introduction of child safety seats legislation, and had a positive experience related to the use of child safety seats. Taxi may be an important area of focus for implementation of child traffic safety. Traffic safety laws and regulations with further impact should be continuously studied.

A Data Model for Using OpenStreetMap to Integrate Indoor and Outdoor Route Planning.

With a rapidly-growing volume of volunteered geographic information (VGI), there is an increasing trend towards using VGI to provide location-based services. In this study, we investigate using OpenStreetMap data to integrate indoor and outdoor route planning for pedestrians. To support indoor and outdoor route planning, in this paper, we focus on the connections inside buildings and propose a data model, which uses OSM primitives (nodes, ways and relations) and tags to capture horizontal and vertical indoor components, as well as the connection between indoor and outdoor environments. A set of new approaches is developed to support indoor modeling and mapping. Based on the proposed data model, we present a workflow that enables automatic generation of a routing graph and provide an algorithm to calculate integrated indoor-outdoor routes. We applied our data model to a set of test cases. The application results demonstrate the capability of our data model in modeling built environments and its feasibility for the integration of indoor and outdoor navigation.

On the equivalent classification of three-dimensional competitive Leslie/Gower models via the boundary dynamics on the carrying simplex.

We study the asymptotic behavior of the competitive Leslie/Gower model (map) [Formula: see text]It is shown that T unconditionally admits a globally attracting 1-codimensional invariant hypersurface [Formula: see text], called carrying simplex, such that every nontrivial orbit is asymptotic to one in [Formula: see text]. More general and easily checked conditions to guarantee the existence of carrying simplex for competitive maps are provided. An equivalence relation is defined relative to local stability of fixed points on [Formula: see text] (the boundary of [Formula: see text]) on the space of all three-dimensional Leslie/Gower models. Using a formula on the sum of the indices of all fixed points on the carrying simplex for three-dimensional maps, we list the 33 stable equivalence classes in terms of simple inequalities on the parameters [Formula: see text] and [Formula: see text] and draw their orbits on [Formula: see text]. In classes 1-18, every nontrivial orbit tends to a fixed point on [Formula: see text]. In classes 19-25, each map possesses a unique positive fixed point which is a saddle on [Formula: see text], and hence Neimark-Sacker bifurcations do not occur. Neimark-Sacker bifurcation does occur within each of classes 26-31, while it does not occur in class 32. Each map from class 27 admits a heteroclinic cycle, which forms the boundary of [Formula: see text]. The criteria on the stability of heteroclinic cycles are also given. This classification makes it possible to further investigate various dynamical properties in respective class.

Monitoring Apoptosis of Breast Cancer Xenograft After Paclitaxel Treatment With 99mTc-Labeled Duramycin SPECT/CT.

Our goal was to validate the feasibility of(99m)Tc-duramycin as a potential apoptosis probe for monitoring tumor response to paclitaxel in breast cancer xenografts. The binding of(99m)Tc-duramycin to phosphatidylethanolamine was validated in vitro using paclitaxel-treated human breast carcinoma MDA-MB-231 cells. Female BALB/c mice (n = 5) bearing breast cancer xenografts were randomized into 2 groups and intraperitoneally injected with 40 mg/kg paclitaxel or phosphate-buffered saline.(99m)Tc-duramycin (37-55.5 MBq) was injected at 72 hours posttreatment, and single-photon emission computed tomography/computed tomography was performed at 2 hours postinjection. Apoptotic cells and activated caspase 3 in explanted tumor tissue were measured by flow cytometry. Cellular ultrastructural changes were assessed by light and transmission electron microscopy.(99m)Tc-duramycin with radiochemical purity of >90% exhibited rapid blood clearance and predominantly renal clearance. The tumor-to-muscle ratio in the paclitaxel-treated group (5.29 ± 0.62) was significantly higher than that in the control. Tumor volume was decreased dramatically, whereas tumor uptake of(99m)Tc-duramycin (ex vivo) significantly increased following paclitaxel treatment, which was consistent with apoptotic index, histological findings, and ultrastructural changes. Our data demonstrated the feasibility of(99m)Tc-duramycin for early detection of apoptosis after paclitaxel chemotherapy in breast carcinoma xenografts.

On heteroclinic cycles of competitive maps via carrying simplices.

We concentrate on the effects of heteroclinic cycles and the interplay of heteroclinic attractors or repellers on the boundary of the carrying simplices for low-dimensional discrete-time competitive systems. Based on the existence of the carrying simplex for the competitive mapping, we provide the criteria on stability of the heteroclinic cycle. This result can be seen as a discrete counterpart of that for the continuous-time systems. Several concrete discrete-time competition models are further analyzed, which do admit heteroclinic cycles. The criteria on the stability of the heteroclinic cycle for each model are also given, which are comparable with the corresponding continuous-time models.

RNF43 Inhibits Cancer Cell Proliferation and Could be a Potential Prognostic Factor for Human Gastric Carcinoma.

BACKGROUND/AIMS: RNF43 is a member of transmembrane E3 ubiquitin ligases and plays important roles in tumor formation progression. In current study, we aimed to explore RNF43 expression and analyze its role in gastric carcinoma. METHODS AND RESULTS: The level of RNF43 was detected in 77 cases of gastric carcinoma and matched normal tissues by real-time PCR, western blotting and immunohistochemistry. We found that the expression of RNF43 was significantly down-regulated in the gastric carcinoma tissues compared to the normal mucosae (all P<0.001). In addition, RNF43 was significantly correlated with histological differentiation (P = 0.001), T-stage cancer (P<0.001), depth of invasion (P<0.001), metastasis of regional lymph nodes (P<0.001), pTNM stage (P<0.001) and survival (P = 0.021). We further explored the biological functions of RNF43 in gastric carcinoma cell lines. Both gain- and loss-function assays show that RNF43 could suppress cell proliferation while promotes cell apoptosis. Further, we found that RNF43 was positively correlated with p53 and cleaved-caspase3 and negatively correlated with Ki67 and Lgr5. CONCOLUSION: In conclusion, RNF43 might act as a tumor suppressor in gastric carcinoma and might be a potential indicator for the clinical assessment of gastric cancer prognosis.

Role of the gut endoderm in relaying left-right patterning in mice.

Establishment of left-right (LR) asymmetry occurs after gastrulation commences and utilizes a conserved cascade of events. In the mouse, LR symmetry is broken at a midline structure, the node, and involves signal relay to the lateral plate, where it results in asymmetric organ morphogenesis. How information transmits from the node to the distantly situated lateral plate remains unclear. Noting that embryos lacking Sox17 exhibit defects in both gut endoderm formation and LR patterning, we investigated a potential connection between these two processes. We observed an endoderm-specific absence of the critical gap junction component, Connexin43 (Cx43), in Sox17 mutants. Iontophoretic dye injection experiments revealed planar gap junction coupling across the gut endoderm in wild-type but not Sox17 mutant embryos. They also revealed uncoupling of left and right sides of the gut endoderm in an isolated domain of gap junction intercellular communication at the midline, which in principle could function as a barrier to communication between the left and right sides of the embryo. The role for gap junction communication in LR patterning was confirmed by pharmacological inhibition, which molecularly recapitulated the mutant phenotype. Collectively, our data demonstrate that Cx43-mediated communication across gap junctions within the gut endoderm serves as a mechanism for information relay between node and lateral plate in a process that is critical for the establishment of LR asymmetry in mice.

The efficacy of sorafenib against hepatocellular carcinoma is enhanced by 5-aza-mediated inhibition of ID1 promoter methylation.

Sorafenib resistance greatly restricts its clinical application in patients with hepatocellular carcinoma (HCC). Numerous studies have reported that ID1 exerts a crucial effect in cancer initiation and development. Our previous research revealed an inhibitory role of ID1 in sorafenib resistance. However, the upstream regulatory mechanism of ID1 expression is unclear. Here, we discovered that ID1 expression is negatively correlated with promoter methylation, which is regulated by DNMT3B. Knockdown of DNMT3B significantly inhibited ID1 methylation status and resulted in an increase of ID1 expression. The demethylating agent 5-aza-2'-deoxycytidine (5-aza) remarkably upregulated ID1 expression. The combination of 5-aza with sorafenib showed a synergistic effect on the inhibition of cell viability.