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Abstract Medical image registration is essential and a key step in many advanced medical image tasks. In recent years, medical image registration has been applied to many clinical diagnoses, but large deformation registration is still a challenge. Deep learning‐based methods typically have higher accuracy but do not involve spatial transformation, which ignores some desirable properties, including topology preservation and the invertibility of transformation, for medical imaging studies. On the other hand, diffeomorphic registration methods achieve a differentiable spatial transformation, which guarantees topology preservation and invertibility of transformation, but registration accuracy is low. Therefore, a diffeomorphic deformation registration with CNN is proposed, based on a symmetric architecture, simultaneously estimating forward and inverse deformation fields. CNN with Efficient Channel Attention is used to better capture the spatial relationship. Deformation fields are optimized explicitly and implicitly to enhance the invertibility of transformations. An extensive experimental evaluation is performed using two 3D datasets. The proposed method is compared with different state‐of‐the‐art methods. The experimental results show excellent registration accuracy while better guaranteeing the diffeomorphic transformation.

Abstract Background Evidence suggests that insulin resistance (IR) is an autonomous risk factor for cardiovascular disease (CVD). Nevertheless, the association between estimated glucose disposal rate (eGDR), a novel indicator of IR, and incident CVD and mortality in chronic kidney disease (CKD) patients without diabetes remains uncertain. Methods The study included 19,906 participants from the UK Biobank who had an estimated glomerular filtration rate (eGFR)

Abstract The direct laser writing (DLW) of photoluminescent metal clusters is inspiring intensive research in functional glasses. However, understanding the influence of the host structure on cluster formation and visualizing DLW-induced clusters at the atomic scale remains challenging. In this work, we develop a highly photosensitive fluorophosphate glass through fluorine incorporation. The addition of fluorine establishes a conducive environment for Ag+ ions before DLW and enhances the availability of reducing agents and diffusion pathways during DLW. These advantages facilitate the formation of Ag clusters under low-energy single-pulsed DLW. Increasing laser energy results in a combination of Ag clusters and glasses defect, forming a dot + ring photoluminescent pattern. Atom probe tomography (APT), a technique capable of mapping the elemental spatial distribution and identifying clustering, is employed to gain more information on laser-induced clusters. Comparison of APT results between samples without and with DLW reveals the formation of Ag clusters after laser writing. The design concept and characterization enrich the understanding of Ag cluster behavior in glasses. This knowledge opens the possibility of rational design of clusters confined in glasses and inspires their synthesis for various applications.

Abstract Background Sepsis-associated acute kidney injury (SA-AKI) has high mortality rates. The osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK)/Toll-like receptor 4 (TLR4) pathway and its potential role in SA-AKI pathogenesis remain to be fully understood. Herein, we addressed this issue using mouse models. Methods An SA-AKI mouse model was established using the cecal ligation and puncture method (CLP). Mice were grouped into sham, CLP model, CLP + recombinant RANKL, and CLP + anti-RANKL groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were measured to assess kidney function. ELISA was used to detect serum IL-1β, TNF-α, and IL-6 levels. Real-time quantitative PCR and Western blot were used to detect the mRNA and protein expression levels of OPG, RANKL, RANK, and TLR4 in kidney tissues. HE staining was performed to evaluate the pathological changes. Results The CLP model group showed higher levels of Scr and BUN, indicating impaired kidney function in SA-AKI, compared to the sham group. Treatment with recombinant RANKL in the CLP + recombinant RANKL group reduced Scr and BUN levels, while anti-RANKL treatment in the CLP + anti-RANKL group elevated their levels. Moreover, the CLP model group had significantly increased IL-1β, TNF-α, and IL-6 than the sham group, indicating elevated inflammation in SA-AKI. The CLP + recombinant RANKL group demonstrated decreased cytokine levels, whereas the CLP + anti-RANKL group showed an increase. Additionally, the histopathological evaluation revealed distinct kidney tissue damage in the CLP model group. Recombinant RANKL treatment reduced this damage, while anti-RANKL treatment exacerbated it. Mechanically, the mRNA and protein expression of RANKL were significantly decreased, while those of OPG, RANK, and TLR4 were significantly increased in the CLP model group and the CLP + anti-RANKL group. Interestingly, treatment with recombinant RANKL reversed these changes, as evidenced by significantly increased RANKL but decreased OPG, RANK, and TLR4. Conclusion The OPG/RANKL/RANK/TLR4 pathway is involved in SA-AKI pathogenesis. Recombinant RANKL treatment attenuates the inflammatory response and kidney tissue damage in SA-AKI, possibly via regulating this pathway. This pathway shows promise as a therapeutic target for SA-AKI.

Abstract Accurate and efficient prediction of drug-target interaction (DTI) is critical to advance drug development and reduce the cost of drug discovery. Recently, the employment of deep learning methods has enhanced DTI prediction precision and efficacy, but it still encounters several challenges. The first challenge lies in the efficient learning of drug and protein feature representations alongside their interaction features to enhance DTI prediction. Another important challenge is to improve the generalization capability of the DTI model within real-world scenarios. To address these challenges, we propose CAT-DTI, a model based on cross-attention and Transformer, possessing domain adaptation capability. CAT-DTI effectively captures the drug-target interactions while adapting to out-of-distribution data. Specifically, we use a convolution neural network combined with a Transformer to encode the distance relationship between amino acids within protein sequences and employ a cross-attention module to capture the drug-target interaction features. Generalization to new DTI prediction scenarios is achieved by leveraging a conditional domain adversarial network, aligning DTI representations under diverse distributions. Experimental results within in-domain and cross-domain scenarios demonstrate that CAT-DTI model overall improves DTI prediction performance compared with previous methods.

Treatments of inflammatory bowel disease (IBD) are diverse, but their efficacy is limited, and it is therefore urgent to find better therapies. Controlling mucosal inflammation is a must in IBD drug treatment. The occurrence of anti-tumor necrosis factor α (TNF-α) monoclonal antibodies has provided a safer and more efficacious therapy. However, this kind of treatment still faces failure in the form of loss of response. β-Carboline alkaloids own an anti-inflammatory pharmacological activity. While Kumujan B contains β-carboline, its biological activity remains unknown. In this study, we attempted to determine the anti-inflammatory effects of Kumujan B using both the TNF-α- induced in vitro inflammation and DSS-induced in vivo murine IBD models. Our data show that Kumujan B attenuated the expression of interleukin 1β (IL-1β) and interleukin 6 (IL-6) induced by TNF-α in mouse peritoneal macrophages. Kumujan B suppressed c-Jun N-terminal protein kinases (JNK) signaling, especially c-Jun, for anti-inflammatory response. Furthermore, Kumujan B promoted K11-linked ubiquitination and degradation of c-Jun through the proteasome pathway. In an in vivo study, Kumujan B inhibited the expression of IL-1β, IL-6, and TNF-α and improved the colon barrier function in dextran sulfate sodium salt (DSS)-induced experimental mice colitis. Kumujan B exhibited in vivo and in vitro anti-inflammatory effects, making it a potential therapeutic candidate for treating IBD.

Abstract Entering the era of AI 2.0, bio‐inspired target recognition facilitates life. However, target recognition may suffer from some risks when the target is hijacked. Therefore, it is significantly important to provide an encryption process prior to neuromorphic computing. In this work, enlightened from time‐varied synaptic rule, an in‐memory asymmetric encryption as pre‐authentication is utilized with subsequent convolutional neural network (ConvNet) for target recognition, achieving in‐memory two‐factor authentication (IM‐2FA). The unipolar self‐oscillated synaptic behavior is adopted to function as in‐memory asymmetric encryption, which can greatly decrease the complexity of the peripheral circuit compared to bipolar stimulation. Results show that without passing the encryption process with suitable weights at the correct time, the ConvNet for target recognition will not work properly with an extremely low accuracy lower than 0.86%, thus effectively blocking out the potential risks of involuntary access. When a set of correct weights is evolved at a suitable time, a recognition rate as high as 99.82% can be implemented for target recognition, which verifies the effectiveness of the IM‐2FA strategy.

This study investigated the low-velocity impact response of titanium-based carbon-fibre/epoxy laminate (TI-CF FML). A comprehensive experimental study was carried out with impact energies ranging from 16.9 J to 91.9 J. Finite element analysis, performed using ABAQUS, was employed to elucidate the failure mechanisms of the laminate. Three distinct damage modes were identified based on the impact energy levels. The energy absorption characteristics of the TI-CF FML were analysed, revealing that maximum energy absorption is achieved and remains constant after penetration occurs. The relationship between impact force and displacement was also explored, showing that the laminate can withstand a peak force of 13.1 kN. The research on the impact resistance, damage mechanisms and energy absorption capacity of TI-CF FML provides an in-depth understanding of the impact behaviour of the laminate and its suitability for various industrial applications.

Abstract High‐performance organic neuromorphic devices with miniaturized device size and computing capability are essential elements for developing brain‐inspired humanoid intelligence technique. However, due to the structural inhomogeneity of most organic materials, downscaling of such devices to nanoscale and their high‐density integration into compact matrices with reliable device performance remain challenging at the moment. Herein, based on the design of a semicrystalline polymer PBFCL10 with ordered structure to regulate dense and uniform formation of conductive nanofilaments, we realize an organic synapse with the smallest device dimension of 50 nm and highest integration size of 1 Kb reported thus far. The as‐fabricated PBFCL10 synapses can switch between 32 conductance states linearly with a high cycle‐to‐cycle uniformity of 98.89% and device‐to‐device uniformity of 99.71%, which are the best results of organic devices. A mixed-signal neuromorphic hardware system based on the organic neuromatrix and FPGA controller is implemented to execute spiking‐plasticity‐related algorithm for decision-making tasks.

Abstract Background Colorectal cancer (CRC) is one of the three deadliest malignant tumors in the world, posing a severe hazard to human health. Nonetheless, the 5-year survival rate for advanced CRC remains unsatisfactory. Grid2 interacting protein (GRID2IP) is a Purkinje fiber postsynaptic scaffold protein implicated in a number of signal transduction pathways in the nervous system. Previous studies have shown that Grid2 is closely related to the occurrence and prognosis of gastric cancer and many other diseases. Therefore, we aim to identify the relationship between GRID2IP and the occurrence and prognosis of CRC. Methods Transcriptome data were retrieved from The Cancer Genome Atlas (TCGA) database to analyze the differential expression of GRID2IP in a variety of malignant tumors and then validate it by quantitative real time polymerase chain reaction(Q-PCR) and Western Blot in HT29 and SW480 cells. "DESeq2" package was used to analyze the differentially expressed genes (DEGs) between the high- and low-GRID2IP subgroups. In relation to DEGs, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. In addition, gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were employed to examine DEGs-associated signaling pathways and GRID2IP-associated immune cell infiltration levels. Besides, overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) were compared between the two subgroups using a Kaplan–Meier analysis. In addition, a prognostic model for GRID2IP and clinical characteristics was developed using the univariate Cox regression method. The "pRRophetic" package was applied to predict the drug sensitivity of different subgroups. Moreover, we also performed single-cell analysis of GRID2IP using the TISCH database. Results GRID2IP is upregulated in CRC patients. The rise of GRID2IP inhibits the invasion of tumor-associated immune cells resulting in a lower immune score. In addition, high GRID2IP expression was associated with poor prognosis in different clinical subgroups. Analysis of single cells revealed that GRID2IP was predominantly expressed in immune cells, myofibroblasts, and cancerous cells. In terms of chemotherapy drug sensitivity, the subgroup with high GRID2IP expression was less sensitive to gemcitabine. Conclusions Our results suggest that rising GRID2IP promotes tumor-associated immune cell infiltration and suggests adverse outcomes in CRC patients, which may be a useful biomarker for determining the prognosis of CRC and a potential target molecule for CRC therapy.

Seagrass is a group of flowering plants capable of completing their life cycle in a marine environment. It not only provides a refuge for biodiversity and essential fish spawning and nursery grounds, but also provides ecologically and socioeconomically important services for urban coasts. Seagrass is widely distributed along temperate and tropical coastlines globally. The biodiversity corresponds with differences in the relative importance of sexual (seed production) and asexual (clonal growth) life history strategies in the maintenance of seagrass populations. Sexual reproduction in predominantly clonal marine plants increases recombination favoring adaptation and enhancing species resilience to environmental change. Flowering induction is an important link in the transition from vegetative growth to reproductive growth of seagrasses. Recent studies on seagrasses suggest that flowering intensity and frequency are correlated with global climate change, and the response of seagrasses will be more complex, and potentially more resilient than previously imagined.Seagrass environments are characterized by physical conditions, such as temperature, salinity, currents, waves, turbulence, and light. Each of these parameters has the potential to affect vegetation from the smallest (molecular and physiological) to the largest (ecosystem as well as global) scale. Based on bibliometric methods, this study summarized the development trend of seagrass flowering formation research. The SCIE database of the Web of Science core collection of the Institute for Scientific Information (ISI) was chosen as the retrieval source, and select published international journals were chosen as the research object. With "seagrass flowering" as the search keyword, a total of 300 related publications were retrieved. In terms of the number of relevant publications each year, there was an overall increasing trend, indicating that this topic has gradually received more attention in recent years, which has great research potential.This review summarizes the research progress of flowering inducement in the sexual reproduction of seagrasses and discusses the influence of physical factors on the flowering induction of seagrasses. It was previously thought that the flowering pathway initiated by seagrasses in response to environmental factors and endogenous signals may focus on the photoperiod, vernalization, and spontaneous pathways. However, the sexual reproduction of different species is different, and studying the interaction between seagrasses and their physical environment may improve understanding of the processes that influence their biology. This review focuses on the following aspects: 1) Clarifying the period of concentrated flowering of the seagrass bed, which is conducive to studying the inducement of flowering of seagrass and protecting the seagrass seed bank. 2) Discussing whether more genotypes of seagrass should be introduced for planting in the process of seagrass bed repair to avoid large-scale clonal reproduction of a single genotype of seagrass. 3) How sexual reproduction of seagrasses under adverse environments can be used to indicate changes in the climate and environment. However, existing studies have paid little attention to the sexual reproduction of seagrass beds, and do not consider the sexual reproduction rate as a long-term monitoring indicator. It is suggested that the sexual reproduction rate should be combined with environmental factors in the future long-term monitoring and assessment of the health status of seagrass beds to jointly assess their pressure status.

Abstract Metal halide crystals are bright but hygroscopic scintillator materials that are widely used in X‐ray imaging and detectors. Precipitating them in situ in glass to form glass ceramics (GCs) scintillator offers an efficient avenue for large‐scale preparation, high spatial resolution, and excellent stability. However, precipitating a high fraction of metal halide nanocrystals in glass to maintain high light yield remains a challenge. Herein, an ionic‐covalent hybrid network strategy for constructing GCs scintillator with high crystallinity (up to ≈37%) of BaCl2: Eu2+ nanocrystals is presented. Experimental data and simulations of glass structure reveal that the Ba2+‐Cl− clustering promotes the high crystallization of BaCl2 nanocrystals. The ultralow phonon energy (≈200 cm−1) of BaCl2 nanocrystals and good Eu reduction effect enable high photoluminescence inter quantum efficiency (≈80.41%) in GC. GCs with varied crystallinity of BaCl2: Eu2+ nanocrystals demonstrate efficient radioluminescence and tunable scintillator performance. They either outperform Bi4Ge3O14 single crystal by over 132% steady‐state light yield or provide impressive X‐ray imaging resolutions of 20 lp mm−1. These findings provide a new design strategy for developing bright transparent GCs scintillators with a high fraction of metal halide nanocrystals for X‐ray high‐resolution imaging applications.

Abstract High‐performance artificial synapse with nonvolatile memory and low power consumption is a perfect candidate for brainoid intelligence. Unfortunately, due to the energy barrier paradox between ultra‐low power and nonvolatile modulation of device conductances, it is still a challenge at the moment to construct such ideal synapses. Herein, a proton‐reservoir type 4,4′,4″,4'''‐(Porphine‐5,10,15,20‐tetrayl) tetrakis (benzenesulfonic acid) (TPPS) molecule and fabricated organic protonic memristors with device width of 10 µm to 100 nm is synthesized. The occurrence of sequential proton migration and interfacial self‐coordinated doping will introduce new energy levels into the molecular bandgap, resulting in effective and nonvolatile modulation of device conductance over 64 continuous states with retention exceeding 30 min. The power consumptions of modulating and reading the device conductance approach the zero‐power operating limits, which range from 16.25 pW to 2.06 nW and 6.5 fW to 0.83 pW, respectively. Finally, a robust artificial synapse is successfully demonstrated, showing spiking‐rate‐dependent plasticity (SRDP) and spiking‐timing‐dependent plasticity (STDP) characteristics with ultra‐low power of 0.66 to 0.82 pW, as well as 100 long‐term depression (LTD)/potentiation (LTP) cycles with 0.14%/0.30% weight variations.

Fine particulate matter (PM2.5)-related health issues have received increasing attention as a worldwide public health problem, and PM2.5-related chronic kidney disease (CKD) has been emerging over the years. Limited research has focused on the mechanism of PM2.5-induced kidney disease. To investigate the impact of PM2.5 on the kidney and its potential mechanism, we generated a PM2.5-exposed C57BL/6 mouse model by using Shanghai Meteorological and Environment Animal Exposure System (Shanghai-METAS) for 12 weeks, urine, blood and kidney tissues were collected. The pathological changes and the function of the kidney were measured after PM2.5 exposure for 12 weeks. Along with glomerular damage, tubular damage was also severe in PM2.5-induced mice. The results of mRNA-seq indicate that pyroptosis is involved. Pyroptosis is defined as caspase-1-dependent programmed cell death in response to insults. The expression of the nucleotide-binding and oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3), Caspase-1, gasdermin D (GSDMD) and IL-1β was detected. NLRP3 inflammasome activation and subsequent pyroptosis were observed in PM2.5-exposed kidney tissues and PM2.5-exposed Bumpt cells too. At the meantime, the inhibitors of NLRP3 and caspase-1 were applied to the PM2.5 exposed Bumpt cells. It turned out to have a significant rescue effect of the inhibitors. This study revealed new insights into PM2.5-induced kidney injury and specific kidney pathological damage, as well as morphological changes, and defined the important role of pyroptosis in PM2.5-induced kidney dysfunction.

ABSTRACT: The gut microbiota is known to have significant involvement in the regulation of lipogenesis and adipogenesis, yet the mechanisms responsible for this relationship remain poorly understood. The current study aims to provide insight into the potential mechanisms by which the gut microbiota modulates lipogenesis in chickens. Using chickens fed with a normal-fat diet (NFD, n = 5) and high-fat diet (HFD, n = 5), we analyzed the correlation between gut microbiota, cecal metabolomics, and lipogenesis by 16s rRNA sequencing, miRNA and mRNA sequencing as well as targeted metabolomics analysis. The potential metabolite/miRNA/mRNA axis regulated by gut microbiota was identified using chickens treated with antibiotics (ABX, n = 5). The possible mechanism of gut microbiota regulating chicken lipogenesis was confirmed by fecal microbiota transplantation (FMT) from chickens fed with NFD to chickens fed with HFD (n = 5). The results showed that HFD significantly altered gut microbiota composition and enhanced chicken lipogenesis, with a significant correlation between 3. Furthermore, HFD significantly altered the hepatic miRNA expression profiles and reduced the abundance of hepatic butyric acid. Procrustes analysis indicated that the HFD-induced dysbiosis of the gut microbiota might affect the expression profiles of hepatic miRNA. Specifically, HFD-induced gut microbiota dysbiosis may reduce the abundance of butyric acid and downregulate the expression of miR-204 in the liver. Multiomics analysis identified ACSS2 as a target gene of miR-204. Gut microbiota depletion by an antibiotic cocktail (ABX) showed a gut microbiota-dependent manner in the abundance of butyric acid and the expression of miR-204/ACSS2, which have been observed to be significantly correlated. Fecal microbiota transplantation from NFD chickens into HFD chickens effectively attenuated the HFD-induced excessive lipogenesis, elevated the abundance of butyric acid and the relative expression of miR-204, and reduced the expression of ACSS2 in the liver. Mechanistically, our results showed that the gut microbiota plays an antiobesity role by regulating the butyric acid/miR-204/ACSS2 axis in chickens. This work contributed to a better understanding of the functions of gut microbiota in regulating chicken lipogenesis.

Context Coreopsis tinctoria Nutt (Asteraceae), named snow chrysanthemum, is known to have a high level of polyphenols. However, the potential prebiotic effect on modulating intestinal microflora is still unclear.Objective The chemical composition, antioxidant properties of snow chrysanthemum polyphenols (SCPs) and their effects on human intestinal microbiota were investigated.Materials and methods SCPs were extracted using ultrasonic-assisted extraction, and further determined using UPLC-QE Orbitrap/MS. Five assays were used to investigate the antioxidant activities of SCPs. Subsequently, the effects of SCPs on intestinal microbiota in vitro were determined by high throughput sequencing and bioinformatics analysis.Results Marein, isookanin and cymaroside were the major phenolic compounds, which accounted for 42.17%, 19.53% and 12.25%, respectively. Marein exhibited higher scavenging capacities in DPPH (EC50 = 8.84 µg/mL) and super anion radical assay (EC50 = 282.1 µg/mL) compared to cymaroside and isookanin. The antioxidant capacity of cymaroside was weakest among the three phenolic compounds due to the highest EC50 values, especially for superoxide anion radical assay, EC50 > 800 µg/mL. The result of in vitro fermentation showed that the three phenolic compounds increased the relative abundances of Escherichia/Shigella, Enterococcus, Klebsiella, etc., and isookanin notably increased the relative abundance of Bifidobacterium and Lactobacillus.Discussion and conclusions SCPs exhibited antioxidant properties and potential prebiotic effects on modulating the gut microbiota composition. The findings indicated that SCPs consumption could exert prebiotic activity that is beneficial for human health.

Background: The elevated Cyclin B1 expression contributes to various tumorigenesis and poor prognosis. Cyclin B1 expression could be regulated by ubiquitination and deubiquitination. However, the mechanism of how Cyclin B1 is deubiquitinated and its roles in human glioma remain unclear. Methods: Co-immunoprecipitation and other assays were performed to detect the interacting of Cyclin B1 and USP39. A series of in vitro and in vivo experiments were performed to investigate the effect of USP39 on the tumorigenicity of tumor cells. Results: USP39 interacts with Cyclin B1 and stabilizes its expression by deubiquitinating Cyclin B1. Notably, USP39 cleaves the K29-linked polyubiquitin chain on Cyclin B1 at Lys242. Additionally, overexpression of Cyclin B1 rescues the arrested cell cycle at G2/M transition and the suppressed proliferation of glioma cells caused by USP39 knockdown in vitro. Furthermore, USP39 promotes the growth of glioma xenograft in subcutaneous and in situ of nude mice. Finally, in human tumor specimens, the expression levels of USP39 and Cyclin B1 are positively relevant. Conclusion: Our data support the evidence that USP39 acts a novel deubiquitinating enzyme of Cyclin B1 and promoted tumor cell proliferation at least in part through Cyclin B1 stabilization, represents a promising therapeutic strategy for tumor patients.

Actively transitioning between clamping and grasping is a challenging problem for most manipulators with limited degrees of freedom. To overcome this problem, a cable-driven rigid–flexible combined manipulator capable of actively transitioning between clamping and grasping is proposed in this paper, which has a certain adaptability and compliance to achieve adaptive operation. First, the cable-driven unit and compliant unit of the cable-driven rigid–flexible combined manipulator are designed. Then, the sensitivity of the mechanism parameters is analyzed using the Monte Carlo method, and then the structure of the cable-driven rigid–flexible combined manipulator is optimized. After that, the force on the finger in two-point clamping mode is modelled using Newton’s second law. Furthermore, the input–output relationship modelling of the finger in envelope grasping mode is deeply analyzed using the principle of energy conservation. Finally, the stable grasping performance of the cable-driven rigid–flexible combined manipulator is verified using numerical simulation and physical prototype tests. The results show that the cable-driven rigid–flexible combined manipulator has good adaptability and compliance, which verifies the effectiveness and rationality of the design and modelling.

Abstract Background Esophageal microbiota may influence esophageal squamous cell carcinoma (ESCC) pathobiology. Therefore, we investigated the characteristics and interplay of the esophageal microbiota in ESCC. Methods We performed 16S ribosomal RNA sequencing on paired esophageal tumor and tumor-adjacent samples obtained from 120 primarily ESCC patients. Analyses were performed using quantitative insights into microbial 2 (QIIME2) and phylogenetic investigation of communities by reconstruction of unobserved states 2 (PICRUSt2). Species found to be associated with ESCC were validated using quantitative PCR. Results The microbial diversity and composition of ESCC tumor tissues significantly differed from tumor-adjacent tissues; this variation between subjects beta diversity is mainly explained by regions and sampling seasons. A total of 56 taxa were detected with differential abundance between the two groups, such as R. mucilaginosa, P. endodontalis, N. subflava, H. Pylori, A. Parahaemolyticus, and A. Rhizosphaerae. Quantitative PCR confirmed the enrichment of the species P. endodontalis and the reduction of H. Pylori in tumor-adjacent tissues. Compared with tumor tissue, a denser and more complex association network was formed in tumor-adjacent tissue. The above differential taxa, such as H. Pylori, an unclassified species in the genera Sphingomonas, Haemophilus, Phyllobacterium, and Campylobacter, also participated in both co-occurrence networks but played quite different roles. Most of the differentially abundant taxa in tumor-adjacent tissues were negatively associated with the epidermal growth factor receptor (EGFR), erb-b2 receptor tyrosine kinase 2 (ERBB2), erb-b2 receptor tyrosine kinase 4 (ERBB4), and fibroblast growth factor receptor 1 (FGFR1) signaling pathways, and positively associated with the MET proto-oncogene, receptor tyrosine kinase (MET) and phosphatase and tensin homolog (PTEN) signaling pathways in tumors. Conclusion Alterations in the microbial co-occurrence network and functional pathways in ESCC tissues may be involved in carcinogenesis and the maintenance of the local microenvironment for ESCC.

The NLRP3 inflammasome plays a critical role in the innate immune response, and its excessive activation will cause pyroptotic cell death and be associated with the onset of inflammatory diseases. However, NLRP3 inflammasome targeting therapies are still to be implemented in the clinic setting. Here, we first isolated, purified and characterized a novel Vitenegu acid from V. negundo L. herb that specifically inhibits NLRP3 inflammasome activation, without affecting NLRC4 or AIM2 inflammasomes. Vitenegu acid blocks the oligomerization of NLRP3, thus inhibiting NLRP3 inflammasome assembly and activation. In vivo data show that Vitenegu acid exerts therapeutic effects on NLRP3 inflammasome-dependent inflammation. Taken together, our results suggest that Vitenegu acid is a candidate therapeutic agent for treating NLRP3 inflammasome related diseases.

Glioma cells are characterized by high migration and invasion ability; however, the molecular mechanism behind both processes still remains to be investigated. Several studies have demonstrated that ubiquitin‐specific protease 39 (USP39) plays an oncogenic role in various cancer types. Here, we investigated the expression and function of USP39 in patients with glioma. Oncomine database analysis revealed that high USP39 expression was significantly correlated with poor overall survival in patients with glioma. Knockdown of USP39 in U251 and U87 cell lines significantly inhibited their migration and invasion in vitro. Gene expression profiling of glioma cells transduced with short hairpin RNA (shRNA) against USP39 revealed that disintegrin and metalloproteinase domain‐containing protein 9 (ADAM9), a molecule previously related to tumor cell migration and invasion, was significantly downregulated. Furthermore, USP39 induced ADAM9 messenger RNA (mRNA) maturation and decreased the expression of integrin β1. Additionally, overexpression of ADAM9 inhibited the migration and invasion of glioma cells caused by USP39 depletion in vitro. USP39 promoted the invasion of glioma cells in vivo and reduced the overall survival of the mice. Altogether, our data show that USP39 induces mRNA maturation and elevates the expression of ADAM9 in glioma cells and may thus be considered potential target for treating patients with glioma.

PurposeIn our study, we aim to analyze the impact of clinicopathological factors on the recommendation of extended endocrine therapy (EET) in patients with ER+ breast cancer and to retrospectively validate the value of CTS5 in EET decision making.Patients and methodsThe retrospective analysis was performed in patients with ER+ breast cancer who have finished 4.5–5 years of adjuvant endocrine therapy and undergone MDT discussion from October 2017 to November 2019. Multivariate logistic regression was used to identify the independent factors for treatment recommendation. CTS5 was calculated for retrospective validation of the EET decision making.ResultsTwo hundred thirty-five patients were received; 4.5–5 years of adjuvant endocrine therapy were included in the study. Multivariate analysis suggested that age (OR 0.460, 95% CI 0.219–0.965, p = 0.04), pN (OR 39.350, 95% CI 9.831–157.341, P < 0.001), and receipt of chemotherapy (OR 3.478, 95% CI 1.336–9.055, p = 0.011) were independent predictors for the recommendation of EET. In the previously selective estrogen receptor modulator (SERM)–treated subgroup, pN and receipt of chemotherapy were independent predictors for the recommendation of EET. In the previously AI-treated subgroup, age, pN, and receipt of chemotherapy were independent predictors. Adverse events did not affect the recommendation in patients previously treated with adjuvant endocrine treatment nor in the previously SERM or AI-treated subgroups. CTS5 (OR 21.887, 95% CI 2.846–168.309, p = 0.003) remained an independent predictor for the recommendation of EET.ConclusionsOur study indicated that age, lymph nodal status, and receipt of chemotherapy were independent predictors for the recommendation of EET. The application of the CTS5 on EET decision making might be valuable among ER+ breast cancer patients.

Global change has generated challenges for oceans, from individuals to the entire ecosystem, and has raised contemporary issues related to ocean conservation and management. Specifically, coral reef ecosystems have been exposed to various environmental and human disturbances. In this study, the Ecopath with Ecosim model was used to explore the impacts of ocean warming and fishing on Xisha Islands coral reef ecosystem in the South China Sea. The variables in this model included two ocean warming scenarios and three fishing scenarios. The model consisted of 23 functional groups including algae, coral, sea birds, and sharks. Our results showed that by the middle of the century, ocean warming and fishing led to a 3.79% and 4.74% decrease in total catch compared with 2009, respectively. In addition, the combined effects of ocean warming and fishing caused a 4.79% decrease in total catch, and the mean trophic level of catch was predicted to decrease by 6.01% under the SSP585-High fishing scenario. Reducing the fishing effort mitigates the effects of ocean warming on some species, such as large carnivorous fish and medium carnivorous fish; however, under low fishing effort, some functional groups, such as small carnivorous and omnivorous fish, have low biomass because of higher predation mortality.

Fungal infections cause serious health problems, especially in patients with an immune-deficiency. Histone deacetylase 11 (HDAC11) mediates various immune functions, yet little is known about its role in regulating host immune responses to fungal infection. Here we report that HDAC11 negatively controls antifungal immunity in macrophages and dendritic cells. Deleting Hdac11 protects mice from morbidity and markedly improves their survival rate upon systemic infection with Candida albicans (C. albicans). Moreover, HDAC11 deficiency results in increased production of NO and reactive oxygen species, which enhances fungal killing. Mechanistically, loss of HDAC11 increases histone 3 and 4 acetylation at the Nos2 promoter and leads to enhanced Nos2 transcription and corresponding iNOS levels in macrophages. In addition, STAT3, a transcriptional repressor of Nos2, physically interacts with HDAC11, serving as a scaffold protein supporting the HDAC11 association with the Nos2 promoter. Notably, treatment with the HDAC11 inhibitor, FT895, exhibits antifungal therapeutic effects in both mouse and human cells challenged with C. albicans. These data support that HDAC11 may be a therapeutic target for fungal infection.

Inflammatory bowel diseases (IBDs) are increasingly common diseases characterized by chronic and relapsing inflammation of the gastrointestinal tract. NLRP3 might be a crucial regulator of the homeostatic balance of the intestine, but its upregulation leads to pyroptosis. Munronoid I is extracted and purified from Munronia sinica, which has shown an anti-inflammatory effect, but the efficacy of Munronoid I in IBD remains unproven. In this study, we attempted to determine the effect of Munronoid I on NLRP3 to regulate the inflammasome activation and pyroptosis in IBD. Our data demonstrated that Munronoid I treatment attenuated DSS-induced body weight loss, pathological injury of the colon, the production of IL-1β and IL-18, and the expression of pyroptosis-associated proteins in colon tissue in mice. Moreover, Munronoid I inhibited LPS/ATP-induced pyroptosis in mouse peritoneal macrophages, MODE-K cells, and DSS-induced pyroptosis in mouse colonic epithelial cells, and decreased the release of inflammatory cytokines IL-1β and IL-18 in mouse peritoneal macrophages. Mechanically, Munronoid I could suppress the NLRP3 inflammasome activation and pyroptosis by promoting the K48-linked ubiquitination and NLRP3 degradation. It is suggested that Munronoid I might be a potential therapeutic candidate for IBD.

Intelligent detection and localization of mature citrus fruits is a critical challenge in developing an automatic harvesting robot. Variable illumination conditions and different occlusion states are some of the essential issues that must be addressed for the accurate detection and localization of citrus in the orchard environment. In this paper, a novel method for the detection and localization of mature citrus using improved You Only Look Once (YOLO) v5s with binocular vision is proposed. First, a new loss function (polarity binary cross-entropy with logit loss) for YOLO v5s is designed to calculate the loss value of class probability and objectness score, so that a large penalty for false and missing detection is applied during the training process. Second, to recover the missing depth information caused by randomly overlapping background participants, Cr-Cb chromatic mapping, the Otsu thresholding algorithm, and morphological processing are successively used to extract the complete shape of the citrus, and the kriging method is applied to obtain the best linear unbiased estimator for the missing depth value. Finally, the citrus spatial position and posture information are obtained according to the camera imaging model and the geometric features of the citrus. The experimental results show that the recall rates of citrus detection under non-uniform illumination conditions, weak illumination, and well illumination are 99.55%, 98.47%, and 98.48%, respectively, approximately 2–9% higher than those of the original YOLO v5s network. The average error of the distance between the citrus fruit and the camera is 3.98 mm, and the average errors of the citrus diameters in the 3D direction are less than 2.75 mm. The average detection time per frame is 78.96 ms. The results indicate that our method can detect and localize citrus fruits in the complex environment of orchards with high accuracy and speed. Our dataset and codes are available at https://github.com/AshesBen/citrus-detection-localization.

The measurement of grapevine phenotypic parameters is crucial to quantify crop traits. However, individual differences in grape bunches pose challenges in accurately measuring their characteristic parameters. Hence, this study explores a method for estimating grape feature parameters based on point cloud information: segment the grape point cloud by filtering and region growing algorithm, and register the complete grape point cloud model by the improved iterative closest point algorithm. After estimating model phenotypic size characteristics, the grape bunch surface was reconstructed using the Poisson algorithm. Through the comparative analysis with the existing four methods (geometric model, 3D convex hull, 3D alpha-shape, and voxel-based), the estimation results of the algorithm proposed in this study are the closest to the measured parameters. Experimental data show that the coefficient of determination (R2) of the Poisson reconstruction algorithm is 0.9915, which is 0.2306 higher than the coefficient estimated by the existing alpha-shape algorithm (R2 = 0.7609). Therefore, the method proposed in this study provides a strong basis for the quantification of grape traits.

Though polymer memristors are promising for low‐power flexible edge computing applications, realizing efficient nanometer‐scale arrays remains a challenge. Here, the authors report a record high 90% production yield in nm‐scale 2D conjugated polymer memristors with homogeneous resistive switching.

The effective and reliable monitoring of fish communities is important for the management and protection of marine ecosystems. Environmental DNA (eDNA) metabarcoding is a relatively new method that has been widely used in recent years, while traditional sampling via fish catching (i.e., gillnets) is one of the most common and reliable fish monitoring methods used to date. We compared the taxonomic and functional diversity of fish detected within a mangrove–seagrass–coral reef continuum using both survey methods. One liter seawater and gillnet samples were collected in August 2021 from mangrove forests, seagrass meadows and coral reef habitats (n = 3 each) in Hainan, China. Surveys using eDNA and gillnets identified 139 genera belonging to 66 families and 58 genera belonging to 42 families, respectively. Regardless of the survey method, fish detected in mangrove, seagrass and coral reef habitats were heterogeneous in their communities; however, the shared species between habitats suggest some degree of connectivity. There were no significant differences between habitats in terms of taxonomic and functional diversity, but a higher taxonomic diversity was detected using eDNA. Both methods were able to distinguish fish assemblages between different habitats; however, gillnet surveys performed better than eDNA surveys for distinguishing mangrove from seagrass assemblages. Therefore, the concurrent use of eDNA and gillnet survey methods provides a more comprehensive approach to understanding the heterogeneity of fish taxonomic and functional diversity along mangrove–seagrass–coral reef continuums.

Growing evidence has shown the involvement of the gut–liver axis in lipogenesis and fat deposition. However, how the gut crosstalk with the liver and the potential role of gut–liver crosstalk in the lipogenesis of chicken remains largely unknown. In this study, to identify gut–liver crosstalks involved in regulating the lipogenesis of chicken, we first established an HFD-induced obese chicken model. Using this model, we detected the changes in the metabolic profiles of the cecum and liver in response to the HFD-induced excessive lipogenesis using ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) analysis. The changes in the gene expression profiles of the liver were examined by RNA sequencing. The potential gut–liver crosstalks were identified by the correlation analysis of key metabolites and genes. The results showed that a total of 113 and 73 differentially abundant metabolites (DAMs) between NFD and HFD groups were identified in the chicken cecum and liver, respectively. Eleven DAMs overlayed between the two comparisons, in which ten DAMs showed consistent abundance trends in the cecum and liver after HFD feeding, suggesting their potential as signaling molecules between the gut and liver. RNA sequencing identified 271 differentially expressed genes (DEGs) in the liver of chickens fed with NFD vs. HFD. Thirty-five DEGs were involved in the lipid metabolic process, which might be candidate genes regulating the lipogenesis of chicken. Correlation analysis indicated that 5-hydroxyisourate, alpha-linolenic acid, bovinic acid, linoleic acid, and trans-2-octenoic acid might be transported from gut to liver, and thereby up-regulate the expression of ACSS2, PCSK9, and CYP2C18 and down-regulate one or more genes of CDS1, ST8SIA6, LOC415787, MOGAT1, PLIN1, LOC423719, and EDN2 in the liver to enhance the lipogenesis of chicken. Moreover, taurocholic acid might be transported from the gut to the liver and contribute to HFD-induced lipogenesis by regulating the expression of ACACA, FASN, AACS, and LPL in the liver. Our findings contribute to a better understanding of gut–liver crosstalks and their potential roles in regulating chicken lipogenesis.

The increasing hazards caused by construction and demolition (C&D) waste is an inevitable problem in the development of the construction industry. Many countries have successively launched many policies to encourage and guide the recycling of C&D waste, which has greatly improved the recycling rate of C&D waste. However, most of these policies only regulate contractors but do not promote C&D waste recycling products enough. It has led to an increase in the production of C&D waste recycling products while the acceptance in the market is generally low. Consumers believe that products made with “garbage” may have problems such as quality defects. In order to explore a measure that can mitigate this problem, this study uses functional near infrared spectroscopy (fNIRS) to investigate whether the influence of media can increase consumers’ willingness to purchase products for recycling construction and demolition waste, and thus increase consumers’ choice to purchase products for C&D recycling waste. This experiment consists of two phases. First, a pre-test experiment to obtain pre-intervention brain images characterizing consumers’ original attitudes toward C&D recycling waste products through a functional near-infrared imaging brain technique and a questionnaire. Second, The post-test builds on the pre-test to investigate the effectiveness of the intervention. The activation mechanism of the consumer purchase decision is further investigated by fNIRS data. The behavioral results showed that the choice of recycled C&D waste products was significantly higher after the intervention. The fNIRS results further revealed the significantly higher activation of the dorsolateral prefrontal cortex (dlPFC), orbitofrontal cortex (OFC), and medial prefrontal cortex (mPFC) after the intervention. These findings suggest that consumers’ purchase willingness is significantly improved after intervention, and their purchase behavior changed substantially. This study also demonstrates the great potential of fNIRS for interdisciplinary research in engineering management and neuroscience.

Succinate is at the crossroads of multiple metabolic pathways and plays a role in several immune responses acting as an inflammation signal. However, whether succinate regulates antiviral immune response remains unclear. Here, we found that the production of succinate was reduced in RAW264.7 cells during vesicular stomatitis virus (VSV) infection. Using diethyl succinate to pretreat the mouse peritoneal macrophages and RAW264.7 cells before VSV infection, the production of interferon-β (IFN-β), chemokine (C–X–C motif) ligand 10 (CXCL-10), and IFN-stimulated genes 15 (ISG15) was significantly decreased, following which the VSV replication in diethyl succinate-pretreated cells was obviously increased. Moreover, succinate decreased the expression of IFN-β in serum, lung, and spleen derived from the VSV-infected mice. The overall survival rate in the VSV-infected mice with diethyl succinate pretreatment was also remarkably downregulated. Furthermore, we identified that succinate inhibited the activation of MAVS-TBK1-IRF3 signaling by suppressing the formation of MAVS aggregates. Our findings provide previously unrecognized roles of succinate in antiviral immune response and establish a novel link between metabolism and innate immune response.

Summary: Purpose: To investigate the effectiveness of a structured death education program for older adults with chronic illness and their family caregivers. Methods: This study adopted two-group, nonrandomized quasi-experimental design. Patient–caregiver dyads in the intervention group (N = 40 dyads) engaged in the death education program at the bedside once a week for 5 weeks, and were compared with participants (N = 40 dyads) in the control group who received usual health education. The program consisted of five sessions based on the Interaction Model of Client Health Behavior. Death attitude, death competence, well-being, family function, and satisfaction were measured at baseline (T0), immediately after the intervention (T1), and 1 month later (T2). Data collection was conducted from July 30, 2019, to December 30, 2019. Results: The intention-to-treat analysis The intention-to-treat analysis of between groups at 1-month follow-up revealed that the intervention group had greater decreases in the fear of death (p=.002, 95% CI -2.53, -0.47; p

Bactericera gobica is the major pest of Goji berry plants and causes severe damage. Psyllids mainly use the antennal sensilla to recognize olfactory cues necessary to find host plants and mates. However, the structure and function of the antenna and the antennal sensilla of B. gobica remains previously unexplored. Here, we identify the external and internal morphology of the antennal sensilla of B. gobica using both scanning electron microscopy (SEM) and transmission electron microscopy (TEM). We found seven types of sensilla on the filiform antennae, including apical setae (LAS, SAS), sensilla basiconica (SB1, SB2), sensilla campaniform (SCA), sensilla chaetica (ChS1, ChS2), cavity sensilla (CvS1, CvS2), antennal rhinaria (AR1, AR2), and sensilla trichodea (ST). Five of these sensilla types—apical setae, sensilla basiconica, sensilla chaetica, cavity sensilla, and antennal rhinaria—may have olfactory functions based on their porous surfaces and internal dendritic outer segments (DOS). We also found several differences between the two sexes of B. gobica in the sensilla array and internal structure. ChS and DOS in the protrusions of AR were more abundant in males than females. Altogether, we comprehensively revealed the fine structure and probable function of B. gobica antennae and identified differences in the distribution and structure between psyllid sexes. Our findings provide important insights for future studies on defining the olfactory function of psyllid antenna using electrophysiological methods.

Inflammation is a biological process closely related to different kinds of diseases, such as cancer and metabolic diseases. Therefore, effective control of the occurrence and development of inflammation is of great significance for disease prevention and control. Recently, 2-substituted indoles have gradually become a research hotspot because of their stability and pharmacological activity. Here we synthesized a series of compound containing 2-substituted indoles and investigated XCR-7a’s role in inflammatory response. Our data show that XCR-7a can inhibit the production of inflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and inflammatory mediator cyclooxygenase-2 (COX-2) induced by lipopolysaccharide (LPS) in mouse peritoneal macrophages. Also, XCR-7a has a protective effect on LPS-induced inflammatory response in mice. Mechanically, we found that XCR-7a could inhibit the phosphorylation of c-Fos induced by LPS, which suggested that the protective effect of XCR-7a on inflammation was related to its negative regulation to phosphorylation of c-Fos. Briefly, our results demonstrated that XCR-7a could be expected to be a potential drug for controlling inflammation.

Summary: Biological visual system can efficiently handle optical information within the retina and visual cortex of the brain, which suggests an alternative approach for the upgrading of the current low-intelligence, large energy consumption, and complex circuitry of the artificial vision system for high-performance edge computing applications. In recent years, retinomorphic machine vision based on the integration of optoelectronic image sensors and processors has been regarded as a promising candidate to improve this phenomenon. This novel intelligent machine vision technology can perform information preprocessing near or even within the sensor in the front end, thereby reducing the transmission of redundant raw data and improving the efficiency of the back-end processor for high-level computing tasks. In this contribution, we try to present a comprehensive review on the recent progress achieved in this emergent field.

Protein-based high internal phase Pickering emulsions (HIPEs) are emulsions using protein particles as a stabilizer in which the volume fraction of the dispersed phase exceeds 74%. Stabilizers are irreversibly adsorbed at the interface of the oil phase and water phase to maintain the droplet structure. Protein-based HIPEs have shown great potential for a variety of fields, including foods, due to the wide range of materials, simple preparation, and good biocompatibility. This review introduces the preparation routes of protein-based HIPEs and summarizes and classifies the preparation methods of protein stabilizers according to their formation mechanism. Further outlined are the types and properties of protein stabilizers used in the present studies, the composition of the oil phase, the encapsulating substances, and the properties of the constituted protein-based HIPEs. Finally, future development of protein-based HIPEs was explored, such as the development of protein-based stabilizers, the improvement of emulsification technology, and the quality control of stabilizers and protein-based HIPEs.

Abstract Background No previous study has investigated the association between oolong tea consumption and esophageal squamous cell carcinoma (ESCC), we aim to elucidate the association between oolong tea consumption and ESCC and its joint effects with a novel composite index. Methods In a hospital-based case-control study, 646 cases of ESCC patients and 646 sex and age matched controls were recruited. A composite index was calculated to evaluate the role of demographic characteristics and life exposure factors in ESCC. Unconditional logistic regression was used to calculate the point estimates between oolong tea consumption and risk of ESCC. Results No statistically significant association was found between oolong tea consumption and ESCC (OR = 1.39, 95% CI: 0.94–2.05). However, drinking hot oolong tea associated with increased risk of ESCC (OR = 1.60, 95% Cl: 1.06–2.41). Furthermore, drinking hot oolong tea increased ESCC risk in the high-risk group (composite index> 0.55) (OR = 3.14, 95% CI: 1.93–5.11), but not in the low-risk group (composite index≤0.55) (OR = 1.16, 95% CI: 0.74–1.83). Drinking warm oolong tea did not influence the risk of ESCC. Conclusions No association between oolong tea consumption and risk of ESCC were found, however, drinking hot oolong tea significantly increased the risk of ESCC, especially in high-risk populations.

BackgroundThe 21-gene assay recurrence score (RS) provides additional information on recurrence risk of breast cancer patients and prediction of chemotherapy benefit. Previous studies that examined the contribution of the individual genes and gene modules of RS were conducted mostly in postmenopausal patients. We aimed to evaluate the gene modules of RS in patients of different ages.MethodsA total of 1,078 estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients diagnosed between January 2009 and March 2017 from Shanghai Jiao Tong University Breast Cancer Data Base were included. All patients were divided into three subgroups: Group A, ≤40 years and premenopausal (n = 97); Group B, >40 years and premenopausal (n = 284); Group C, postmenopausal (n = 697). The estrogen, proliferation, invasion, and HER2 module scores from RS were used to characterize the respective molecular features. Spearman correlation and analysis of the variance tests were conducted for RS and its constituent modules.ResultsIn patients >40 years, RS had a strong negative correlation with its estrogen module (ρ = −0.76 and −0.79 in Groups B and C) and a weak positive correlation with its invasion module (ρ = 0.29 and 0.25 in Groups B and C). The proliferation module mostly contributed to the variance in young patients (37.3%) while the ER module contributed most in old patients (54.1% and 53.4% in Groups B and C). In the genetic high-risk (RS >25) group, the proliferation module was the leading driver in all patients (ρ = 0.38, 0.53, and 0.52 in Groups A, B, and C) while the estrogen module had a weaker correlation with RS. The impact of ER module on RS was stronger in clinical low-risk patients while the effect of the proliferation module was stronger in clinical high-risk patients. The association between the RS and estrogen module was weaker among younger patients, especially in genetic low-risk patients.ConclusionsRS was primarily driven by the estrogen module regardless of age, but the proliferation module had a stronger impact on RS in younger patients. The impact of modules varied in patients with different genetic and clinical risks.

Compound extremes pose immense challenges and hazards to communities, and this is particularly true for compound hydrometeorological extremes associated with deadly floods, surges, droughts, and heat waves. To mitigate and better adapt to compound hydrometeorological extremes, we need to better understand the state of knowledge of such extremes. Here we review the current advances in understanding compound hydrometeorological extremes: compound heat wave and drought (hot-dry), compound heat stress and extreme precipitation (hot-wet), cold-wet, cold-dry and compound flooding. We focus on the drivers of these extremes and methods used to investigate and quantify their associated risk. Overall, hot-dry compound extremes are tied to subtropical highs, blocking highs, atmospheric stagnation events, and planetary wave patterns, which are modulated by atmosphere-land feedbacks. Compared with hot-dry compound extremes, hot-wet events are less examined in the literature with most works focusing on case studies. The cold-wet compound events are commonly associated with snowfall and cold frontal systems. Although cold-dry events have been found to decrease, their underlying mechanisms require further investigation. Compound flooding encompasses storm surge and high rainfall, storm surge and sea level rise, storm surge and riverine flooding, and coastal and riverine flooding. Overall, there is a growing risk of compound flooding in the future due to changes in sea level rise, storm intensity, storm precipitation, and land-use-land-cover change. To understand processes and interactions underlying compound extremes, numerical models have been used to complement statistical modeling of the dependence between the components of compound extremes. While global climate models can simulate certain types of compound extremes, high-resolution regional models coupled with land and hydrological models are required to simulate the variability of compound extremes and to project changes in the risk of such extremes. In terms of statistical modeling of compound extremes, previous studies have used empirical approach, event coincidence analysis, multivariate distribution, the indicator approach, quantile regression and the Markov Chain method to understand the dependence, greatly advancing the state of science of compound extremes. Overall, the selection of methods depends on the type of compound extremes of interests and relevant variables.

Polyoxometalates (POMs) can enable energy level tuning to match perovskite layers. They are considered electronic bridges to modify perovskite and improve the performance of photovoltaic devices. Therefore, in the present work, we dispersed the vacancy POMs K8[α-SiW11O39]·H2O ({SiW11}) in the metal-organic frameworks (MOFs) to modify the perovskite layer. {SiW11} could adjust the energy level between the layers of the perovskite photodetector. Moreover, the hydrogen bonds formed between SiW11@ZIF-8 and perovskite effectively passivated the grain boundaries (GBs) of the perovskite layer. X-ray diffraction spectroscopy (XRD) showed that the crystallinity of perovskite was significantly improved. In addition, scanning electron microscopy (SEM) images demonstrated that the average size of perovskite grains increased from 254.50 to 719.27 nm, proving the effective passivation of the GBs. Furthermore, a series of tests such as infrared spectroscopy (IR), N2 adsorption/desorption isotherms, transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) also proved that {SiW11} could be successfully loaded into the pores of ZIF-8 through electrostatic interactions. The photocurrent of the SiW11@ZIF-8 doped device reached 41.95 μA, about three times as high as that of the blank device (14.41 μA). Also, under unencapsulated conditions, it could still maintain more than 90% stability for nearly 700 h. This work demonstrates the potential application of POM@MOF-type composites in the field of perovskite photodetectors.

To improve the adaptive clamping performance of traditional single-tendon-driven underactuated grippers for grasping multiple categories of objects, a novel dual-tendon-driven underactuated gripper is proposed in this paper. First, two independent tendons with different winding paths are designed in the gripper to realize the changeable resultant moment of the end knuckle rotating joint and the movement sequences of gripper knuckles driven by different tendons are analysed too. Then, some kinematic analysis and dynamical simulations are carried out to verify the validation of the knuckle structure and dual-tendon winding path design. At last, a prototype of the novel gripper is manufactured and some grasping experiments are carried out on multiple categories of objects, with different sizes and shapes. The experimental results show that all the objects can be clamped tightly. Compared with the traditional single-tendon-driven gripper, the novel one can achieve a more flexible grasping operation and a larger end clamping force, which are more suitable for the adaptive grasping requirements of robotic automatic sorting.

The growth and development of skeletal muscle determine the productivity of pigeon meat production, and miRNA plays an important role in the growth and development of this type of muscle. However, there are few reports regarding miRNA regulating the growth and development of skeletal muscle in pigeons. To explore the function of miRNA in regulating the growth and development of pigeon skeletal muscle, we used RNA sequencing technology to study the transcriptome of pigeons at two embryonic stages (E8 and E13) and two growth stages (D1 and D10). A total of 32,527 mRNAs were identified in pigeon skeletal muscles, including 14,378 novel mRNAs and 18,149 known mRNAs. A total of 2362 miRNAs were identified, including 1758 known miRNAs and 624 novel miRNAs. In total, 839 differentially expressed miRNAs (DEmiRNAs) and 11,311 differentially expressed mRNAs (DEGs) were identified. STEM clustering analysis assigned DEmiRNAs to 20 profiles, of which 7 were significantly enriched (p-value < 0.05). These seven significantly enriched profiles can be classified into two categories. The first category represents DEmiRNAs continuously downregulated from the developmental stage to the growth stage of pigeon skeletal muscle, and the second category represents DEmiRNAs with low expression at the development and early growth stage, and significant upregulation at the high growth stage. We then constructed an miRNA–mRNA network based on target relationships between DEmiRNAs and DEGs belonging to the seven significantly enriched profiles. Based on the connectivity degree, 20 hub miRNAs responsible for pigeon skeletal muscle development and growth were identified, including cli-miR-20b-5p, miR-130-y, cli-miR-106-5p, cli-miR-181b-5p, miR-1-z, cli-miR-1a-3p, miR-23-y, cli-miR-30d-5p, miR-1-y, etc. The hub miRNAs involved in the miRNA–mRNA regulatory networks and their expression patterns during the development and growth of pigeon skeletal muscle were visualized. GO and KEGG enrichment analysis found potential biological processes and pathways related to muscle growth and development. Our findings expand the knowledge of miRNA expression in pigeons and provide a database for further investigation of the miRNA–mRNA regulatory mechanism underlying pigeon skeletal muscle development and growth.

Acute lung injury (ALI) is a severe lung disease with limited therapeutic strategies. Munronoid I, a limonoid, which is extracted and purified from Munronia sinica, exhibits effective anti-neoplastic activities. In this study, we attempted to determine the anti-inflammatory effects of Munronoid I using both the lipopolysaccharide (LPS)-induced in vivo murine ALI models and in vitro assays. Our results demonstrated that Munronoid I treatment ameliorated LPS-induced ALI and inflammation in mice. Moreover, it also significantly inhibited LPS-induced pathological injuries, infiltration of inflammatory cells, and production of IL-1β and IL-6. Furthermore, the in vitro assay showed that Munronoid I could inhibit the LPS-induced expression of inflammatory mediators such as iNOS, COX2, and production of pro-inflammatory cytokines by suppressing the activation of NF-κB signaling pathway in mouse peritoneal macrophages. Munronoid I reduced the LPS-, tumor necrosis factor alpha (TNF-α)- or interleukin 1 beta (IL-1β)-induced transforming growth factor beta-activated kinase 1 (TAK1) phosphorylation and protein expression. Furthermore, the Munronoid I also promoted K48-linked ubiquitination and proteasomal degradation of TAK1. Taken together, these results demonstrated that Munronoid I exhibited anti-inflammatory activities both in vitro and in vivo, which might be a potential therapeutic candidate for the treatment of ALI and pulmonary inflammation.

Background: Thallium (Tl) is a cumulative high toxicant in the environment, but few longitudinal studies have investigated the respiratory impairment of Tl exposure. Objectives: This study aimed to evaluate the effect of Tl and its interaction with smoking on lung function decline, and explore the potential mechanisms. Methods: The baseline and follow-up lung functions were measured from a prospective cohort study of 1243 workers, who were followed from 2010 to 2014. Their baseline urinary levels of Tl were determined. We also measured the plasma C-reactive protein (CRP) and urinary 8-iso-prostaglandin-F2α (8-iso-PGF2α) in a randomly selected subcohort of 474 subjects. Results: The results showed that a 2-fold increase in urinary Tl was associated with 29.81 mL (95%CI: 3.83–55.80) increased decline in forced expiratory volume in 1 s (FEV1). The effect was more pronounced among heavy-smokers (≥15 pack-years) [β(95%CI) = 56.42 mL (9.66–103.19)]. In particular, compared to never-smokers with low Tl, heavy-smokers with high Tl had a separate 158.44 mL (95%CI: 54.88–262.00) and 4.58% (95%CI: 1.40–7.76) increased declines in FEV1 and percentage of predicted (ppFEV1), respectively. There was a significant interaction between Tl and smoking intensity on ppFEV1 decline (Pint = 0.034). More importantly, the increasing level of urinary Tl was correlated with elevated CRP and 8-iso-PGF2α. Conclusion: Our prospective cohort study identified that exposure to high Tl had a deleterious effect on lung function, and this effect may be enhanced by tobacco smoking. Increased inflammation may partly contribute to the joint effects of Tl and smoking on impaired lung function, but the biological mechanisms need further explorations. Keywords: Thallium, Smoking, Lung function decline, Prospective cohort study, C-reactive protein

Objective: Essential metals play important roles in the carcinogenic process. However, seldom longitudinal investigations have evaluated their roles in lung cancer development. We aimed to investigate the associations between multiple essential metals and lung cancer incidence and to explore the potential mechanisms. Methods: A nested case-control study of 440 incident lung cancer cases and 1:3 frequency matched 1320 healthy controls from the Dongfeng-Tongji Cohort was conducted. The baseline plasma concentrations of 11 essential metals (cobalt, copper, iron, manganese, molybdenum, rubidium, selenium, strontium, stannum, vanadium, and zinc) were measured, and their associations with lung cancer incidence were estimated. Effect of positive metal (zinc) on 4-year telomere attrition was then evaluated among an occupational cohort of 724 workers. We also assessed the transcriptional regulation effects of plasma zinc on mRNA expression profiles, and the expressions of zinc-related genes were further compared in pair-wised lung tumor and normal tissues. Results: Elevated plasma level of zinc was associated with lower incident risk of lung cancer [OR (95% CI) = 0.89 (0.79, 0.99)] and decreased 4-year telomere attrition [β (95% CI) = −0.73 (−1.27, −0.19)]. These effects were pronounced among males. In particularly, zinc could regulate the expressions of 8 cancer-related genes, including SOD1, APE, TP53BP1, WDR33, LAPTM4B, TRIT1, HUWE1, and ZNF813, which were over-expressed in lung tumor tissues. Conclusions: We propose that high plasma zinc could prevent incident lung cancer, probably by slowing down telomere attrition and regulating the expressions of cancer-related genes. These results provided a new insight into lung cancer prevention. Keywords: Essential metals, Zinc, Lung cancer, Cohort study, Telomere attrition, Gene expression

Objective: This study aimed to investigate the associations of multiple metals with chromosome damage, and further explore the mediation roles of microRNAs (miRNAs) and their potentials in lung cancer. Methods: We determined the urinary levels of 23 metals, lymphocytic micronucleus (MN) frequency, and ten candidate miRNAs in plasma among 365 healthy workers. Poisson and linear regression models were conducted to analyze the associations of urinary metals with MN frequency and miRNAs, respectively. The mediation effects of miRNAs on the metal-MN frequency associations were assessed by causal mediation analysis. Additionally, the levels of effective metal and miRNAs were measured in 43 pair-wised tumor and normal lung tissues. Results: The urinary level of titanium was inversely associated with MN frequency after Bonferroni correction [frequency ratio (FR) and 95% confidence interval (95%CI) = 0.88 (0.82, 0.94), p = 5.0 × 10−4]. A doubling in urinary titanium was associated with 14.72%–38.17% decrease in plasma miRNAs. After multiple comparison, miR-24-3p and miR-28-5p significantly mediated 24.8% (7.7%, 70.0%) and 20.4% (5.7%, 52.0%) of the association between titanium and MN frequency (pmediation = 0.002 and 0.004, respectively). Besides, a doubling in titanium was associated with a separate 53.4% and 47.2% decreased miR-24-3p and miR-28-5p expression in normal lung tissues. Lower titanium but higher levels of miR-24-3p and miR-28-5p were shown in tumor than normal tissues of lung squamous cell carcinoma patients (all p

Rheumatic diseases are a group of chronic autoimmune disorders that involve multiple organs or systems and have high mortality. The mechanisms of these diseases are still ill-defined, and targeted therapeutic strategies are still challenging for physicians. Recent research indicates that cell metabolism plays important roles in the pathogenesis of rheumatic diseases. In this review, we mainly focus on lipid metabolism profiles (dyslipidaemia, fatty acid metabolism) and mechanisms in rheumatic diseases and discuss potential clinical applications based on lipid metabolism profiles.

Cancer has been threatening the safety of human life. In order to treat cancer, many methods have been developed to treat tumor, such as traditional therapies like surgery, chemotherapy, radiotherapy, as well as new strategies like photodynamic therapy, photothermal therapy, sonodynamic therapy, and other emerging therapies. Although there are so many ways to treat tumors, these methods all face the dilemma that they are incapable to cope with metastasis and recurrence of tumors. The emergence of immunotherapy has given the hope to conquer the challenge. Immunotherapy is to use the body's own immune system to stimulate and maintain a systemic immune response to form immunological memory, resist the metastasis and recurrence of tumors. At the same time, immunotherapy can combine with other treatments to exhibit excellent antitumor effects. Upconversion nanoparticles (UCNPs) can convert near-infrared (NIR) light into ultraviolet and visible light, thus have good performance in bioimaging and NIR triggered phototherapy. In this review paper, we summarize the design, fabrication, and application of UCNPs-based NIR photoimmunotherapy for combined cancer treatment, as well as put forward the prospect of future development.