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Silicosis is one of several potentially fatal occupational pathologies caused by the prolonged inhalation of respirable crystalline silica. Previous studies have shown that lung epithelial-mesenchymal transition (EMT) plays a significant role in the fibrosis effect of silicosis. Human umbilical cord mesenchymal stem cells-derived Extracellular vesicles (hucMSC-EVs) have attracted great interest as a potential therapy of EMT and fibrosis-related diseases. However, the potential effects of hucMSC-EVs in inhibiting EMT in silica-induced fibrosis, as well as its underlying mechanisms, remain largely unknown. In this study, we used the EMT model in MLE-12 cells and observed the effects and mechanism of hucMSC-EVs inhibition of EMT. The results revealed that hucMSC-EVs can indeed inhibit EMT. MiR-26a-5p was highly enriched in hucMSC-EVs but was down-regulated in silicosis mice. We found that miR-26a-5p in hucMSC-EVs was over-expressed after transfecting miR-26a-5p expressing lentivirus vectors into hucMSCs. Subsequently, we explored if miR-26a-5p, attained from hucMSC-EVs, was involved in inhibiting EMT in silica-induced lung fibrosis. Our findings suggested that hucMSC-EVs could deliver miR-26a-5p into MLE-12 cells and cause the inhibition of the Adam17/Notch signalling pathway to ameliorate EMT in silica-induced pulmonary fibrosis. These findings might represent a novel insight into treating silicosis fibrosis.

People exhibit a range of negative reactions to noise. However, previous study on masking secondary radiation noise focused on its impact on a single negative reaction, namely dissatisfaction. This is a gap in understanding the mechanisms that mitigate multi-dimensional negative reactions (MNR), which encompass various emotional responses to noise, including annoyance, dissatisfaction, and others. Therefore, this study selected four mutually independent critical reactions (subjective loudness, depression, discomfort, and dissatisfaction) and analyzed the masking effects of adding four types of water sounds (fountain, stream, water-drop, and waterfall sounds) on MNR caused by secondary radiation noise. Seventy-nine participants were presented with a series of combined sound samples before casting their votes of MNR in an auditory test booth. The results revealed that adding the four types of water sounds mitigated the MNR induced by secondary radiation noise. Among them, the water-drop sound was the most effective, while the waterfall sound was the least capable. The fountain sound was preferred over the stream sound for optimizing the MNR, focusing on subjective loudness, discomfort and dissatisfaction, which were caused by higher level of combined sound. Furthermore, as global A-weighted sound level (LAeq) increased from 55 to 65 dBA, the mean subjective loudness levels generally remained the highest. Beyond the subjective loudness, when global LAeq increased to 65 dBA, the mean depression level exceeded the mean discomfort level and mean dissatisfaction level when the fountain or water-drop sound was added, whereas the three mean levels remained approximately equal when the stream or waterfall sound was added.

Permafrost in Northeastern China is not only controlled by latitude and elevation, but also locally environmental factors, such as vegetation cover and human activities. During 2009–2022, thinning active layer, increasing annual maximum frost depth in talik zones and lowering ground temperature above the depth of dividing point (DDP) between permafrost cooling and warming have been observed in many places, possibly due to the global warming hiatus (GWH). However, the responses of permafrost below DDP did not show a clear trend to the GWH, despite an evident ground warming. The warming and degradation of permafrost below DDP in the Da Xing’anling Mountains are more strongly influenced by the overall climate warming than by regional GWH. This study improves our understanding of changing permafrost temperature and its drivers. It also helps to provide data support and references for the management of the ecological and hydrological environment of the northern Da Xing’anling Mountains and the Heilongjiang-Amur River Basin.

In the above article [1], an esteemed author was inadvertently excluded. Qingxue Huang has been appropriately added to the end of the author list.

The differentiated characteristics of the silver (elderly) group from other groups means that the previous interaction mechanism in short-form video (SFV) e-commerce is no longer applicable. Drawing on sociotechnical systems theory and the ERG theory, this study is motivated to explore the purchase intention of silver consumers in SFV platforms. We categorize the characteristics of SFV platforms into social and technical aspects, and analyze silver consumers’ purchasing decisions in terms of existence, relatedness, and growth needs. The empirical results of 284 samples show that social belonging, perceived trust, and product relevance are positive factors that promote purchase. Information diversity and social interaction have significant positive effects on social belonging and perceived trust. Recommendation affordance is significantly positively associated with perceived trust and product relevance, while platform ease of use did not have a significant effect on perceived trust. The findings provide management insights into SFV platforms to better understand the digital divide faced by silver consumers and to facilitate increased consumption.

Terpyridine (TPY) platinum(II) chloride with a triphenylamine (TPA) group was successfully synthesized. The strong intramolecular Donor(TPA)-Acceptor(TPY) interaction induced the low-energy absorption band, mixing the spin-allowed singlet dπ(Pt)→π*(TPY) metal-to-ligand charge transfer (MLCT) with the chloride ligand-to-metal charge transfer (LMCT) and chloride ligand-to-ligand (TPY) charge transfer (LLCT) transitions, to bathochromically shift to λmax = 449 nm with significant enhancement and broadening effects. Using the cyclic voltammetry method, its oxidative electropolymerization (EP) films on working Pt disk and ITO electrodes were produced with tunable thickness and diffusion controlled redox behavior, which were characterized by the SEM, EDS, FT-IR, and AC impedance methods. Upon applying +1.4 V voltage, the sandwich-type electrochromic device (ECD) with ca. 290 nm thickness of the EP film exhibits a distinct color transformation from red (CIE coordinates: L = 50.75, a = 18.58, b = 5.69) to dark blue (CIE coordinates: L = 45.65, a = −1.35, b = −12.49). Good electrochromic (EC) parameters, such as a large optical contrast (ΔT%) of 78%, quick coloration and bleaching response times of 2.9 s and 1.1 s, high coloration and bleaching efficiencies of 278.0 and 390.5 C−1·cm2, and good cycling stability (maintains 70% of the initial ΔT% value after 3200 voltage switching cycles), were obtained.

Rolling bearings are a key component for ensuring the safe and smooth operation of rotating machinery and are very prone to failure. Therefore, intelligent fault diagnosis research on rolling bearings has become a crucial task in the field of mechanical fault diagnosis. This paper proposes research on the fault diagnosis of rolling bearings based on an adaptive nearest neighbor strategy and the discriminative fusion of multi-feature information using supervised manifold learning (AN-MFIDFS-Isomap). Firstly, an adaptive nearest neighbor strategy is proposed using the Euclidean distance and cosine similarity to optimize the selection of neighboring points. Secondly, three feature space transformation and feature information extraction methods are proposed, among which an innovative exponential linear kernel function is introduced to provide new feature information descriptions for the data, enhancing feature sensitivity. Finally, under the adaptive nearest neighbor strategy, a novel AN-MFIDFS-Isomap algorithm is proposed for rolling bearing fault diagnosis by fusing various feature information and classifiers through discriminative fusion with label information. The proposed AN-MFIDFS-Isomap algorithm is validated on the CWRU open dataset and our experimental dataset. The experiments show that the proposed method outperforms other traditional manifold learning methods in terms of data clustering and fault diagnosis.

To investigate the influencing factors and mechanisms of shear strength of red clay with a high liquid limit, which was selected at different milepost locations based on the Nanning Bobai Nabu Section Project of the Nanning Zhanjiang Expressway, the basic physical properties of red clay were determined using a liquid plastic limit test, compaction test, inductively coupled plasma optical emission spectrometer (ICP-OES), and X-ray fully automatic diffractometer (XRD). Red clay with a high liquid limit was selected. Furthermore, the direct shear test was used to study the effect of different water contents and compaction degrees on the shear strength. The experimental results demonstrate that under the same compaction degree, the shear stress of the soil sample increases significantly with an increase in normal stress, and the greater the water content, the smaller the shear stress of the soil sample. At 200 kPa, the shear strength of soil samples with 24% water content is 57%, 46%, and 35% of the shear strength of soil samples with 15% water content under different compaction degrees(K) of 86%, 90%, and 93%, respectively. Under the same moisture content, the shear stress of the soil sample shows an increasing trend with an increase in the degree of compaction, and the greater the compaction degrees, the greater the shear stress of the soil sample. The cohesion c and internal friction angle φ of soil samples increase with an increase in the compaction degree, but the increase in cohesion c is also affected by the water content. Under the condition of low water content, the cohesion c of soil samples can be increased by 1.06 times when the water content is 15% and by 0.47 times when the water content is 18%. Under the condition of high water content, the cohesion c of soil samples with 21% water content only increases by 0.3 times, and that with 24% water content only increases by 0.35 times.

Objective To compare the effect of percutaneous endoscopic lumbar discectomy (PELD) using a double‐cannula guide tube (DGT), traditional PELD, and open lumbar discectomy (OLD) to treat large lumbar disc herniations (LLDHs). Methods Seventy patients who presented with LLDH without cauda equina syndrome and were treated with surgery in our hospital from October 2015 to October 2017 were included. The detailed index included the visual analog scale (VAS) for back and radicular leg pain and the Oswestry Disability Index (ODI) in the immediate preoperative period and at the final follow‐up. The operation time, radiation exposure time, surgical satisfaction rate, and modified MacNab criteria score were also recorded. Results The leg and back pain of the patients in these groups improved significantly in the postoperative period. No significant differences were observed in leg pain improvement between the other two groups; however, patients in the PELD group (with or without DGT) presented with significantly higher improvement in back pain than the OLD group (t = 9.965, p

Abstract Background Inflammatory microenvironment promotes odontoblastic differentiation in human dental pulp stem cells (hDPSCs), but the regulatory mechanisms remain unclear. In this study, we aimed to explore the role of TAS2R in odontoblastic differentiation of hDPSCs in the inflammatory microenvironment. Methods Microarray analysis was performed to explore the differential mRNA profiles in inflammatory and healthy pulp tissues from the patients. hDPSCs isolated from the healthy pulp tissues were stimulated by LPS, TNFα and IL-6, respectively, to verify the effect of TAS2R. The expression markers related to odontoblastic differentiation of hDPSCs were observed by qPCR and chemical staining methods. TAS2R10 was overexpressed or silenced to observe the effect on odontoblastic differentiation of hDPSCs under LPS stimulation. The G protein and intracellular Ca2+ were detected, respectively, by qPCR and Fluo-4AM Ca2+ fluorescent probe. Results The expression of TAS2R was significantly upregulated in the inflammatory pulp tissues. In vitro, 5 subtypes of TAS2R mRNA expressions including TAS2R10, TAS2R14, TAS2R19, TAS2R30 and TAS2R31 in hDPSCs increased under the stimulation of LPS, TNFα or IL-6. In odontoblastic differentiation medium, we found LPS, TNFα or IL-6 stimulation promoted odontoblastic differentiation of hDPSCs. TAS2R10 overexpression in hDPSCs significantly increased the expression markers related to odontoblastic differentiation, whereas TAS2R10 silencing revealed the opposite effect. Furthermore, G protein was activated, and at the same time, intracellular Ca2+ enhanced when TAS2R10 was overexpressed, but decreased when TAS2R10 was silenced. Conclusions This study demonstrated that TAS2R was found to be expressed in hDPSCs, and TAS2R promoted odontoblastic differentiation of hDPSCs by mediating the increase in intracellular Ca2+ via the G protein-coupled receptors (GPCR) conventional signaling pathway in inflammatory microenvironment, which may be a potential target for the development of effective conservative treatments for dental pulp repair.

In order to investigate the corporate effect of vacuum mixing and freezing-thawing treatment on microstructure and quality of quick-frozen Youtiao dough and fritters, frozen Youtiao dough was prepared under the vacuum mixing (0~0.08 MPa) and freezing-thawing treatment (0~3 times). Combined analytical methods covering multiple instruments (e.g., low field nuclear magnetic resonance, scanning electron microscopy, and fourier infrared spectrum analyzer) were used to investigate the water distribution, microstructure, and secondary structure of treated frozen Youtiao dough. Meanwhile, the oil content, water content, specific volume and textural quality of Youtiao were analyzed. Results showed that freezing-thawing treatment destroyed the structure of the dough, declined the strong bonding water content of dough and α-helical content in gluten (14.80%~13.61%), resulting in the loose and disordered protein structure. However, with the increase of vacuum degree, the strong bonding water content in quick-frozen Youtiao dough gradually increased, and the ordered degree of protein network structure in dough also improved. Furthermore, freezing-thawing treatment could also decrease the volume (1.82 cm3/g~1.47 cm3/g), increase the oil content (15.08%~16.88%) and reduce the textural quality of Youtiao, while vacuum mixing could effectively decrease the oil content (15.08%~12.64%), improve volume (1.82 cm3/g~2.38 cm3/g), reduce hardness and improve other qualities of Youtiao. These results indicated that vacuum mixing could reduce the quality deterioration caused by freezing-thawing treatment by regulating the water distribution and protein structure in quick-frozen Youtiao dough. Therefore, this study can provide theoretical basis and guidance for large-scale production of quick-frozen Youtiao.

Abstract Background Both the protein domains and transcript structures influence protein functional variation. The genomic location of both protein domains and transcript structural features can be described using the genomic coordinates of their encoded sequences. However, the coordinates of protein domains and transcriptional features often differ greatly, and it is difficult to view them in combination at the genome-wide level. In this paper, we describe the development of a new tool that allows users to visualize domains and transcript features together, using either built-in or uploaded genome datasets, and export publication-ready figures. Results We developed a user-friendly, independent R package and Shiny web application named “VisProDom”. VisProDom consists of a genome-wide database containing entire annotated transcripts merged with annotated protein domains from the Pfam database. The built-in dataset includes 82 files, which merge genome general feature format (GFF) annotations with rpsblast tabular outputs from protein sequence searches in the Pfam database. Multiple genomes can be simultaneously screened for protein domains or transcript names. VisProDom includes step-by-step introductions and clickable elements for ease of use. Conclusion VisProDom can display hundreds of transcripts alongside protein domains and export figures in a publication-ready format. This makes it a valuable tool for molecular evolution and comparative genomics.

Cholangiocarcinoma is a heterogenous group of cancers, with large genetic variation seen within subtypes. Here, the authors find 12 significantly mutated genes and 5 focal CNA regions were found in perihilar cholangiocarcinoma, and identified METTL14 to have a potential tumour suppressive role.

Abstract Visualization of complex geological structures can technically support the accurate prediction and prevention of coal mine disasters. This study proposed a new digital reconstruction method to visualize geological structures based on establishing a virtual model in the digital twin system. This methodology for the digital reconstruction of complex fault structures comprises the following four aspects: (1) collection and fidelity of multi-physical field data of the fault structures, (2) the transmission of multi-physical field data, (3) the normalization of multi-physical field data, and (4) digital model reconstruction of fault structures. The key scientific issues of this methodology to be resolved include in situ fidelity of multi-field data and normalized programming of multi-source data. In addition, according to the geological background and conditions in Da’anshan coal mine in western Beijing, China, a preliminary attempt is made to reconstruct a digital model of fault and fold structures using the methodology proposed in this study.

Measurement(s) train operation data of China high-speed railway network • locations of railway stations • weather and temperature and wind power Technology Type(s) web scraping with python • Geographic Information System Factor Type(s) high-speed train departure delay time • high-speed train arrival delay time • various external factors affecting train operation • bad weather exposure time of railway stations • railway station community size Sample Characteristic - Organism high-speed train Sample Characteristic - Environment railway system Sample Characteristic - Location China

In order to suppress the formation of Fe-Ti IMCs in NiTi SMA/304 SS laser-welded joint and improve the properties of the joint. In this study, NiTi SMA/304 SS dissimilar alloys joints with and without CoCrFeNiMn high entropy alloy interlayer were obtained by micro laser welding process. The effect of CoCrFeNiMn high entropy alloy interlayer on the microstructure and properties of NiTi SMA/304 SS laser-welded joint was investigated systematically. Results showed that the addition of HEA interlayer significantly reduced the formation of the brittle intermetallic compounds (IMCs) such as FeTi phase. The addition of high entropy alloy interlayer promotes the formation of (Fe,Ni) solid solution phase, therefor, the joint with HEA interlayer is composed of (Fe,Ni) solid solution and small amount of FeTi IMCs and B2 phase. On the other hand, the average microhardness of weld metal was decreased from 732 HV to 221 HV by adding the HEA interlayer. The addition of HEA interlayer significantly improves the tensile shear properties of the joint, and the tensile shear load of the joint can reached 175 N, which is 6 times higher than that of the joint without HEA interlayer.

Measurement(s) spatial distribution data of cultural sites Technology Type(s) Geographic Information System • digital curation Independent variable(s) geographic location • age • geographical landscape type Sample Characteristic - Environment prehistoric human sites Sample Characteristic - Location China

Catalytic performance of Pt based nanocatalysts significantly depends on their morphologies, compositions and structures. In this work, the generation-4 phenylazomethine-tetraphenylmethane dendrimer (TPMG4)-encapsulated PtSn bimetallic ultrafine nanoparticles with tunable ratio of Pt and Sn (PtnSn60-n@TPMG4/GMC, n = 56, 48, 32) supported on graphitic mesoporous carbon (GMC) were fabricated through co-reduction method by using the phenylazomethine dendrimer as a template. The morphologies, compositions, and structures of resulting PtnSn60-n@TPMG4/GMC were detected by UV–vis absorption spectra (UV–vis), inductively coupled plasma-optical emission spectroscopy (ICP-OES), high angle annular dark field scanning transmission electron microscopy (HAADF-STEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) measurements. These physical characterizations show that dendrimer-encapsulated PtnSn60-n nanoparticles are anchored on the surface of graphitic mesoporous carbon with highly dispersion and uniformly ultrafine size of ∼1 nm, The atomic ratio of Pt and Sn in PtnSn60-n bimetallic nanoparticles can be accurately controlled. The electrochemical characterizations demonstrate that all PtnSn60-n@TPMG4/GMC samples exhibit more excellent electrocatalytic performance for methanol oxidation than single metal Ptm@TPMG4/GMC and commercial carbon supported platinum catalyst (Pt/C). Especially, the Pt56Sn4@TPMG4/GMC displays the highest catalytic activity with 1.6 times higher than Pt60/GMC and 1.9 times higher than Pt/C. Also, the Pt56Sn4@TPMG4/GMC exhibits the high carbon monoxide (CO) tolerance and superior catalytic stability towards methanol oxidation. Consequently, constructing Pt based bimetallic nanoparticles with controllable compositions and structures is an effective way to improve the catalytic performance and reduce the amount of Pt used in the catalysts, which will be widely concerned in the field of direct methanol fuel cells.

Human idiopathic hypercalciuria (IH) is the most common cause of calcium oxalate nephrolithiasis with perturbed calcium metabolism with increased bone resorption and decreased renal calcium reabsorption, which can be phenotype-copied in the genetic hypercalciuric stone-forming (GHS) rat model. We previously demonstrated that high VDR expression plays important roles in the development of hypercalciuria in the GHS rats. However, the underlying mechanism through which VDR impact hypercalciuria development remains to be fully understood. Here, we sought to determine how VDR regulated its target genes that are implicated in calcium homeostasis and potentially hypercalciuria. We found that VDR expression in the GHS rats was elevated in the calcium transporting tissues, as well as in the thymus and prostate, but not in lung, brain, heart, liver and spleen, when compared with control SD rats. Snail expression in the GHS rats was significantly downregulated in kidney, intestine, thymus and testis. Intraperitoneal injection of 1,25(OH)2D3 significantly upregulated the expression of renal calcium sensing receptor (CaSR), intestinal calcium transporters transient receptor potential vanilloid type 6 (TRPV6), and VDR in GHS rats, compared with that in control SD rats. ChIP assays revealed that VDR specifically bound to the proximal promoters of target genes, followed by histone H3 hyperacetylation or hypermethylation. Collectively, our results suggest that elevated VDR expression may contribute to the development of hypercalciuria by sensitizing VDR target genes to 1,25(OH)2D3 through histone modifications at their promoter regions in a genetic hypercalciuric stone-forming (GHS) rat model.

Background: Traumatic Heterotopic Ossification (tHO) is one of complications of elbow fractures to the detriment of patients’ rehabilitation, and the severity of tHO corresponds to the size of ectopic bone. It has yet to be elucidated which proteins and pathways underlying the progression of tHO, and biomarkers to predict the severity of tHO at early stage of the disease also need further investigation. Methods: In this study, a new rat model with distinct volume of ectopic bone was established first. Then a data-independent acquisition proteomics approach was used to investigate injured site tissues sequentially obtained from these rats (2, 7, 14, and 28 days post-injury). Differentially expressed analysis, functional annotation and co-expression analysis and protein–protein interaction network were performed to explore the pathways and hub proteins in the tHO progression. Clinical samples from a nest case–control study were used to validate the selected proteins for predicting the severity of tHO. Results: The Achilles Tenotomy (AT) induced significantly larger sizes of ectopic bone compared to Partial Achilles Tenotomy (PAT) in rat models. A total of 3547 quantifiable proteins were screened for differential expression analysis among the AT, PAT and control groups. The hierarchical clustering and expression pattern analysis revealed more apparent difference in the pathways such as oxidative phosphorylation, mitochondrial function, and sirtuin signaling between AT and PAT group at the early stage (2 dpi) of tHO. The co-expression analysis identified five hub proteins, UBA1, EIF3E, RPL17, RPL27, and RPS28. qPCR assay, immunoblot assay and immunohistochemistry assay verified that these proteins had higher expression level in the tissue samples of clinically relevant HO patients and clinically irrelevant HO patients than HO negative patients. Conclusion: The new established animal model and proteome profile could serve as a solid foundation for the comprehensive investigation of the progression of traumatic heterotopic ossification. And the identified 5 proteins (UBA1, EIF3E, RPL17, RPL27, and RPS28) may serve as potential biomarkers to predict the severity of tHO. The translational potential of this article: The proteins identified in this study may be the potential biomarkers and therapeutic targets for predicting and treating the tHO at early stage.

Pyroxasulfone (PYS) is an isoxazole herbicide favored for its high activity. However, the metabolic mechanism of PYS in tomato plants and the response mechanism of tomato to PYS are still lacking. In this study, it was found that tomato seedlings had a strong ability to absorb and translocate PYS from roots to shoots. The highest accumulation of PYS was in the apex tissue of the tomato shoots. Using UPLC-MS/MS, five metabolites of PYS were detected and identified in tomato plants, and their relative contents in different parts of tomato plants varied greatly. The serine conjugate, DMIT [5, 5-dimethyl-4, 5-dihydroisoxazole-3-thiol (DMIT)] &Ser, was the most abundant metabolites of PYS in tomato plants. In tomato plants, the conjugation of thiol-containing metabolic intermediates of PYS to serine may mimic the cystathionine β-synthase-catalyzed condensation of serine and homocysteine (in the pathway sly00260 sourced from KEGG database). This study ground breakingly proposed that serine may play an important role in plant metabolism of PYS and fluensulfone (whose molecular structure is similar to PYS). PYS and atrazine (whose toxicity profile is similar to PYS but not conjugate with serine) produced different regulatory outcomes for endogenous compounds in the pathway sly00260. Differential metabolites in tomato leaves exposed to PYS compared with the control, including amino acids, phosphates, and flavonoids, may play important roles in tomato response to PYS stress. This study provides inspiration for the biotransformation of sulfonyl-containing pesticides, antibiotics and other compounds in plants.

Patients with metastatic pancreatic cancer have limited treatment options and a dismal prognosis. While RET fusion is rare (0.6%) in pancreatic cancer, the efficacy of RET-targeted treatment in patients with TRIM33-RET fusion has not been previously reported. Herein, we presented a case of a 68-year-old man with pancreatic cancer harboring TRIM33-RET fusion who responded remarkably to pralsetinib despite being intolerant to chemotherapy. To our knowledge, this is the first report on the clinical value of a single TRIM33-RET fusion in pancreatic cancer, which may benefit from the targeted therapy.

Radiotherapy (RT) incorporated multidisciplinary treatment is producing excellent clinical results, but its efficacy in treating late-stage gastric cancer is constrained by radioresistance and RT-related toxicity. Especially, since reactive oxygen species are the pivotal effectual molecules of ionizing radiation, improving ROS production by nanoparticles and other pharmacological modulation to amplify oxidation of polyunsaturated fatty acids and subsequent ferroptotic cell death is shown to enhance cancer cell radioresponse. Herein, we constructed a nanosystem by loading Pyrogallol (PG), a polyphenol compound and ROS generator, into mesoporous organosilica nanoparticles named as MON@pG. The nanoparticles exhibit proper size distribution with amplified ROS production and substantial glutathione depletion under X-ray radiation in gastric cancer cell line. Meanwhile, MON@PG enhanced radiosensitivity of gastric cancer in xenograft tumor model by ROS-mediated accumulation of DNA damage and apoptosis. Furthermore, this augmented oxidative process induced mitochondrial dysfunction and ferroptosis. In summary, MON@PG nanoparticles show the capacity to improve RT potency in gastric cancer by disrupting redox balance and augmenting ferroptosis.

Abstract Keratoacanthoma‐like squamous cell carcinoma (KA‐like SCC) is a malignant classification of KA. We report here a case of surgical combined with 5‐aminolevulinic acid‐photodynamic therapy (ALA‐PDT) to treat KA‐like SCC in an elderly male with successful tumor removal. The tumor resection was performed before ALA‐PDT. One week later, the lesion site was further treated with 20% ALA for 3 h when it was unknown whether the tumor was resected entirely or not. The irradiation was performed with a 633 nm light‐emitting diode lamp at 100 mW/cm2 for 200 J/cm2 after wiping off the ALA cream. Two sessions of ALA‐PDT were performed at a 2 weeks interval. One month after ALA‐PDT, the surgical trace of the lesion was found to have disappeared entirely, with a little scab, and the cancer did not recur. After 1 year of follow‐up, there was no recurrence. The combination with surgery and ALA‐PDT may provide a new idea for the treatment of KA‐like SCC for a wide range of patients.

ObjectiveUmbilical cord mesenchymal stem cells (UCMSCs) have significant regenerative, tissue repair, and immunomodulatory properties that can help reduce inflammatory responses in patients with ankylosing spondylitis (AS). In this study, we used a combination of bovine proteoglycan and dimethyldioctadecylammonium (DDA) to establish a mouse model of proteoglycan-induced spondylitis (PGISp). To evaluate the therapeutic effects of UCMSCs, we treated PGISp mice with different doses of hUCMSCs via tail vein injection.MethodsAt week 13, the PGISp mice exhibited thickened, erythematous paws, erythema in the extremities, and lameness. CT scans revealed necrotic lysis of chondrocytes, formation of fissures, visible hemorrhage, connective tissue hyperplasia, and focal infiltration of lymphocytes in the intervertebral discs. At week 14, the PGISp mice were randomly divided into three groups and administered different doses of hUCMSCs (0.25, 0.5, and 1.0×107 cells/kg, iv, QOW×2, n=10). To assess the therapeutic effects of hUCMSCs, we evaluated Th cell subsets in the spleen, spleen and thymus coefficients, peripheral blood inflammatory factors, and pathological and imaging observations of the spines and lumbar spines in the PGISp mice.ResultsThe results demonstrated that injection of hUCMSCs shifted the balance axis between Th1 and Th2 cells in the spleen towards Th2 cells. Moreover, the spleen coefficient and levels of inflammatory cytokines (TNF-α and CCL-2) in the serum decreased after hUCMSC injection. CT imaging and pathological analysis indicated that hUCMSC treatment inhibited ectopic osteogenesis and maintained clear small joint gaps, which slowed down the progression of structural lesions in the disc, nucleus pulposus, fibrous ring, and cartilage in PGISp mice.ConclusionAdministering hUCMSCs at the 14th week after modeling proved to be an effective treatment for PGISp mice. This experiment offers a valuable reference for the pre-clinical use of hUCMSCs in the treatment of AS.

Abstract In the field of industrial design and manufacture, computer‐supported collaborative work (CSCW) systems have been widely deployed for better teamwork. However, the traditional CSCW systems have a main drawback in effectively processing and utilising knowledge across different industrial workflows. To bridge this gap, we propose a framework for collaboration between members across the manufacturing value chains to increase efficiency and reduce duplication in team cooperation. The framework contains three parts, namely workflow, knowledge mining, and services. Specifically, the workflow part provides a collaborative environment for multiple users. The knowledge mining part, as the core of the framework, extracts in‐context knowledge from workflows. The part of services can interact with users with different users in each workflow, including information recommendation they need in the future or information retrieval they want to know from other workflows. Furthermore, we develop a prototype system for supporting multiple value chains collaboration to verify the effectiveness and efficiency of the framework.

Water hypoxia intensification in lakes and reservoirs has become a global problem under global warming. The Mn/Fe ratio is frequently employed to reconstruct historical redox conditions, but interpretation of this ratio may be problematic when the accumulation of Fe and Mn is governed by factors in addition to redox processes. We tested the Fe and Mn contents and bacterial diversity of a 250 cm sediment column in a monomictic reservoir. The deposition time frame and sedimentary rate (approximately 60 cm/y) were determined by integrating the Fe and Mn contents with the hydrological time series, providing a sufficient archive to reconstruct the intra-year variation in water qualities. The inapplicability of the Mn/Fe ratio observed because redox processes, mixing patterns, and biological activity jointly affected the net accumulation of Fe and Mn in the sediment. The causes of the vertical variations in the sediment Fe and Mn contents are discussed, considering the runoff sediment input, hydrodynamic and thermodynamic characteristics of this reservoir, and bacterial distributions in the sediment column. High-speed deposition intensively occurred in summer and autumn; thus, during this period, fluvial sediment was the main source of Fe and Mn. Another source was biochemical sedimentation due to mixing and oxygenation in this reservoir, which played a larger role in spring and winter. Our study showed that the easily accessible current hydrological data of the reservoir provide a reference time frame for identifying historical environmental events and that the use of the Fe/Mn ratio alone is inconclusive for interpreting the historic oxygenation regimes of reservoirs. Future applications of this method should consider the individual reservoir characteristics that impact the mobility and net accumulation of Fe and Mn in the sediment.

IntroductionPatients with intermediate or locally advanced hepatocellular carcinoma (HCC) who are not eligible for radical treatment typically have a poor overall prognosis. Treatment strategies that can convert unresectable HCC into resectable HCC may improve patient survival. We conducted a single arm phase 2 trial to evaluate the efficacy and safety of Sintilimab plus Lenvatinib as conversion therapy for HCC.MethodsA single-arm, single-center study conducted in China (NCT04042805). Adults (≥18 years) with Barcelona Clinic Liver Cancer (BCLC) Stage B or C HCC ineligible for radical surgery with no distant/lymph node metastasis received Sintilimab 200 mg IV on day 1 of a 21-day cycle plus Lenvatinib 12 mg (body weight ≥60 kg) or 8 mg (body weight

The coal water co-mining of shallow coal seams in the loess gully area of Northern Shaanxi is affected by the coupling effect of overburden rock structure and topography. The development characteristics of mining fracture are complex and can induce mining and environmental disasters. To predict the disaster formation, taking the 113101 working face of the Kunyuan Coal Mine as the engineering background, numerical simulation, physical similarity simulation experiment, and theoretical analysis methods were used to analyze the mining gully of a shallow coal seam in a loess gully area. Based on the dynamic evolution characteristics of stress at different locations, the formation positions, dynamic development, and evolution processes of various fractures were studied; disaster-causing mechanisms were revealed and comprehensive methods were proposed. The results showed that in across-gully mining, the maximum horizontal compressive stress at the bottom of Gully No. 2 was approximately 20.00 MPa, the maximum horizontal tensile stress of the reverse slope section was approximately 1.50 MPa, the width of the F5 fracture of Gully No. 2 was 46.00 cm, and the elevation difference was up to 52.00 cm. The working face across-gully mining formed tensile fractures in most areas, collapsed fractures at the gully bottom, and extruded fractures in the reverse slope section. The fracture at the gully bottom could easily induce water–sand inrush and roof caving and supports crushing. The slope fracture could also induce a gully-induced landslide. According to the mechanisms and distribution areas of fracture disasters, the disaster areas were divided into water–sand inrush areas at the gully bottom, roof caving and supports crushing areas at the gully bottom and at the base of the slope section, and landslide areas at the upper part of the slope section and reverse slope section. Appropriate prevention and control measures were proposed, such as the upstream interception of surface water, slope reinforcement in the middle and upper part of the downhill section, artificial precracking of the roof in the middle and upper part of the downhill section, and grouting reinforcement at the gully bottom and slope toe of the downhill section. These measures were proven to effectively guarantee the safe and efficient mining efficiency of the working face.

IntroductionGadoxetic acid–enhanced magnetic resonance imaging (MRI) contributes to evaluating the prognosis of small hepatocellular carcinoma (sHCC) following treatment. We have investigated the potential role of gadoxetic acid–enhanced MRI based on LI-RADS (Liver Imaging Reporting and Data System) v2018 imaging features in the prognosis prediction of patients with sHCC treated with radiofrequency ablation (RFA) as the first-line treatment and formulated a predictive nomogram.MethodsA total of 204 patients with sHCC who all received RFA as the first-line therapy were enrolled. All patients had undergone gadoxetic acid–enhanced MRI examinations before RFA. Uni- and multivariable analyses for RFS were assessing using a Cox proportional hazards model. A novel nomogram was further constructed for predicting RFS. The clinical capacity of the model was validated according to calibration curves, the concordance index (C-index), and decision curve analyses.ResultsAlpha fetoprotein (AFP) > 100 ng/ml (HR, 2.006; 95% CI, 1.111–3.621; P = 0.021), rim arterial phase hyperenhancement (APHE) (HR, 2.751; 95% CI, 1.511–5.011; P = 0.001), and targetoid restriction on diffusion-weighted imaging (DWI) (HR, 3.289; 95% CI, 1.832–5.906; P < 0.001) were considered as the independent risk features for recurrence in patients with sHCC treated with RFA. The calibration curves and C-indexes (C-index values of 0.758 and 0.807) showed the superior predictive performance of the integrated nomogram in both the training and validation groups.DiscussionThe gadoxetic acid–enhanced MRI features based on LI-RADS v2018, including rim APHE, targetoid restriction on DWI, and the AFP level, are the independent risk factors of recurrence in patients with sHCC treated with RFA as the first-line therapy. The predictive clinical-radiological nomogram model was constructed for clinicians to develop individualized treatment and surveillance strategies.

Silicosis is a progressive inflammatory disease with poorly defined mechanisms and limited therapeutic options. Recent studies found that microRNAs (miRNAs) and circular RNAs (circRNAs) were involved in the development of respiratory diseases; however, the function of non-coding RNAs in silicosis was still needed to be further explored. We found that miR-223–3p was significantly decreased in macrophages and lung tissues of mice after silica treatment, which were consistent with the results of GEO database microarray analysis. Notably, NLRP3 is a target gene downstream of miR-223–3p. And circular RNA PWWP2A (circPWWP2A) was significantly elevated after silica stimulation. To elucidate the role of these RNAs in silica-induced inflammation in macrophages and lung tissues, we investigated the upstream molecular mechanisms of circPWWP2A on the inflammatory response. The inhibitory effect of miR-223–3p on its target NLRP3 was suppressed by circPWWP2A, which led to lung fibrosis. Our study found that circPWWP2A could adsorb miR-223–3p to regulate NLRP3 after silica stimulation in pulmonary fibrosis. And our results revealed that the circPWWP2A–miR-223–3p–NLRP3 axis was potentially instrumental in managing silica-induced inflammation and fibrosis. Previous studies have demonstrated that human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs) exhibit anti-inflammatory and anti-fibrotic effects in multiple organs. However, the potential effectiveness of hucMSC-EVs against silicosis or the underlying mechanisms of their biological outcomes remains unclear. Therefore, we used 3D culture technology to extract hucMSC-EVs and observed their effects in macrophages and lung tissues, respectively. According to the EVmiRNA database, miR-223–3p was abundant in MSC-EVs. In addition, hucMSC-EVs may modulate lung function, reduce the secretion of inflammatory factors (NLRP3, IL-1β, IL-18 and cleaved Caspase-1) and attenuate the deposition of fibrosis-related factors (Collagen Ⅰ, Collagen Ⅲ, fibronectin and α-SMA). In vitro results evinced that hucMSC-EVs reduced the inflammatory response of macrophages and restricted the activation and proliferation of fibroblasts. Moreover, our study showed that hucMSCs-EVs acted as a mediator to transfer miR-223–3p to suppress circPWWP2A, thereby alleviating pulmonary fibrosis through the NLRP3 signaling pathway. These data may provide potentially novel strategies for investigating the pathogenesis of silicosis and developing novel treatments for this disease.

Abstract Background The onset and progression of cervical intraepithelial neoplasia (CIN) are closely associated with the persistent infection of high-risk HPV (especially type16), which is mainly caused by immune escape. Natural killer (NK) cells play an important role against virally infected cells and tumor cells through a fine balance of signals from multiple surface receptors. Overexpression of non-MHC-I specific inhibitory receptors TIGIT, KLRG1, Siglec-7, LAIR-1, and CD300a on NK cells correlates with cellular exhaustion and immune evasion, but these receptors have not been investigated in CIN. The aim of the present study was to examine the potential role of NK cell non-MHC-I specific inhibitory receptors expression in immune escape from HPV16(+)CIN patients. Methods The subset distribution, IFN-γ and TNF-α expression levels and immunophenotype of TIGIT, KLRG1, Siglec-7, LAIR-1, and CD300a of NK cells were investigated in peripheral blood mononuclear cell samples by flow cytometry from 82 women who were HPV16(+) with CIN grades 0, I, II–III or HPV(−) CIN 0. Immunohistochemistry was applied to detect the expression of ligands for NK receptors in the cervical tissues. HPV types were identified by PCR assays. Results The HPV16(+) subjects with high-grade lesions had an increased number of circulating peripheral blood CD56bright NK cells with reduced functionality and IFN-γ secretion. The expression levels of the inhibitory molecules TIGIT and KLRG1 on CD56bright NK cells increased in parallel with increasing CIN grade. In addition, TIGIT and KLRG1 related ligands, Poliovirus receptor (PVR), N-Cadherin and E-Cadherin expression level was also elevated with increasing CIN grade. Conclusions Our results suggest that up-regulation of the inhibitory TIGIT, KLRG1 and their ligands may negatively regulate cervical CD56bright NK-mediated immunity to HPV16 and contribute to the progression of CIN. These results may facilitate the development of early-warning immune predictors and therapeutic strategies for HPV16(+) CIN based on the TIGIT and KLRG1 inhibitory pathways of NK cells.

Abstract Psoriasis is a chronic inflammatory cutaneous disease; it has been discovered that stimulation of the nervous system increases susceptibility to psoriasis. Although the cholinergic anti-inflammatory pathway, which is mediated by the alpha-7 nicotinic acetylcholine receptor (α7nAChR), is critical for controlling multiple types of inflammation, its expression pattern and pathogenesis function in psoriatic lesioned skin tissue are unknown. We hereby analyzed the expression of α7nAchR in human and mouse psoriatic skin tissue. In vivo, PNU-282987 or Methyllycaconitine, a specific agonist or antagonist of α7nAchR, were administered to imiquimod (IMQ)-induced psoriatic mouse models. The macroscopic appearance and histopathological features of the psoriatic mice skin were evaluated. In addition, cell proliferation and differentiation markers were investigated. The level of pro-inflammatory cytokines released from the lesioned skin, as well as the activation of the relevant signaling pathways, were measured. Our findings indicated that psoriatic lesional skin expressed an increased level of α7nAChR, with its tissue distribution being primarily in skin keratinocytes and macrophages. In an IMQ-induced murine psoriasis model, α7nAChR agonist PNU-282987 treatment alleviated psoriasis-like inflammation by down-regulating the expression of multiple types of pro-inflammatory mediators and normalized keratinocyte proliferation and differentiation, whereas α7nAChR antagonist treatment exacerbated its effect. Mechanically, we observed that activation of the α7nAChR inhibited the activation of the STAT3 and NF-κB signaling pathways in in vitro cultured HaCaT cells induced by Th17-related cytokine IL-6/IL-22 or Th1-related cytokine TNF-α. Taken together, these findings demonstrate that attenuation of psoriatic inflammation via the cholinergic anti-inflammatory pathway is dependent on α7nAChR activation.

Abstract When studying the human settlement process, it is of great significance to understand the prehistoric environment, economy and society by exploring the human–land relationship and the evolution of civilization reflected by the settlement environment. This paper explores the natural and social environmental preferences of early human settlements in Xinjiang, China, from the Palaeolithic to the Bronze Age (45 ka BP–2250 a BP). Through the characteristics of settlement preferences, the distribution of settlements is accurately predicted, and the relationship between settlement preferences and the evolution of the environment and civilization is verified and discussed. We summarize the needs and conditions of early human settlement from the perspectives of the social environment and natural environment and explain the stages, consistency and differentiation of the spatial and temporal evolution of settlement preferences with the interaction of adaptation and transformation. On this basis, we discuss the logical focuses and content of early human settlement preference research. This research provides a reference for the process, representation, driving mode, and research ideas of early human settlement preferences.

A state-of-the-art tool in synthetic organic chemistry is a rhodium diazocarbene species, which despite its flexibility, is derived from expensive and highly reactive species. Here the authors present a methodology for C–H benzylation of ethers via an analogous silver carbene species, obtained from a more common metal and a more stable starting material.

Abstract The epigenomic abnormality of pancreatic ductal adenocarcinoma (PDAC) has rarely been investigated due to its strong heterogeneity. Here, we used single-cell multiomics sequencing to simultaneously analyze the DNA methylome, chromatin accessibility and transcriptome in individual tumor cells of PDAC patients. We identified normal epithelial cells in the tumor lesion, which have euploid genomes, normal patterns of DNA methylation, and chromatin accessibility. Using all these normal epithelial cells as controls, we determined that DNA demethylation in the cancer genome was strongly enriched in heterochromatin regions but depleted in euchromatin regions. There were stronger negative correlations between RNA expression and promoter DNA methylation in cancer cells compared to those in normal epithelial cells. Through in-depth integrated analyses, a set of novel candidate biomarkers were identified, including ZNF667 and ZNF667-AS1, whose expressions were linked to a better prognosis for PDAC patients by affecting the proliferation of cancer cells. Our work systematically revealed the critical epigenomic features of cancer cells in PDAC patients at the single-cell level.

Anticipated permafrost thaw in upcoming decades may exert significant impacts on forest soil nitrogen (N) dynamics. The rate of soil N mineralization (Nmin) plays a crucial role in determining soil N availability. Nevertheless, our understanding remains limited regarding how biotic and abiotic factors influence the Nmin of forest soil in response to permafrost thaw. In this study, we investigated the implications of permafrost thaw on Nmin within a hemiboreal forest based on a field investigation along the degree of permafrost thaw, having monitored permafrost conditions for eight years. The results indicate that permafrost thaw markedly decreased Nmin values. Furthermore, Nmin demonstrated positive associations with soil substrates (namely, soil organic carbon and soil total nitrogen), microbial biomass carbon and nitrogen, and soil moisture content. The decline in Nmin due to permafrost thaw was primarily attributed to the diminished quality and quantity of soil substrates rather than alterations in plant community composition. Collectively, our results underscore the pivotal role of soil substrate and microbial biomass in guiding forest soil N transformations in the face of climate-induced permafrost thaw.

Environmental nanoparticles are known to be present in various aquatic environments, exerting significant influences on water quality, particularly in water distribution systems. However, there has been a notable dearth of research on the presence and impact of environmental nanoparticles in mineral water, a unique water resource. In this study, we employed Nanoparticle Tracking Analysis (NTA) and conducted High-Resolution Transmission Electron Microscopy (HRTEM) to address this research gap. This groundbreaking study represents the first comprehensive exploration of environmental nanoparticles within natural mineral water from Zibo City, Shandong Province, China. The results of the NTA showed that the concentration of the particles was 5.5 × 105 particles/mL and the peak diameter of the size distribution was 180 nm. The HRTEM showed that the nanoparticles were granular, pinniform, rodlike, and flakey in shape, and some of the nanoparticles existed in aggregation. The energy-dispersive spectrometry results showed that most of the nanoparticles contained O, Mg, Ca, Si, Fe, Ti, and P, and some of them also contained F, V, S, and Mn. When combined with the characteristics of the selected area electron diffraction pattern, the nanoparticles were confirmed to be Ca-bearing nanoparticles, attapulgite nanorods, MnO2 nanosheets, and TiO2 nanoparticles. These findings shed light on a novel manifestation of elemental compositions in mineral water. Furthermore, considering the chemical and physical attributes of both the nanoparticles and mineral water, it is highly plausible that these environmental nanoparticles result from the weathering of minerals. The presence of these nanoparticles within mineral water offers a unique opportunity to advance our comprehension of nanoparticle behavior across diverse systems. Significantly, the realm of environmental nanoparticle science holds paramount importance for ongoing endeavors in ensuring water safety, enhancing treatment processes, and facilitating effective remediation procedures.

Silicosis is a fatal occupational respiratory disease caused by the prolonged inhalation of respirable silica. The core event of silicosis is the heightened activity of fibroblasts, which excessively synthesize extracellular matrix (ECM) proteins. Our previous studies have highlighted that human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs) hold promise in mitigating silicosis and the significant role played by microRNAs (miRNAs) in this process. Delving deeper into this mechanism, we found that miR-148a-3p was the most abundant miRNA of the differential miRNAs in hucMSC-EVs, with the gene heat shock protein 90 beta family member 1 (Hsp90b1) as a potential target. Notably, miR-148a-3p’s expression was downregulated during the progression of silica-induced pulmonary fibrosis both in vitro and in vivo, but was restored after hucMSC-EVs treatment (p < 0.05). Introducing miR-148a-3p mimics effectively hindered the collagen synthesis and secretion of fibroblasts induced by transforming growth factor-β1 (TGF-β1) (p < 0.05). Confirming our hypothesis, Hsp90b1 was indeed targeted by miR-148a-3p, with significantly reduced collagen activity in TGF-β1-treated fibroblasts upon Hsp90b1 inhibition (p < 0.05). Collectively, our findings provide compelling evidence that links miR-148a-3p present in hucMSC-EVs with the amelioration of silicosis, suggesting its therapeutic potential by specifically targeting Hsp90b1, thereby inhibiting fibroblast collagen activities. This study sheds light on the role of miR-148a-3p in hucMSC-EVs, opening avenues for innovative therapeutic interventions targeting molecular pathways in pulmonary fibrosis.

The coal mine in deep mining can easily form a compound dynamic disaster with the characteristics of rock burst and gas outburst. In this paper, the analytic hierarchy process (AHP) and the entropy weight method (EWM) are combined, and the fuzzy comprehensive evaluation (FCE) secondary evaluation model of compound dynamic disaster is proposed to evaluate the risk of compound dynamic disaster, which avoids the problems of the imperfect evaluation index system and strong subjectivity of index weight. Based on the statistical analysis of typical compound dynamic disaster cases in China, three first-level indicators were established, and sixteen second-level indicators were developed. The verification results show that the accuracy and weight are better than the traditional evaluation methods. Combined with geological and mining data, the compound dynamic disaster risk assessment was carried out on the second mining area of mine B, in the Pingdingshan mining area, and the result was grade II (weak risk). Corresponding prevention measures and parameters were implemented, and no compound dynamic disaster occurred during the working face excavation.

Light-emitting diodes (LEDs) can be programmed to provide specialized light sources and spectra for plant growth. UV-A (397.6 nm), blue (460.6 nm), green (520.7 nm), and red (661.9 nm) LED light sources were used to study the effects of different monochromatic lights on the growth, antioxidant system, and photosynthetic characteristics of Spathiphyllum floribundum ‘Tian Jiao’ (a shade-loving species) and Chrysanthemum morifolium ‘Huang Xiu Qiu’ (a sun-loving species). This research revealed that green and blue light could enhance the morphological indicators, Chl a/b, photosynthetic electron transfer chain performance, and photosystem activity of S. floribundum, blue and red light could enhance the solution protein, Chl a, and photosynthetic electron transfer chain performance of C. morifolium, red and UV-A light viewed the highest SOD and CAT activities of S. floribundum (275.56 U·min·g−1; 148.33 U·min·g−1) and C. morifolium (587.03 U·min·g−1; 98.33 U·min·g−1), respectively. Blue and green light were more suitable for the growth and development of the shade-loving plant S. floribundum, while red and blue light were more suitable for the sun-loving plant C. morifolium. UV-A light could be used for their stress research. The research revealed the different adaptation mechanism of different plants to light environmental conditions.

Taking the strong motion records of Yangbi Station obtained by the May 21, 2021 M6.4 Yunnan Yangbi earthquake as input, this study performed dynamic time history analysis on frame structures of different heights and a low-rise brick-concrete structure. Based on this, we explore the response characteristics of the frame structure in the strong earthquake, compare the difference between the seismic response of the brick-concrete structure and low-rise frame structure, and evaluate the performance of the brick-concrete structure. The main analysis results show that the vertical acceleration amplification effect is significant in the floor acceleration response to all structures, especially in the lower frame. The peak value of the floor Fourier amplitude spectrum for the frame is mainly in the frequency range of 1~2.5 Hz in Y direction. Compared with the low-rise and high-rise, the maximum inter-story drift ratios response of the multi-story frame is greater. The inter-story drift ratios of all structures do not exceed the medium damage limit. Compared with the low-rise frame structure, the brick-concrete structure of a shorter basic period has a more significant horizontal acceleration amplification effect to the floor. The fortified brick-concrete structure has good aseismic performance. The analysis results can provide reference for the analysis and evaluation of earthquake damage of buildings after strong earthquake.

The volatility of tourism demand is often caused by some irregular events in recent years. Typically, inbound tourists are quite sensitive to various factors, including the exchange rate fluctuation, consumer price index, personal or household income or consumption expenditure. We combine these multivariate time series data onto an ingenious multi-factor fusion strategy to contribute to precise tourism demand forecasting. A novel hybrid deep learning forecasting approach is developed by integrating several modules such as improved complete ensemble empirical mode decomposition with adaptive noise, intrinsic mode functions classification, multi-factors fusion and predictors matching. The monthly tourist flow data of Shanghai inbounding from USA, Korea and Japan are conducted to verify the performance of the proposed approach, which outperforms all benchmark models for different prediction horizons. The experimental results show that introducing external influencing factors can improve the prediction accuracy significantly, and therefore confirm the rationality and validity of the proposed approach.

Abstract Background Bread wheat (Triticum aestivum) is an important staple cereal grain worldwide. The ever-increasing environmental stress makes it very important to mine stress-resistant genes for wheat breeding programs. Therefore, dehydrin (DHN) genes can be considered primary candidates for such programs, since they respond to multiple stressors. Results In this study, we performed a genome-wide analysis of the DHN gene family in the genomes of wheat and its three relatives. We found 55 DHN genes in T. aestivum, 31 in T. dicoccoides, 15 in T. urartu, and 16 in Aegilops tauschii. The phylogenetic, synteny, and sequence analyses showed we can divide the DHN genes into five groups. Genes in the same group shared similar conserved motifs and potential function. The tandem TaDHN genes responded strongly to drought, cold, and high salinity stresses, while the non-tandem genes respond poorly to all stress conditions. According to the interaction network analysis, the cooperation of multiple DHN proteins was vital for plants in combating abiotic stress. Conclusions Conserved, duplicated DHN genes may be important for wheat being adaptable to a different stress conditions, thus contributing to its worldwide distribution as a staple food. This study not only highlights the role of DHN genes help the Triticeae species against abiotic stresses, but also provides vital information for the future functional studies in these crops.

Purpose. This study aimed to investigate the potential mechanism underlying the therapeutic effect of sildenafil in combination with islet transplantation for diabetic peripheral neuropathy. Methods. A streptozotocin-induced diabetic mouse model was established to evaluate the effects of islet transplantation and sildenafil intervention. The mice were subjected to different interventions for 6 weeks, and histopathological staining and immunohistochemistry techniques were employed to examine the pathological changes and protein expressions of BDNF, MBP, and cleaved caspase-3 in the sciatic nerve tissue. Moreover, RSC96 cells were cocultured with islet cells and sildenafil under high glucose conditions to investigate the potential involvement of the mTOR/S6K1 pathway, BDNF, and MBP proteins. Western blotting was used to detect protein expression in each group. Results. The results showed that islet transplantation can restore sciatic nerve injury in diabetic mice, and sildenafil can enhance the therapeutic effect of islet transplantation. In addition, the combination of sildenafil and islet cells significantly upregulated the expression levels of mTOR/S6K1, BDNF, and MBP in RSC96 cells under high glucose conditions. Conclusions. Islet transplantation can reverse sciatic nerve injury in diabetic mice, and islet cells exhibit a protective effect on RSC96 cells under high glucose conditions via the activation of the mTOR/S6K1 pathway. Sildenafil enhances the therapeutic effect of islet transplantation, which may represent a potential treatment strategy for diabetic peripheral neuropathy.

It is common for elderly patients to develop postoperative cognitive dysfunction (POCD), but the pathophysiological mechanisms have not yet been fully explored. NLRP3 inflammasome activation and mitophagy impairment was involved in neurodegenerative disease. This study investigated the interaction of NLRP3 inflammasome and mitophagy in sevoflurane-induced cognitive dysfunction. We found that sevoflurane induced cleaved caspase-1 level, IL-1β and IL-18 maturation, and activated NLRP3 inflammasome in aged mice and the primary hippocampus neuron. The cleaved caspase-1 was demonstrated in microglia of hippocampus. Ac-YVAD-cmk, a selected caspase-1 inhibitor, reduced the expression of cleaved caspase-1, IL-1β, IL-18 and NLRP3 inflammasome activation induced by sevoflurane. Ac-YVAD-cmk ameliorated learning ability impairment in aged mice induced by sevoflurane using Morris water maze. Moreover, Ac-YVAD-cmk reversed the mitophagy flux dysfunction induced by sevoflurane in aged mice by western blotting, immunostaining and mt-Keima reporters. For the first time, we found caspase-1 inhibitor mitigated mitochondria dysfunction and revised mitophagy impairment induced by sevoflurane.

ObjectiveThis study explored the underlying therapeutic mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) for ischemic stroke (IS), and determined the optimal administration time windows and dose-effect relationship.MethodsThe levels of SDF-1α, IL-10, IL-6, TNF-α, BDNF, IL-1β, and VEGF-A factors in serum and brain tissue lysate were measured by ELISA. The pathological status of brain tissues was evaluated by Hematoxylin-Eosin (HE) staining, and apoptosis of nerve cells was detected by tunel. The protein expression of CXCR-4, NeuN, and Nestin in the brain tissues was assessed through immunofluorescence. The balance beam, forelimb muscle strength, and limb placement were tested on MCAO rats at different time points and doses. The infarct area of the rat brain tissues was measured at the end of the experiment.ResultsThe hUCMSC treatment during the acute phase of MCAO significantly reduced the secretion of IL-6, TNF-α, IL-1β but increased IL-10 in serum, and the levels of SDF-α and BDNF in serum and brain tissues lysate were also increased. The pathological results showed that there were more neurons in the treatment group compared to the model group. Immunofluorescence assays showed that the expression of CXCR4、Nestin、NeuN was relatively higher than that in the model group. The d4 and d7 treatment significantly improves the motor function, promotes the recovery of forelimb muscle strength, increases the forelimb placement rate and reduces the scope of cerebral infarction, but the d14 treatment group has less therapeutic effect compared to the d4 and d7 treatment. The 2×107/kg treatment showed the best therapeutic effect, followed by the 1×107/kg treatment, and the worst is 0.5×107/kg treatment from the test of balance beam, forelimb muscle strength, limb placement and the infarct area of the rat brain tissues.ConclusionThe hUCMSCs can inhibit the infiltration of inflammatory cells in the brain tissue, and promote the repair of brain tissue structure and function. Early intervention by injecting high-dose of hUCMSCs can significantly improve the recovery of neurological/motor function and reduce the size of cerebral infarction in rats.