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Plumbagin (PLB), a naphthoquinone compound, has been proven to have anti-cancer properties in different types of cancers. However, the anti-tumor actions as well as molecular processes in osteosarcoma (OS) remain unclear. This study investigates the underlying mechanisms of PLB in human OS cells in vitro. Our study showed that PLB significantly inhibited the proliferation of human OS cells in a time- and dosage-dependent manner. RNA sequencing data revealed that the efficacy of PLB is related to cell cycle, cell death, and p38 MAPK signaling pathway in KHOS-240S cells. Further studies indicated that PLB triggers G2/M phase arrest, mitochondrial-dependent apoptosis, as well as ferroptosis in human OS cells. Mechanistically, PLB treatment increased ROS generation that activates the p38 MAPK signaling pathway. BIRB 796, a p38 MAPK inhibitor, partly reversed PLB-induced phase arrest of G2/M and cell death. Furthermore, N-acetylcysteine (NAC), a ROS scavenger, significantly decreased G2/M phase arrest and cell death and reversed p38 MAPK activation caused by PLB. In conclusion, PLB induces arrest G2/M arrest, apoptosis as well as ferroptosis in human OS cells via ROS generation and p38 MAPK activation. There is potential for PLB to be an effective treatment for OS.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) coexisting with pulmonary adenocarcinoma (ADC) is rare. Herein, we report a new case and review the cases published previously in the English literature. The clinicopathological features of similar cases reported in the English literature were summarized, and a putative association between DIPNECH and pulmonary ADC was suggested.Among the 22 cases studied, the majority of patients were female and older adults. DIPNECH lesions were usually recognized beyond the lobe or segment in which the ADC was located. Most ADCs were of a low- or intermediate-grade. DIPNECH and pulmonary ADC were interspersed in six patients. In particular, two cases of ADC showed neuroendocrine differentiation.We consider that DIPNECH accompanied by ADC is not coincidental, and that the two lesions may have a causal relationship. Analogous to the tumor histogenesis association of large cell neuroendocrine carcinoma/small cell carcinoma with ADC, we hypothesized that DIPNECH may also arise from a multipotent precursor cell and associate with a subgroup of ADC. However, further studies are required to explore this possibility.

Metastasis is the main cause of death in cancer patients, the lung is one of the most common metastatic organs of malignant solid tumors. Before tumor cells metastasize to the lungs, they interact with immunosuppressive cells, alveolar epithelial cells, and lung fibroblasts to form a pre-metastatic niche. The pre-metastatic niche is a key factor leading to tumor cell metastasis to the lungs. Research has found that traditional Chinese medicine and its components can inhibit the formation of pre-metastatic niche. Therefore, this article reviewed the research progress on the formation of lung pre-metastatic niche and the intervention of traditional Chinese medicine in pulmonary PMN, in order to provide new Chinese medicine prescriptions and research ideas for further clinical prevention and treatment of tumor metastasis to the lung.

Summary: Mesenchymal stem cells (MSCs) are heterogeneous in morphology and transcriptome, resulting in varying therapeutic outcomes. In this study, we found that 3D spheroid culture of heterogeneous MSCs, which have undergone conventional 2D monolayer culture for 5–6 passages, synchronized the cells into a uniform cell population with dramatically reduced cell size, and considerably increased levels of immunosuppressive genes and growth factors. Single-cell RNA sequencing (scRNA-seq) analysis of the cells revealed that 3D MSCs consisted of 2 major cell subpopulations and both expressed high levels of immunosuppressive factors, compared to 6 subpopulations in 2D MSCs. In addition, 3D MSCs showed a greater suppressive effect on T cells. Moreover, intravenous infusion of a large dose of 3D MSCs prior to imiquimod (IMQ) treatment significantly improved psoriatic lesion. Thus, our results indicate that 3D spheroid culture reprograms heterogeneous MSCs into a uniform immunosuppressive phenotype and promises a novel therapeutic potential for inflammatory diseases.

ABSTRACT: High-laying ducks are often fed high-energy, nutritious feeds to maintain high productivity, which predisposes them to lipid metabolism disorders and the development of fatty liver syndrome (FLS), which seriously affects production performance and has a substantial economic impact on the poultry industry. Therefore, it is necessary to elucidate the mechanisms underlying the development of fatty liver syndrome. In this study, seven Shan Partridge ducks, each with fatty liver syndrome and normal laying ducks, were selected, and Hematoxylin Eosin staining (HE staining), Masson staining, and transcriptome sequencing were performed on liver tissue. In addition to exploring key genes and pathways using conventional analysis methods, we constructed the first Kyoto Encyclopedia of Genes and Genomes (KEGG) database-based predefined gene set containing 12,764 pathways and 16,836 genes and further performed gene set enrichment analysis (GSEA) on the liver transcriptome data. Finally, key nodes and biological processes were identified via the protein-protein interaction (PPI) network. The results showed that the liver in the FL group exhibited steatosis and fibrosis, and a total of 3,663 genes with upregulated expression versus 2,296 downregulated genes were screened by conventional analysis. GSEA analysis and PPI network analysis revealed that the liver in the FL group exhibited disruption of the mitochondrial electron transport chain, leading to decreased oxidative phosphorylation and the secretion of excessive proinflammatory factors amid the continuous accumulation of lipids. Under continuous chronic inflammation, cell cycle arrest triggers apoptosis, while fibrosis becomes more severe, and procarcinogenic genes are activated, leading to the continuous development and deterioration of the liver. In conclusion, the predefined gene set constructed in this study can be used for GSEA, and the identified hub genes provide useful reference data and a solid foundation for the study of the genetic regulatory mechanism of fatty liver syndrome in ducks.

Summary: Background: Omicron sub-variants breakthrough infections (BTIs) have led to millions of coronavirus disease 2019 (COVID-19) cases worldwide. The acute-phase immune status is critical for prognosis, however, the dynamic immune profiling of COVID-19 during the first month after BTIs remains unclear. Methods: In this study, we monitored the immune dynamics at various timepoints in a longitudinal cohort during the first month post-BTIs through clinical evaluation, single-cell RNA sequencing (scRNA-seq), T cell receptor (TCR)/B cell receptor (BCR) sequencing, and antibody mass spectrometry. Findings: Serological analysis revealed limited impairment to functions of major organs, active cellular and humoral immunity at 2 weeks post-BTI, with significant increases in cytokines (CKs) and neutralizing antibody levels. However, 1 month post-BTI, organ function parameters and CK levels reverted to pre-infection levels, whereas neutralizing antibody levels remained high. Notably, scRNA-seq showed that lymphocytes maintained strong antiviral activity and cell depletion at 2 weeks and 1 month post-BTI, with genes CD81, ABHD17A, CXCR4, DUSP1, etc. upregulated, and genes PFDN5, DYNLRB1, CD52, etc. downregulated, indicating that lymphocytes status take longer to recover to normal levels than that routine blood tests revealed. Additionally, T cell-exhaustion associated genes, including LAG3, TIGIT, PDCD1, CTLA4, HAVCR2, and TOX, were upregulated after BTI. TCRs and BCRs exhibited higher clonotypes, mainly in CD8Tem or plasmablast cells, at 2 weeks post-BTI comparing 1 month. More IgG and IgA-type BCRs were found in the groups of 1 month post-BTI, with higher somatic hypermutation, indicating greater maturity. Verification of monoclonal antibodies corresponding to amplified BCRs highlighted the antigen-specific and broad-spectrum characteristics. Interpretation: Our study elucidated the dynamic immune profiling of individuals after Omicron BA.5 sublineages BTI. Strong immune activation, antiviral response, antibody maturation and class transition at 2 weeks and 1 month after BTI may provide essential insights into pathogenicity, sequential immune status, recovery mechanisms of Omicron sublineage BTI. Funding: This study was supported by the National Key R&D Program of China, the China Postdoctoral Science Foundation, Guangdong Basic and Applied Basic Research Foundation, the National Natural Science Foundation of China, CAS Project for Young Scientists in Basic Research, and the Air Force Special Medical Center Science and Technology Booster Program.

2-Ethylhexyl diphenyl phosphate (EHDPP) is a representative organophosphorus flame retardant (OPFR) that has garnered attention due to its widespread use and potential adverse effects. EHDPP exhibits cytotoxicity, genotoxicity, developmental toxicity, and endocrine disruption. However, the toxicity of EHDPP in mammalian oocytes and the underlying mechanisms remain poorly understood. Melatonin is a natural free radical scavenger that has demonstrated cytoprotective properties. In this study, we investigated the effect of EHDPP on mouse oocytes in vitro culture system and evaluated the rescue effect of melatonin on oocytes exposed to EHDPP. Our results indicated that EHDPP disrupted oocyte maturation, resulting in the majority of oocytes arrested at the metaphase I (MI) stage, accompanied by cytoskeletal damage and elevated levels of reactive oxygen species (ROS). Nevertheless, melatonin supplementation partially rescued EHDPP-induced mouse oocyte maturation impairment. Results of single-cell RNA sequencing (scRNA-seq) analysis elucidated potential mechanisms underlying these protective effects. According to the results of scRNA-seq, we conducted further tests and found that EHDPP primarily disrupts mitochondrial distribution and function, kinetochore-microtubule (K-MT) attachment, DNA damage, apoptosis, and histone modification, which were rescued upon the supplementation of melatonin. This study reveals the mechanisms of EHDPP on female reproduction and indicates the efficacy of melatonin as a therapeutic intervention for EHDPP-induced defects in mouse oocytes.

The present study sought to investigate the protective effect of Lycopene (LYC) on Bisphenol A (BPA)-induced lipid accumulation and elucidate the potential molecular mechanism. In vitro, the PK15 cells with or without LYC were exposed to BPA for 6 h to detect the lipid accumulation using Nile red’s and Oil Red O’ staining. Meanwhile, redox status, mitochondrial function, gene expression and protein levels relating to lipid accumulation were evaluated by cellular biochemical assays, immunofluorescence staining, quantitative real-time PCR (qRT-PCR) and Western blot, respectively. In addition, ROS scavenger N-acetylcysteine (NAC), SIRT1 inhibitor EX527, SIRT1 siRNA and PGC-1α siRNA were used to verify the target signaling pathways responsible for the protective effect of LYC against BPA-indcued lipid accumulation. In vivo, the twenty four male Wistar rats were randomly divided into three groups, received either BPA (50 mg/kg/day BW) or LYC (10 mg/kg/day BW) orally for 60 days. The kidney tissues were evaluated by HE’s and Oil Red O’s staining, lipid-associated genes and proteins expression were detected through qRT-PCR and Western blot. The results showed that BPA-exposed PK15 cells and rats had increased lipid droplets with elevated transcription of lipogenic factors SREBP1 and PPARγ, and down-regulated PPARα expression, and which is accompanied by redox imbalance and abnormal mitochondrial function. Conversely, LYC prevented BPA-induced lipid metabolism disorder and lipid accumulation through impeding ROS overproduction. Moreover, PK15 cells and rats exposed to BPA showed decrease in SIRT1 and PGC-1α levels, whereas LYC blocked the decrease of SIRT1 and PGC-1α protein levels. Furthermore, inhibition or silence of SIRT1 and PGC-1α abrogated the improvements of LYC on ROS generation, mitochondrial mass impairement and lipid accumulation in BPA-treated PK15 cells. Collectively, these findings indicate that SIRT1/PGC-1α signaling pathway is involved in the protective effect of LYC on BPA-induced lipid accumulation. These results also provide a potential promising therapeutic of LYC against BPA-induced lipid accumulation in kidney cells and organs.

In recent years, there has been a notable rise in the incidence of pregnancies complicated by gestational diabetes mellitus (GDM), characterized by glucose intolerance first identified during pregnancy. Analysis of placental tissue has revealed that placentas from women with GDM tend to be larger and heavier compared to control placentas, indicating potential changes in trophoblast proliferation, differentiation, and apoptosis. In this study, transcriptome sequencing was conducted on placentas obtained from both normal pregnancies and pregnancies with GDM to investigate the molecular mechanisms underlying this condition. The original sequencing data were subjected to sequencing analysis, resulting in the identification of 935 upregulated genes and 256 downregulated genes. The KEGG and GO analysis techniques on differential genes uncovered evidence suggesting that the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway may contribute to the pathogenesis of GDM. Subsequent analysis indicated that the expression levels of matrix metalloproteinases (MMP) 11, MMP12, MMP14, and MMP15, which are regulated by the PI3K/Akt pathway, were upregulated in the placentas of patients with GDM when compared to those of individuals with normal placental function. Additionally, our investigation into alternative splicing patterns revealed an increase in exon skipping alternative splicing of CSF3R in the placenta of patients with GDM compared to that in the control group. The CSF3R–PI3K-MMP pathway is speculated to regulate the pathogenesis of GDM.

Electroacupuncture pretreatment is considered as an optimal strategy for inducing cerebral ischaemic tolerance. However, the underlying neuroprotective mechanism of this approach has never been explored from the perspective of calcium homeostasis. Intracellular calcium overload is a key inducer of cascade neuronal injury in the early stage after cerebral ischaemia attack and the Na+/Ca2+ exchanger (NCX) is the main plasma membrane calcium extrusion pathway maintaining post-ischaemic calcium homeostasis. This study aims to investigate whether the regulation of NCX-mediated calcium transport contributes to the cerebroprotective effect of electroacupuncture pretreatment against ischaemic injury and to elucidate the underlying mechanisms involved in this process. Following five days of repeated electroacupuncture stimulation on Baihui (GV20), Neiguan (PC6), and Sanyinjiao (SP6) acupoints in rats, in vivo and in vitro models of cerebral ischaemia were induced through middle cerebral artery occlusion and oxygen/glucose deprivation (OGD), respectively. Firstly, we verified the neuroprotective effect of electroacupuncture pretreatment from the perspective of neurological score, infarct volume and neuronal apoptosis. Our findings from brain slice patch-clamp indicated that electroacupuncture pretreatment enhanced the Ca2+ efflux capacity of NCX after OGD. NCX1 expression in the ischaemic penumbra exhibited a consistent decline from 1 to 24 h in MCAO rats. Electroacupuncture pretreatment upregulated the expression of NCX1, especially at 24 h, and silencing NCX1 by short hairpin RNA (shRNA) administration reversed the protective effect of electroacupuncture pretreatment against cerebral ischaemic injury. Furthermore, we administered LY294002, a phosphatidylinositol 3 kinase (PI3K) inhibitor, prior to inducing ischaemia to investigate the upstream regulatory mechanism of electroacupuncture pretreatment on NCX1 expression. Electroacupuncture pretreatment activates PI3K/Akt pathway, leading to an increase in the expression of NCX1, which facilitates calcium extrusion and exerts a neuroprotective effect against cerebral ischaemia. These findings provided a novel insight into the prevention of ischemic stroke and other similar conditions characterized by brain ischaemia or hypoperfusion.

To fully utilize the aromatic ring structure of lignin and realize high value addition, organosolv lignin (OL) extracted from papermaking waste liquid was subjected to catalytic pyrolysis for the production of phenolic compounds. Using self-made carbon nanospheres as a template, cellular La0.8Pr0.2NiO3 perovskite was prepared by the sol-gel method and used as catalyst in the pyrolysis of OL at 600 °C for 3 h. The yield of liquid-phase product was 21.34 %, and the selectivity of phenolic compounds reached 70.20 %, constituting increases by 43.41 % and 25.87 % compared with the yield and selectivity of the catalyst-free process, respectively. After four cycles of regeneration, La0.8Pr0.2NiO3 perovskite still demonstrated good structural and catalytic stability. This work provides a theoretical basis for the development of green and sustainable chemical products.

Triocresyl phosphate (TOCP) was commonly used as flame retardant, plasticizer, lubricant, and jet fuel additive. Studies have shown adverse effects of TOCP on the reproductive system. However, the potential harm brought by TOCP, especially to mammalian female reproductive cells, remains a mystery. In this study, we employed an in vitro model for the first time to investigate the effects of TOCP on the maturation process of mouse oocytes. TOCP exposure hampered the meiotic division process, as evidenced by a reduction in the extrusion of the first polar body from oocytes. Subsequent research revealed the disruption of the oocyte cell cytoskeleton induced by TOCP, resulting in abnormalities in spindle organization, chromosome alignment, and actin filament distribution. This disturbance further extended to the rearrangement of organelles within oocytes, particularly affecting the mitochondria. Importantly, after TOCP treatment, mitochondrial function in oocytes was impaired, leading to oxidative stress, DNA damage, cell apoptosis, and subsequent changes of epigenetic modifications. Supplementation with nicotinamide mononucleotide (NMN) alleviated the harmful effects of TOCP. NMN exerted its mitigating effects through two fundamental mechanisms. On one hand, NMN conferred stability to the cell cytoskeleton, thereby supporting nuclear maturation. On the other hand, NMN enhanced mitochondrial function within oocytes, reducing the excess reactive oxygen species (ROS), restoring meiotic division abnormalities caused by TOCP, preventing oocyte DNA damage, and suppressing epigenetic changes. These findings not only enhance our understanding of the molecular basis of TOCP induced oocyte damage but also offer a promising avenue for the potential application of NMN in optimizing reproductive treatment strategies.

It is of great significance to prepare liners with excellent inhibition of energetic plasticizer migration and gas barrier properties. Here, we have successfully prepared magnetic iron oxide decorated reduced-graphene-oxide nanosheets (MRGO) by using ultrasound-assisted method. The obtained MRGO nanosheet-fillers were filled into hydroxyl-terminated polybutadiene (HTPB) which was exposed to a magnetic field (200 mT) to achieve ordered orientation of MRGO in the HTPB matrix (Ordered MRGO/HTPB). The laser confocal microscopy demonstrates that MRGO exhibit ordered orientation structure in HTPB matrix with good dispersion, which renders the HTPB composite liners exhibiting high gas and plasticizer barrier capability, with a reduction of 18.9 % in water vapor permeability and a decrease of 14.1 % in dibutyl phthalate (DBP) migration equilibrium concentration as compared with those of random MRGO embedded HTPB composite liners (Random MRGO/HTPB). Moreover, a theoretical model accounting for such enhanced gas/plasticizer barrier performance of HTPB due to the implantation of order aligned MRGO was established, which shows that the effective diffusion pathways of plasticizer/gas for liner penetration would be significantly enhanced when the MRGO nanosheets are oriented within the HTPB matrix. This work provides an effective and facile strategy toward the design and development of composite liners with high plasticizer/gas barrier performance for industrial applications.

In high-altitude cold areas, freeze-thaw (F-T) cycles induced by day-night and seasonal temperature changes cause numerous rock mass slope engineering disasters. To investigate the dynamic properties of rock in the natural environment of a high-altitude cold area, standard specimens were drilled from the slope of the Jiama copper mine in Tibet, and dynamic compression tests were performed on water-saturated and frozen sandstone with different numbers of F-T cycles (0, 10, 20, 30, and 40) by the split Hopkinson pressure bar (SHPB) system with a cryogenic control system. The influence of water-saturated and frozen conditions on the dynamic performance of sandstone was investigated. The following conclusions are drawn: (1) With increasing strain rate, the attenuation factor (λa) of water-saturated sandstone and the intensifying factor (λi) of frozen sandstone linearly increase. As the number of F-T cycles increases, the dependence factor (λd) of water-saturated sandstone linearly decreases, whereas the λd of frozen sandstone linearly increases. (2) The prediction equation of the dynamic compressive strength of water-saturated and frozen sandstone is obtained, which can be used to predict the dynamic compressive strength of sandstone after various F-T cycles based on the strain rate. (3) The mesoscopic mechanism of water-saturated and frozen sandstone's dynamic compressive strength evolution is investigated. The water softening effect causes the dynamic compressive strength of water-saturated sandstone to decrease, whereas the strengthening effect of pore ice causes it to increase. (4) The decrease in the relative dynamic compressive strength of water-saturated sandstone and the increase in the relative dynamic compressive strength of frozen sandstone can be attributed to the increased porosity.

The effectiveness and safety of traditional Chinese medicine's active ingredients in anti-tumor effects have attracted widespread attention worldwide. Solasonine is the main anti-tumor component of the traditional Chinese medicine Solanum nigrum L, which can inhibit tumor cell proliferation, induce apoptosis, induce ferroptosis in tumor cells, and inhibit of tumor cell metastasis, thereby inhibiting tumor progression. Therefore, we summarized anti-tumor mechanisms and targets of solasonine to provide new ideas and theoretical basis for its further development and application.

Changes in hydrothermal conditions have significant effects on vegetation, but there is still a lack of understanding of how vegetation responds to land surface (surface temperature and soil moisture) and meteorological (temperature and precipitation) conditions in mountain regions. This study examined the trends of leaf area index (LAI) in the Yan Mountains over the last four decades using Global Land Surface Satellite (GLASS) data. The results showed a persistent increase of LAI (greening) over 20 % to 80 % of the study area in growing season, spring, summer and autumn. Anthropogenic activities caused the greening trend by crop management before 2000 and afforestation after 2000. The increasing rate of LAI varied with elevation, and the most significant increase occurred in areas between 300 and 900 m, and the lowest increase occurred in areas below 300 m. Moreover, we found that LAI was negatively correlated with land surface temperature and soil moisture, but positively correlated with precipitation and air temperature. The time-lag effect was found between hydrothermal factors and LAI in the past four decades. There was a time lag of 2–3 months between LAI changes and temperature/precipitation during the early and late stages of the growing season, and a time lag of 0–1 month during the middle stage. Specifically, there was no time lag in vegetation response to surface soil moisture, and a time lag of 2–3 months in vegetation response to land surface temperature from July to October. Our findings provide insights into how vegetation adapts to land surface and climatic hydrothermal conditions in mountain regions and can be used by governments to develop policies for ecological protection.

Azobenzene is a typical photoisomerization material that is widely used in photochemical energy conversion. However, it's generally operated below 200 °C to avoid thermal decomposition. To improve the thermal stability of azobenzene for higher temperature applications, this paper discussed an option that grafting azobenzene onto graphite-like carbon nitride sheets. The synthesis was evaluated based on the performance of micro morphology and structure, thermal stability, and photochemical energy conversion. Furthermore, the photochemical conversion performance was analyzed with diverse irradiation intensities. The results demonstrate that the synthesis has a strong thermal stability below 530 °C. In this study, the most favorable excitation wavelength for photochemical conversion was 445 nm with an irradiation intensity of 40 mW/cm2.

ABSTRACT: Fatty liver hemorrhagic syndrome is a widespread metabolic disease in laying hens that decreases egg production and even causes death in severe cases. Many traditional Chinese medicine ingredients, such as saikosaponin a (SSa), have been shown to alleviate fatty liver, but the underlying mechanisms remain unclear. In this study, we aimed to explore the alleviation of dietary SSa on excessive hepatic lipid deposition and the interactions between intestinal microbiota and bile acid (BA) in laying hens. Fifty-four 35-wk-old laying hens were randomly allocated into 3 treatment groups with 6 replicates (3 birds per replicate) and fed with a basal diet (CON), high-energy and low-protein diet (HELP), and HELP diet with 30 mg/kg SSa (HELP + SSa). SSa reversed diet-induced egg production rate decrease (P < 0.05). SSa could potently ameliorate HELP-induced accumulation of hepatic cholesterol and liver injury via the increase (P < 0.05) of mRNA expression of BA synthesis gene, such as cholesterol 7 alpha-hydroxylase 1. SSa treatment alleviated gut dysbiosis, especially reducing (P < 0.05) the relative abundance of bile salt hydrolase (BSH)-producing bacteria such as Lactobacillus, Bifidobacterium, and Turicibacter. Ileal BA metabolomic analysis revealed that SSa increased (P < 0.05) the content of tauro-conjugated BAs, mainly taurochenodeoxycholic acid and tauro-α-muricholic acid. The mRNA expression of farnesoid X receptor (FXR) and fibroblast growth factor 19 were decreased (P < 0.05) in intestine, which was associated with increased gene expression of enzymes in the BA synthesis that reduced the levels of cholesterol. Moreover, SSa treatment inhibited intestinal BA reabsorption via decreasing (P < 0.05) the mRNA expression of apical sodium-dependent bile acid transporter. Our findings indicated that SSa reduced liver cholesterol accumulation and alleviated fatty liver in laying hens through microbiota-BA-intestinal FXR crosstalk.

To study the physical properties and dynamic mechanical response characteristics of rock materials in seasonally frozen regions, density, P-wave velocity, nuclear magnetic resonance, and dynamics Brazilian disc tests were carried out on sandstones treated with different numbers of freeze-thaw cycles. The experimental results show that the water-saturated density and P-wave velocity of sandstone decrease and the Nuclear magnetic resonance porosity increases as the number of freeze-thaw cycles increases. Under a certain loading rate, the dynamic tensile strength of water-saturated sandstone gradually decreases and that of frozen sandstone gradually increases as the number of freeze-thaw cycles increases; at the same time, the dynamic tensile strength of both water-saturated and frozen sandstone increases as the loading rate increases under the same number of freeze-thaw cycles. The reason for the variability of dynamic tensile strength between water-saturated and frozen sandstones with the increase in the number of freeze-thaw cycles can be attributed to the change in porosity. On this basis, the concept of relative dynamic tensile strength of sandstones was introduced and regression analysis was carried out with the increase ratio of porosity, and it was found that the correlation between the relative dynamic tensile strength and the increase ratio of porosity was strong. The relative dynamic tensile strength of water-saturated sandstone decreases exponentially with the increase ratio of porosity; the relative dynamic tensile strength of frozen sandstone increases exponentially with the increase ratio of porosity.

The minimally invasive biomarkers that can facilitate a rapid dose assessment are valuable for the early medical treatment when accidental or occupational radiation exposure happens. Our previous proteomic research identified one kind of circulating protein, Insulin-like Growth Factor Binding Protein 3 (IGFBP-3), which showed a significant increase after total body exposure of mice to carbon ions and X-rays. However, several critical issues such as the responses to diverse radiation, the origin and underlying mechanism in radiation response obstruct the utilization of circulating IGFBP-3 as a reliable radiation biomarker. In this study, mice were subjected to total or partial body irradiation with carbon ions, protons or X-rays, or treated with chloroform as a comparison. The level of IGFBP-3 in serum and different organs were measured via Enzyme Linked Immunosorbent Assay (ELISA), Western blot (WB) and Immunohistochemistry (IHC). A significant increase of IGFBP-3 was discovered in serum and liver tissue post-irradiation with three kinds of radiation, but absent when challenged with chloroform. Likewise, a similar response was also observed in blood samples from patients receiving radiotherapy. Moreover, the effect of radiation on three main hepatic cells was investigated, the findings indicated that IGFBP-3 could be detected in the culture medium of Kupffer cells (MKC) alone and was elevated in cells and cultured medium of MKC post-irradiation. Additionally, we observed a co-expression effect between P53 and IGFBP-3 in liver tissues and MKC post-irradiation. Along with down-regulation of Trp53 by siRNA, the response of IGFBP-3 to radiation was attenuated. The present study demonstrated that circulating IGFBP-3 could be a promising universal biomarker for complex environmental radiation exposure, and the upregulation of IGFBP-3 is attributed to the MKC in a P53-dependent manner. Circulating IGFBP-3 assays would offer rapid, convenient and effective dose and toxicity assessment methods in occupational exposure or radiation disaster management.

Endometriosis is a common disease in the field of gynaecology, exhibiting clinical manifestations such as dysmenorrhoea, pelvic masses, and infertility, affecting 2–10% of women of reproductive age worldwide. Currently, the acceptance rate of hormonal drugs in patients is low and certain side effects exist. In this study, based on network pharmacology, it was found that the Yushenhuoxue (YSHX) formula could potentially affect endometriosis through the TNF signalling pathway. Clinical studies indicated that YSHX demonstrated the ability to reduce the vas score of dysmenorrhoea, resulting in a significant down-regulation of serum ca125 and inflammatory factors (IL-6, IL-1β, TNF-α). In vivo studies showed that stem cell mice in the YSHX group exhibited significantly reduced lesion volumes than those in the model group. Serum levels of IL-1β and IL-6 were significantly decreased. Moreover, the phosphorylation levels of NF-κB p65 and the expression of TNF-α protein were significantly decreased. In vitro studies have shown that YSHX inhibits the proliferation, invasion, and migration of endometriotic cells. This study partially verified that YSHX contributed to the treatment of endometriosis by regulating the TNF signalling pathway and improving the inflammatory state of endometriosis.

Chemoresistance to paclitaxel (PTX) is one of the main reasons for treatment failure and poor prognosis in patients with advanced ovarian cancer. Therefore, it is imperative to explore the mechanisms related to chemotherapy resistance in ovarian cancer to find potential therapeutic targets. Circular RNAs (circRNAs) play important roles in cancer development and progression. However, their biological functions and clinical significance in ovarian cancer have not been fully elucidated. Therefore, in this study, we aimed to investigate the function and underlying mechanism of hsa_circ_0002782 (circSLC39A8), identified by circRNA sequencing, in regulating PTX resistance. The effects of circSLC39A8 on PTX resistance was assessed by cell viability, colony formation, flow cytometry assays and an in vivo subcutaneous xenografted tumor mouse model. RNA immunoprecipitation and dual-luciferase reporter assays were performed to verify the interaction between circSLC39A8 and the miR-185–5p/BMF signal axis. We found that circSLC39A8 was downregulated in PTX-resistant ovarian cancer cells and tissues, and its low expression was associated with poor prognosis. Biologically, circSLC39A8 knockdown promoted PTX resistance in vitro and in vivo, while circSLC39A8 overexpression showed the opposite effect. Mechanistically, circSLC39A8, acting as an endogenous sponge for miR-185–5p, could relieve the inhibition of miR-185–5p on the expression of its downstream target, BMF; thus enhancing the sensitivity of ovarian cancer to PTX. Our findings demonstrate that circSLC39A8 can promote PTX sensitivity by regulating the miR-185–5p/BMF axis. This may be a valuable prognostic biomarker and a promising therapeutic target for patients with ovarian cancer.

Multi-scale habitat selection modeling (HSM) has garnered attention due to its ability to incorporate scale dependence of species. The key of multi-scale HSM is to select the appropriate combination of scales for different resources or environmental conditions, and then construct a set of multi-scale environmental covariates as the features of HSM. However, the existing scale selection methods do not determine the combination of scales under a unified model. In this study, a combinatorial optimization approach is proposed. We regard the combination of different scales as a search space, and use a heuristic optimization algorithm to search for the best-fitting model to determine the optimal scales for each resource or environmental condition. In a case study conducted in Yancheng National Nature Reserve, the proposed approach is applied to model the habitat selection of the endangered red-crowned crane. We compare the proposed method with single-scale, random-scale and other multi-scale approaches. The results show that the combination of scales selected based on the proposed method obtained the best accuracy in the spatial prediction of habitat suitability with a test AUC of 0.865 for the daytime scenario and 0.932 for the nighttime scenario. Moreover, the selected scales are utilized to generate response curves, providing suggestions for habitat restoration and management of the red-crowned crane population in the nature reserve.

Purpose: To evaluate the effects of chalazion excision on the ocular surface, taking into account the subjective symptoms and the objective parameters of the tear film. Methods: This prospective, interventional clinical study included 52 eyes from 26 patients with eyelid chalazion who underwent excision of the lesions between March and August 2022. Chalazion excision was performed on the patient's chalazion eye, and the contralateral eye served as the control. The following parameters were investigated both preoperatively and 1 week, 1 month, and 3 months postoperatively: the Ocular Surface Disease Index (OSDI), Schirmer I test, corneal fluorescein stain (CFS), tear meniscus height (TMH), noninvasive first breakup time (NifBUT), noninvasive average breakup time (NiaBUT), bulbar conjunctival redness score, the thickness of the lipid layer, and meibomian gland loss. Results: Before surgery, the OSDI score of the chalazion eye was significantly higher than the contralateral eye. The bulbar conjunctival redness score (p = 0.043) and the OSDI score (p = 0.004) improved significantly in the first month after surgery. In the third month after surgery, the objective parameters showed significant improvements, including TMH (p = 0.032), NiaBUT (p = 0.028), bulbar conjunctival redness score (p

The accurate diagnosis and effective therapy of malignant tumors is still a challenge owing to its poor prognosis, recurrence, and drug resistance. In this study, a tumor microenvironment responsive and high O2-economic effect nano-theranostic agent GOx@NPs was constructed through the self-assembly of GOx and CDDO-Fe, which was synthesized by coupling natural chemotherapeutic drug CDDO-Me blocked by ferrocene (Fc) with near-infrared (NIR) fluorescence probe hemicyanine (I-CyOH) via redox-responsive linker dimercaptoisopropionyl, and then introducing tamoxifen (estrogen receptor target fragment) to hemicyanine to enhance the active targeting ability. The NIR fluorescence probe I-CyOH not only achieved an accurate diagnosis, but also possessed photodynamic therapy (PDT) effect. The active targeting fragment tamoxifen enhanced the accumulation of pathological site and alleviated the hypoxia microenvironment through the inhibition of mitochondrial respiratory to reinforce the PDT efficiency of I-CyOH. Moreover, the combination of Fc and GOx could achieve starvation therapy and enhance chemodynamic therapy (CDT). In vitro and vivo experiments exhibited that the effective dual sensitive synergistic therapy possessed significant therapy efficiency and lower side effects. This study provides a valuable strategy for constructing dual sensitization and high economic of intelligent nano-theranostic agents for tumor diagnosis and synergistic cancer therapy.

The antitumor effects of traditional drugs have received increasing attention and active antitumor components extracted from traditional drugs have shown good efficacy with minimal adverse events. Cepharanthine(CEP for short) is an active component derived from the Stephania plants of Menispermaceae, which can regulate multiple signaling pathways alone or in combination with other therapeutic drugs to inhibit tumor cell proliferation, induce apoptosis, regulate autophagy, and inhibit angiogenesis, thereby inhibiting tumor progression. Therefore, we retrieved studies concerning CEP's antitumor effects in recent years and summarized the antitumor mechanism and targets, in order to gain new insights and establish a theoretical basis for further development and application of CEP.

Introduction and Objectives: The development of hepatocellular carcinoma (HCC) is a multi-step process that accumulates genetic and epigenetic alterations, including changes in circular RNA (circRNA). This study aimed to understand the alterations in circRNA expression in HCC development and metastasis and to explore the biological functions of circRNA. Materials and Methods: Ten pairs of adjacent chronic hepatitis tissues and HCC tissues from patients without venous metastases, and ten HCC tissues from patients with venous metastases were analyzed using human circRNA microarrays. Differentially expressed circRNAs were then validated by quantitative real-time PCR. In vitro and in vivo assays were performed to assess the roles of the circRNA in HCC progression. RNA pull-down assay, mass spectrometry analysis, and RNA-binding protein immunoprecipitation were conducted to explore the protein partners of the circRNA. Results: CircRNA microarrays revealed that the expression patterns of circRNAs across the three groups were significantly different. Among these, hsa_circ_0098181 was validated to be lowly expressed and associated with poor prognosis in HCC patients. Ectopic expression of hsa_circ_0098181 delayed HCC metastasis in vitro and in vivo. Mechanistically, hsa_circ_0098181 sequestered eukaryotic translation elongation factor 2 (eEF2) and dissociated eEF2 from filamentous actin (F-actin) to prevent F-actin formation, which blocked activation of the Hippo signaling pathway. In addition, the RNA binding protein Quaking-5 bound directly to hsa_circ_0098181 and induced its biogenesis. Conclusions: Our study reveals changes in circRNA expression from chronic hepatitis, primary HCC, to metastatic HCC. Further, the QKI5-hsa_circ_0098181-eEF2-Hippo signaling pathway exerts a regulatory role in HCC.

This paper presents a novel Adaptive Mutation Quantum-inspired Squirrel Search Algorithm (AM-QSSA). Firstly, based on the population mutation, a location-update of quantum state correlative and attractor method is proposed. By introducing a random process to modify the sliding factor of the local attractor, the inevitable lack of diversity in the population renewal method is solved. The premature convergence problem of adaptive mutation rate improvement algorithm based on squirrel position update mode is introduced. Meanwhile, the paper decomposes the location update process of the SSA, and improves it with quantum-behavior. Furthermore, it proposes a novel quantum-inspired squirrels search algorithm. This method finds the complementary effect between quantum behavior and squirrel search algorithm, and solves the problem of premature convergence probability of SSA. In addition, it improves population diversity, and achieves the balance between global and local search. The efficiency of the proposed AM-QSSA is evaluated using exploitation analysis, exploration analysis, success rate analysis, convergence rate analysis on classical benchmark functions as well as Congress on Evolutionary Computation (CEC) 2017 test functions. For further study, AM-QSSA optimizes an image registration problem for an extensive study to check its applicability. The results reveal that AM-QSSA is more efficient and stable than SSA. And it is comparable to the most advanced optimization algorithms.

Summary: Meiotic crossovers are required for the faithful segregation of homologous chromosomes and to promote genetic diversity. However, it is unclear how crossover formation is regulated, especially on the XY chromosomes, which show a homolog only at the tiny pseudoautosomal region. Here, we show that ATF7IP2 is a meiosis-specific ortholog of ATF7IP and a partner of SETDB1. In the absence of ATF7IP2, autosomes show increased axis length and more crossovers; however, many XY chromosomes lose the obligatory crossover, although the overall XY axis length is also increased. Additionally, meiotic DNA double-strand break formation/repair may also be affected by altered histone modifications. Ultimately, spermatogenesis is blocked, and male mice are infertile. These findings suggest that ATF7IP2 constraints autosomal axis length and crossovers on autosomes; meanwhile, it also modulates XY chromosomes to establish meiotic sex chromosome inactivation for cell-cycle progression and to ensure XY crossover formation during spermatogenesis.

Succinate is a vital signaling metabolite produced by the host and gut microbiota. Succinate has been shown to regulate host metabolic homeostasis and inhibit obesity-associated inflammation in macrophages by engaging its cognate receptor, SUCNR1. However, the contribution of the succinate-SUCNR1 axis to intestinal barrier dysfunction in obesity remains unclear. In the present study, we explored the effects of succinate-SUCNR1 signaling on high-fat diet (HFD)-induced intestinal barrier dysfunction. Using a SUCNR1-deficient mouse model under HFD feeding conditions, we identified the effects of succinate-SUCNR1 axis on obesity-associated intestinal barrier impairment. Our results showed that HFD administration decreased goblet cell numbers and mucus production, promoted intestinal pro-inflammatory responses, induced gut microbiota composition imbalance, increased intestinal permeability, and caused mucosal barrier dysfunction. Dietary succinate supplementation was sufficient to activate a type 2 immune response, trigger the differentiation of barrier-promoting goblet cells, suppress intestinal inflammation, restore HFD-induced mucosal barrier impairment and intestinal dysbiosis, and eventually exert anti-obesity effects. However, SUNNR1-deficient mice failed to improve the intestinal barrier function and metabolic phenotype in HFD mice. Our data indicate the protective role of the succinate-SUCNR1 axis in HFD-induced intestinal barrier dysfunction.

Objectives: This study aimed to evaluate the effects of factors related to periapical lesions (PALs) on sinus membrane thickening (SMT) in the Chinese population using cone-beam computed tomography (CBCT). Methods: In this retrospective study, CBCT images (n = 512) of maxillary sinuses of 446 patients were evaluated by two examiners for SMT and PALs, PAL size, and the distance between the maxillary sinus floor (MSF), and the PAL’s edge/root apex. The data were analyzed using analysis of variance, the Kruskal-Wallis test, χ2-test, and logistic regression. Results: A binary logistic regression model showed that the prevalence and severity of SMT > 2 mm were significantly associated with older age (>60 years) (odds ratio [OR]: 4.03, 95% confidence interval [CI]): 2.24–7.72, P 2 mm than did distance after adjusting for confounding factors, including age and sex (PALs: OR = 10.17 and 14.57, P

Summary: The one-carbon metabolism enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is involved in the regulation of tumor oncogenesis and immune cell functions, but whether it can contribute to macrophage polarization remains elusive. Here, we show that MTHFD2 suppresses polarization of interferon-γ-activated macrophages (M(IFN-γ)) but enhances that of interleukin-4-activated macrophages (M(IL-4)) both in vitro and in vivo. Mechanistically, MTHFD2 interacts with phosphatase and tensin homolog (PTEN) to suppress PTEN’s phosphatidylinositol 3,4,5-trisphosphate (PIP3) phosphatase activity and enhance downstream Akt activation, independent of the N-terminal mitochondria-targeting signal of MTHFD2. MTHFD2-PTEN interaction is promoted by IL-4 but not IFN-γ. Furthermore, amino acid residues (aa 215–225) of MTHFD2 directly target PTEN catalytic center (aa 118–141). Residue D168 of MTHFD2 is also critical for regulating PTEN’s PIP3 phosphatase activity by affecting MTHFD2-PTEN interaction. Our study suggests a non-metabolic function of MTHFD2 by which MTHFD2 inhibits PTEN activity, orchestrates macrophage polarization, and alters macrophage-mediated immune responses.

Wastewater-based epidemiology has become a powerful surveillance tool for monitoring the pandemic of COVID-19. Although it is promising to quantitatively correlate the SARS-CoV-2 RNA concentration in wastewater with the incidence of community infection, there is still no consensus on whether the viral nucleic acid concentration in sewage should be normalized against the abundance of endogenous biomarkers and which biomarker should be used as a reference for the normalization. Here, several candidate endogenous reference biomarkers for normalization of SARS-CoV-2 signal in municipal sewage were evaluated. The human fecal indicator virus (crAssphage) is a promising candidate of endogenous reference biomarker for data normalization of both DNA and RNA viruses for its intrinsic viral nature and high and stable content in sewage. Without constructing standard curves, the relative quantification of sewage viral nucleic acid against the abundance of the reference biomarker can be used to correlate with community COVID-19 incidence, which was proved via mimic experiments by spiking pseudovirus of different concentrations in sewage samples. Dilution of pseudovirus-seeded wastewater did not affect the relative abundance of viral nucleic acid, demonstrating that relative quantification can overcome the sewage dilution effects caused by the greywater input, precipitation and/or groundwater infiltration. The process of concentration, recovery and detection of the endogenous biomarker was consistent with that of SARS-CoV-2 RNA. Thus, it is necessary to co-quantify the endogenous biomarker because it can be not only an internal reference for data normalization, but also a process control.

Pain is a distressing experience associated with tissue damage or potential tissue damage, and its occurrence is related to sensory, emotional, cognitive and social factors. Inflammatory pain is one of the chronic pains where pain hypersensitivity are functional features of inflammation used to protect tissues from further damage. Pain has a serious impact on people's lives and has become a social problem that cannot be ignored. MiRNAs are small non-coding RNA molecules that exert directing effects on RNA silencing by complementary binding to the 3′UTR of target mRNA. MiRNAs can target a number of protein-coding genes and participate in almost all developmental and pathological processes in animals. Growing studies have suggested that miRNAs have significant implications for inflammatory pain via participating in multiple processes during the occurrence and development, such as affecting the activation of glial cells, regulating pro-inflammatory cytokines and inhibiting central and peripheral sensitization. In this review, the advances in the role of miRNAs in inflammatory pain were discussed. miRNAs as a class of micro-mediators are potential biomarkers and therapeutic targets for inflammatory pain, which provides a better diagnostic and treatment approach for inflammatory pain.

Metastasis is the main cause of cervical cancer lethality, but to date, no effective treatment has been developed to block metastasis. Circular RNAs (circRNAs) were recently found to be involved in cancer metastasis. In this study, we identified a downregulated circRNA derived from the host gene Gli1 (hsa_circ_0005358) in cervical cancer tissues, which was expressed at lower levels in tissues with extracervical metastasis than in those without extracervical metastasis. Upregulation of hsa_circ_0005358 significantly suppressed the migration and invasion of cervical cancer cells in vitro, and downregulation of hsa_circ_0005358 had the opposite effect. A mouse model revealed that cervical cancer cells overexpressing hsa_circ_0005358 possessed weaker metastatic potential in vivo. RNA-pull-down assay, mass spectrometry, and RNA immunoprecipitation validated the findings that hsa_circ_0005358 functions via its 215–224 sequence, which interacts with polypyrimidine tract-binding protein 1 (PTBP1). RNA-sequencing profiling revealed that CUB-domain-containing protein 1 (CDCP1) is a common target for hsa_circ_0005358 and PTBP1. We further confirmed that hsa_circ_0005358 sequestered PTBP1, preventing it from stabilizing CDCP1 mRNA, reducing CDCP1 protein translation and ultimately suppressing cancer metastasis. Our findings reveal the function of hsa_circ_0005358 in tumor metastasis, which may be applied to a potential therapeutic approach for patients with metastatic cervical cancer.

ABSTRACT: Objectives: The aim of this study was to explore the prevalence of blaCTX-M and elucidate the characteristics of transferable blaCTX-M-55 plasmids. Methods: Escherichia coli were isolated from 10 large-scale duck farms from nine counties and cities in Guizhou Province. They were identified, subjected to antimicrobial susceptibility testing and screened for antibiotic resistance genes. blaCTX-M-positive strains were subtyped, and blaCTX-M-55-containing strains were further analysed by multilocus sequence typing, conjugation experiments and polymerase chain reaction–based replicon typing. Three transferable plasmids were selected for whole genome sequencing sequencing and further analysis of genetic context. Results: In total, 128 E. coli strains were identified, and 23 were blaCTX-M-positive. Subtype analysis of blaCTX-M-positive strains revealed that 23 were blaCTX-M-55 and one of the strains contained both blaCTX-M-65 and blaCTX-M-55. They were divided into 12 multilocus sequence typing types, and 6 were undetermined. blaCTX-M-55-bearing plasmids in seven were transferred to E. coli C600 at frequencies between 10−6 and 10−9, and blaCTX-M-55 was found to be located on IncN, IncFⅡ and IncFII-N fusion type plasmids. Three plasmids (IncFⅡ plasmids pEC99_Plas3 and pS1_Plas2 and IncFII-N plasmid pD2_plas2) shared a homologous region of IS26-ARGs-IS26-blaTEM-orf477-blaCTX-M-55-ISEcp1△-IS26. Conclusion: Our study demonstrates the environmental presence of blaCTX-M-55 harbouring E. coli in Guizhou. Analysis of the genetic context of blaCTX-M-55 aids in understanding possible dissemination routes of ESBL genes and controlling widespread antibiotic resistance.

Amorphophallus konjac, a perennial herb in the Araceae family, is a cash crop that can produce a large amount of konjac glucomannan. To explore mechanisms underlying such large genomes in the genus Amorphophallus as well as the gene regulation of glucomannan biosynthesis, we present a chromosome-level genome assembly of A. konjac with a total genome size of 5.60 Gb and a contig N50 of 1.20 Mb. Comparative genomic analysis reveals that A. konjac has undergone two whole-genome duplication (WGD) events in quick succession. Two recent bursts of transposable elements are identified in the A. konjac genome, which contribute greatly to the large genome size. Our transcriptomic analysis of the developmental corms characterizes key genes involved in the biosynthesis of glucomannan and related starches. High expression of cellulose synthase-like A, Cellulose synthase-like D, mannan-synthesis related 1, GDP-mannose pyrophosphorylase and phosphomannomutase fructokinase contributes to glucomannan synthesis during the corm expansion period while high expression of starch synthase, starch branching enzyme and phosphoglucomutase is responsible for starch synthesis in the late corm development stage. In conclusion, we generate a high-quality genome of A. konjac with different sequencing technologies. The expansion of transposable elements has caused the large genome of this species. And the identified key genes in the glucomannan biosynthesis provide valuable candidates for molecular breeding of this crop in the future.

Cancer-related fatigue (CRF) is one of the common complications of cancer patients, with occult onset, long duration, and unfavorable treatment outcomes, which is disturbing to patients and clinicians. Chinese medicine has natural and unique advantages in improving CRF symptoms. Bu-Zhong-Yi-Qi decoction is commonly applied for treating CRF. In this study, we intend to further study the effect and mechanism of Bu-Zhong-Yi-Qi decoction in the treatment of CRF, and explore the active chemical components of the medicinal herbs. To this end, we reviewed the previous clinical research and experiments, analyzed the molecular mechanism, pharmacological effect, active chemical composition and its target of action in the treatment of CRF with tonic and Bu-Zhong-Yi-Qi decoction, which provided a theoretical basis for future research and practice.

Cemented sand and gravel is widely used in water conservancy project construction due to its advantages of low material consumption, strong adaptability and environmental protection. Due to the single design of the dam section, its application scope is limited. Aiming at the design problem of the cemented sand gravel dam section, In this paper, the modified Duncan-Chang nonlinear elastic model is used as the constitutive model of dam material, and the design concept of dam functional zoning is combined with the mechanical properties of Cemented sand and gravel dam material to propose the optimal design scheme of functional zoning in line with the CSG dam. The Tobetsu dam in Japan is used as a prototype for finite element optimization design analysis, and the analysis results are compared with the engineering data. The results show that: (1) The optimized scheme changes the upstream slope to 1:0.34 and the downstream slope to 1:0.77 under the condition of ensuring the safe operation of the dam, which reduces the amount of cementitious admixture per unit dam section by 34.2% and 23.6% respectively, significantly reducing the amount of cementitious materials used, in line with the concept of optimal design; (2) The vertical stress of the dam body is compressive stress during the completion period, but both during the operation period, the location of the dam heel appears; (3)The upstream side of the dam axis should have a large modulus of deformation during the operation period, and the modulus of deformation can be reduced from upstream to downstream in order to ensure that the dam deformation is coordinated after water storage.

In order to address the shortcoming of feature representation limitation in machine translation(MT) system, this paper presents a feature transfer method in MT. Meta feature transfer of the decoding process considered not only their own translation system, but also transferred knowledge of another translation system. The domain meta feature and the objective function of domain adaptation are used to better model the domain transfer task. In this paper, extensive experiments and comparisons are made. The experiment results show that the proposed model has a significant improvement in domain transfer task. The first model has better performance than baseline system, which improves 3.06 BLEU score on the news test set, improves 3.27 BLEU score on the education test set, and improves 3.93 BLEU score on the law test set; The second model improves 3.16 BLEU score on the news test set, improves 3.54 BLEU score on the education test set, and improves 4.2 BLEU score on the law test set.

As a globally complicated disease, malignant tumor has long been posing a threat to human health with increasingly high morbidity and mortality. Notably, existing treatments for tumors like chemotherapy generally carry intolerable toxicity, necessitating novel agents balancing safety and potency. Among them, the anti-tumor potency of herbs, featuring few adverse effects and promising efficacy, has attracted much attention recently. Pristimerin, a Quinone formamide triterpenoid compound extracted from Celastraceae and Portulacaceae, carries pronounced anti-tumor activity. It applies to various malignant tumors, including breast cancer, bile duct cancer, gastric cancer, pancreatic cancer, prostate cancer, glioblastoma, colorectal cancer, oral squamous cell carcinoma, cervical cancer, and lung cancer. In state-of-the-art understanding, pristimerin, alone or combined, can inhibit tumor cell proliferation, induce tumor cell apoptosis, inhibit tumor migration and invasion, inhibit angiogenesis, induce tumor cell autophagy, regulate the occurrence of inflammation related tumors, enhance chemosensitivity and regulate tumor microenvironment and immune cells. Despite the abundance of pristimerin-based research, systematic reviews on its anti-tumor mechanism remain needed. This study presented the anti-tumor mechanism of pristimerin by literature review, which might serve as a reference for further research and clinical practice.

Ovarian cancer is one of the three most common female reproductive system cancers and has been a hot topic in the field of gynecology and oncology. Currently, surgery with chemotherapy is the common strategy in treatment of ovarian cancer, while it is always accompanied by drug resistance and some adverse effects. Over the past few years, traditional Chinese medicine (TCM) has been embraced by a large population of clinicians and researchers due to its high efficiency, low toxicity and minor side effects. Guizhi-Fuling Wan as a classical TCM formula has manifested certain efficacy in treating ovarian cancer. This article intends to further study the role and mechanism of Guizhi-Fuling Wan in treatment of ovarian cancer and explore the effective chemical components contained in the herbs of the formula. To this end, we reviewed the previous clinical studies and experiments to analyze the molecular mechanisms, pharmacological effects, active chemical components and their targets of action in treatment of ovarian cancer, thereby providing a theoretic basis for future studies and practices.

The pathogenesis of coronary heart disease is closely related to blood stasis. Taohong Siwu decoction (THSW for short) is one of the most widely used prescriptions for activating blood and removing stasis. Clinical research has confirmed its curative effect on coronary heart disease. However, its underlying mechanism remains unclear. Therefore, this paper reviewed the clinical efficacy of THSW and determine its effective components based on a comprehensive literature review. Furthermore, the core components and targets of THSW in treating coronary heart disease using molecular docking were verified, and the interaction sites were predicted to construct a theoretical basis for the clinical application of THSW.

Circular RNAs (circRNAs) function as efficient microRNA (miRNA) sponges that regulate gene expression in the pathogenesis of many human malignancies. However, their roles in cervical adenocarcinoma remain largely unknown. In this study, we aimed to seek novel circRNAs that regulate cervical adenocarcinoma carcinogenesis and to explore their regulatory mechanisms as well as clinical significance. We identified that 24 circRNAs were differentially expressed in cervical adenocarcinoma tissues by RNA sequencing. Among them, circEYA1 was the most significantly downregulated circRNA in cervical adenocarcinoma. In cervical adenocarcinoma cells, circEYA1 overexpression led to suppression of cell viability and colony formation, promotion of apoptosis, and a decrease of the xenograft tumor growth. The mechanism underlying these observations is that circEYA1 functioned as a sponge of miR-582-3p and abrogated its suppression of CXCL14 expression. Consistently, miR-582-3p inhibition phenocopied the biological effects of circEYA1 overexpression in cervical adenocarcinoma cells. Moreover, miR-582-3p overexpression reversed the suppressive behaviors of circEYA1 in vitro and in vivo. In addition, the expression, correlation, and clinical diagnostic value of circEYA1/miR-582-3p/CXCL14 were confirmed in 198 clinical cervical tissue samples. In summary, our findings highlight a novel tumor suppressive role of circEYA1 in cervical adenocarcinoma tumorigenesis and may provide a potential diagnostic marker and therapeutic target for patients with cervical adenocarcinoma.

In osteochondral defects, oxidative stress caused by elevated levels of reactive oxygen species (ROS) can disrupt the normal endogenous repair process. In this study, a multifunctional hydrogel composed of silk fibroin (SF) and tannic acid (TA), the FDA-approved ingredients, was developed to alleviate oxidative stress and enhance osteochondral regeneration. In this proposed hydrogel, SF first interacts with TA to form a hydrogen-bonded supramolecular structure, which is subsequently enzymatically crosslinked to form a stable hydrogel. Furthermore, TA had multiple phenolic hydroxyl groups that formed interactions with the therapeutic molecule E7 peptide for controlled drug delivery. In vitro investigations showed that SF-TA and SF-TA-E7 hydrogels exhibited a multitude of biological effects including scavenging of ROS, maintaining cell viability, and promoting the proliferation of bone marrow mesenchymal stem cells (BMSCs) against oxidative stress. The proteomic analysis indicated that SF-TA and SF-TA-E7 hydrogels suppressed oxidative stress, which in turn improved cell proliferation in multiple proliferation and apoptosis-related pathways. In rabbit osteochondral defect model, SF-TA and SF-TA-E7 hydrogels promoted enhanced regeneration of both cartilage and subchondral bone as compared to hydrogel without TA incorporation. These findings indicated that the multifunctional SF-TA hydrogel provided a microenvironment suitable for the endogenous regeneration of osteochondral defects.

Ascites is one of the common complications in patients with decompensated liver cirrhosis and liver cancer. Wuling powder (WLP) is a classic prescription for the treatment of water retention caused by bladder gasification. It is also widely used in the treatment of ascites. This systematic review aimed to evaluate the clinical efficacy of WLP and determine its effective chemical components based on a large number of related pieces of literature. The pharmacological effects and chemical constituents of WLP were summarized. Besides, the clinical research status of WLP in the treatment of ascites caused by liver cancer and cirrhosis was analyzed. The key targets and pathways of WLP in the treatment of ascites based on network pharmacology analysis were also discussed. Furthermore, the core components and core targets of WLP in the treatment of ascites using molecular docking were verified and the interaction sites were predicted, to provide a theoretical and scientific basis for the clinical application of WLP.

ABSTRACT: This study evaluated the changes in eggshell mechanical properties, ultrastructure, calcium metabolism-related serum indices, and gene expression in eggshell gland during eggshell formation between laying ducks in the peak (young duck) and late phase (aged duck) of production. A total of 84 healthy young (31 wk of age) and 84 healthy aged (65 wk of age) Longyan laying ducks were each divided into 6 replicates of 14 birds, and caged individually. All the ducks were fed in one house with the same corn-soybean meal-based diet for 5 wk. The eggshell mechanical properties (shell proportion, thickness, breaking strength, and fracture toughness) and chemical components (matrix proteins, calcium, phosphorus, and magnesium) decreased in aged laying ducks (P < 0.05). Shell structural indices: total thickness, effective thickness and its proportion decreased, whereas mammillary knob width and its proportion increased (P < 0.05). The regulation values of early fusion, cuffing, caps, and total score of mammillary knobs were higher in aged laying ducks relative to the young ducks (P < 0.05). During the initial, growth and terminal stages of eggshell formation, shell thickness and breaking strength (terminal), shell weight, and its proportion (terminal) decreased in aged laying ducks (P < 0.05). Ultrastructural changes during shell formation indicated that the mammillary-knob density and effective thickness decreased (P < 0.05). Decreases occurred in serum content of phosphorus (growth), and estradiol and calcium contents (terminal) (P < 0.05). Relative expression of Ca2+ transporter and HCO3− exchanger, and matrix proteins genes decreased in aged laying ducks (P < 0.05) at all stages of eggshell formation. Collectively, the decreased incidence of early fusion and caps, increased thickness and width of mammillary knobs, and decreased effective thickness are the crucial differences leading to the compromised mechanical properties of eggshell in the late laying period. A disturbed regulation of calcium metabolism and uterine expression of ion transporters, especially for HCO3− exchange of aged laying ducks likely contribute to age-induced ultrastructural deterioration of the eggshell.

ABSTRACT: This study evaluated dietary Zn supplementation on productive performance, eggshell quality and ultrastructure, and calcium metabolism during eggshell formation in laying ducks. A total of 360 Longyan laying ducks (45-wk) were randomly divided into 5 treatment groups with 6 replicates of 12 birds each and fed for 20 wk. The 6 treatments fed the basal diet supplemented with 0 (control), 20, 40, 80, or 160 mg Zn/kg (ZnSO4·H2O). Dietary supplemental level at 80 mg/kg increased egg production (4.3%) and mass (5.7%), and decreased FCR (2.9%) compared to the basal diet, and these indices increased quadratically with increasing Zn supplemental levels (P < 0.05). The shell breaking strength (15.8%) and fracture toughness (10.6%) were higher with the supplementation of Zn at 80 mg/kg than the basal diet, and increased quadratically with Zn supplementation (P < 0.05). Dietary supplementation of Zn at 80 mg/kg improved shell ultrastructure by increasing total (9.0%) and effective thickness (14.2%) and decreasing mammillary thickness (12.0%), and their responses were quadratic with increasing Zn levels (P < 0.05). The supplementation of Zn affected the calcium contents in plasma, tibias and ulna, ulna phosphorus content, and linear and quadratic effects were observed, and higher values were observed with 160 mg/kg Zn supplementation than control (P < 0.05). The supplemental Zn level at 80 mg/kg increased shell effective thickness in growth stage (P < 0.05), and shell calcium and phosphorus content in initial and growth stages (P < 0.05). Dietary Zn supplementation did not affect the gene expression of Ca2+ transporters in the eggshell gland, but affected the expression of HCO3− exchanger in initial and growth stage (P < 0.05). Overall, dietary Zn supplementation could improve productive performance and shell quality in laying ducks at late phase of production, and calcium metabolism and deposition were modulated by Zn influencing HCO3− secretion and thus affecting shell ultrastructure and quality. A supplemental level of 80 mg/kg Zn in the diet with a basal content of 34.0 mg/kg was optimal, and higher level (160 mg/kg) decreased shell calcium deposition by depressing its metabolism.

The anthranilic diamide insecticide chlorantraniliprole is highly effective against Lepidoptera pests, but the underlying mechanisms of toxic effects of chlorantraniliprole exposures for adapting to the chemical environment are poorly known in fall armyworm (FAW), Spodoptera frugiperda (J.E.Smith). FAW being one of the most pests of maize in Latin America, suddenly appeared in China in 2019 and spread rapidly. In this study, using bioassay and transcriptomic and biochemical analyses, we comprehensively investigated gene expression changes of third instar larvae in response to different sublethal concentrations (LC10 and LC30) of chlorantraniliprole in this insect. Exposure to LC10 chlorantraniliprole (0.73 mg/L) causes 1266 differentially expressed genes (DEGs), of which 578 are up-regulated and 688 down-regulated. Exposure to LC30 (2.49 mg/L) causes differential expression of 3637 DEGs (1545 up-, 2092 down-regulated). Interestingly, the LC30 treatment led to a significant increase in the number of DEGs compared to that of the LC10, indicating a concentration effect manner. Moreover, enrichment analysis identified important DEGs belonging to specific categories, such as amino acid, carbohydrate, lipid, energy, xenobiotics metabolisms, signal transduction, and posttranslational modification pathways, and enzymes activities in enriched pathways were significantly altered at the LC10 and LC30, which matched transcriptome analysis to mediate toxic mechanisms. The DEGs encoding detoxification-related genes were identified and validated by quantitative real-time PCR (qRT-PCR), which correlated with the RNA-sequencing (RNA-seq) data. To our knowledge, these findings provide the first toxicity mechanisms for a better understanding of chlorantraniliprole action and detoxification in FAW and other insect pests at molecular level.