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This study investigated the enhancing effects of soil treatment with ethylene diamine tetraacetic acid (EDTA) and oxalic acid (OA) on the remediation of Cr(VI) contaminated soil by Datura stramonium L. A greenhouse pot experiment was conducted, where Cr(VI) contaminated soil was treated with 100 mg/kg Cr(VI) and varying concentrations of EDTA (5 and 10 mmol/kg) and OA (5 and 10 mmol/kg). The effects of these soil treatments on biomass, chlorophyll content, antioxidant enzyme activities, and Cr(VI) enrichment and translocation efficiency of D. stramonium were evaluated. The results showed that added OA to soil significantly increased the biomass and chlorophyll content of D. stramonium. The addition of 10 mmol/kg of OA to soil increased the plant biomass by 67.16 % and chlorophyll b content by 40.01 %. In addition, OA soil treatment significantly enhanced the activities of superoxide dismutase (SOD) by 6.36 %, peroxidase (POD) by 163.13 %, catalase (CAT) by 36.92 %, and ascorbate peroxidase (APX) by 32.12 %, which effectively alleviated the oxidative stress induced by Cr(VI). In contrast, soil treatment with a high concentration of EDTA (10 mmol/kg) significantly reduced plant biomass and chlorophyll content, although it increased the biological concentration factor (BCF) of the stem and leaf, as well as the translocation factor (TF). In conclusion, appropriate amounts of EDTA and OA added to soil can enhance the phytoremediation efficiency of D. stramonium grown in Cr(VI) contaminated soil, with OA added to soil being more effective than addition of EDTA. This study revealed the potential mechanisms of chelating agents EDTA and OA in enhancing the phytoremediation of Cr(VI) contaminated soil by D. stramonium, providing a scientific basis for further optimization of phytoremediation techniques.

Abstract Background Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for noninvasive cancer diagnostics, particularly in the context of metastatic non‐small‐cell lung cancer (NSCLC). Detecting targetable variants through ctDNA analysis offers the potential to guide treatment decisions, especially in cases where tissue samples are insufficient or unavailable. Method In this study, we developed and validated a next‐generation sequencing panel targeting 101 cancer‐related genes (101‐test) to detect somatic variants in ctDNA from a large cohort of Chinese patients with metastatic NSCLC. The performance of the 101‐test was assessed by evaluating its limit of detection (LOD), accuracy, and precision in identifying molecular variants. Additionally, the concordance between ctDNA and tissue samples for detecting targetable variants was analyzed in 904 patients. Results The 101‐test demonstrated a LOD of 0.38% for single‐nucleotide variants (SNVs), 0.33% for insertions and deletions (InDels), and 0.33% for fusions. Sensitivity was 98.3% for SNVs, 100% for InDels, and 100% for fusions when compared to digital droplet PCR (ddPCR)/breakpoint PCR reference methods. The by‐variant sensitivity for somatic variants was 97.5%, with a specificity of 99.9% between tumor‐only and tumor‐normal analyses. In a real‐world cohort, the concordance between ctDNA and tissue samples for identifying targetable variants was 72.2% (457/633). Notably, the EGFR S768I variant, recently recommended by clinical guidelines, achieved an 80% concordance rate. Furthermore, 4.3% of patients (27/633) with targetable variants were identified exclusively through ctDNA testing. Conclusion The ctDNA‐based 101‐test is a highly sensitive and specific tool for detecting targetable variants in metastatic NSCLC, particularly in cases with insufficient tissue samples. The findings support the use of ctDNA testing as a reliable and complementary method to traditional tissue‐based molecular analysis, enhancing the precision of treatment strategies for NSCLC patients.

Oil pollution is a common type of soil organic pollution that is harmful to the ecosystem. Bioremediation, particularly microbe-assisted phytoremediation of oil-contaminated soil, has become a research hotspot in recent years. In order to explore more appropriate bioremediation strategies for soil oil contamination and the mechanism of remediation, we compared the remediation effects of three plants when applied in combination with a microbial agent and biochar. The combined remediation approach of Tagetes erecta, microbial agent, and biochar exhibited the best plant growth and the highest total petroleum hydrocarbons degradation efficiency (76.60%). In addition, all of the remediation methods provided varying degrees of restoration of carbon and nitrogen contents of soils. High-throughput sequencing found that microbial community diversity and richness were enhanced in most restored soils. Some soil microorganisms associated with oil degradation and plant growth promotion such as Cavicella, C1_B045, Sphingomonas, MND1, Bacillus and Ramlibacter were identified in this study, among which Bacillus was the major component in the microbial agent. Bacillus was positively correlated with all soil remediation indicators tested and was substantially enriched in the rhizosphere of T. erecta. Functional gene prediction of the soil bacterial community based on the KEGG database revealed that pathways of carbohydrate metabolism and amino acid metabolism were up-regulated during remediation of oil-contaminated soils. This study provides a potential method for efficient remediation of oil-contaminated soils and thoroughly examines the biochar–bacteria–plant combined remediation mechanisms of oil-contaminated soil, as well as the combined effects from the perspective of soil bacterial communities.

ABSTRACTPreeclampsia (PE), a pregnancy-specific syndrome, has been associated with the gut bacteriome. Here, to investigate the impact of the gut virome on the development of PE, we identified over 8,000 nonredundant viruses from the fecal metagenomes of 40 early-onset PE and 37 healthy pregnant women and profiled their abundances. Comparison and correlation analysis showed that PE-enriched viruses frequently connected to Blautia species enriched in PE. By contrast, bacteria linked to PE-depleted viruses were often the Bacteroidaceae members such as Bacteroides spp., Phocaeicola spp., Parabacteroides spp., and Alistipes shahii. In terms of viral function, PE-depleted viruses had auxiliary metabolic genes that participated in the metabolism of simple and complex polysaccharides, sulfur metabolism, lipopolysaccharide biosynthesis, and peptidoglycan biosynthesis, while PE-enriched viruses had a gene encoding cyclic pyranopterin monophosphate synthase, which seemed to be special, that participates in the biosynthesis of the molybdenum cofactor. Furthermore, the classification model based on gut viral signatures was developed to discriminate PE patients from healthy controls and showed an area under the receiver operating characteristic curve of 0.922 that was better than that of the bacterium-based model. This study opens up new avenues for further research, providing valuable insights into the PE gut virome and offering potential directions for future mechanistic and therapeutic investigations, with the ultimate goal of improving the diagnosis and management of PE.IMPORTANCEThe importance of this study lies in its exploration of the previously overlooked but potentially critical role of the gut virome in preeclampsia (PE). While the association between PE and the gut bacteriome has been recognized, this research takes a pioneering step into understanding how the gut virome, represented by over 8,000 nonredundant viruses, contributes to this condition. The findings reveal intriguing connections between PE-enriched viruses and specific gut bacteria, such as the prevalence of Blautia species in individuals with PE, contrasting with bacteria linked to PE-depleted viruses, including members of the Bacteroidaceae family. These viral interactions and associations provide a deeper understanding of the complex dynamics at play in PE.

Background: In thyroid cancers, a reduction in the expression of the sodium/iodide symporter (NIS) is observed concomitant with a diminution in cancer cell differentiation. The β-catenin/LEF-1 pathway emerges as a crucial regulatory pathway influencing the functional expression of NIS in human thyroid cancer cells. Further research is required to comprehensively elucidate the role of NIS overexpression in impeding the progression of thyroid cancer cells. Methods: Human papillary thyroid carcinoma (PTC) cell lines, specifically PTC-1 and KTC-1, were subjected to Scratch and Transwell assays, colony formation, and tumor sphere formation tests to investigate invasion and migration, focusing on the impact of NIS overexpression. The assessment involved the use of western blot to analyze the expression levels of β-catenin, NIS, CD133, SRY-related HMG box2 (Sox2), lymphoid enhancer-binding factor 1 (LEF-1), NANOG, octamer-binding transcription factor 4 (Oct4), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), and epithelial cellular adhesion molecule (EpCAM). Statistical analysis was conducted using SPSS version 20.0, and the graphs were developed using GraphPad Prism 7 (GraphPad Software, Inc.). Results: Our observations revealed that Nthy-ori-3-1 cell lines exhibited notably higher average expression levels of NIS, yet significantly lower levels of LEF-1 and β-catenin compared to PTC-1 and KTC-1 cell lines. Furthermore, the overexpression of β-catenin resulted in reduced binding of LEF-1 to NIF promotion but concurrently increased the expression of NIS. The downregulation of NIS markedly enhanced the expression of ALDH1A1, CD133, OCT4, Nanog, SOX2, and EpCam—all of which are targets within the Wnt/β-catenin signaling pathway. Conversely, the upregulation of NIS suppressed the expression of these proteins. Moreover, cells treated with β-catenin activators demonstrated an increased capability to form more spheroids and displayed heightened aggressiveness. Conversely, the NIS overexpression (OE) group exhibited suppressed abilities in invasion and colony formation. Conclusion: Thyroid cancer cells exhibit diminished expression of NIS, and the invasion and maintenance of stem cells in thyroid cancer cells were hindered by NIS OE through the inhibition of the β-catenin/LEF-1 pathway. Further research is warranted to comprehensively assess this outcome, which holds promise as a potential targeted treatment for thyroid cancer.

Summary: Orexin is a neuropeptide released from hypothalamus regulating feeding, sleeping, arousal, and cardiovascular activity. Past research has demonstrated that orexin receptor 2 (OX2R) agonist infusion in the brain results in sympathoexcitatory responses. Here, we found that epicardial administration of OX2R agonism leads to opposite responses. We proved that OX2R is expressed mainly in DRG neurons and transported to sensory nerve endings innervating the heart. In a capsaicin-induced cardiac sympathetic afferent reflex (CSAR) model, we recorded the calcium influx in DRG neurons, measured heart rate variability, and examined the PVN c-Fos activity to prove that epicardial OX2R agonism administration could attenuate capsaicin-induced CSAR. We further showed that OX2R agonism could partially rescue acute myocardial infarction by reducing sympathetic overactivation. Our data indicate that epicardial application of OX2R agonist exerts a cardioprotective effect by attenuating CSAR. This OX2R-mediated heart-brain axis may provide therapeutic targets for acute cardiovascular diseases.

Inferring small molecule-miRNA associations (MMAs) is crucial for revealing the intricacies of biological processes and disease mechanisms. Deep learning, renowned for its exceptional speed and accuracy, is extensively used for predicting MMAs. However, given their heavy reliance on data, inaccuracies during data collection can make these methods susceptible to noise interference. To address this challenge, we introduce the joint masking and self-supervised (JMSS)-MMA model. This model synergizes graph autoencoders with a probability distribution-based masking strategy, effectively countering the impact of noisy data and enabling precise predictions of unknown MMAs. Operating in a self-supervised manner, it deeply encodes the relationship data of small molecules and miRNA through the graph autoencoder, delving into its latent information. Our masking strategy has successfully reduced data noise, enhancing prediction accuracy. To our knowledge, this is the pioneering integration of a masking strategy with graph autoencoders for MMA prediction. Furthermore, the JMSS-MMA model incorporates a node-degree–based decoder, deepening the understanding of the network’s structure. Experiments on two mainstream datasets confirm the model’s efficiency and precision, and ablation studies further attest to its robustness. We firmly believe that this model will revolutionize drug development, personalized medicine, and biomedical research.

Abstract The role of C‐type natriuretic peptide (CNP) in the regulation of cardiac function in humans remains to be established as previous investigations have been confined to animal model systems. Here, we used well‐characterized engineered cardiac tissues (ECTs) generated from human stem cell‐derived cardiomyocytes and fibroblasts to study the acute effects of CNP on contractility. Application of CNP elicited a positive inotropic response as evidenced by increases in maximum twitch amplitude, maximum contraction slope and maximum calcium amplitude. This inotropic response was accompanied by a positive lusitropic response as demonstrated by reductions in time from peak contraction to 90% of relaxation and time from peak calcium transient to 90% of decay that paralleled increases in maximum contraction decay slope and maximum calcium decay slope. To establish translatability, CNP‐induced changes in contractility were also assessed in rat ex vivo (isolated heart) and in vivo models. Here, the effects on force kinetics observed in ECTs mirrored those observed in both the ex vivo and in vivo model systems, whereas the increase in maximal force generation with CNP application was only detected in ECTs. In conclusion, CNP induces a positive inotropic and lusitropic response in ECTs, thus supporting an important role for CNP in the regulation of human cardiac function. The high degree of translatability between ECTs, ex vivo and in vivo models further supports a regulatory role for CNP and expands the current understanding of the translational value of human ECTs.

The contradiction between flammability and packing density is the technical bottleneck for combustible smoke agent. Herein, polyurethane (PU) foams with flammability and resilience were prepared with polyol and isocyanate as raw materials by chemical foaming method, then compounded with metal powders, polytetrafluoroethylene (PTFE), phthalic annychide (PA), etc. in a certain proportion and pressed into pyrotechnic grain to obtain eco-friendly combustion aerosols with compact density of about 1.15 g/cm3. The resulting combustion smoke agent combined the advantages of PU foam and pyrotechnic with easy ignition, large smoke production, long duration and low environmental pollution. The transmittance of aerosols for 532 nm and 1064 nm lasers was close to 0, and the EMI SE reached up to 65 dB and 35 dB in GPS band and X band, respectively. In addition, the resulting pyrotechnic grains exhibited good mechanical strength and elasticity for sample 1:25, with a compressive strength of 22 MPa and an elastic modulus of 195 MPa. The resulting combustion smoke agent is expected to play a potential role in the field of electromagnetic damage and protection.

Objective The purpose of this study was to identify potential biomarkers in the tubulointerstitium of focal segmental glomerulosclerosis (FSGS) and comprehensively analyze its mRNA–miRNA-lncRNA/circRNA network.Methods The expression data (GSE108112 and GSE200818) were downloaded from the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo/). Identification and enrichment analysis of differentially expressed genes (DEGs) were performed. the PPI networks of the DEGs were constructed and classified using the Cytoscape molecular complex detection (MCODE) plugin. Weighted gene coexpression network analysis (WGCNA) was used to identify critical gene modules. Least absolute shrinkage and selection operator regression analysis were used to screen for key biomarkers of the tubulointerstitium in FSGS, and the receiver operating characteristic curve was used to determine their diagnostic accuracy. The screening results were verified by quantitative real-time-PCR (qRT–PCR) and Western blot. The transcription factors (TFs) affecting the hub genes were identified by Cytoscape iRegulon. The mRNA–miRNA-lncRNA/circRNA network for identifying potential biomarkers was based on the starBase database.Results A total of 535 DEGs were identified. MCODE obtained eight modules. The green module of WGCNA had the greatest association with the tubulointerstitium in FSGS. PPARG coactivator 1 alpha (PPARGC1A) was screened as a potential tubulointerstitial biomarker for FSGS and verified by qRT–PCR and Western blot. The TFs FOXO4 and FOXO1 had a regulatory effect on PPARGC1A. The ceRNA network yielded 17 miRNAs, 32 lncRNAs, and 50 circRNAs.Conclusions PPARGC1A may be a potential biomarker in the tubulointerstitium of FSGS. The ceRNA network contributes to the comprehensive elucidation of the mechanisms of tubulointerstitial lesions in FSGS.

AbstractObjective The aim of our study was to identify key biomarkers of glomeruli in focal glomerulosclerosis (FSGS) and analyze their relationship with the infiltration of immune cells.Methods The expression profiles (GSE108109 and GSE200828) were obtained from the GEO database. The differentially expressed genes (DEGs) were filtered and analyzed by gene set enrichment analysis (GSEA). MCODE module was constructed. Weighted gene coexpression network analysis (WGCNA) was performed to obtain the core gene modules. Least absolute shrinkage and selection operator (LASSO) regression was applied to identify key genes. ROC curves were employed to explore their diagnostic accuracy. Transcription factor prediction of the key biomarkers was performed using the Cytoscape plugin IRegulon. The analysis of the infiltration of 28 immune cells and their correlation with the key biomarkers were performed.Results A total of 1474 DEGs were identified. Their functions were mostly related to immune-related diseases and signaling pathways. MCODE identified five modules. The turquoise module of WGCNA had significant relevance to the glomerulus in FSGS. TGFB1 and NOTCH1 were identified as potential key glomerular biomarkers in FSGS. Eighteen transcription factors were obtained from the two hub genes. Immune infiltration showed significant correlations with T cells. The results of immune cell infiltration and their relationship with key biomarkers implied that NOTCH1 and TGFB1 were enhanced in immune-related pathways.Conclusion TGFB1 and NOTCH1 may be strongly correlated with the pathogenesis of the glomerulus in FSGS and are new candidate key biomarkers. T-cell infiltration plays an essential role in the FSGS lesion process.

The Stimulator of Interferon Genes (STING) is predominantly expressed in immune cells, including macrophages, natural killer cells, dendritic cells, and T cells, functioning as a pattern recognition receptor. STING activation upon detecting cytosolic DNA released from damaged cells initiates downstream pathways, leading to the production of inflammatory cytokines such as IFNs, IL-6, and TNF-α. Dysregulated STING activation has been implicated in inflammatory and metabolic diseases. Ischemia/reperfusion injury (I/RI) is common in stroke, acute myocardial infarction, organ transplantation, and surgeries for certain end-stage diseases. Recent studies suggest that STING could be a novel therapeutic target for I/RI treatment. In this review, we provide a concise overview of the cGAS-STING signaling pathway's general functions and summarize STING's role in I/RI across various organs, including the heart, liver, kidney, and lung. Moreover, we explore potential therapeutic approaches for I/RI by targeting STING.

Abstract Background Glomerular damage is a common clinical indicator of nephrotic syndrome. High-dose hormone treatment often leads to hormone resistance in patients. How to avoid resistance and improve the efficiency of hormone therapy draws much attention to clinicians. Methods Adriamycin (ADR) was used to induce nephropathy model in SD rats. The rats were treated with dexamethasone (DEX), icariin (ICA), and DEX + ICA combination therapy. The changes in urinary protein (UP), urea nitrogen (BUN), and serum creatinine (SCR) contents in rats were detected by enzyme-linked immunosorbent assay (ELISA), and the degree of pathological injury and the expression level of podocin were detected by HE staining and immunohistochemistry, to test the success of the model and the therapeutic effects of three different ways. The effect of treatments on podocytes autophagy was evaluated via transfection of mRFP-GFP-LC3 tandem adenovirus in vitro. Results The contents of UP, SCR, and BUN were significantly increased, the glomerulus was seriously damaged, and the expression of Nephrosis2 (NPHS2) was significantly decreased in the ADR-induced nephrotic syndrome rat model compared to that of the control group. DEX, ICA, and the DEX + ICA combined treatment significantly alleviated these above changes induced by ADR. The combined treatment of DEX + ICA exhibited better outcome than single treatment. The combined treatment also restored the podocyte autophagy, increased the expression of microtubule-associated protein light-chain 3II (LC3II), and reduced the expression of p62 in vitro. The combined treatment protects podocytes by mediating the PI3K/AKT/mTOR (rapamycin complex) signaling pathway. Conclusion ICA enhances the therapeutic effect of DEX on the nephrotic syndrome.

BackgroundStimulation of IFN genes (STING) is central to the production of interferon and proinflammatory cytokines in response to microbial DNA or self-DNA in the cytosol. The detrimental role of the activation of STING during sepsis has been well documented.MethodsHere, we found that gelsevirine (GS) potently inhibit interferon and inflammatory cytokine induction in macrophages exposed to STING agonists (2'3'-cGAMP, IFN stimulatory DNA (ISD), and poly(dA:dT)). I n silico docking analysis and surface plasmon resonance binding study showed that GS bonds with high affinity to the cyclic dinucleotide (CDN)-binding pocket of STING. Biotin pull-down assay also confirmed that GS competitively bonded to STING protein. Furthermore, GS inhibited 2’3’-cGAMP-induced STING dimerization and subsequent activation. In addition, GS induced K48-linked STING ubiquitination and degradation, which was likely through upregulating and recruiting TRIM21. In mice exposed to cecal ligation and puncture (CLP)-induced sepsis, post-operative administration of GS significantly extended the survival period and mitigated acute organ damage.ResultsOverall, GS inhibited STING signaling by competitively binding to the CDN-binding pocket to lock STING in an inactive open conformation, while also promoting K48-linked STING ubiquitination and degradation.ConclusionsOur findings identify a novel STING-specific inhibitor that could be applied in the treatment of sepsis.

Stimulator of Interferon Gene (STING) is a critical signaling linker protein that plays a crucial role in the intrinsic immune response, particularly in the cytoplasmic DNA-mediated immune response in both pathogens and hosts. It is also involved in various signaling processes in vivo. The musculoskeletal system provides humans with morphology, support, stability, and movement. However, its aging can result in various diseases and negatively impact people’s lives. While many studies have reported that cellular aging is a leading cause of musculoskeletal disorders, it also offers insight into potential treatments. Under pathological conditions, senescent osteoblasts, chondrocytes, myeloid cells, and muscle fibers exhibit persistent senescence-associated secretory phenotype (SASP), metabolic disturbances, and cell cycle arrest, which are closely linked to abnormal STING activation. The accumulation of cytoplasmic DNA due to chromatin escape from the nucleus following DNA damage or telomere shortening activates the cGAS-STING signaling pathway. Moreover, STING activation is also linked to mitochondrial dysfunction, epigenetic modifications, and impaired cytoplasmic DNA degradation. STING activation upregulates SASP and autophagy directly and indirectly promotes cell cycle arrest. Thus, STING may be involved in the onset and development of various age-related musculoskeletal disorders and represents a potential therapeutic target. In recent years, many STING modulators have been developed and used in the study of musculoskeletal disorders. Therefore, this paper summarizes the effects of STING signaling on the musculoskeletal system at the molecular level and current understanding of the mechanisms of endogenous active ligand production and accumulation. We also discuss the relationship between some age-related musculoskeletal disorders and STING, as well as the current status of STING modulator development.

Accurate monitoring of crop drought thresholds at different growth periods is crucial for drought monitoring. In this study, the canopy temperature (Tc) of winter wheat (‘Weilong 169’ variety) during the three main growth periods was extracted from high-resolution thermal and multispectral images taken by a complete unmanned aerial vehicle (UAV) system. Canopy-air temperature difference (ΔT) and statistic Crop Water Stress Index (CWSIsi) indicators were constructed based on Tc. Combined experiment data from the field and drought thresholds for the ΔT and CWSIsi indicators for different drought levels at three main growth periods were monitored. The results showed a strong correlation between the Tc extracted using the NDVI-OTSU method and ground-truth temperature, with an R2 value of 0.94. The CWSIsi was more stable than the ΔT index in monitoring the drought level affecting winter wheat. The threshold ranges of the CWSIsi for different drought levels of winter wheat at three main growth periods were as follows: the jointing–heading period, where the threshold ranges for normal, mild drought, moderate drought, and severe drought are 0.48, respectively; the heading–filling period, where the threshold ranges for normal, and mild, moderate, and severe drought are 0.53, respectively; and the filling–maturation period, where the threshold ranges for normal, mild drought, moderate drought, and severe drought are 0.59, respectively. The UAV thermal threshold method system can improve the accuracy of crop drought monitoring and has considerable potential in crop drought disaster identification.

Datura stramonium is an invasive herb of the family Solanaceae from Mexico and has been invading seriously in China. The effects of invasive plants on the functional traits of native plants and the stoichiometric characteristics of soil carbon, nitrogen and phosphorus in different habitats were explored by taking the invasive plant D. stramonium and coexisting native plants as the research object. The species, quantity and height of plants in sample plots in farmland, wasteland and roadside habitats were investigated and the specific leaf area (SLA), leaf carbon content (C), nitrogen content (N), carbon-to-nitrogen ratio (C:N), construction cost (CCmass) and stoichiometric characteristics of soil carbon (C), nitrogen (N) and phosphorus (P) were analyzed. The results showed that compared with the noninvaded area, the species and quantity of native plants decreased in the invaded area, and SLA and leaf N showed a decreasing trend. The plant height of native plants in the invaded area of the farmland and wasteland decreased by 23.19% and 15.26%, respectively, while the height of native plants along the roadside increased by 95.91%. The leaf C:N ratio of native plants in the invaded area along the roadside significantly increased by 54.07%. The plant height and leaf N of D. stramonium in the three habitats were higher than those of the native plants. The soil N in the invaded area of the three habitats increased, with the soil N in the farmland increasing by 21.05%, in the wasteland increasing by 9.82% and along the roadside significantly increasing by 46.85%. The soil carbon-to-phosphorus ratio (C:P) in the three habitats showed an increasing trend. The soil C:P ratio in the farmland increased by 62.45%, in the wasteland it increased by 11.91% and along the roadside it significantly increased by 71.14%. These results showed that invasion by D. stramonium has a great effect on the local ecosystem, and it has a high ability to capture resources. D. stramonium can improve its own competitiveness by enhancing invasiveness by changing the functional traits of native plants and the stoichiometric characteristics of soil C, N and P, which may be the reason for its invasive success.

Mixing different kind inhalation medications for simultaneous inhalation is widely used in the treatment of chronic respiratory diseases, and it can minimize the administration time and improve patient adherence. To our knowledge, it is unclear whether beclomethasone (BDP, Clenil®) can bemixed with acetylcysteine (NAC, Fluimucil®), because the in vitro physico-chemical compatibility and aerosol characteristics of the mixture are unknown. In this study, we investigated physical compatibility, including the appearance, pH, osmotic pressure and chemical stability, as well as aerosol characteristics, including particle size corresponding to 10%/50%/90% of the cumulative percentage of total particle volume (X10/X50/X90), volume median droplet diameter (VMD), mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), fine particle dose (FPD) and geometric standard deviation (GSD), delivery rate, and total delivery of the above solutions. After mixing, there were no significant changes in visual appearance, pH, osmolality and drug content of the mixtures at room temperature for 12 h. The FDP of BDP in the mixture decreased by 16.49%, whereas the NAC increased by 10.85%. The delivery rates of BDP and NAC in the mixture decreased by 66.05% and 45.54%, and total delivery increased by 13.20% and 25.29%, respectively. However, the MMAD, FPF, particle size and GSD of the mixture were almost unchanged. We demonstrated that these admixtures are physico-chemically compatible but that coadministration of beclomethasone with acetylcysteine can markedly affect output and aerosol characteristics.

Stroke, especially ischemic stroke, is an important cause of neurological morbidity and mortality worldwide. Growing evidence suggests that the immune system plays an intricate function in the pathophysiology of stroke. Gelsevirine (Gs), an alkaloid from Gelsemium elegans, has been proven to decrease inflammation and neuralgia in osteoarthritis previously, but its role in stroke is unknown. In this study, the middle cerebral artery occlusion (MCAO) mice model was used to evaluate the protective effect of Gs on stroke, and the administration of Gs significantly improved infarct volume, Bederson score, neurobiological function, apoptosis of neurons, and inflammation state in vivo. According to the data in vivo and the conditioned medium (CM) stimulated model in vitro, the beneficial effect of Gs came from the downregulation of the over-activity of microglia, such as the generation of inflammatory factors, dysfunction of mitochondria, production of ROS and so on. By RNA-seq analysis and Western-blot analysis, the JAK-STAT signal pathway plays a critical role in the anti-inflammatory effect of Gs. According to the results of molecular docking, inhibition assay, and thermal shift assay, the binding of Gs on JAK2 inhibited the activity of JAK2 which inhibited the over-activity of JAK2 and downregulated the phosphorylation of STAT3. Over-expression of a gain-of-function STAT3 mutation (K392R) abolished the beneficial effects of Gs. So, the downregulation of JAK2-STAT3 signaling pathway by Gs contributed to its anti-inflammatory effect on microglia in stroke. Our study revealed that Gs was benefit to stroke treatment by decreasing neuroinflammation in stroke as a potential drug candidate regulating the JAK2-STAT3 signal pathway.

ObjectiveTo analyze the factors influencing the distribution of 131-I in the liver of patients with advanced hepatic carcinoma treated with the combination of Licartin (131I Metuximab) and transcatheter arterial chemoembolization (TACE). This study provides a reference and basis for the clinic on how to choose the best time for the treatment of Licartin and how to reduce other possible factors affecting the role of Licartin.MethodsData from 41 patients with advanced hepatic carcinoma treated with the combination of Licartin and TACE in the Interventional Department of our hospital from March 2014 to December 2020 were collected. This included general characteristics, history of open and interventional surgery, interval between the last interventional surgery and the Licartin treatment, selected arteries in the Licartin perfusion, and 131-I distribution in the liver. Regression analysis was conducted to investigate the factors affecting the distribution of 131I in the liver.ResultsIn 14 cases (34.1%), 131-I was evenly distributed in the liver, and there was no correlation between the cause of even distribution with age(OR=0.961, P = 0.939), previous open surgery history(OR=3.547,P= 0.128), previous history of interventional therapy(OR=0.140,P = 0.072), the interval between the last interventional surgery and the Licartin treatment(OR=0.858,P = 0.883), or the choice of the perfusion artery in the Licartin treatment (OR=1.489,P = 0.419). In 14 cases (34.1%), there was higher aggregation in the tumor than in the normal liver, which was related to previous interventional surgery (OR=7.443,P = 0.043). In 13 cases (31.7%), there was lower aggregation in the tumor than in the normal liver, which was related to the selected vessels in the Licartin perfusion (OR=0.23,P = 0.013).ConclusionThe effective aggregation of 131-I in the liver, even in tumors, the previous history of TACE, and the choice of vessels in the Licartin infusion might be the factors influencing the distribution of 131-I in the liver during hepatic artery infusion of Licartin in combination with TACE therapy.

Soil moisture is a crucial factor that directly influences agricultural drought. As such, investigating drought-monitoring methods utilizing soil moisture data is of significant importance for accurately evaluating and predicting agricultural drought. However, the current soil moisture data for the Daling River Basin is insufficient. Therefore, the variable infiltration capacity (VIC) hydrological model was utilized to simulate soil moisture in the Daling River Basin. The simulated data were then analyzed in conjunction with the standardized moisture anomaly index (SMAPI) to analyze and evaluate the spatio-temporal characteristics of agricultural drought in the Darling River Basin. The results indicate that the frequency of drought occurrence in the basin follows a seasonal pattern of winter > spring > autumn > summer. Between 1981 and 2019, 24 out of 39 years experienced slight or greater drought, 15 years experienced moderate or more severe drought, and 4 years experienced severe drought. Drought conditions have become exceptionally severe in the 21st century. Specifically, the frequency of drought occurrence from 2001 to 2019 was nearly 10 times higher compared to the period from 1981 to 2000. The droughts were most severe in the southeast and southwest of the Daling River Basin, while the northeast and northwest experienced relatively mild drought. Agricultural drought is influenced by numerous complex factors. The contribution of climate change (CC) and other factors (OF) to agricultural drought was quantified by using a partial derivative under six different scenarios. Results showed that SMAPI was positively correlated with precipitation and solar radiation, while negatively correlated with temperature. From 1981 to 2000, SMAPI exhibited an increasing trend that accounted for 61.66% of variability, while a decreasing trend accounted for 38.34%. From 2001 to 2019, SMAPI exhibited a significant decreasing trend that accounted for 93.53% of the variability, while the increasing trend only accounted for 6.47%. CC was the dominant factor in most of the areas with increased SMAPI. OF was the main controlling factor for areas with decreased SMAPI.

Abstract Background Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. Methods We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan–Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass

Introduction Orthopaedic trauma patients are at high risk of venous thromboembolism (VTE). As VTE prophylaxis has gradually raised public concerns, guidelines related to this topic have increased over time. However, the existing recommendations of thromboprophylaxis guidelines in orthopaedic trauma patients are still inconsistent, and the quality of the guidelines and recommendations for the topic still lacks comprehensive assessments. This review aims to critically appraise clinical practice guidelines for thromboprophylaxis in orthopaedic trauma patients.Methods and analysis We will conduct a comprehensive literature search up to 31 October 2022 in databases (PubMed, EMBASE, CINAHL, Web of Science, the Cochrane Library, etc), academic websites and guideline repositories. The quality of the guidelines and recommendations will be assessed by five reviewers independently using the Appraisal of Guidelines Research and Evaluation II instrument (AGREE-II) and the AGREE - Recommendation EXcellence (AGREE-REX). We will summarise the characteristics of the guidelines and compare the differences between these recommendations.Ethics and dissemination This study will follow the Declaration of Helsinki and has received approval from the Ethics Committee on Biomedical Research, West China Hospital, Sichuan University (ethics approval no. 2021-989). The results will be summarised as a paper, disseminated through peer-reviewed journals, and will help guide further research in the future.Protocol registration number CRD42021273405.

Preeclampsia (PE) is a pregnancy complication characterized by severe hypertension and multiple organ damage. Gut microbiota has been linked to PE by previous amplicon sequencing studies. To resolve the PE gut microbiota in a higher taxonomy resolution, we performed shotgun metagenomic sequencing on the fecal samples from 40 early-onset PE and 37 healthy pregnant women. We recovered 1,750 metagenome-assembled genomes (representing 406 species) from the metagenomic dataset and profiled their abundances. We found that PE gut microbiota had enriched in some species belonging to Blautia, Pauljensenia, Ruminococcus, and Collinsella and microbial functions such as the bacitracin/lantibiotics transport system, maltooligosaccharide transport system, multidrug efflux pump, and rhamnose transport system. Conversely, the gut microbiome of healthy pregnant women was enriched in species of Bacteroides and Phocaeicola and microbial functions including the porphyrin and chlorophyll metabolism, pyridoxal-P biosynthesis, riboflavin metabolism, and folate biosynthesis pathway. PE diagnostic potential of gut microbial biomarkers was developed using both species and function profile data. These results will help to explore the relationships between gut bacteria and PE and provide new insights into PE early warning.

Most dams in China have been operating for a long time and are products of the economic and technical limitations at the time of construction. Due to decades of aging engineering and ancillary problems, these reservoirs pose great threats to the safety of local people and the development of the surrounding economy. In this study, the surface deformation information for the Banqiao Reservoir is monitored with the small baseline subset–synthetic aperture radar interferometry (SBAS-InSAR) method using 80 Sentinel-1A images acquired from 3 January 2020 to 20 August 2022. Additionally, ground measurements from the BeiDou ground-based deformation monitoring stations were collected to validate the InSAR results. Based on the InSAR results, the spatiotemporal deformation features of the dam were analyzed in detail. The results show that the deformation in most areas, including the dam in the study area, is relatively stable, and the regional deformation velocity of the Banqiao Reservoir dam and other hydraulic engineering facilities varies between −1 mm/y and −4 mm/y. The Ru River area has a relatively obvious subsidence trend, and the maximum subsidence velocity reaches 30 mm/y. The InSAR monitoring results are consistent with the change trend in the BeiDou ground-based deformation measurement results. The monitoring results for the reservoir dam area provide a reference for local sustainable development and geological disaster prevention.

Knowledge regarding the soil erosion change patterns in Northeast Inner Mongolia (NIM) is essential for ecological security and sustainable development. Multisource satellite remote sensing with auxiliary data, including meteorology, land use, vegetation coverage, and digital elevation, was collected to establish a distributed soil erosion model to quantify the soil erosion intensity in Northeast Inner Mongolia. The results showed that soil erosion in Northeast Inner Mongolia, China, decreased by 100,654 km2 from 1978 to 2018. The area change rates of the mild, moderate, strong, intensive and severe soil erosion intensities were −48.91%, −41.41%, 32.63%, −91.15%, and −91.14%, respectively. The decrease in soil erosion was mainly located in the Hulunbuir and Tongliao regions. Our findings from satellite observations provide information about the soil erosion intensity and spatial distribution required for policy-making and the management of soil erosion prevention in Northeast Inner Mongolia.

ObjectivesThe first objective of this study was to probe the effects of genkwanin (GKA) on osteoclast. The second goal of this study was to study whether GKA can protect lipopolysaccharide (LPS) and ovariectomized (OVX) induced bone loss.Materials and MethodsVarious concentrations of GKA (1 and 10 mg/kg) were injected into mice. Different concentrations of GKA (1 and 5 μM) were used to detect the effects of GKA on osteoclast and osteoblast.Key FindingsGKA attenuated the osteoclast differentiation promoted by RANKL and expression of marker genes containing c-fos, ctsk as well as bone resorption related gene Trap and to the suppression of MAPK signaling pathway. In addition, GKA induced BMMs cell apoptosis in vitro. Moreover, GKA prevented LPS-induced and ovariectomized-induced bone loss in mice.ConclusionOur research revealed that GKA had a potential to be an effective therapeutic agent for osteoclast-mediated osteoporosis.

With the extensive use and improper treatment of antibiotics, antibiotic pollution in aquaculture wastewater has become increasingly severe. Tetracycline antibiotics have become one of the most commonly used fishery antibiotics. In this study, a Z-scheme heterostructure LaMnO3/g-C3N4 was constructed by the sol–gel method as a photocatalyst to degrade tetracycline, and the influence of anions on the degradation effect was investigated. The LaMnO3/g-C3N4 hybrid was successfully constructed by scanning electron microscope, Fourier transform infrared spectrum, and X-ray diffraction. The results of degradation experiments demonstrated that the maximum tetracycline degradation efficiency of LaMnO3/g-C3N4-10 (LMO/CN-10) was 80%, the removal rate of TC decreased from 71% to 48% when the concentration of chloride ions increased from 0 mM to 10 mM, and the removal rate of TC decreased from 75% to 28% when the concentration of carbonate ions increased from 0 mM to 10 mM. This enhanced photocatalytic activity was attributed to the formation of a Z-scheme structure that promoted the separation of photoinduced electron holes while maintaining its own strong redox ability. Finally, the photocatalytic mechanism was designed based on the free radical trapping experiment, electrochemical impedance, and photoluminescence spectra, providing an opportunity for the construction of a new photocatalyst for the treatment of aquaculture tailwater in the future.

Droughts are serious natural disasters that adversely affect water resources, agriculture, the economy, and the environment. Reconstructing historical drought records is necessary to assess the impact of droughts and their evolution and has become a top priority to support and improve sustainable water management decisions. In this study, we used Shanxi Province as the research area, and meteorological data from the early years of Guangxu in the Qing Dynasty were reconstructed using historical rain and snow records. The Variable Infiltration Capacity (VIC) model is driven by the reconstruction of historical meteorological data. The study area’s monthly runoff and soil water sequence from 1875 to 1879 were simulated, and the hydrology and soil of the ancient historical period were reproduced in the absence of data. The results show the following: (1) The idea of reconstructing hydrological parameters using historical data is feasible and the VIC model can be used to study drought characteristics under specific scenarios. (2) The proportions of areas with runoff depths less than 10 mm throughout Shanxi from 1875 to 1879 were 55%, 48%, 58%, 19%, and 30%. The annual runoff depth in each region from 1875 to 1877 was less than 60 mm. The hydrological drought from 1875 to 1877 was very serious, and the area covered by the drought was relatively large. (3) The annual average soil water content of various regions was stable between 150 and 510 mm from 1875 to 1879. The soil water content had no apparent interannual variation. The area with soil water content less than 180 mm accounted for ratios as high as 31%. This research provides new ideas for ancient drought research and a scientific basis for regional drought prevention, mitigation, and water resources management, and ensures the orderly progress of agricultural production activities.

The vitamin K antagonist is a commonly prescribed effective oral anticoagulant with a narrow therapeutic range, and the dose requirements for different patients varied greatly. In recent years, studies on human intestinal microbiome have provided many valuable insights into disease development and drug reactions. A lot of studies indicated the potential relationship between microbiome and the vitamin K antagonist. Vitamin K is absorbed by the gut, and the intestinal bacteria are a major source of vitamin K in human body. A combined use of the vitamin K antagonist and antibiotics may result in an increase in INR, thus elevating the risk of bleeding, while vitamin K supplementation can improve stability of anticoagulation for oral vitamin K antagonist treatment. Recently, how intestinal bacteria affect the response of the vitamin K antagonist remains unclear. In this review, we reviewed the research, focusing on the physiology of vitamin K in the anticoagulation treatment, and investigated the potential pathways of intestinal bacteria affecting the reaction of the vitamin K antagonist.

Abstract Objective Type I sialidosis (ST‐1) is a rare autosomal recessive inherited disorder. To date, there has been no study on ST‐1 patients in mainland China. Methods We reported in detail the cases of five Chinese ST‐1 patients from two centers, and summarized all worldwide cases. Then, we compared the differences between Chinese and foreign patients. Results A total of 77 genetically confirmed ST‐1 patients were identified: 12 from mainland China, 23 from Taiwan, 10 from other Asian regions, and 32 from European and American regions. The mean age of onset was 16.0 ± 6.7 years; the most common symptoms were myoclonus seizures (96.0%), followed by ataxia (94.3%), and blurred vision (67.2%). Compared to other groups, the onset age of patients from mainland China was much younger (10.8 ± 2.7 years). The incidence of visual impairment was lower in patients from other Asian regions than in patients from mainland China and Taiwan (28.6% vs. 81.8%–100%). Cherry‐red spots were less frequent in the Taiwanese patients than in patients from other regions (27.3% vs. 55.2%–90.0%). Furthermore, 48 different mutation types were identified. Chinese mainland and Taiwanese patients were more likely to carry the c.544A > G mutation (75% and 100%, respectively) than the patients from other regions (only 0%–10.0%). Approximately 50% of Chinese mainland patients carried the c.239C > T mutation, a much higher proportion than that found in the other populations. In addition, although the brain MRI of most patients was normal, 18F‐FDG‐PET analysis could reveal cerebellar and occipital lobe hypometabolism. Interpretation ST‐1 patients in different regions are likely to have different mutation types; environmental factors may influence clinical manifestations. Larger studies enrolling more patients are required.

Abstract Background Patients positive for anti-glutamic acid decarboxylase 65 (GAD65) antibodies have attracted increasing attention. Their clinical manifestations are highly heterogeneous and can be comorbid with tumors. Currently, there is no consensus on the therapeutic regimen for anti-GAD65-associated neurological diseases due to the clinical complexity, rarity and sporadic distribution. We reported six anti-GAD65 autoimmune encephalitis (AE) patients who received intravenous methylprednisolone (IVMP) or immunoglobulin (IVIG) or both. Then, we evaluated the therapeutic effect of both by summarizing results in previous anti-GAD65 AE patients from 70 published references. Results Our six patients all achieved clinical improvements in the short term. Unfortunately, there was no significant difference between IVMP and IVIG in terms of therapeutic response according to the previous references, and the effectiveness of IVMP and IVIG was 45.56% and 36.71%, respectively. We further divided the patients into different subgroups according to their prominent clinical manifestations. The response rates of IVMP and IVIG were 42.65% and 32.69%, respectively, in epilepsy patients; 60.00% and 77.78%, respectively, in patients with stiff-person syndrome; and 28.57% and 55.56%, respectively, in cerebellar ataxia patients. Among 29 anti-GAD65 AE patients with tumors, the response rates of IVMP and IVIG were 29.41% and 42.11%, respectively. There was no significant difference in effectiveness between the two regimens among the different subgroups. Conclusion Except for stiff-person syndrome, we found that this kind of AE generally has a poor response to IVMP or IVIG. Larger prospective studies enrolling large numbers of patients are required to identify the optimal therapeutic strategy in the future.

The difference of deashing performance between the areas of positive-to-blowing holes and that of non-positive-to-blowing holes is an important problem that causes a non-uniform deashing performance to a flat box filter cartridge, which limits the improvement of raising the ash cleaning efficiency to this kind of filter. In order to solve the above problems, the influence of blowing pressure, blowing distance and blowing hole area on cleaning performance was studied. Industrial coating test was also carried out to investigate and verify the actual ash cleaning performance under the optimal conditions obtained from the above investigations. Finally, the design method of the size of the slotted blowing hole was optimized. The results showed that at 0.3 MPa of the pulse pressure, the cleaning performance can meet the cleaning requirements and the best cleaning uniformity can be obtained. With the increase in slot-type nozzle area, the pressure at the areas facing the non-positive nozzles increased significantly, and thus the overall cleaning uniformity increased. The slot-type nozzle area of 273, 546 and 819 mm2 had the best cleaning effects at the jet distances of 40, 20~40 and 20 mm, respectively. The findings of this study are of great significance and can provide theoretical and experimental reference for important parameters selection of the flat cartridges filter in industrial application to improve the efficiency of dust removal.

Abstract Background and purpose How to protect the ovarian function during radiotherapy is uncertain. The purpose of this study was to explore the association between the location of the transposed ovary and the ovarian dose in patients with cervical cancer received radical hysterectomy, ovarian transposition, and postoperative pelvic radiotherapy. Methods A retrospective analysis was conducted of 150 young patients with cervical cancer who received radical hysterectomy, intraoperative ovarian transposition, and postoperative adjuvant radiotherapy in Zhejiang Cancer Hospital. Association between location of the transposed ovaries and ovarian dose was evaluated. The transposed position of ovaries with a satisfactory dose was explored using a receiver operator characteristic curve (ROC) analysis. Patients’ ovarian function was followed up 3 months and 1 year after radiotherapy. Results A total of 32/214 (15%) transposed ovaries were higher than the upper boundary of the planning target volume (PTV). The optimum cutoff value of > 1.12 cm above the iliac crest plane was significantly associated with ovaries above the upper PTV boundary. When the ovaries were below the upper boundary of PTV, the optimum cutoff value of transverse distance > 3.265 cm between the ovary and PTV was significantly associated with ovarian max dose (Dmax) ≤ 4Gy, and the optimum cutoff value of transverse distance > 2.391 cm was significantly associated with ovarian Dmax≤5Gy. A total of 77 patients had received complete follow-up, and 56 patients (72.7%) showed preserved ovarian function 1 year after radiotherapy, which was significantly increased compared with 3 months (44.2%) after radiotherapy. Conclusions The location of transposed ovaries in patients with cervical cancer is significantly correlated with ovarian dose in adjuvant radiotherapy. We recommend transposition of ovaries > 1.12 cm higher than the iliac crest plane to obtain ovarian location above PTV. When the transposed ovary is below the upper boundary of PTV, ovarian Dmax ≤4Gy may be obtained when the transverse distance between the ovary and PTV was > 3.265 cm, and the ovarian Dmax≤5Gy may be obtained when the transverse distance was > 2.391 cm.

The problem of serious ash accumulation at the lower part of flat box filter cartridges is an important limitation for the improvement of ash cleaning efficiency in this kind of filter. To solve the above-mentioned problem, the type of slotted blowing hole impacting the performance of the ash removing under the same ash cleaning area was studied. In the present work, a total of four types of slotted blowing holes with different length were designed. The influence of blowing distance and blowing pressure on dust removal performance were investigated. Numerical simulation was conducted to demonstrate the mechanism of the dust removal process. An industrial coating test was also carried out to investigate and verify the actual ash cleaning performance under the optimal conditions as obtained from the above investigations. The results showed that: (1) the performance of dust cleaning produced by a three-slit blowhole was better than that by a four-slit blowhole; (2) 0.2 MPa was determined to be the optimal blowing pressure, which meets the requirement of ash cleaning; (3) 20 mm was selected as the optimal blowing distance, as this was the distance at which the surface side wall pressure at the non-positive-to-blow hole area was obviously increased, indicating that the whole performance of ash cleaning could be improved. The results obtained in this study are of great significance for improving the efficiency of dust removal in the use of flat box filters, promoting the development of dust removal technology, protection of environment, and reduction of human health damage.

One effective treatment for postmenopausal osteoporosis is to inhibit osteoclasts and subsequent bone resorption. In our study, we demonstrated that acacetin, a flavone with potential therapeutic effects in infections, cancers, and several metabolic disorders, inhibited osteoclast differentiation and bone resorption in vitro. For improving the efficacy of acacetin in vivo, we developed an acid-sensitive bone-targeting delivery system composed of an acid-sensitive linker (N-ε-maleimidocaproic acid hydrazide, EMCH) for ensuring an effective release of acacetin at the site of action and a hydrophilic aspartic acid hexapeptide ((Asp)6, D6) as the effective bone targeting agent. Our results revealed that Acacetin-EMCH-D6 specifically bound to the bone surface once administrated in vivo, prolonged the retention time in bone and released acacetin at the osteoclastic bone resorption sites where the acidity is higher. We further demonstrated that, in ovariectomy-induced osteoporosis mice, treatment with Acacetin-EMCH-D6 inhibited osteoclast formation and increased trabecular bone mass. On the contrary, neither acacetin nor EMCH-D6 with the same dosage alone showed significant anti-osteoporosis effects in vivo. Mechanistically, targeted delivery of acacetin to the bone resorption sites by Acacetin-EMCH-D6 inhibited autophagy through activating PI3K/AKT/mTOR pathway in osteoclasts, while the activation of autophagy by rapamycin partially reversed the inhibitory effects of acacetin in vitro and in vivo. In summary, our study, for the first time, showed that the acid-sensitive bone-targeting delivery system carrying acacetin was effective for the treatment of postmenopausal osteoporosis. Thus, targeted delivery of acacetin using Acacetin-EMCH-D6 to bone resorption sites is a promising therapy for osteoporosis.

Fruit size is an important fruit quality trait that influences the production and commodity values of loquats (Eriobotrya japonica Lindl.). The Small Auxin Upregulated RNA (SAUR) gene family has proven to play a vital role in the fruit development of many plant species. However, it has not been comprehensively studied in a genome-wide manner in loquats, and its role in regulating fruit size remains unknown. In this study, we identified 95 EjSAUR genes in the loquat genome. Tandem duplication and segmental duplication contributed to the expansion of this gene family in loquats. Phylogenetic analysis grouped the SAURs from Arabidopsis, rice, and loquat into nine clusters. By analyzing the transcriptome profiles in different tissues and at different fruit developmental stages and comparing two sister lines with contrasting fruit sizes, as well as by functional predictions, a candidate gene (EjSAUR22) highly expressed in expanding fruits was selected for further functional investigation. A combination of Indoleacetic acid (IAA) treatment and virus-induced gene silencing revealed that EjSAUR22 was not only responsive to auxin, but also played a role in regulating cell size and fruit expansion. The findings from our study provide a solid foundation for understanding the molecular mechanisms controlling fruit size in loquats, and also provide potential targets for manipulation of fruit size to accelerate loquat breeding.

Non-alcoholic fatty liver disease (NAFLD), an important chronic disease, is one of the major causes of high mortality and creates a substantial financial burden worldwide. The various immune cells in the liver, including macrophages, NK cells, dendritic cells, and the neutrophils involved in the innate immune response, trigger inflammation after recognizing the damage signaled from infection or injured cells and tissues. The stimulator of interferon genes (STING) is a critical molecule that binds to the cyclic dinucleotides (CDNs) generated by the cyclic GMP-AMP synthase (cGAS) to initiate the innate immune response against infection. Previous studies have demonstrated that the cGAS-STING pathway plays a critical role in inflammatory, auto-immune, and anti-viral immune responses. Recently, studies have focused on the role of STING in liver diseases, the results implying that alterations in its activity may be involved in the pathogenesis of liver disorders. Here, we summarize the function of STING in the development of NAFLD and present the current inhibitors and agonists targeting STING.

Background: This study aimed to analyze the clinical characteristics of anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis patients and investigate prognostic factors by using a large-sample and long-term follow-up cohort.Methods: The clinical data of 45 patients (29 males; mean age, 57.0 years) from May 2014 to August 2019 were collected. All patients were followed up by face-to-face interviews in the third month after discharge and then by telephone and/or face-to-face interviews every 6 months until November 2020. We evaluated each patient's response to the initial treatments at the first interview and divided them into “responders” and “nonresponders.” Relapses were recorded. At the end of follow-up, each patient was evaluated and reclassified into “complete recovery” or “unhealed” groups. Intergroup differences were assessed.Results: All patients presented with seizures at the initial consultation. Other common manifestations included cognitive dysfunction (82.2%), psychiatric disturbance (66.7%), sleep disorder (54.5%), and hyponatremia (66.7%). During the follow-up period (32.8 ± 13.5 months), six patients experienced relapse within 6–37 months. We observed that the patients who did not respond to the initial treatments and those who relapsed all had a poor long-term prognosis. The patients in the “unhealed” group were older (p = 0.009), had a lower incidence of generalized tonic–clonic seizures (p = 0.041), and had a higher probability of cerebrospinal fluid (CSF) abnormalities (p = 0.024) than those in the “complete recovery” group.Conclusion: Anti-LGI1 encephalitis was characterized by seizures, cognitive impairment, psychiatric disturbance, and sleep disorders and was often accompanied by hyponatremia. Patients who responded poorly to the initial treatments and those patients who relapsed had dismal long-term prognoses. Advanced age and CSF abnormalities may be risk factors for poor prognosis, but these still need to be verified.

Abstract Background Hepatitis C virus (HCV) infection is commonly associated with a disturbance of glucose metabolism. However, there have been conflicting reports on whether the clearance of the HCV may be followed by changes of serum blood glucose and insulin resistance. The aim of the present study was to evaluate the impact of HCV and antiviral treatment on serum glucose levels and other glucose metabolism parameters. Methods A retrospective analysis of 306 HCV-infected patients was performed. Fasting serum blood glucose (FBG) levels in these patients were compared with that of 325 healthy individuals. Serum parameters of glucose metabolism were measured in 183 patients with chronic hepatitis C at baseline, at the end of interferon α-2b plus ribavirin treatment, and at 24 weeks post-treatment. Results Patients with HCV infection had significantly higher FBG level than healthy controls (5.57 ± 0.74 vs. 5.11 ± 0.83 mmol/l, P

Context: Paeoniflorin is reported to possess numerous pharmacological activities. Paeoniflorin and glycyrrhizin are always used together for the treatment of disease in China clinics; however, the drug–drug interaction between glycyrrhizin and paeoniflorin is still unknown. Objective: This study investigates the effects of glycyrrhizin on the pharmacokinetics of paeoniflorin in rats. Materials and methods: The pharmacokinetics of orally administered paeoniflorin (20 mg/kg) with or without glycyrrhizin pre-treatment (at a dose of 100 mg/kg/day for 7 days) were investigated in male Sprague–Dawley rats using LC-MS/MS. Additionally, Caco-2 cell transwell model and rat liver microsome incubation experiments were also conducted to investigate its potential mechanism. Results: The results showed that when the rats were pre-treated with glycyrrhizin, the Cmax of paeoniflorin decreased from 59.57 ± 10.24 to 45.36 ± 8.61 ng/mL, and AUC0-inf also decreased from 282.02 ± 35.06 to 202.29 ± 28.28 μg·h/L. The t1/2 value of paeoniflorin decreased from 8.48 ± 2.01 to 5.88 ± 1.15 h (p

Radioresistance is a crucial factor for the failure of iodine 131 ( 131 I)-based radiotherapy for differentiated thyroid carcinoma (DTC). This study aimed to explore the effect of circ_NEK6 on the development of 131 I resistance in DTC and its potential mechanism. In this study, we demonstrated that circ_NEK6 expression was significantly elevated in 131 I-resistant DTC tissues and cell lines. Knockdown of circ_NEK6 significantly repressed 131 I resistance via inhibiting cell proliferation, migration, invasion abilities, and inducing cell apoptosis and DNA damage in 131 I-resistant DTC cells. Mechanistically, knockdown of circ_NEK6 suppressed 131 I resistance in DTC by upregulating the inhibitory effect of miR-370-3p on the expression of myosin heavy chain 9 (MYH9). In vivo experiments showed that circ_NEK6 inhibition aggravated 131 I radiation-induced inhibition of xenograft tumor growth. Taken together, knockdown of circ_NEK6 repressed 131 I resistance in DTC cells by regulating the miR-370-3p/MYH9 axis, indicating that circ_NEK6 may act as a potential biomarker and therapeutic target for DTC patients with 131 I resistance.

The extensive usage of portable electronic products and the acceleration of their replacement have led to the discarding of a growing amount of LiCoO2 batteries. It is necessary to recycle the batteries from the both viewpoints of environment and economic benefits. Current recycling approaches for LiCoO2 are dominantly based on hydrometallurgy and pyrometallurgy, which usually require multiple complicated steps and involve the use of high temperature or harmful chemicals, like acids and alkalis. There remains an urgent need for a green and simple process. In this paper, suspension electrolysis technology is proposed to recycle spent batteries, in order to achieve the leaching, purification and regeneration of LiCoO2 in one step. The most advantageous of the present technology are that reacting in one reactor at atmospheric condition and no use of highly corrosive and harmful reagents. The reaction of LiCoO2 leaching in the anode region and simultaneously re-synthesizing in the cathode region in ammonia electrochemical system is established for the first time. This work provides a promising method for recovering LiCoO2 efficiently and environmentally friendly, promoting the sustainable utilization of the resources.