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Acute Myocardial Infarction (AMI) has seen rising cases, particularly in younger people, leading to public health concerns. Standard treatments, like coronary artery recanalization, often don't fully repair the heart's microvasculature, risking heart failure. Advances show that Mesenchymal Stromal Cells (MSCs) transplantation improves cardiac function after AMI, but the harsh microenvironment post-AMI impacts cell survival and therapeutic results. MSCs aid heart repair via their membrane proteins and paracrine extracellular vesicles that carry microRNA-125b, which regulates multiple targets, preventing cardiomyocyte death, limiting fibroblast growth, and combating myocardial remodeling after AMI. This study introduces ultrasound-responsive phase-change bionic nanoparticles, leveraging MSCs' natural properties. These particles contain MSC membrane and microRNA-125b, with added macrophage membrane for stability. Using Ultrasound Targeted Microbubble Destruction (UTMD), this method targets the delivery of MSC membrane proteins and microRNA-125b to AMI's inflamed areas. This aims to enhance cardiac function recovery and provide precise, targeted AMI therapy.

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This research aimed to enhance the performance of surface-enhanced Raman scattering (SERS) substrates through the implementation of periodic nanostructures, effectively increasing surface area and uniformity. The approach involved a two-step process: initially, magnetron sputtering was employed to minimize the Raman background signal from the polymer substrate, and subsequently, the microplasma nanoparticle coating method was utilized to augment the presence of silver nanoparticles (AgNPs) for enhancing SERS efficacy. The outcome revealed several key findings: a coefficient of variation (CV) of approximately 8% for individual substrates (3 × 3 cm2), a CV of 6% between different fabrication batches, and a sustained signal strength of 85% over a storage period exceeding two months in a moisture-proof enclosure, thus meeting commercial product standards. Moreover, the substrate demonstrated a limit of detection of 8.4 × 10-7 M (306.5 ppb) for malachite green under non-resonance Raman excitation conditions along with an impressive enhancement factor of 2.69 × 106, establishing it as a high-performance and stable SERS substrate.

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PURPOSE: Exploring the therapeutic effect and mechanism of isorhamnetin in the treatment of DMED. METHODS: Using a high glucose environment to induce endothelial cells damage in the corpus cavernosum, and combining with intervention agents such as ferroptosis inhibitors to observe the process of cell damage and repair, evaluating cell status through CCK-8 and DAPI; To establish the STZ-induced diabetes rat model and detect the erectile function and tissue changes; Perform transcriptomic sequencing on rat models and samples treated with isorhamnetin to analyze differentially expressed genes and their GO functions; Identify critical pathways by combining with the ferroptosis database; Flow cytometry was used to detect ROS and mitochondrial membrane potential, and RT-PCR was used to verify gene expression, Seahorse detects mitochondrial oxygen consumption rate, revealing the mechanism of action of isorhamnetin. RESULTS: Ferroptosis inhibitors and isorhamnetin can effectively reverse the damage of corpus cavernosum endothelial cells induced by high glucose and ferroptosis agonists. Isorhamnetin has the ability to reinstate the erectile function of diabetic rats, while enhancing the quantity of endothelial cells and refining the morphology of collagen fibers. Immunohistochemistry revealed that ferroptosis existed in the penis tissue of diabetes rats. Transcriptomic analysis showed that isorhamnetin improves gene expression in DM rats by regulating genes such as GFER, IGHM, GPX4 and HMOX1, involving multiple pathways and biological processes. Flow cytometry and RT-PCR confirmed that isorhamnetin can reduce reactive oxygen species levels, restore essential gene expression, improve mitochondrial membrane potential, and alleviate oxidative stress and ferroptosis. Seahorse detection found that isorhamnetin can restore mitochondrial oxygen consumption rate. CONCLUSION: Isorhamnetin attenuates high glucose damage to cavernous endothelial cells by inhibiting ferroptosis and oxidative stress, restores erectile function and improves tissue morphology in diabetic rats, and its multi-pathway and multi-targeting regulatory mechanism suggests that it is promising to be an effective drug for the treatment of DMED.

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Objective: This study aims to investigate how changes in peripheral blood metabolites in Alzheimer's Disease (AD) patients affect the development of Pelvic Organ Prolapse (POP) using a multi-omics approach. We specifically explore the interactions of signaling pathways, gene expression, and protein-metabolite interactions, with a focus on GZMA and cysteine in age-related diseases. Methods: This study utilized multi-omics analysis, including metabolomics and transcriptomics, to evaluate the perturbations in peripheral blood metabolites and their effect on POP in AD patients. Additionally, a comprehensive pan-cancer and immune infiltration analysis was performed on the core targets of AD combined with POP, exploring their potential roles in tumor progression and elucidating their pharmacological relevance to solid tumors. Results: We identified 47 differential metabolites linked to 9 significant signaling pathways, such as unsaturated fatty acid biosynthesis and amino acid metabolism. A thorough gene expression analysis revealed numerous differentially expressed genes (DEGs), with Gene Set Enrichment Analysis (GSEA) showing significant changes in gene profiles of AD and POP. Network topology analysis highlighted central nodes in the AD-POP co-expressed genes network. Functional analyses indicated involvement in critical biological processes and pathways. Molecular docking studies showed strong interactions between cysteine and proteins PTGS2 and GZMA, and molecular dynamics simulations confirmed the stability of these complexes. In vitro validation demonstrated that cysteine reduced ROS levels and protected cell viability. GZMA was widely expressed in various cancers, associated with immune cells, and correlated with patient survival prognosis. Conclusion: Multi-omics analysis revealed the role of peripheral blood metabolites in the molecular dynamics of AD and their interactions with POP. This study identified potential biomarkers and therapeutic targets, emphasizing the effectiveness of integrative approaches in treating AD and POP concurrently. The findings highlight the need for in-depth research on novel targets and biomarkers to advance therapeutic strategies.

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How to improve the growth efficiency of microalgae is the bottleneck of microalgae large-scale application. The addition of trace substances can promote the growth of microalgae, but there is no suitable model that can be used to predict the effects of trace substance concentrations on the growth of microalgae. In the present study, a mathematical model based on hormesis is proposed to describe the effects produced by trace substances on the biomass of microalgae and applied to assess the dose-response of four phytohormones on Scenedesmus sp. LX1 with a high coefficient of determination (R2 ≥ 0.90). Several new mathematical parameters, such as starting effective dose (SD), inflection point dose (PD), concentration for 0 % of maximal effect, end effective dose (ED), maximum stimulatory effect (MSE), and maximum inhibitory effect (MIE), were extracted and useful to help researchers in applying trace substances to assist in the production of microalgal biomass for data reference and prediction. In concrete terms, the above model parameters can be well applied to screen the trace substances, dominant algal species and determine the concentration range. This study provides valuable insights into the potential of using phytohormones to enhance the biomass production of microalgae and offers a new approach to optimizing the culture of microalgae.

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One-dimensional nanomaterials have become one of the most available nanoreinforcing agents for developing next-generation high-performance functional self-healing composites owing to their unique structural characteristics and surface electron structure. However, nanoscale control, structural regulation, and crystal growth are still enormous challenges in the synthesis of specific one-dimensional nanomaterials. Here, oxygen-defective MoO3-x nanowires with abundant surface dynamic bonding were successfully synthesized as novel nanofillers and photothermal response agents combined with a polyurethane matrix to construct composite elastomers, thus achieving mechanically enhanced and self-healing properties. Benefiting from the surface plasmon resonance of the MoO3-x nanowires and interfacial multiple dynamic bonding interactions, the composite elastomers demonstrated strong mechanical performance (with a strength of 31.45 MPa and elongation of 1167.73%) and ultrafast photothermal toughness self-healing performance (20 s and an efficiency of 94.34%). The introduction of MoO3-x nanowires allows the construction of unique three-dimensional cross-linked nanonetworks that can move and regulate interfacial dynamic interactions under 808 nm infrared laser stimulation, resulting in controlled mechanical and healing performance. Therefore, such special elastomers with strong photothermal responses and mechanical properties are expected to be useful in next-generation biological antibacterial materials, wearable devices, and artificial muscles.

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The green peach aphid, Myzus persicae, is a worldwide agricultural pest. Chlorpyrifos has been widely used to control M. persicae for decades, thus leading to a high resistance to chlorpyrifos. Recent studies have found that insect odorant binding proteins (OBPs) play essential roles in insecticide resistance. However, the potential resistance mechanism underlying the cross-link between aphid OBPs and chlorpyrifos remains unclear. In this study, two OBPs (MperOBP3 and MperOBP7) were found overexpressed in M. persicae chlorpyrifos-resistant strains (CRR) compared to chlorpyrifos-sensitive strains (CSS); furthermore, chlorpyrifos can significantly induce the expression of both OBPs. An in vitro binding assay indicated that both OBPs strongly bind with chlorpyrifos; an in vivo RNAi and toxicity bioassay confirmed silencing either of the two OBPs can increase the susceptibility of aphids to chlorpyrifos, suggesting that overexpression of MperOBP3 and MperOBP7 contributes to the development of resistance of M. persicae to chlorpyrifos. Our findings provide novel insights into insect OBPs-mediated resistance mechanisms.

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Anoplophora glabripennis (Motschulsky), the Asian longhorned beetle, is a serious wood-boring pest of hardwood trees. There have been records that suggest Elaeagnus angustifolia L. (Elaeagnaceae) might be an "attract and kill" tree species for A. glabripennis, i.e., a tree that is attractive to A. glabripennis adults but kills their oviposited eggs. To evaluate the possibility of E. angustifolia as a control measure for A. glabripennis, we carried out a series of behavioral experiments in the laboratory and in the field. Results showed that: (i) A. glabripennis females preferred E. angustifolia branches and leaves over poplar tree species evaluated; the weight of feces from both female and male A. glabripennis feeding on E. angustifolia was significantly higher than from those feeding on Populus deltoides 'Shalinyang' or Populus alba. L. var. pyramidalis; (ii) the average lifespan of females and males feeding on E. angustifolia was significantly longer than those feeding on other host trees evaluated; (iii) in the laboratory oviposition choice experiment, there were significantly fewer egg notch grooves on E. angustifolia than on P. deltoides 'Shalinyang', and those made in E. angustifolia were without eggs; (iv) in the field, the number of egg notch grooves on E. angustifolia was 43.6 ±â€…18.1 per stem, but the number of eggs laid was only 14.4 ±â€…6.4 per stem; and (v) Field surveys of existing mixed forests showed that when E. angustifolia was planted with P. alba. var. pyramidalis or Populus simonii × (Populus pyramidalis + Salix matsudana) 'Poparis' in the mixed forest, both poplar varieties suffered greater infestation than E. angustifolia. Therefore, E. angustifolia is not a suitable attract and kill tree to be extensively planted in mixed forests for control of A. glabripennis.

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A Gram-stain-negative, aerobic, motile and rod-shaped bacterium, the color of the bacterial colony ranges from light yellow to yellow, designated YC-2023-2T, was isolated from sediment sample of Yuncheng salt lake. Growth occurred at 15-45℃ (optimum 37℃), pH 6.0-9.0 (optimum pH 7.0-8.0) and with 0-8.0% NaCl (w/v, optimum 2.0%). The phylogenetic analysis based on 16S rRNA gene sequences showed that strain YC-2023-2T belonged to the family Kordiimonadaceae. The closely related members were Gimibacter soli 6D33T (92.38%), Kordiimonas lipolytica M41T (91.88%), Eilatimonas milleporae DSM 25217T (91.88%) and Kordiimonas gwangyangensis JCM 12864T (91.84%). The genome of strain YC-2023-2T was 2957513 bp, and the genomic DNA G+C content was 63.91%. The main respiratory quinone was Q-10 and the major fatty acids (>10%) were iso-C15:0, C16:0, C19:0 cyclo ω8c, Summed Feature 8 (C18:1 ω6c or C18:1 ω7c) and Summed Feature 9 (iso-C17:1 ω9c or C16:0 10-methyl). The major polar lipids consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, unidentified glycolipid, unidentified lipid, and two unidentified aminolipids. Based on the phylogenetic, phenotypic and chemotaxonomic characteristics, strain YC-2023-2T is proposed to represent a novel species of a novel genus named Yunchengibacter salinarum gen. nov., sp. nov., within the family Kordiimonadaceae. The type strain is YC-2023-2T (= GDMCC 1.4502T = KCTC 8546T).

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The prevalence and severity of overactive bladder increase with age, and mirabegron is an approved treatment for this condition. This meta-analysis systematically evaluated the efficacy and safety of mirabegron compared with placebo for overactive bladder treatment. We searched PubMed and the Cochrane Library (30 October 2023) for relevant articles (source: MEDLINE, EMBASE, ClinicalTrials.gov, ICTRP, CINAHL). We included randomized controlled trials involving adults with overactive bladder syndrome that compared mirabegron with placebo treatment. Data were analyzed according to the Cochrane Handbook for Systematic Reviews of Interventions [Review Manager (computer program) Version 5.4]. Nine parallel-group trials (10 articles) were included. The evaluation included a total of 8,527 adults, including 6,445 women and 2,082 men, of whom 5,726 were White, 2,462 were Asian, and 161 were Black. The mean age of the participants ranged from 53.4 to 60.3 years. This evaluation involved three specifications of mirabegron: 25 mg, 50 mg, and 100 mg. In all trials, patients were enrolled in a 12-week double-blind treatment period, and the dose was once daily. The review of trials found that on average, people taking mirabegron had about 13 ml more volume voided per micturition, five fewer micturitions, and four fewer incontinence episodes every week, with moderate improvements in quality of life. About one in five people taking the drug reported TRAEs. Mirabegron treatment is well tolerated, with the risk of adverse events similar to that of a placebo. For best results, a dose of 50 mg once daily is recommended for long-term use. It is unclear whether any benefits are sustained after treatment discontinuation. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42023430737).

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Liquid biopsy provides a convenient and safer procedure for the diagnosis and genomic profiling of tumors that are inaccessible to biopsy by analyzing exfoliated tumor cells (ETCs) or tumor-derived cell-free DNA (cfDNA). However, its primary challenge lies in its limited accuracy in comparison to tissue-based approaches. We report a parallel single-ETC genomic sequencing (Past-Seq) method for the accurate diagnosis and genomic profiling of hard-to-biopsy tumors such as cholangiocarcinoma (CCA) and upper tract urothelial carcinoma (UTUC). For CCA, a prospective cohort of patients with suspicious biliary strictures (n = 36) was studied. Parallel single-cell whole genome sequencing and whole exome sequencing were performed on bile ETCs for CCA diagnosis and resolving mutational profiles, respectively, along with bile cfDNA sequenced for comparison. Concordant single-cell copy number alteration (CNA) profiles in multiple ETCs provided compelling evidence for generating a malignant diagnosis. Past-Seq yielded bile-based accurate CCA diagnosis (96% sensitivity, 100% specificity, and positive predictive value), surpassing pathological evaluation (56% sensitivity) and bile cfDNA CNA analysis (13% sensitivity), and generated the best performance in the retrieval tissue mutations. To further explore the applicability of Past-Seq, 10 suspicious UTUC patients were investigated with urine specimens, and Past-Seq exhibited 90% sensitivity in diagnosing UTUC, demonstrating its broad applicability across various liquid biopsies and cancer types.

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Cyclosporine A (CsA) is the prevalent immunosuppressive drug for preventing and treating graft-versus-host disease after hematopoietic stem cell transplantation (HSCT) in both children and adults. Population pharmacokinetic studies have identified covariates, owing to their large between-subject variability, facilitating individualized therapy. However, no review has summarized CsA's population pharmacokinetics post-HSCT. This systematic review aims to synthesize population pharmacokinetic studies of CsA therapy in HSCT recipients and explore influencing covariates. Thirteen studies, comprising five involving children, one involving both children and adults and seven involving adults, were included. The median apparent clearance in children surpassed that in adults, influenced notably by hematocrit level and body. While liver function impacted clearance, the effect was insignificant. Co-administration with cytochrome P450 enzyme inhibitors (e.g., fluconazole or itraconazole) decreased drug clearance, whereas inducers (e.g., rifampicin or rifapentine) increased it. Area under the curve analysis is recommended over trough concentration-based monitoring for HSCT recipients on CsA. In cases of insufficient trough concentration, additional sampling points are recommended for improved area under the curve estimation. Further studies are needed to evaluate the optimal sampling points required for the area under the curve estimation in CsA therapy post-HSCT.

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Chronic lateral epicondylitis (LE), normally known as tennis elbow, is often managed by conservative treatments. Extracorporeal shock wave therapy (ESWT) and local corticosteroid injection (LCI) are among the most commonly used conservative treatments. However, the comparison between these two interventions remains controversial. This study aimed to compare the effectiveness and safety of ESWT and LCI for chronic LE. A systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. PubMed, EMBASE, Cochrane Library, and Web of Science were searched for eligible studies until April 20, 2024. Meta-analyses were conducted using Manager V.5.4.1. Pooled effect sizes were expressed as the weighted mean difference (WMD) or odds ratio (OR), with 95% confidence intervals (CIs). A total of six randomized controlled trials (RCTs) were included. Compared with LCI, ESWT had inferior change in visual analogue scale (Δ VAS) (WMD, 1.14; 95% CI, 0.80 to 1.48; I2 = 20%; p < 0.001), Δ grip strength (WMD, -4.01; 95% CI, -5.57 to -2.44; I2 = 36%; p < 0.001), change in patient-rated tennis elbow evaluation (Δ PRTEE) score (WMD, 8.64; 95% CI, 4.70 to 12.58; I2 = 0%; p < 0.001) at 1-month follow-up, but superior Δ VAS (WMD, -1.15; 95% CI, -1.51 to -0.80; I2 = 6%; p < 0.001), Δ grip strength (WMD, 2.04; 95% CI, 0.90 to 3.18; I2 = 3%; p = 0.0005), Δ PRTEE score (WMD, -9.50; 95% CI, -14.05 to -4.95; I2 = 58%; p < 0.001) at 3-month follow-up, and superior Δ VAS (WMD, -1.81; 95% CI, -2.52 to -1.10; I2 = 33%; p < 0.001), Δ grip strength (WMD, 3.06; 95% CI, 0.90 to 5.21; I2 = 0%; p = 0.005) at 6-month follow-up. The two groups had a similarly low rate of adverse events (OR, 0.69; 95% CI, 0.05 to 8.60; I2 = 67%; p = 0.77), all of which were mild. Both ESWT and LCI are effective and safe in treating chronic LE. Compared with LCI, ESWT showed inferior short-term (1-month) but superior long-term (3-month and 6-month) outcomes regarding pain relief and function recovery, with a similar rate of mild adverse events.

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Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide, and endoplasmic reticulum stress (ERS) and mitochondrial Ca2+ overload have been involved in apoptotic cardiomyocyte death during MI. 13-Methylpalmatine (13-Me-PLT) is a natural isoquinoline alkaloid isolated from Coptis chinensis and has not been systematically studied for their potential pharmacological effects in cardiovascular diseases. We conducted the present study to elucidate whether 13-Me-PLT modulates MI pathology in animal MI and cellular hypoxic models, employing state-of-the-art molecular techniques. The results demonstrated that 13-Me-PLT preserved post-ischemic cardiac function and alleviated cardiomyocyte apoptosis. 13-Me-PLT decreased ERS and the communication between ER and mitochondria, which serves as a protective mechanism against mitochondrial Ca2+ overload and structural and functional injuries to mitochondria. Our data revealed mitigating mitochondrial Ca2+ overload and apoptosis by inhibiting CHOP-mediated Ca2+ transfer between inositol 1,4,5-trisphosphate receptor (IP3R) in ER and VDAC1 in mitochondria as an underlying mechanism for 13-Me-PLT action. Furthermore, 13-Me-PLT produced superior effects in alleviating cardiac dysfunction and apoptosis post-MI to diltiazem and palmatine. Collectively, our research suggests that the CHOP/IP3R/VDAC1 signaling pathway mediates ER-mitochondrial Ca2+ transfer and 13-Me-PLT activates this axis to maintain cellular and organellar Ca2+ homeostasis, protecting against ischemic myocardial injury. These findings may offer an opportunity to develop new agents for the therapy of ischemic heart disease.

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PURPOSE: Radiation cystitis (RC) is a complex and common complication after radiotherapy for pelvic cancer. Icariside II (ICAII) is a flavonoid compound extracted from Epimedium, a traditional Chinese medicine, with various pharmacological activities. The aim of the present study was to investigate the cysto-protective effects of ICAII in RC rats and its possible mechanisms. MATERIALS AND METHODS: A rat model of induced radiation cystitis using pelvic X-ray irradiation was used, and bladder function was assessed by bladder volume and bladder leakage point pressure (LPP) after ICAII treatment. HE and Masson stains were used to assess the histopathological changes in the bladder. IL-6, TNF-α, IL-10, IL-4 and IL-1ß were measured by ELISA to assess the level of inflammation. The gene-level changes in ICAII-treated RC were observed by transcriptome sequencing, and then the potential targets of action and biological mechanisms were explored by PPI, GO and KEGG enrichment analysis of the differentially expressed genes. Finally, the predicted targets of action were experimentally validated using immunohistochemistry, RT-qPCR, molecular docking and CETSA. RESULTS: ICAII significantly increased bladder volume and the LPP, ameliorated pathological damage to bladder tissues, decreased the levels of IL-6, TNF-α, and IL-1ß, and increased the levels of IL-10 and IL-4 in radiation-injured rats. A total of 90 differentially expressed genes were obtained by transcriptome sequencing, and PPI analysis identified H3F3C, ISG15, SPP1, and LCN2 as possible potential targets of action. GO and KEGG analyses revealed that these differentially expressed genes were mainly enriched in the pathways metabolism of xenobiotics by cytochrome P450, arachidonic acid metabolism, Staphylococcus aureus infection and chemical carcinogenesis - reactive oxygen species. Experimental validation showed that ICAII could significantly increase the expression of H3F3C and ISG15 and inhibit the expression of SPP1 and LCN2. ICAII binds well to H3F3C, ISG15, SPP1 and LCN2, with the best binding ability to H3F3C. Furthermore, ICAII inhibited the protein degradation of H3F3C in bladder epithelial cells. CONCLUSIONS: ICAII may alleviate the bladder inflammatory response and inhibit the fibrosis process of bladder tissues through the regulation of H3F3C, ISG15, SPP1, and LCN2 targets and has a protective effect on the bladder of radioinjured rats. In particular, H3F3C may be one of the most promising therapeutic targets.

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The Bohai Rim Plain is an important grain-producing area in China. The cultivated land resources have great potential for production, but there are many influencing factors. Understanding the spatiotemporal change characteristics and driving factors of the net primary productivity （NPP） of cultivated land vegetation in this region is of great significance to improve the regional cultivated land production conditions, excavate and enhance the production capacity of cultivated land, and ensure national food security. In this study, Theil-Sen Median trend analysis, Mann-Kendall significance test, Hurst index, and other methods were used to explore the spatiotemporal change characteristics, stability, and sustainability of regional cultivated land NPP. The influence of driving factors on the spatial heterogeneity of cultivated land NPP was analyzed by using optical parameters-based geographical detectors. The results showed that： ① From 2001 to 2019, due to the expansion of construction land during industrialization and urbanization, the cumulative decrease in the area of cultivated land in the Shandong area around the Bohai Sea was 2 004.51 km2. ② During the selected research period, the interannual variation of average cultivated land NPP showed a fluctuating and increasing trend. In terms of spatial distribution, the NPP of cultivated land was bounded by the Dongying District, with the spatial heterogeneity in the north being significantly lower than that in the south. ③ The area with increasing NPP of cultivated land accounted for 88.06% of the total area of cultivated land, mainly with low and medium fluctuations. The NPP of cultivated land will maintain an overall sustained trend of increase across the region in the future. ④ The average annual relative humidity study area had the strongest explanatory power for the spatial variability of NPP in cropland, with a q-value of 0.26, followed by surface soil salinity and subsoil salinity, with q-values greater than 0.2. The interactions between the different drivers all showed either nonlinear enhancement or bifactorial enhancement. The results of this study will help to reveal the characteristics of the changes in cultivated land production capacity and its driving forces in the Bohai Sea region and also provide a theoretical basis for the ecological protection and sustainable development of the region.

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BACKGROUND: Syndecan 4 (SDC4), a type I transmembrane proteoglycan, serves as a critical link between chondrocytes and the extracellular matrix. OBJECTIVE: This study aimed to explore the role of SDC4 in cartilage degeneration of temporomandibular joint osteoathritis (TMJOA). METHODS: Condylar chondrocytes were stimulated with varying concentrations of recombinant rat interleukin-1ß (rrIL-1ß) and SDC4 small interfering RNA (si-SDC4). Anti-SDC4 ectodomain-specific antibodies or IgG were intra-articularly administrated in a TMJOA model rats. SDC4 conditional knockout (SDC4-cKO) and Sdc4flox/flox mice were induced TMJOA. Cartilage degeneration was assessed using haematoxylin & eosin (H&E) and safranin O (SO) staining. Protein levels of SDC4, matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with a thrombospondin motifs 5 (ADAMTS5), tumour necrosis factor α (TNFα), type II collagen (Col-II), aggrecan (ACAN), cleaved caspase 3 (CASP3), Ki67 and related pathways in condylar cartilage were evaluated by immunohistochemical (IHC) staining or western blot assays. RESULTS: SDC4 expression was evidently increased in MIA-model animals compared to control groups. rrIL-1ß stimulation increased the expression of SDC4, MMP3 and ADAMTS5 expression in chondrocytes, while decreasing the expression of Col-II. These effects were reversed by si-SDC4 in vitro. In vivo, SDC4 blockade reduced the death of chondrocytes and the loss of cartilage matrix, which was evidenced by increased expression of Col-II and ACAN, and a decrease in SDC4, MMP13 and cleaved-CASP3-positive cells. Furthermore, the protein levels of ACAN and Ki67 were elevated, and the ERK1/2 and P38 signalling pathways were activated following SDC4 inhibition. CONCLUSIONS: SDC4 inhibition significantly ameliorates condylar cartilage degeneration, which was mediated, at least partly, through P38 and ERK1/2 signalling. Inhibition of SDC4 may be of great value for the treatment of TMJOA.

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The obstacle to effectively treating Diffuse Large B-cell Lymphoma (DLBCL) lies in the resistance observed toward standard therapies. Identifying therapeutic targets that prove effective for relapsed or refractory patients poses a significant challenge. OTUD3, a deubiquitinase enzyme, is overexpressed in DLBCL tissues. However, its role in DLBCL has not been investigated. Our study has brought to light the multifaceted impact of OTUD3 in DLBCL. Not only does it enhance cell survival through the deubiquitination of MYL12A, but it also induces CD8+ T cell exhaustion within the local environment by deubiquitinating PD-L1. Our findings indicate that the OTUD3 inhibitor, Rupatadine, exerts its influence through competitive binding with OTUD3. This operation diminishes the deubiquitination of both MYL12A and PD-L1 by OTUD3. This research unveils the central and oncogenic role of OTUD3 in DLBCL and highlights the potential clinical application value of the OTUD3 inhibitor, Rupatadine. These findings contribute valuable insights into addressing the challenges of resistant DLBCL cases and offer a promising avenue for further clinical exploration.

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This research focuses on preparing a series of new TiO2/Ag hybrid aerogels with varying TiO2 contents, and demonstrates their application as ultrasensitive SERS substrates. The synthesized TiO2/Ag hybrid aerogels exhibited excellent SERS behavior when detecting 4-Mercaptobenzoic acid (4-MBA), and the calculated SERS enhancement factor (EF) was 6.34 × 106. 3D structured aerogels can create more hot spots and adsorption sites, and multiple interband chemical transfer (CT) pathways emerged and enhanced CT efficiency because of the large number of surface oxygen vacancies of meso-TiO2 NPs. Therefore, the synergy of electromagnetic field enhancement and chemical enhancement leads to SERS enhancement. In addition, the composite SERS substrate has high sensitivity, and the detection limit of adsorbed 4-MBA probe molecules reaches 10-11 M. Furthermore, the TiO2/Ag hybrid aerogels demonstrate good reproducibility with minimal standard deviation in terms of SERS signals. In addition, even after standing for 6 months, there is almost no attenuation in the SERS signal intensity, which highlights the excellent stability of this substrate. Therefore, these highly sensitive TiO2/Ag hybrid aerogels SERS substrates have important practical value in environmental monitoring, medical inspection and food supervision.

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Hydrodynamics analysis and control are very significant for the seabed operations, particularly for the intelligent manipulation process of streamlined intervention autonomous underwater vehicles (I-AUVs). The computation fluid dynamics simulations and verification were conducted in the consideration with water channel domain, mesh insensitivity, support straight bar connector, free surface and other boundary conditions. The variation trend of hydrodynamic coefficients in the process of manipulation is obtained, by simulations of streamlined I-AUV manipulation under dynamic manipulation state. To further realize underwater floating manipulation, a novel controller with an integral termed nonlinear sliding mode surface and disturbance observer has been developed. The disturbance observer can make quantity analysis on the interaction forces between I-AUV and the environment from hydrodynamic analysis. Simulations and experiments have verified the controller performance.