Distinguished biomimetic dECM system facilitates early detection of metastatic breast cancer cells.

Breast cancer is the most prevalent malignant tumor affecting women's health. Bone is the most common distant metastatic organ, worsening the quality of life and increasing the mortality of patients. Early detection of breast cancer bone metastasis is urgent for halting disease progression and improving tumor prognosis. Recently, extracellular matrix (ECM) with biomimetic tissue niches opened a new avenue for tumor models in vitro. Here, we developed a biomimetic decellularized ECM (dECM) system to recapitulate bone niches at different situations, bone mimetic dECM from osteoblasts (BM-ECM) and bone tumor mimetic dECM from osteosarcoma cells (OS-ECM). The two kinds of dECMs exhibited distinct morphology, protein composition, and distribution. Interestingly, highly metastatic breast cancer cells tended to adhere and migrate on BM-ECM, while lowly metastatic breast cancer cells preferred the OS-ECM niche. Epithelial-to-mesenchymal transition was a potential mechanism to initiate the breast cancer cell migration on different biomimetic dECMs. Importantly, in the nude mice model, the dECM system captured metastatic breast cancer cells as early as 10 days after orthotopic transplantation in mammary gland pads, with higher signal on BM-ECM than that on OS-ECM. Collectively, the biomimetic dECM system might be a promising tumor model to distinguish the metastatic ability of breast cancer cells in vitro and to facilitate early detection of metastatic breast cancer cells in vivo, contributing to the diagnosis of breast cancer bone metastasis.

Advances in mesenchymal stem cells therapy for tendinopathies.

Tendinopathies are chronic diseases of an unknown etiology and associated with inflammation. Mesenchymal stem cells (MSCs) have emerged as a viable therapeutic option to combat the pathological progression of tendinopathies, not only because of their potential for multidirectional differentiation and self-renewal, but also their excellent immunomodulatory properties. The immunomodulatory effects of MSCs are increasingly being recognized as playing a crucial role in the treatment of tendinopathies, with MSCs being pivotal in regulating the inflammatory microenvironment by modulating the immune response, ultimately contributing to improved tissue repair. This review will discuss the current knowledge regarding the application of MSCs in tendinopathy treatments through the modulation of the immune response.

Non-Negligible Ecological Risks of Urban Wetlands Caused by Cd and Hg on the Qinghai-Tibet Plateau, China.

The Huangshui National Wetland Park (HNWP) is a unique national wetland park in a city on the Qinghai-Tibetan Plateau, containing three zones: Haihu, Beichuan, and Ninghu. In this study, a total of 54 soil samples (18 sampling points with depths of 0-10 cm, 10-20 cm, and 20-30 cm) were collected in these three zones, and the contents of heavy metals (Cr, Cd, Cu, Hg, Ni, Pb, Zn, and As) of each sample were determined. The ecological risk of eight kinds of heavy metals was evaluated by using the geo-accumulation index (Igeo), and the ecological risk-controlling effect of the Xining urban wetlands on heavy metals was explored by comparative analysis, and the possible sources of heavy metals in the soil were analyzed via correlation analysis and principal component analysis (PCA). The results revealed that the total heavy metal concentration order was Haihu > Beichuan > Ninghu zone. As and Cu presented vertical accumulation characteristics in the surface and lower horizon, respectively. Cr, Cd, Hg, Ni, Pb, and Zn accumulated downwards along the depth. On the spatial scale, the enrichments of Cd and Hg brought non-negligible ecological risks in plateau urban wetlands. The results of PCA indicated that soil heavy metals mainly came from compound sources of domestic and atmospheric influences, traffic pollution sources, and industrial pollution sources. The study has revealed that human activities have inevitable negative impacts on wetland ecosystems, while the HNWP provides a significant weakening effect on heavy metal pollution.

Repairing gastric ulcer with hyaluronic acid/extracellular matrix composite through promoting M2-type polarization of macrophages.

The treatment of gastric ulcer and perforation using synthetic and biomaterials has been a clinical challenge. In this work, a drug-carrying layer of hyaluronic acid was combined with a gastric submucosal decellularized extracellular matrix called gHECM. The regulation of macrophage polarization by the extracellular matrix's components was then investigated. This work proclaims how gHECM responds to inflammation and aids in the regeneration of the gastric lining by altering the phenotype of surrounding macrophages and stimulating the body's whole immune response. In a nutshell, gHECM promotes tissue regeneration by changing the phenotype of macrophages around the site of injury. In particular, gHECM reduces the production of pro-inflammatory cytokines, decreases the percentage of M1 macrophages, and further encourages differentiation of macrophage subpopulation to the M2 phenotype and the release of anti-inflammatory cytokines, which could block the NF-κB pathway. Activated macrophages are capable of immediately delivering through spatial barriers, modulating the peripheral immune system, influencing the inflammatory microenvironment, and ultimately promoting the recovery of inflammation and healing of ulcers. They contribute to the secreted cytokines that act on local tissues or enhance the chemotactic ability of macrophages through paracrine secretion. In this study, we focused on the immunological regulatory network of macrophage polarization to further develop the mechanisms behind this process. Nevertheless, the signaling pathways involved in this process need to be further explored and identified. We think that our research will encourage more investigation into how the decellularized matrix affects immune modulation and will help the decellularized matrix perform better as a new class of natural biomaterials for tissue engineering.

Ecological Risks of Antibiotics in Urban Wetlands on the Qinghai-Tibet Plateau, China.

Although the ecological risks of antibiotics have been extensively researched globally, fewer studies have been conducted in sensitive and fragile plateau wetland ecosystems. To evaluate the ecological risk of antibiotics in plateau urban wetlands, 18 water samples, 10 plant samples, and 8 sediment samples were collected in March 2022 in the Xining urban wetlands on the Qinghai-Tibet Plateau. The liquid chromatography-electrospray ionization tandem mass spectrometry method was utilized to measure the concentrations of 15 antibiotics in three categories in three types of environmental media. Risk quotients were adopted to assess the ecological risk of antibiotics, and the principal component analysis-multiple linear regression model was used to analyze the source of antibiotics. The results showed that (1) the maximum concentrations of antibiotics in water samples, plants, and sediments reached 1220.86 ng/L, 78.30 ng/g, and 5.64 ng/g, respectively; (2) Tylosin (TYL), norfloxacin (NFX), ofloxacin (OFX), and ciprofloxacin (CFX) in water were at medium and high-risk levels, and OFX had the highest risk value, of 108.04; and (3) the results of source apportionment indicate that 58.94% of the antibiotics came from the Huangshui river and wastewater treatment plant (WWTP) near the wetlands. The current study may provide a reference for the risks and management of antibiotics in plateau urban wetlands.

Enhancement of Tendon Repair Using Tendon-Derived Stem Cells in Small Intestinal Submucosa via M2 Macrophage Polarization.

(1) Background: Reconstruction of Achilles tendon defects and prevention of postoperative tendon adhesions were two serious clinical problems. In the treatment of Achilles tendon defects, decellularized matrix materials and mesenchymal stem cells (MSCs) were thought to address both problems. (2) Methods: In vitro, cell adhesion, proliferation, and tenogenic differentiation of tendon-derived stem cells (TDSCs) on small intestinal submucosa (SIS) were evaluated. RAW264.7 was induced by culture medium of TDSCs and TDSCs-SIS scaffold groups. A rat Achilles tendon defect model was used to assess effects on tendon regeneration and antiadhesion in vivo. (3) Results: SIS scaffold facilitated cell adhesion and tenogenic differentiation of TDSCs, while SIS hydrogel coating promoted proliferation of TDSCs. The expression of TGF-ß and ARG-1 in the TDSCs-SIS scaffold group were higher than that in the TDSCs group on day 3 and 7. In vivo, the tendon regeneration and antiadhesion capacity of the implanted TDSCs-SIS scaffold was significantly enhanced. The expression of CD163 was significantly highest in the TDSCs-SIS scaffold group; meanwhile, the expression of CD68 decreased more significantly in the TDSCs-SIS scaffold group than the other two groups. (4) Conclusion: This study showed that biologically prepared SIS scaffolds synergistically promote tendon regeneration with TDSCs and achieve antiadhesion through M2 polarization of macrophages.

Association between hospital-acquired pneumonia and proton pump inhibitor prophylaxis in patients treated with glucocorticoids: a retrospective cohort study based on 307,622 admissions in China.

Background: Prophylaxis with proton pump inhibitor (PPI) in patients treated with glucocorticoid therapy is a common phenomenon in the general wards of Chinese hospitals. Many of these prescriptions are inappropriate and lead to overuse. Hospital-acquired pneumonia (HAP) is a possible adverse effect for this combination but remains controversial. Methods: We designed a retrospective cohort study using electronic medical record databases from multiple hospitals to investigate whether PPI prophylaxis increases the risk of HAP in hospitalized patients receiving glucocorticoid therapy. The study population was adult patients who were not critical and treated with at least 1 dose of glucocorticoid during hospitalization and the exposure factor was PPIs prophylaxis. The odds ratio of HAP between the exposed and unexposed groups was calculated based on the cohort which was established by propensity score matching. The dose-effect relationship between PPI prophylaxis and HAP was also evaluated. Results: Among the 307,622 admissions eligible for the study, a total of 217,460 (70.7%) admissions had a record of PPI prophylaxis. After reconstructed the cohort by propensity score matching, the exposed and unexposed groups both included 83,786 admissions. The incidence of HAP in the exposed group was higher than that in the unexposed group (2.1% vs. 1.5%, OR: 1.4, 95% CI: 1.3 to 1.5). The risk of HAP increased when the cumulative dose of PPI during hospital was more than 2 defined drug doses. Compared to the unexposed group, the adjusted odds ratio was 1.3 (95% CI: 1.2 to 1.4) in the medium-dose group (2-7 defined drug doses) and 1.9 (95% CI: 1.8 to 2.1) in the high-dose group (>7 defined drug doses). Conclusions: PPI prophylaxis increased the risk of HAP in hospitalized patients treated with glucocorticoid therapy and the risk of HAP increased as the dose of PPIs accumulated.

Responses of Soil Microbial Metabolic Activity and Community Structure to Different Degraded and Restored Grassland Gradients of the Tibetan Plateau.

Climate change and land-use disturbances are supposed to have severely affected the degraded alpine grasslands on the Tibetan Plateau. Artificial grassland establishment has been implemented as a restoration tool against grassland degradation. However, the impact of such degradation and restoration processes on soil microbial communities and soil quality is not clearly understood. Here, we aim to investigate how the dynamics of microbial community and soil quality of alpine grasslands respond to a gradient of degradation and that of restoration, respectively. We conducted a randomised experiment with four degradation stages (light, moderate, heavy, and extreme degradation) and three restoration stages (artificial restoration for 1, 5, and 10 years). We analysed the abundance and diversity of soil bacteria and fungi, and measured soil nutrients, enzymatic activity and microbial biomass. The concentration of soil nitrogen (TN), soil organic matter (OM) in heavy degraded grassland decreased significantly by 37.4 and 45.08% compared with that in light degraded grassland. TN and OM in 10-years restored grassland also increased significantly by 33.10 and 30.42% compared to that in 1-year restored grassland. Four soil enzymatic activity indicators related to microbial biomass decreased with degradation gradient and increased with recovery time (i.e., restoration gradient). Both bacterial and fungal community structure was significantly different among grassland degradation or restoration successional stages. The LEfSe analysis revealed that 29 fungal clades and 9 bacterial clades were susceptible to degraded succession, while16 fungal clades and 5 bacterial clades were susceptible to restoration succession. We conclude that soil quality (TN, OM, and enzymatic activity) deteriorated significantly in heavy degraded alpine grassland. Soil microbial community structure of alpine is profoundly impacted by both degradation and restoration processes, fungal communities are more sensitive to grassland succession than bacterial communities. Artificial grasslands can be used as an effective method of restoring degraded grassland, but the soil functions of artificial grassland, even after 10 years of recovery, cannot be restored to the original state of alpine grassland.

Gelatin-grafted tubular asymmetric scaffolds promote ureteral regeneration via activation of the integrin/Erk signaling pathway.

Introduction: The repair of a diseased ureter is an urgent clinical issue that needs to be solved. A tissue-engineered scaffold for ureteral replacement is currently insufficient due to its incompetent bioactivity, especially in long-segment abnormalities. The primary reason is the failure of urothelialization on scaffolds. Methods: In this work, we investigated the ability of gelatin-grafted tubular scaffold in ureteral repairment and its related biological mechanism. We designed various porous asymmetric poly (L-lactic acid) (PLLA)/poly (L-lactide-co-e-caprolactone) (PLCL) tubes with a thermally induced phase separation (TIPS) method via a change in the ratio of solvents (named PP). To regulate the phenotype of urothelial cells and ureteral reconstruction, gelatin was grafted onto the tubular scaffold using ammonolysis and glutaraldehyde crosslinking (named PP-gel). The in vitro and in vivo experiments were performed to test the biological function and the mechanism of the scaffolds. Results and Discussion: The hydrophilicity of the scaffold significantly increased after gelatin grafting, which promoted the adhesion and proliferation of urothelial cells. Through subcutaneous implantation in rats, PP-gel scaffolds demonstrated good biocompatibility. The in vivo replacement showed that PP-gel could improve urothelium regeneration and maintain renal function after the ureter was replaced with an ∼4 cm-long PP-gel tube using New Zealand rabbits as the experimental animals. The related biologic mechanism of ureteral reconstruction was detected in detail. The gelatin-grafted scaffold upgraded the integrin α6/ß4 on the urothelial cell membrane, which phosphorylates the focal adhesion kinase (FAK) and enhances urothelialization via the MAPK/Erk signaling pathway. Conclusion: All these results confirmed that the PP46-gel scaffold is a promising candidate for the constitution of an engineered ureter and to repair long-segment ureteral defects.

Current usage status of somatostatin and its analogs and trypsin inhibitors: a real-world study of 34,654 Chinese adult patients with acute pancreatitis.

BACKGROUND: Although somatostatin and its analogs and trypsin inhibitors (TSI) are widely recommended for acute pancreatitis (AP), there is a lack of high-quality multicenter trials that validate these drug classes. We aimed to examine the current usage status of somatostatin and its analogs and TSI in Chinese adult AP patients. METHODS: We conducted a retrospective study which collected information for adult patients who were diagnosed with AP from January 1, 2015 to June 30, 2017 at 192 hospitals in China. Subsequently, we conducted a statistical analysis of the baseline information of patients, and revealed the usage of somatostatin, octreotide, ulinastatin, and gabexate. Thereafter, we stratified AP by severity and analyzed the current status of treatment. RESULTS: A total of 34,654 patients were included in this study. Mean age of patients was 49.9 years and 63% were males. Fifty-five percent of mild AP patients opted to receive octreotide, while 53.66% and 64.61% of moderate AP and severe AP patients respectively opted to receive somatostatin. At treatment initiation, somatostatin was mainly prescribed for mild and moderate AP patients, which were 723 and 894 daily defined doses (i.e., defined dose per day for a drug used by every 1,000 patients). Ulinastatin was mainly prescribed for severe AP patients, with a prescription volume of 1,230 daily defined doses. The consumption of ulinastatin in later stages of severe AP treatment was significantly greater than other drugs. CONCLUSIONS: Somatostatin analogs and TSI are widely used as therapeutic drugs for AP treatment in China, with usage beginning at the early stages of the disease and lasting on average for 1 week. Of these drugs, somatostatin and octreotide were identified as the most commonly-used drugs, while ulinastatin was found to be widely used at the late stages of severe AP.

Porous cellulose diacetate-SiO2 composite coating on polyethylene separator for high-performance lithium-ion battery.

The developments of high-performance lithium ion battery are eager to the separators with high ionic conductivity and thermal stability. In this work, a new way to adjust the comprehensive properties of inorganic-organic composite separator was investigated. The cellulose diacetate (CDA)-SiO2 composite coating is beneficial for improving the electrolyte wettability and the thermal stability of separators. Interestingly, the pore structure of composite coating can be regulated by the weight ratio of SiO2 precursor tetraethoxysilane (TEOS) in the coating solution. The electronic performance of lithium ion batteries assembled with modified separators are improved compared with the pristine PE separator. When weight ratio of TEOS in the coating solution was 9.4%, the composite separator shows the best comprehensive performance. Compared with the pristine PE separator, its meltdown temperature and the break-elongation at elevated temperature increased. More importantly, the discharge capacity and the capacity retention improved significantly.

Ecological network analysis on global virtual water trade.

Global water interdependencies are likely to increase with growing virtual water trade. To address the issues of the indirect effects of water trade through the global economic circulation, we use ecological network analysis (ENA) to shed insight into the complicated system interactions. A global model of virtual water flow among agriculture and livestock production trade in 1995-1999 is also built as the basis for network analysis. Control analysis is used to identify the quantitative control or dependency relations. The utility analysis provides more indicators for describing the mutual relationship between two regions/countries by imitating the interactions in the ecosystem and distinguishes the beneficiary and the contributor of virtual water trade system. Results show control and utility relations can well depict the mutual relation in trade system, and direct observable relations differ from integral ones with indirect interactions considered. This paper offers a new way to depict the interrelations between trade components and can serve as a meaningful start as we continue to use ENA in providing more valuable implications for freshwater study on a global scale.