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ABSTRACT: Myopia is a global public issue with a dramatically increasing incidence. Myopia is currently characterized by its earlier onset, quick development in preschool (0-5 years old), and continued progression particularly during the coronavirus-19 epidemic phase. It has been established that myopia experienced during childhood earlier resulted in vision impairment. In order to intervene in myopia development and offer a novel tool for earlier detection, the review attempts to identify known environmental and genetic risk factors for juvenile myopia (6-18 years old). Medline, Embase, and Web of Science databases were thoroughly searched for articles on myopia that had been published within the previous 10 years. The searches were carried out separately by two experts. The study's inclusion criteria were met by 28 articles. All studies that examined the link between risk factors and myopia were recruited. Parental myopia, near work, time spent outdoors, and a high level of education are all significant risk factors for juvenile myopia. It is clear that there is a strong environmental connection, especially in high myopia; nevertheless, more research is needed to identify any potential links between myopia and screen use. Myopia's genesis and mechanism are ambiguous and unclear. Further genetic studies could aid in examining genes to comprehend the development of myopia.
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Introduction: Angong Niuhuang Wan (AGNHW), developed during the Qing dynasty (18th century) for the treatment of consciousness disturbances caused by severe infections, has been used to treat brain edema caused by ischemiaâreperfusion. However, it remains unclear whether AGNHW can ameliorate vascular-origin brain edema caused by lipopolysaccharides (LPS). This study explored the ameliorative effects of AGNHW on LPS-induced cerebrovascular edema in mice, as well as the potential underlying mechanisms. Methods: A cerebrovascular edema model was established in male C57BL/6N mice by two intraperitoneal injections of LPS (15 mg/kg), at 0 and 24 h. AGNHW was administered by gavage at doses of 0.2275 g/kg, 0.455 g/kg, and 0.91 g/kg, 2 h after LPS administration. In control mice, normal saline (NS) or AGNHW (0.455 g/kg) was administered by gavage 2 h after intraperitoneal injection of NS. The survival rate, cerebral water content, cerebral venous FITC-dextran leakage, Evans blue extravasation, and expression of vascular endothelial cadherin (VE-cadherin), zonula occludens-1 (ZO-1), claudin-5, phosphorylated caveolin-1 (CAV-1), and cytomembrane and cytoplasmic aquaporin 1 (AQP1) and aquaporin 4 (AQP4) were evaluated. The cerebral tissue phosphoproteome, blood levels of AGNHW metabolites, and the relationships between these blood metabolites and differentially phosphorylated proteins were analyzed. Results: AGNHW inhibited the LPS-induced decrease in survival rate, increase in cerebral water content, decrease in VE-Cadherin expression and increase in phosphorylated CAV-1 (P-CAV-1). AGNHW treatment increased the expression of AQP4 on astrocyte membrane after LPS injection. AGNHW also inhibited the LPS-induced increases in the phosphorylation of 21 proteins, including protein kinase C-α (PKC-α) and mitogen-activated protein kinase 1 (MAPK1), in the cerebral tissue. Eleven AGNHW metabolites were detected in the blood. These metabolites might exert therapeutic effects by regulating PKC-α and MAPK1. Conclusion: AGNHW can ameliorate cerebrovascular edema caused by LPS. This effect is associated with the inhibition of VE-Cadherin reduction and CAV-1 phosphorylation, as well as the upregulation of AQP4 expression on the astrocyte membrane, following LPS injection.
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BACKGROUND: Surgical resection is the cornerstone treatment for colorectal cancer. Rapid rehabilitation care predicated on evidence-based medical theory aims to improve postoperative nursing care, subsequently reducing the physical and mental traumatic stress response and helping patients who undergo surgery recover rapidly. AIM: To assess the effect of rapid rehabilitation care on clinical outcomes, including overall postoperative complications, anastomotic leaks, wound infections, and intestinal obstruction in patients with colorectal cancer. METHODS: We searched the PubMed, Web of Science, Embase, Elsevier Science Direct, and Springer Link databases from January 1, 2010, to January 1, 2024, to screen eligible studies on rapid rehabilitation care among patients who underwent colorectal cancer surgery. Patients were screened based on the inclusion and exclusion criteria. RevMan 5.4 software was used for statistical analysis of the data. RESULTS: Twelve studies were enrolled, which included 2420 patients. The results showed that rapid rehabilitation care decreased the incidence of overall postoperative complications (OR: 0.44, 95%CI: 0.26-0.74, P = 0.002), anastomotic leaks (OR: 0.68, 95%CI: 0.41-1.12, P = 0.13), wound infections (OR: 0.45, 95%CI: 0.29-0.72, P = 0.0007), and intestinal obstruction (OR: 0.54, 95%CI: 0.34-0.86, P = 0.01) compared to conventional care. Further trials and studies are needed to confirm these results. CONCLUSION: Rapid rehabilitation care decreased the occurrence of postoperative complications, anastomotic leaks, wound infections, and intestinal obstruction compared to conventional care in patients who underwent colorectal surgery. Therefore, promoting the application of rapid rehabilitation care in clinical practice cannot be overemphasized.
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Highly sensitive photoelectrochemical (PEC) sensors for trace carcinogens, such as heavy metal chromium(VI) [Cr(VI)] and antibiotic tetracycline (TC) are crucial. Herein, by integration of photoactive and redox phosphomolybdates with conjugated organic components, types of dual-mode PEC sensors were synthesized for sensing trace Cr(VI) and TC pollutants, with formulas of (H2bimb)2[Co2(bimb)1.5][Co(H2O)4][Co(P4Mo6O31H6)2]·6H2O (1), (H2bib)2[Co(H2O)3][Co2(H2O)5][Co(P4Mo6O31H6)2]·9H2O (2), and (H2bib)6[Co(Hbib)2(H2O)5][Co(P4Mo6O31H7)2]2·15H2O (3), where bimb represents 1,4-bis(1-imidazolyl)benzene and bib is 4,4'-bis(imidazolyl)bibphenyl. Hybrid 1 consisted of a three-dimensional framework structure constructed by Co{P4Mo6}2 clusters and one-dimensional (1D) {Co-bimb} chains, hybrid 2 exhibited 1D Co ion-bridged Co{P4Mo6}2 chains hydrogen-bonding with [H2bib]2+ cations, and hybrid 3 showed a discrete hybrid structure built upon a Co{P4Mo6}2 cluster modified by the {Co-bib} unit. Hybrids 1-3 displayed wide spectral absorption and excellent electrochemical redox properties, enabling dual-mode PEC responses to Cr(VI) reduction and TC oxidation. For Cr(VI) detection, hybrids 1-3 exhibited high sensitivities of 364.40, 225.72, and 124.29 µA·µM-1 as well as "nM" level detection limits (LODs) of 4.9, 10.0, and 11.0 nM, respectively. For TC detection, the sensitivities of hybrids 1-3 were 494.72, 308.78, and 174.03 µA·µM-1 and the LODs were 5.2, 6.1, and 12.9 nM, respectively. This research offers significant insights into designing efficient PEC sensors for the detection of environmental pollutants.
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Objectives: To avoid postoperatively acquired cholesteatoma, whether there was any squamous epithelial tissues residue around the tip of the malleus handle, and the need to remove these tissues were explored. Methods: This prospective study enrolled 197 patients who underwent endoscopic tympanoplasty. A postoperative pathological evaluation of the tissue around the tip of the malleus handle was performed to determine the presence of squamous epithelium. Analyzed correlation of epithelial remnants with exposure of malleus handle and microbial infection of middle ear. Results: The detection rate of squamous epithelial retention around the tip of the malleus handle differed significantly among patients with adhesive otitis media (AdOM), acquired cholesteatoma, and chronic suppurative otitis media (CSOM). The detection rate was significantly higher in the acquired cholesteatoma group than in the AdOM and CSOM groups (P < .001). The rate of squamous epithelial retention around the tip of the malleus handle was not significantly associated with microbial infection of the middle ear, the surgical side (P = .672), dry or wet ear status (P = .702), or exposure of the malleus handle (P = .06). Conclusions: In patients with acquired cholesteatoma, AdOM, or COM with severe tympanic sclerosis, the tissue around the tip of the malleus handle should be removed completely. For patients with simple COM, that is, without tympanic sclerosis or keratinizing stratified squamous epithelium at the edge of the perforation, the tissue can be retained.
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Focal segmental glomerulosclerosis (FSGS), a common cause of primary glomerulonephritis, has a poor prognosis and is pathologically featured by tubulointerstitial injury. Thrombospondin-1 (TSP-1) is an extracellular matrix protein that acts in combination with different receptors in the kidney. Here, we analyzed the tubular expression of TSP-1 and its receptor integrin ß3 (ITGB3) in FSGS. Previously the renal interstitial chip analysis of FSGS patients with tubular interstitial injury showed that the expression of TSP-1 and ITGB3 were upregulated. We found that the expression of TSP-1 and ITGB3 increased in the tubular cells of FSGS patients. The plasma level of TSP-1 increased and was correlated to the degree of tubulointerstitial lesions in FSGS patients. TSP-1/ITGB3 signaling induced renal tubular injury in HK-2 cells exposure to bovine serum albumin and the adriamycin (ADR)-induced nephropathy model. THBS1 KO ameliorated tubular injury and renal fibrosis in ADR-treated mice. THBS1 knockdown decreased the expression of KIM-1 and caspase 3 in the HK-2 cells treated with bovine serum albumin, while THBS1 overexpression could induce tubular injury. In vivo, we identified cyclo-RGDfK as an agent to block the binding of TSP-1 to ITGB3. Cyclo-RGDfK treatment could alleviate ADR-induced renal tubular injury and interstitial fibrosis in mice. Moreover, TSP-1 and ITGB3 were colocalized in tubular cells of FSGS patients and ADR-treated mice. Taken together, our data showed that TSP-1/ITGB3 signaling contributed to the development of renal tubulointerstitial injury in FSGS, potentially identifying a new therapeutic target for FSGS.
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OBJECTIVE: To analyze the serum metabolic targets of the "Zhibian (BL54) through Shuidao (ST28)" acupuncture technique in cyclophosphamide (CTX)-induced premature ovarian insufficiency (POI) model rats and to elucidate the potential molecular mechanism of acupuncture in improving POI. METHODS: We used an intraperitoneal injection of CTX to establish the POI rat model (POI group) and compared serum hormone levels and ovarian histopathological changes to evaluate the effect of the Zhibian (BL54) through Shuidao (ST28) technique (ZS + POI group) on ovarian function. Then, nontargeted metabolomics was performed using rat serum by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). RESULTS: After acupuncture intervention, the serum hormone levels and ovarian pathological morphology of POI rats were effectively improved. Moreover, UPLC-Q-TOF/MS results showed that the ZS + POI group showed a significant reversal of the levels of 6 differential metabolites. Among them, the levels of four serum metabolic markers, divanillyltetrahydrofuran ferulate, trans-ferulic acid, tryptamine, and neuraminic acid, increased significantly. Further analysis of biological effects showed that all metabolites were involved in the regulation of reproductive hormone levels and antioxidant and antiapoptotic effects. CONCLUSIONS: The "Zhibian (BL54) through Shuidao (ST28)" acupuncture method may improve the ovarian function of POI rats by regulating serum metabolite markers to exert antioxidant and antiapoptotic effects, which provides a theoretical basis for the clinical application of acupuncture in the treatment of POI.
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Terapia por Acupuntura , Metabolómica , Insuficiencia Ovárica Primaria , Animales , Insuficiencia Ovárica Primaria/terapia , Insuficiencia Ovárica Primaria/sangre , Insuficiencia Ovárica Primaria/metabolismo , Femenino , Ratas , Humanos , Ratas Sprague-Dawley , Puntos de Acupuntura , Ovario/metabolismo , Modelos Animales de EnfermedadRESUMEN
BACKGROUND AND STUDY AIMS: Adherent invasive Escherichia coli (AIEC) are enriched in IBD (inflammatory bowel disease) patients, but the role and mechanism of AIEC in the intestinal epithelial barrier is poorly defined. We evaluated the role of the AIEC strain E. coli LF82 in vitro and investigated the role of Th17 in this process. MATERIAL AND METHODS: After coincubation with AIEC, the epithelial barrier integrity was monitored by epithelial resistance measurements. The permeability of the barrier was evaluated by TEER (trans-epithelial electrical resistance) and mucosal-to-serosal flux rate. The presence of interepithelial tight junction proteins ZO-1 and Claudin-1 were determined by immunofluorescence and western blot analysis. Cytokines in the cell culture supernatant were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: AIEC infection decreased TEER and increased the mucosal-to-serosal flux rate of Lucifer yellow in the intestinal barrier model in a time- and dose-dependent manner. AIEC infection decreased the expression and changed the distribution of ZO-1 and claudin-1. It also induced the secretion of cytokines such as TNF-α and IL-17. CONCLUSION: AIEC strain E. coli LF82 increased the permeability and disrupted the tight junctions of the intestinal epithelial barrier, revealing that AIEC plays an aggravative role in the inflammatory response.
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Objective: The aim of the study was to explore the factors influencing the availability of medications for children, and establish a machine learning model to provide an empirical basis for the subsequent formulation and improvement of relevant policies. Methods: Design: Cross-sectional survey. Setting: 12 provinces, China. Medical doctors from 25 public hospitals were enrolled. All data were randomly divided into a training set and a validation set at a ratio of 7:3. Three prediction models, namely random forest (RF), logistic regression (LR), and extreme gradient boosting (XGBoost), were developed and compared. The receiver operating characteristic curve (ROC) and the associated area under the curve (AUC) were used to evaluate the three models. A nomogram and clinical impact curve (CIC) for availability of medication were developed. Results: Fifteen of 29 factors in the database that were most likely to be selected were considered to establish the prediction model. The XGBoost model (AUC = 0.915) demonstrated better performance than the RF model (AUC = 0.902) and the LR model (AUC = 0.890). According to the Shapley additive explanation values, the five factors that most significantly affected the availability of medications for children in the XGboost model were as follows: the relatively small number of specialized dosage forms for children; unaffordable medications for children; public education on the accessibility and safety of medication for children; uneven distribution of medical resources, leading to insufficient access to medication for children; and years of service as a doctor. The CIC was used to assess the practical applicability of the factor prediction nomogram. Conclusions: The XGBoost model can be used to establish a prediction model to screen the factors associated with the availability of medications for children. The most important contributing factors to the models were the following: the relatively small number of specialized dosage forms for children; unaffordable medications for children; public education on the accessibility and safety of medication for children; uneven distribution of medical resources, leading to insufficient access to medication for children; and years of service as a doctor.
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BACKGROUND: Although clear cell sarcoma of kidney (CCSK) is rare, it is the second most common renal tumor in children after Wilms' tumor. NWTS and SIOP are two major groups which had made tremendous efforts on renal tumors, but the strategies are different, for NWTS follows the upfront surgery principle providing definite pathology and the SIOP follows the upfront chemotherapy principle, each has its own advantages. Here we aimed to evaluate the outcomes of CCSK in China following NWTS strategies to analyze the prognostic factors. METHODS: For this multicenter retrospective study, a total of 54 patients were enrolled from three children's hospitals, between April 2003 and December 2021. Treatment comprised upfront radical nephrectomy, followed by radiotherapy and intensive chemotherapy. Clinical records were regularly updated. Prognostic factors and survival rates were evaluated. RESULTS: The 54 enrolled patients had a median age of 37 months (range, 4 months to 11.4 years). The stage distribution was 16% stage I (n = 9), 30% stage II (n = 16), 39% stage III (n = 21), and 15% stage IV (n = 8). Among stage IV, metastasis sites included the lung (n = 6), bone (n = 1), and intra-orbital/cervical lymph node (n = 1). After a median follow-up of 5.6 years, the 5-year event-free survival (EFS) was 82.4±5.4%, and overall survival was 88.1±4.6%. The EFS was 100% for stage I, 93.8 ±6.1% for stage II, 71.1±10.0% for stage III, and 68.6±18.6% for stage IV. Univariate analysis revealed that staging (III/IV), tumor rupture, and inferior vena cava tumor thrombus were inferior prognostic factors. Multivariate analysis revealed that tumor rupture was independent poor prognostic factor (P = 0.01, HR 5.9). Among relapsed patients, relapse occurred a median of 11 months after diagnosis (range, 4-41 months), and 50% (4/8) achieved a second complete remission after multiple treatment. None of the six lung metastasis patients received lung RT, only one patient developed a relapse and was salvaged by RT after relapse. CONCLUSIONS: Tumor rupture was independent poor prognostic factor. Upfront surgery of NWTS strategies can make a definite pathology diagnosis, but how to reduce tumor rupture during surgery is important especially in developing countries. The outcomes of patients with stage I-III CCSK in China were comparable to findings in other developed countries. Better outcomes were achieved in stage IV CCSK by using an intensive chemotherapy regimen including carboplatin, which require further confirmation by AREN0321. Lung RT may be safely omitted in selected patients who achieve a compete radiographic response after 6 weeks of systemic treatment (including surgery). Treatment should be encouraged even in CCSK cases with metastasis and relapse.
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Neoplasias Renales , Nefrectomía , Sarcoma de Células Claras , Humanos , Sarcoma de Células Claras/patología , Sarcoma de Células Claras/terapia , Masculino , Femenino , Niño , Neoplasias Renales/patología , Neoplasias Renales/terapia , Preescolar , China/epidemiología , Lactante , Estudios Retrospectivos , Pronóstico , Resultado del Tratamiento , Tasa de Supervivencia , Estadificación de Neoplasias , Terapia CombinadaRESUMEN
Oxidative stress (OS) plays an important role in the emergence and prevention of neurodegenerative diseases, such as Alzheimer's disease (AD). Excess reactive oxygen species (ROS) accumulated in a neuronal cell can lead to OS, producing cell injury and death. Seeking nanoantioxidants against AD-related oxidative stress has attracted a lot of attention, especially those potential antioxidant agents derived from natural polyphenols. However, the transformation of abundant plant polyphenols to antioxidative biomaterials against OS is still challenging. In this work, we report a new method to transform amorphous tannic acid (TA) into tailorable shaped ellagic acid (EA) crystalline particles without using an organic solvent. EA crystalline particles were generated from TA, which underwent a chemical transformation, in situ metal phenolic coordination and acid-induced assembly process, and the size and shape could be controlled by varying the amount of acid. As-prepared EA crystalline particles showed excellent stability in water and lysosomal mimicking fluid and possess unique fluorescence properties and a strong response in mass spectrometry, which is beneficial for their imaging analysis in cells and tissues. More importantly, EA particles have shown significant H2O2-related ROS scavenging ability, a high cellular uptake capacity, an excellent neuroprotective effect in PC12 cells, a high drug loading capacity and BBB permeability to enter the brain. Our study suggested that the EA crystalline particles show great potential for OS-mediated AD treatment.
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Ácido Elágico , Fármacos Neuroprotectores , Estrés Oxidativo , Especies Reactivas de Oxígeno , Taninos , Ácido Elágico/farmacología , Ácido Elágico/química , Taninos/farmacología , Taninos/química , Estrés Oxidativo/efectos de los fármacos , Células PC12 , Animales , Ratas , Especies Reactivas de Oxígeno/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/síntesis química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Peróxido de Hidrógeno/farmacología , Peróxido de Hidrógeno/química , Neuroprotección/efectos de los fármacos , Tecnología Química Verde , PolifenolesRESUMEN
Inflammatory cytokines, interleukin-36 (IL-36), IL-37, IL-38 belong to IL-1 family. The IL-36 subfamily obtains pro- and anti-inflammatory effects on various immune responses. Cytokine IL-37, has anti-inflammatory functions in immunity, and the recently identified IL-38 negatively associated with disease pathogenesis. To date, expression of IL-36, IL-37, IL-38 is reported dysregulated in osteoarthritis (OA) and rheumatoid arthritis (RA), and may be disease markers for arthritis-related diseases. Interestingly, expression of IL-38 was different either in OA patients or animal models, and expression of IL-36Ra in synovium was different in OA and RA patients. Moreover, functional studies have demonstrated significant role of these cytokines in OA and RA progress. These processes were related to immune cells and non-immune cells, where the cytokines IL-36, IL-37, IL-38 may regulate downstream signalings in the cells, and then involve in OA, RA development. In this review, we comprehensively discuss recent advancements in cytokines and the development of OA, RA. We hope that targeting these cytokines will become a potential treatment option for OA and RA in the future.
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Owing to the rising demand for vegetable soybean products, there is an increasing need for high-yield soybean varieties. However, the complex correlation patterns among quantitative traits with genetic architecture pose a challenge for improving vegetable soybean through breeding. Herein, a genome-wide association study (GWAS) was applied to 6 yield-related traits in 188 vegetable soybean accessions. Using a BLINK model, a total of 116 single nucleotide polymorphisms (SNPs) were identified for plant height, pod length, pod number, pod thickness, pod width, and fresh pod weight. Furthermore, a total of 220 genes were found in the 200 kb upstream and downstream regions of significant SNPs, including 11 genes encoding functional proteins. Among them, four candidate genes, Glyma.13G109100, Glyma.03G183200, Glyma.09G102200, and Glyma.09G102300 were analyzed for significant haplotype variations and to be in LD block, which encode MYB-related transcription factor, auxin-responsive protein, F-box protein, and CYP450, respectively. The relative expression of candidate genes in V030 and V071 vegetable soybean (for the plant height, pod number, and fresh pod weight of V030 were lower than those of the V071 strains) was significantly different, and these genes could be involved in plant growth and development via various pathways. Altogether, we identified four candidate genes for pod yield and plant height from vegetable soybean germplasm. This study provides insights into the genomic basis for improving soybean and crucial genomic resources that can facilitate genome-assisted high-yielding vegetable soybean breeding.
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Porous organic polymers (POPs) are a class of materials composed of organic building blocks usually consisting of the elements C, H, O, N, and B and other light elements connected by covalent bonds. Owing to the diversity of synthesis methods in organic chemistry, POPs can be prepared by Suzuki coupling, Sonogashira-Hagihara cross-coupling, Schiff-base condensation, Knoevenagel condensation, and Friedel-Crafts alkylation. POPs show great application potential in the field of sample pretreatment because of their large specific surface area, adjustable pore size, high tailorability, and easy modification. The design of new functional building blocks is an important factor in advancing the development of POPs and is key to the efficient separation and enrichment of target molecules in complex substrates. In recent years, supramolecular-derived compounds have provided new inspiration and breakthroughs in the construction of POPs on account of their excellent host-guest recognition properties, simple functionalization strategies, and adjustable topological configurations. The "cavitand-to-framework" approach, that is, the knitting of 0D macrocycles into hierarchical 2D or 3D POPs using suitable linkers, and extension of the research scope of supramolecular chemistry from discrete cavities to rigidly layered porous organic frameworks can lead to significant improvements in the porosity and stability of supramolecular-derived compounds. They can also provide an effective means to expand the structural diversity of POPs and generate layered structures with high porosity. This review summarizes the preparation strategies and structural characteristics of supramolecular-derived POPs with different structures, such as crown ether-based POPs, cyclodextrin-based POPs, and calixarene-based POPs. The promising applications of these materials in sample pretreatment focusing on food analysis and environmental monitoring, including epoxides, organic dyes, heavy metals, algatoxins, halogens, and antibiotic drugs, are then summarized. Next, the extraction mechanisms mainly attributed to host-guest recognition, π-π stacking, and hydrogen-bonding and electrostatic interactions between the supramolecular structures and analytes are described. The key role and potential advantages of the different preparation strategies and structural characteristics of these POPs in sample pretreatment are also discussed. Finally, the future prospects and remaining challenges of supramolecular-derived POPs are proposed. Supramolecular-derived POPs can not only achieve the rapid and selective extraction of target analytes during sample pretreatment but also improve the extraction effect of online solid phase extraction technologies. However, although numerous supramolecular-derived POPs have been developed, few have been applied in the field of sample pretreatment. Thus, the expansion of the application potential of more POP materials requires further exploration and research. The design and synthesis of supramolecular-derived POPs with highly selective recognition performance remains an important research direction in the field of sample pretreatment.
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Severe immunosuppression is a hallmark of colorectal cancer (CRC). Myeloid-derived suppressor cells (MDSCs), one of the most abundant components of the tumor stroma, play an important role in the invasion, metastasis, and immune escape of CRC. MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells, including T and natural killer cells, as well as by inducing the proliferation of immunosuppressive cells, such as regulatory T cells and tumor-associated macrophages, which, in turn, promote the growth of cancer cells. Thus, MDSCs are key contributors to the emergence of an immunosuppressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity. In this narrative review, we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment, the current therapeutic approaches and technologies targeting MDSCs, and the therapeutic potential of modulating MDSCs in CRC treatment. This study provides ideas and methods to enhance survival rates in patients with CRC.
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A novel fibrinolytic enzyme was produced by the liquid fermentation of Coprinus comatus. The enzyme was purified from the culture supernatant by hydrophobic interactions, gel filtration, and ion exchange chromatographies. It was purified by 241.02-fold, with a specific activity of 3619 U/mg and a final yield of 10.02%. SDS-PAGE analysis confirmed the purity of the enzyme, showing a single band with a molecular weight of 19.5 kDa. The first nine amino acids of the N-terminal of the purified enzyme were A-T-Y-T-G-G-S-Q-T. The enzyme exhibited optimal activity at a temperature of 42 °C and pH 7.6. Its activity was significantly improved by Zn2+, K+, Ca2+, Mn2+, and Mg2+ while being inhibited by Fe2+, Fe3+, Al2+, and Ba2+. The activity of the enzyme was completely inhibited by ethylenediamine tetraacetic acid (EDTA), and it was also dose-dependently inhibited by phenylmethylsulfonyl fluoride (PMSF) and soy trypsin inhibitor (SBTI). However, inhibitors such as N-α-tosyl-L-phenylalanine chloromethyl ketone (TPCK), aprotinin, and pepstatin did not significantly affect its activity, suggesting that the enzyme was a serine-like metalloproteinase. The enzyme acted as both a plasmin-like fibrinolytic enzyme and a plasminogen activator, and it also exhibited the capability to hydrolyze fibrinogen and fibrin. In vitro, it demonstrated the ability to dissolve blood clots and exhibit anticoagulant properties. Furthermore, it was found that the enzyme prolonged activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT), and reduced the levels of fibrinogen (FIB) and prothrombin activity (PA). Based on these studies, the enzyme has great potential to be developed as a natural agent for the prevention and treatment of thrombotic diseases.
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Compared to filiform needle therapy, fire-needle therapy has both the stimulation of needles and the warming effect of heat, making it have unexpected effects on some chronic diseases and incurable diseases. Osteoporosis (OP) has a high incidence in postmenopausal women and middle-aged and elderly men, and the treatment cycle is long. According to Traditional Chinese Medicine (TCM), Lingnan fire-needle therapy has shown potential in treating osteoporosis. However, there is still a long way to go before it can be widely used. This article focuses on the application of Lingnan fire-needle therapy in the intervention of OP in rats. It covers the selection of needle tools, acupuncture point selection, positioning of rats' bodies, and fixation methods. We also outline the steps and precautions to be taken during and after needling with fire needles. The experiment was done with three groups: a normal group, a model group, and a fire-needle group, each containing 10 rats. The rats in the fire-needle group were treated with fire-needle intervention for six sessions. After the intervention period, we collected femoral specimens and performed micro-CT scans. The results suggest that fire needling can enhance bone morphology and mineral density in OP rats. This information can serve as a methodological basis for conducting basic research on fire-needle therapy.
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Terapia por Acupuntura , Modelos Animales de Enfermedad , Osteoporosis , Animales , Ratas , Osteoporosis/terapia , Femenino , Terapia por Acupuntura/métodos , Terapia por Acupuntura/instrumentación , Ratas Sprague-Dawley , Agujas , Medicina Tradicional China/métodos , MasculinoRESUMEN
Destructive periodontitis destroys alveolar bone and eventually leads to tooth loss. While guided bone regeneration, which is based on creating a physical barrier to hinder the infiltration of epithelial and connective tissues into defect sites, has been widely used for alveolar bone regeneration, its outcomes remain variable. In this work, a multifunctional nanofibrous hollow microsphere (NFHMS) is developed for enhanced alveolar bone regeneration. The NFHMS is first prepared via combining a double emulsification and a thermally induced phase separation process. Next, E7, a short peptide with high specific affinity to bone marrow-derived stem cells (BMSCs), is conjugated onto the surface of NFHMS. After that, bone forming peptide (BFP), a short peptide derived from bone morphology protein 7 is loaded in calcium phosphate (CaP) nanoparticles, which are further encapsulated in the hollow space of the NFHMS-E7 to form NFHMS-E7-CaP/BFP. The NFHMS-E7-CaP/BFP selectively promoted the adhesion of BMSCs and expelled the adhesion of fibroblasts and epithelial cells. In addition, the BFP is sustainedly released from the NFHMS-E7-CaP/BFP to enhance the osteogenesis of BMSCs. A rat challenging fenestration defect model showed that the NFHMS-E7-CaP/BFP significantly enhanced alveolar bone tissue regeneration. This work provides a novel bioengineering approach for guided bone regeneration.
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Regeneración Ósea , Microesferas , Nanofibras , Animales , Regeneración Ósea/fisiología , Regeneración Ósea/efectos de los fármacos , Ratas , Nanofibras/química , Osteogénesis/fisiología , Osteogénesis/efectos de los fármacos , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Fosfatos de Calcio/química , MasculinoRESUMEN
ß-Galactosidase (ß-Gala) is an essential biomarker enzyme for early detection of breast tumors and cellular senescence. Creating an accurate way to monitor ß-Gala activity is critical for biological research and early cancer detection. This work used fluorometric, colorimetric, and paper-based color sensing approaches to determine ß-Gala activity effectively. Via the sensing performance, the catalytic activity of ß-Gala resulted in silicon nanoparticles (SiNPs), fluorescent indicators obtained via a one-pot hydrothermal process. As a standard enzymatic hydrolysis product of the substrate, kaempferol 3-O-ß-d-galactopyranoside (KOßDG) caused the fluorometric signal to be attenuated on kaempferol-silicon nanoparticles (K-SiNPs). The sensing methods demonstrated a satisfactory linear response in sensing ß-Gala and a low detection limit. The findings showed the low limit of detection (LOD) as 0.00057 and 0.098 U/mL for fluorometric and colorimetric, respectively. The designed probe was then used to evaluate the catalytic activity of ß-Gala in yogurt and human serum, with recoveries ranging from 98.33 to 107.9%. The designed sensing approach was also applied to biological sample analysis. In contrast, breast cancer cells (MCF-7) were used as a model to test the in vitro toxicity and molecular fluorescence imaging potential of K-SiNPs. Hence, our fluorescent K-SiNPs can be used in the clinic to diagnose breast cellular carcinoma, since they can accurately measure the presence of invasive ductal carcinoma in serologic tests.