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Drip fertigation (DF) is a widely used technology to increase grain yield with water and fertilizer conservation. However, the mechanism of high grain yield (GY) under DF is still unclear. Here, a four-year field experiment assessed the impacts of four treatments (i.e., conventional irrigation and nitrogen application, CK; drip irrigation with conventional nitrogen fertilization, DI; split-nitrogen fertigation with conventional irrigation, SF; and drip fertigation, DF) on maize phenology, leaf photosynthetic rates, grain filling processes, plant biomass, and GY. The results showed that DF significantly increased maize GY by affecting phenology, grain filling traits, aboveground biomass (BIO) accumulation, and translocation. Specifically, DF significantly increased leaf chlorophyll content, which enhanced leaf photosynthetic rates, and together with an increase of leaf area index, promoted BIO accumulation. As a result, the BIO at the silking stage of DF increased by 29.5%, transported biomass increased by 109.2% (1.2 t ha-1), and the accumulation of BIO after silking increased by 23.1% (1.7 t ha-1) compared with CK. Meanwhile, DF prolonged grain filling days, significantly increased the grain weight of 100 kernels, and promoted GY increase. Compared with CK, the four-year averaged GY and BIO increased by 34.3% and 26.8% under DF; a 29.7%, 46.1%, and 24.2% GY increase and a 30.7%, 39.5%, and 29.9% BIO increase were contributed by irrigation, nitrogen, and coupling effects of irrigation and nitrogen, respectively. These results reveal the high yield mechanism of drip-fertigated maize, and are of important significance for promoting the application of drip fertigation.
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Prussian blue (PB) is authenticated in clinical treatment, while it generally exhibits unfavorable chemodynamic therapy (CDT) performance. Herein, we developed manganese-doped prussian blue (PBM) nanoparticles to significantly enhance both CDT and photothermal therapy (PTT) effect. The lower redox potential of Mn3+/2+ (0.088â¯V) in PBM against that of Fe2+/3+ (0.192â¯V) in PB leads to favorable electron transfer of PBM with respect to PB. Besides, PBM has a lower charge-transfer resistance (Rct) of 2.98 Ω than 4.83 Ω of PB. Once PBM entering the tumor microenvironment (TME), Mn3+ may be readily reduced by glutathione (GSH) and therein to enhance intracellular oxidative stress. Meanwhile, the superoxide dismutase (SOD)-like activity of PBM facilitates the conversion of endogenous superoxide (O2â¢-) into H2O2. Mn2+ subsequently catalyzes H2O2 to generate toxic hydroxyl radicals (â¢OH). Notably, the PBM plus laser irradiation can effectively trigger a robust immunogenic cell death (ICD) due to the combination therapy of CDT and PTT. Additionally, the mice treated by PBM followed by laser irradiation efficiently avoided splenomegaly and lung metastasis, along with significant up-regulation of the Stimulator of Interferon Genes (STING) expression. Overall, PBM significantly inhibits tumor growth and metastasis, making it a promising multifunctional nanoplatform for cancer treatment.
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Ferrocianuros , Manganeso , Nanopartículas , Terapia Fototérmica , Ferrocianuros/química , Ferrocianuros/farmacología , Manganeso/química , Manganeso/farmacología , Animales , Ratones , Humanos , Nanopartículas/química , Electrodos , Ratones Endogámicos BALB C , Terapia Combinada , Tamaño de la Partícula , Línea Celular Tumoral , Microambiente Tumoral/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Propiedades de Superficie , Estrés Oxidativo/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/químicaRESUMEN
1,2-Difunctionalization of alkynes offers a straightforward approach to access polysubstituted alkenes. However, simultaneous multi-component cascade transformations including difunctionalization of two alkynes with both syn- and anti-selectivity in one catalyst system is undeveloped and proves to be a significant challenge. Herein, we report a Nickel-catalyzed four-component reaction to access polysubstituted 1,3-dienes using two terminal alkynes, aryl boroxines, and perfluoroalkyl iodides, wherein the reaction forms three new C-C bonds in a single vessel and serve as a modular strategy to access polysubstituted 1,3-dienes with excellent chemoselectivity, good regioselectivity and exclusive stereoselectivity. Control experiments reveal the plausible reaction mechanism and DFT calculations explain the cause for the formation of this unusual four-component reaction. Furthermore, we successfully incorporate two biologically active units into 1,2,3,4-tetrasubstituted 1,3-dienes, which greatly increases the diversity of molecular scaffolds and brings more potential values to medicinal chemistry, the synthetic utility of our protocol is further demonstrated by the late-stage transformations.
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Objective: This study aimed to determine the associated risk factors for proximal deep vein thrombosis (DVT) in patients with lower extremity and pelvic-acetabular fractures. Methods: The medical records of 4,056 patients with lower extremity and pelvic-acetabular fractures were retrospectively reviewed. The patients were classified into proximal or non-proximal DVT groups. Logistic regression models were used to determine the independent risk variables for proximal DVT. The predictive value of the related risk factors was further analyzed using receiver operating characteristic curves. Results: The prevalence of proximal DVT was 3.16%. Sex, body mass index (BMI), fracture site, injury mechanism, diabetes, coronary heart disease (CHD), injury-to-admission interval, hematocrit, platelet counts, and D-dimer levels differed significantly between the two groups. BMI ≥ 24.0â kg/m2, femoral shaft fractures, high-energy injury, diabetes, injury-to-admission interval >24â h were independent risk factors for proximal DVT. CHD decreased the risk of proximal DVT. The platelet and D-dimer had high negative predictive value for predicting proximal DVT formation, with cut-off values of 174 × 109/L and 2.18â mg/L, respectively. Conclusion: BMI ≥ 24.0â kg/m2, femoral shaft fractures, high-energy injury, diabetes, injury-to-admission interval >24â h were independent risk factors for proximal DVT in patients with lower extremity and pelvic-acetabular fractures. Platelet count and D-dimer level were effective indicators for excluding proximal DVT occurrence. CHD decreased the risk of proximal DVT.
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The π-bond enrichment frameworks not only serve as a crucial building block in organic synthesis but also assume a pivotal role in the fields of materials science, biomedicine, photochemistry, and other related disciplines owing to their distinctive structural characteristics. The incorporation of various substituents into the CâC double bonds of tetrasubstituted alkenes is currently a highly significant research area. However, the synthesis of tetrasubstituted alkenes with diverse substituents on double bonds poses a significant challenge in achieving stereoselectivity. Here, we reported an efficient and convergent route of Cu-catalyzed borylalkynylation of both symmetrical and unsymmetrical 1,3-diynes, B2pin2, and acetylene bromide to the construction of boronated phenyldiethynylethylene (BPDEE) derivatives with excellent chemo-, stereo-, and regioselectivities. BPDEE derivatives could transform into novel tetrasubstituted organic π-conjugated gem-diphenyldiethynylethylene (DPDEE), vinylphenyldiethynylethylene (VPDEE), and phenyltriethynylethylene (PTEE) derivatives by a stepwise process, which provides a flexible platform for the synthesis of complex π-bond enrichment frameworks that were difficult to synthesize by previous methods. The initial optical characterization revealed that the synthesized molecules exhibited aggregation-induced emission (AIE) properties, which further establishes the groundwork for future applications and enriches and advances the field of functional π-conjugated frameworks research.
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Single-view cone-beam X-ray luminescence computed tomography (CB-XLCT) has recently gained attention as a highly promising imaging technique that allows for the efficient and rapid three-dimensional visualization of nanophosphor (NP) distributions in small animals. However, the reconstruction performance is hindered by the ill-posed nature of the inverse problem and the effects of depth variation as only a single view is acquired. To tackle this issue, we present a methodology that integrates an automated restarting strategy with depth compensation to achieve reconstruction. The present study employs a fast proximal gradient descent (FPGD) method, incorporating L0 norm regularization, to achieve efficient reconstruction with accelerated convergence. The proposed approach offers the benefit of retrieving neighboring multitarget distributions without the need for CT priors. Additionally, the automated restarting strategy ensures reliable reconstructions without the need for manual intervention. Numerical simulations and physical phantom experiments were conducted using a custom CB-XLCT system to demonstrate the accuracy of the proposed method in resolving adjacent NPs. The results showed that this method had the lowest relative error compared to other few-view techniques. This study signifies a significant progression in the development of practical single-view CB-XLCT for high-resolution 3-D biomedical imaging.
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The pandemic of coronavirus disease 2019 (COVID-19) has been the foremost modern global public health challenge. The airway is the primary target in severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) infection, with substantial cell death and lung injury being signature hallmarks of exposure. The viral factors that contribute to cell death and lung injury remain incompletely understood. Thus, this study investigated the role of open reading frame 7b (Orf7b), an accessory protein of the virus, in causing lung injury. In screening viral proteins, we identified Orf7b as one of the major viral factors that mediates lung epithelial cell death. Overexpression of Orf7b leads to apoptosis and ferroptosis in lung epithelial cells, and inhibitors of apoptosis and ferroptosis ablate Orf7b-induced cell death. Orf7b upregulates the transcription regulator, c-Myc, which is integral in the activation of lung cell death pathways. Depletion of c-Myc alleviates both apoptotic and ferroptotic cell deaths and lung injury in mouse models. Our study suggests a major role of Orf7b in the cell death and lung injury attributable to COVID-19 exposure, supporting it as a potential therapeutic target.
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COVID-19 , Ferroptosis , Lesión Pulmonar , Proteínas Virales , Animales , Ratones , Apoptosis , Lesión Pulmonar/virología , Sistemas de Lectura Abierta , SARS-CoV-2 , Proteínas Virales/genéticaRESUMEN
BACKGROUND: Primary membranous nephropathy (PMN) is the most common pathological type of nephrotic syndrome in adults. Intrarenal small artery intimal thickening can be observed in most renal biopsies. The purpose of this study was to investigate the association between intrarenal small artery intimal thickening and clinicopathological features and prognosis in PMN patients. METHODS: Data were continuously collected from patients who were diagnosed with PMN in Shenzhen Second People's Hospital (The First Affiliated Hospital of Shenzhen University) from 2008 to 2021 for a retrospective cohort study. Regression analysis and survival analysis were used to analyze the relationship between intrarenal small artery intimal thickening and renal prognosis in PMN patients. RESULTS: 300 PMN patients were enrolled in this study, including 165 patients (55%) with intrarenal small artery intimal thickening. Patients with intimal thickening were older, with higher BMI, systolic blood pressure and diastolic blood pressure, serum uric acid, a higher proportion of hypertension, acute kidney injury, nephrotic syndrome, more urine protein, and lower eGFR. Multivariate Cox regression analysis showed that after adjusting for age, gender, hypertension, BMI, urine protein, eGFR, and the use of ACEI/ARB and hormone immunosuppressants, intimal thickening was a risk factor for renal prognosis in PMN patients (HR = 3.68, 95% CI 1.36-9.96, p < 0.05). Kaplan-Meier survival curve analysis showed that the incidence of reaching the renal composite outcome was higher in the intimal thickening group (p < 0.05). CONCLUSION: The prognosis of PMN patients with intrarenal small artery intimal thickening is worse, so early intervention is very important for these patients.
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Glomerulonefritis Membranosa , Hipertensión , Síndrome Nefrótico , Adulto , Humanos , Estudios Retrospectivos , Antagonistas de Receptores de Angiotensina , Ácido Úrico , Inhibidores de la Enzima Convertidora de Angiotensina , Arterias , PronósticoRESUMEN
Objectives: To explore the risk factors associated with postoperative hypoxaemia in elderly patients who have recovered from coronavirus disease (COVID-19) and underwent hip fracture surgery in the short term. Design: Multicentre retrospective study. Setting: The study was performed in three first 3A-grade hospitals in China. Participants: A sequential sampling method was applied to select study participants. Medical records of 392 patients aged ≥65 years who had recovered from COVID-19 and underwent hip fracture surgery at three hospitals in China between 1 November, 2022, and 15 February, 2023, were reviewed. Interventions: Patients were assigned to hypoxaemia or non-hypoxaemia groups, according to whether hypoxaemia occurred after surgery. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for postoperative hypoxaemia. Results: The incidence of postoperative hypoxaemia was 38.01%. Statistically significant differences were found between the two groups in terms of age, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, presence of expectoration symptoms, preoperative hypoxaemia, chronic obstructive pulmonary disease, pulmonary inflammation, time between recovery from COVID-19 and surgery, anaesthetic mode, surgical procedure, intraoperative blood loss, intraoperative infusion, duration of surgery, and length of hospital stay (p < 0.05). Furthermore, patients with BMI ≥28.0 kg/m2, expectoration symptoms, presence of preoperative hypoxaemia, ASA classification III, time between recovery from COVID-19 and surgery ≤2 weeks, and general anaesthesia were potential risk factors for postoperative hypoxaemia. Conclusion: Obesity, expectoration symptoms, preoperative hypoxaemia, ASA classification III, time between recovery from COVID-19 and surgery ≤2 weeks, and general anaesthesia were potential risk factors for postoperative hypoxaemia in elderly patients who recovered from COVID-19 and underwent hip fracture surgery in the short term.
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To identify risk factors of admission deep vein thrombosis (DVT) in patients with traumatic fractures. Medical records of 1596 patients with traumatic fractures were reviewed. According to the ultrasound reports of the lower extremity veins, patients were assigned to the DVT or non-DVT group. Univariate and multivariate logistic regression analyses were used to identify the independent risk factors of DVT, and the receiver operating characteristic (ROC) curve was used to analyze the predictive value of the D-dimer level for DVT. DVT admission incidence was 20.67%. Statistically significant differences were revealed between the 2 groups in terms of age, sex, fracture site, presence of hypertension, coronary heart disease, stroke, smoking status, time from injury to admission, and levels of fasting blood glucose, hemoglobin, fibrinogen, D-dimer, and hematocrit. Multivariate analysis results showed that age above 50 years, female, above-knee fracture, cigarette smoking, injury-to-admission delay beyond 48â h, low hemoglobin levels, high fasting blood glucose levels, and high D-dimer levels were independent risk factors for admission DVT. ROC analysis showed that the D-dimer level was effective for the prediction of admission DVT in patients with peri-knee and below-knee fractures (area under the curve [AUC] = 0.7296, cutoff point = 1.21â mg/L). An age over 50 years, female, above-knee fracture, smoking, injury-to-admission delay beyond 48â h, decreased hemoglobin level, and increased fasting blood glucose and D-dimer levels were found to be potential independent risk factors for admission DVT. In patients with peri-knee and below-knee fractures, the plasma D-dimer level was effective in predicting admission DVT.
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Fracturas Óseas , Trombosis de la Vena , Humanos , Femenino , Persona de Mediana Edad , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Estudios Retrospectivos , Incidencia , Glucemia , Fracturas Óseas/complicaciones , Fracturas Óseas/epidemiología , Factores de Riesgo , Productos de Degradación de Fibrina-Fibrinógeno/análisisRESUMEN
With the advantages of low cost, high safety, and environmental friendliness, quasi-solid-state zinc-ion microbatteries (ZIMBs) have received widespread attention in the field of flexible wearable devices and on-chip integratable energy storage. However, hysteresis Zn-ion transport kinetics and inhomogeneous growth of the zinc anode result in the poor capacity reversibility and cycling stability. Herein, a quasi-solid-state planar zinc-ion cell was developed by employing a vertical graphene (VG) film as an effective conductive modification layer for both the cathode and anode. The VG distinctly induces uniform Zn deposition/stripping, accelerates the charge transport, and enhances the adhesion between the active materials and current collectors. As a result, planar Zn@VG//MnO2@VG exhibits a high areal capacity of 159 µAh cm-2, a remarkably high areal energy/power density of 201.5 µWh cm-2/67.16 µW cm-2, and a high capacity retention of 95.6% at a bending angle of 180°. The proposed facile strategy for electrode modification provides a new insight into the design of high-performance flexible and planar ZIMBs.
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BACKGROUND AND OBJECTIVE: As an emerging dual-mode optical molecular imaging, cone-beam X-ray luminescence computed tomography (CB-XLCT) has shown potential in early tumor diagnosis and other applications with increased depth and little autofluorescence. However, due to the low transfer efficiency of PNPs to convert X-ray energy to visible or near-infrared (NIR) light and X-ray dose limitation, the signal to noise ratio of projections is quite low, making the quality of CB-XLCT relatively poor. METHODS: To improve the reconstruction quality of low-counts CB-XLCT imaging, an adaptive reconstruction algorithm (named ADFISTA-MLEM) based on the maximum likelihood expectation estimation (MLEM) framework is proposed for CB-XLCT reconstruction from Poisson distributed projections. In the proposed framework, the image reconstructed by fast iterative shrinkage-thresholding algorithm (FISTA) is used as the initial image for MLEM iterations to improve reconstruction accuracy, in which both the projection noise model and the sparsity constraint of the image could be considered. For relative quantitative imaging, a specific normalization is applied to the projection data and system matrix. To determine the hyperparameter of FISTA, which may be different for different projections, an adaptive strategy (ADFISTA) is then designed for adaptive update of the hyperparameter with reconstructed image in each iteration. RESULTS AND CONCLUSIONS: Results from numerical simulations and phantom experiments indicate that the proposed framework can obtain superior reconstruction accuracy in terms of contrast to noise ratio and shape similarity. In addition, high intensity-concentration linearity between different probe targets indicates its potential for quantitative CB-XLCT imaging.
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Procesamiento de Imagen Asistido por Computador , Luminiscencia , Rayos X , Procesamiento de Imagen Asistido por Computador/métodos , Tomografía Computarizada de Haz Cónico/métodos , Fantasmas de Imagen , AlgoritmosRESUMEN
BACKGROUND: Peri-implantitis is one of the most common complications in oral implantation and could lead to the loss of the function of bone tissues around implants. METHODS: This study used lipopolysaccharide (LPS) as a stimulant for MC3T3-E1 cells and N-acetyl cysteine (NAC) as an inhibitor to inhibit the effect of LPS to investigate the effect of NAC on the expression of bone formation related factors and inflammatory-related factors of osteoblasts under the action of LPS. RESULTS: In this study, we found that the cell proliferation and cell differentiation were significantly promoted when NAC concentrations were between 0 ~ 0.5 mM, but were inhibited when the concentration exceeded 0.5 mM. LPS had a slightly promoting effect on the cell proliferation before 20 µg/mL but inhibited the cell proliferation after 20 µg/mL. LPS reduced protein and gene expressions of Runx2, ALP and BGP and increased protein and gene expressions of NF-κB and TNF-α. NAC reversibly regulated the LPS's regulation on the expression of MC3T3-E1 cell cytokine gene and protein. CONCLUSION: The optimal NAC concentration for treating MC3T3-E1 cells is 0.5 mM, and the optimal LPS concentration for stimulating MC3T3-E1 cells is 20 µg/mL. NAC plays an active role in regulating the differentiation of MC3T3-E1 cells, and can inhibit LPS to regulate the differentiation of MC3T3-E1 cells. NAC promotes the expression of an osteogenic factor of MC3T3-E1cells and inhibits the expression of inflammatory cytokines.
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Acetilcisteína , Citocinas , Línea Celular , Acetilcisteína/farmacología , Lipopolisacáridos/farmacología , Diferenciación Celular , Osteogénesis , Proliferación CelularRESUMEN
Fluorine-containing organoboron compounds have emerged as novel building blocks in chemical synthesis; among them, fluorinated sp2/sp3 diborylated compounds are particularly appealing, since they might undergo chemoselective and diversified transformations of different C-B bonds with fluorinated functionality, thus bringing versatility and complexity to the eventual products. However, expedient, synthetic strategies for the construction of such fluorinated diborylative compounds are very sparse. Herein, we disclose enantioselective Cu-catalyzed sp2/sp3 diborylations of 1-chloro-1-trifluoromethylalkenes, leading to diborylated compounds bearing a gem-difluoroalkenyl moiety; most intriguingly, the new formed C-B bonds include one stereoselective and optically pure Csp3-B bond. Further transformations on the eventual products demonstrated the values of our presented strategy.
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The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has become a severe global public health crisis. Therefore, understanding the molecular details of SARS-CoV-2 will be critical for fighting the virus's spread and preventing future pandemics. In this study, we globally profiled the stability of SARS-CoV-2-encoded proteins, studied their degradation pathways, and determined their correlation with the antibody responses in patient plasma. We identified 18 proteins with unstable half-lives and 6 relatively stable proteins with longer half-lives. The labile SARS-CoV-2 proteins were degraded mainly by the ubiquitin-proteasome pathway. We also observed a significant correlation between antibody levels and protein half-lives, which indicated that a stable antigen of SARS-CoV-2 could be more effective for eliciting antibody responses. In addition, levels of antiviral antibodies targeting NSP10 were found to be negatively correlated with systemic levels of interleukin 6 (IL-6) in patients. These findings may facilitate the development of novel therapeutic or diagnostic approaches. IMPORTANCE SARS-CoV-2, the etiological cause of COVID-19, carries 29 genes in its genome. However, our knowledge of the viral proteins in biological and biochemical aspects is limited. In this study, we globally profiled the stability of the viral proteins in living lung epithelial cells. Importantly, the labile SARS-CoV-2-encoded proteins were mainly degraded through the ubiquitin-proteasome pathway. Stable proteins, including spike and nucleocapsid, of SARS-CoV-2 were more effective in eliciting antibody production. The levels of antiviral antibodies targeting NSP10 were negatively correlated with systemic levels of IL-6 in COVID-19 patients.
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COVID-19 , Humanos , Anticuerpos Antivirales , Antivirales/química , Interleucina-6 , Complejo de la Endopetidasa Proteasomal/genética , SARS-CoV-2/genética , Ubiquitinas , Proteínas ViralesRESUMEN
BACKGROUND: The emergence and spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) pose a threat to public health. Antimicrobial peptides provide a new treatment option for CRKP infections. OBJECTIVES: We studied antibacterial activities of WAM-1 against CRKP in vitro and in vivo and explored its possible mechanism. We verified safety and factors affecting antibacterial effect. Furthermore, anti-inflammatory effects were investigated. METHODS: We selected eight CRKP and eight carbapenem-susceptible K. pneumoniae to explore the antibacterial activity of WAM-1 by broth microdilution (BMD). The possible mechanism was investigated by alkaline phosphatase leakage and propidium iodide (PI). We evaluated safety of WAM-1 by cytotoxicity and haemolysis and effects of temperature and serum on the antibacterial activity. We investigated in vivo efficacy of WAM-1 by the Galleria mellonella infection model. We investigated the effect of WAM-1 on TNF-α. RESULTS: BMD showed that WAM-1 had a good antibacterial effect with MICs of 2-4â mg/L and MBCs of 4-8â mg/L. RT-qPCR showed that WAM-1 could inhibit the expression of TNF-α. The cytotoxicity and haemolysis test proved that WAM-1 had certain potential application in vivo. Alkaline phosphatase leakage and PI fluorescence showed that WAM-1 was highly likely to exert an antibacterial effect by destroying bacterial membrane. The G. mellonella infection model suggested that WAM-1 may have a good therapeutic effect in vivo. Temperature had little effect on the activity of WAM-1. Serum, however, reduced WAM-1 activity. CONCLUSIONS: WAM-1 has good antibacterial effect and potential anti-inflammatory effect on infection caused by CRKP.
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Antibacterianos , Antiinflamatorios , Péptidos Antimicrobianos , Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Klebsiella , Fosfatasa Alcalina , Animales , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Péptidos Antimicrobianos/farmacología , Carbapenémicos/farmacología , Farmacorresistencia Bacteriana , Hemólisis , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana , Mariposas Nocturnas , Factor de Necrosis Tumoral alfaRESUMEN
AIMS: This study aimed to explore the effect of Taohong Siwu Decoction (THSWD) on bone marrow mesenchymal stem cells (BMSCs) at the cellular level and the possible mechanism of systemic regulation of gut microbiota on fracture recovery. METHODS AND RESULTS: Cell Counting Kit-8 (CCK-8) experiments show that THSWD effectively promotes the proliferation of BMSCs. Transwell and wound healing assays show that THSWD effectively promotes the invasion and migration of BMSCs. Alizarin red staining showed that the THSWD model enhanced the osteogenic differentiation of BMSCs. Moreover, the effect of THSWD on BMSCs is time- and concentration-dependent. RT-qPCR and western blot results showed that THSWD treatment up-regulated the expression of vascular endothelial growth factor (VEGF) and focal adhesion kinase (FAK) at mRNA and protein levels, respectively. Haematoxylin-eosin and crocin O-quick green staining showed that after 14 days of THSWD treatment, the area of callus and cartilage regeneration at the fracture site increased significantly in rats with right femoral shaft fractures. Gut microbiota was changed in fractured rats, such as the abundance of Bacteroidetes and Firmicutes was increased. THSWD showed positive regulation of both to a certain extent. CONCLUSION: THSWD up-regulates VEGF and activates the FAK signalling pathway to enhance the development and differentiation of BMSCs, and systematically regulates the gut microbiota to promote fracture healing. SIGNIFICANCE AND IMPACT OF STUDY: This study provides new insights on the cellular and systemic level to understand the mechanism of THSWD in the treatment of fractures.
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Curación de Fractura , Microbioma Gastrointestinal , Animales , Diferenciación Celular , Medicamentos Herbarios Chinos , Proteína-Tirosina Quinasas de Adhesión Focal , Osteogénesis , Ratas , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/farmacologíaRESUMEN
OBJECTIVE: To observe the effects of Taohong Siwu Decoction(, THSWD) on the mesenchymal stem cells(MSCs) migration, homing number and cytokine expression in callus during the early process of fracture healing, and to explore the mechanism of THSWD on accelerationg fracture healing by regulating the homing of MSCs in rats. METHODS: A rat model of right femoral shaft open fracture was established. Thirty-two 5-week-old male Sprague-Dawley rats, weighting 110 to 130 g, were divided into control group, low-dose group, medium-dose group and high-dose group by using random number table. Distilled water was given to the control group, and the other groups were given Taohong Siwu Decoction. The rats were gavaged twice a day for 5 consecutive days after surgery. Bone volume/tissue volume(BV/TV) and bone mineral density(BMD) were observed using micro-computed tomography (micro-CT) at 21 days after surgery. At 5 days post-fracture, peripheral blood MSCs from THSWD treated and untreated rats were cultured in vitro. Subsequently, the migration ability of MSCs was observed by cell migration assay. The number of MSCs homing to the callus at the early stage of fracture (5 d) was detected by Immunohistochemistry (IHC). Protein chip was used to detect the expression of cytokines in callus. RESULTS: Micro-CT results showed that BV/TV was higher in the high-dose group than in the medium-dose group (P=0.032), and higher in the medium-dose group than in the low-dose group(P=0.041), with no difference between the control and low-dose group (P=0.651). In addition, there was no difference in BMD between low-dose group and the model group (P=0.671), and lower in the low-dose group than in the medium-dose group(P=0.018), and the medium-dose group was lower than the high-dose group(P=0.008). Cell migration assay showed that THSWD promotes enhanced the migration ability of peripheral blood MSCs. IHC assay revealed that CD45-, CD90+, CD29+ MSCs significantly increased in bone callus after THSWD intervention compared with the control group. Protein chip showed that THSWD promoted the upregulation of CINC-1(×2.91), CINC-3(×1.59), LIX(×1.5), Thymus Chemokine (×2.55), VEGF (×1.22) and the down-regulation of TIMP-1 (×2.98). CONCLUSION: THSWD, a representative formula of "promoting blood circulation and removing blood stasis", can significantly accelerate fracture healing, and its mechanism may be related to enhancing the migration ability of peripheral blood MSCs and up-regulating CINC-1, CINC-3, LIX, Thymus Chemokine, VEGF and down-regulating TIMP-1 in bone callus, which promotes the peripheral blood MSCs homing in the early stage of fracture.
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Fracturas Óseas , Células Madre Mesenquimatosas , Animales , Medicamentos Herbarios Chinos , Curación de Fractura , Fracturas Óseas/tratamiento farmacológico , Humanos , Masculino , Ratas , Ratas Sprague-Dawley , Inhibidor Tisular de Metaloproteinasa-1/farmacología , Factor A de Crecimiento Endotelial Vascular , Microtomografía por Rayos XRESUMEN
Lithium (Li) has garnered considerable attention as an alternative anodes of next-generation high-performance batteries owing to its prominent theoretical specific capacity. However, the commercialization of Li metal anodes (LMAs) is significantly compromised by non-uniform Li deposition and inferior electrolyte-anode interfaces, particularly at high currents and capacities. Herein, a hierarchical three-dimentional structure with CoSe2 -nanoparticle-anchored nitrogen-doped carbon nanoflake arrays is developed on a carbon fiber cloth (CoSe2 -NC@CFC) to regulate the Li nucleation/plating process and stabilize the electrolyte-anode interface. Owing to the enhanced lithiophilicity endowed by CoSe2 -NC, in situ-formed Li2 Se and Co nanoparticles during initial Li nucleation, and large void space, CoSe2 -NC@CFC can induce homogeneous Li nucleation/plating, optimize the solid electrolyte interface, and mitigate volume change. Consequently, the CoSe2 -NC@CFC can accommodate Li with a high areal capacity of up to 40 mAh cm-2 . Moreover, the Li/CoSe2 -NC@CFC anodes possess outstanding cycling stability and lifespan in symmetric cells, particularly under ultrahigh currents and capacities (1600 h at 10 mA cm-2 /10 mAh cm-2 and 5 mA cm-2 /20 mAh cm-2 ). The Li/CoSe2 -NC@CFC//LiFePO4 full cell delivers impressive long-term performance and favorable flexibility. The developed CoSe2 -NC@CFC provides insights into the development of advanced Li hosts for flexible and stable LMAs.
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BACKGROUND: The incidence of bone fracture and bone-related diseases is increasing every year. Angiogenesis plays a vital role in fracture healing and bone repair. This study assessed the benefits of Taohong Siwu (TSW) decoction on angiogenesis in isolated rat aortic endothelial cells (RAEC) treated with TSW-containing serum. METHODS: The components of TSW decoction were analyzed by liquid chromatography-mass spectrometry (LC-MS). TSW-containing serum was prepared by gavage of TSW decoction to Sprague-Dawley (SD) rats. The effects of TSW-containing serum on the viability, migration, wound healing, and angiogenesis of RAEC were detected by the MTT, transwell, wound healing, and Matrigel lumen formation assays, respectively. In addition, the effects of an HIF-1α inhibitor on TSW-containing serum-induced RAEC were also assessed. The effects of TSW-containing serum on the expression of the HIF-1α signaling pathway were evaluated by qRT-PCR and western blot analysis. RESULTS: LC-MS revealed that TSW decoction primarily contained isomaltulose, choline, D-gluconic acid, L-pipecolic acid, hypotaurine, albiflorin, and tryptophan. TSW-containing serum significantly increased the viability, migration, wound healing, and angiogenesis of RAEC in a dose-dependent manner. Furthermore, our results demonstrated that HIF-1α and VEGF expressions were increased in the cells of TSW-containing serum groups, whereas VHL expression was decreased. The effects of TSW-containing serum were reversed by treatment with an HIF-1α inhibitor. CONCLUSION: These results suggested that TSW decoction enhanced angiogenesis by regulating the VHL/HIF-1α/VEGF signaling pathway.