Cathepsin B: The dawn of tumor therapy.

Cathepsin B (CTSB) is a key lysosomal protease that plays a crucial role in the development of cancer. This article elucidates the relationship between CTSB and cancer from the perspectives of its structure, function, and role in tumor growth, migration, invasion, metastasis, angiogenesis and autophagy. Further, we summarized the research progress of cancer treatment related drugs targeting CTSB, as well as the potential and advantages of Traditional Chinese medicine in treating tumors by regulating the expression of CTSB.

Ononin promotes radiosensitivity in lung cancer by inhibiting HIF-1α/VEGF pathway.

BACKGROUND: In our previous study, we provided evidence that Astragalus mongholicus Bunge(AM) and its extracts possess a protective capability against radiation-induced damage, potentially mediated through the reduction of reactive oxygen species (ROS) and nitric oxide (NO). However, we were pleasantly surprised to discover during our experimentation that AM not only offers protection against radiation damage but also exhibits a radiation sensitization effect. This effect may be attributed to a specific small molecule present in AM known as ononin. Currently, radiation sensitizers are predominantly found in nitrazole drugs and nanomaterials, with no existing reports on the radiation sensitization properties of ononin, nor its underlying mechanism. PURPOSE: This study aims to investigate the sensitization effect of the small molecule ononin derived from AM on lung cancer radiotherapy, elucidating its specific molecular mechanism of action. Additionally, the safety profile of combining astragalus small molecule ononin with radiation therapy will be evaluated. METHODS: The effective concentration of ononin was determined through cell survival experiments, and the impact of ononin combined with varying doses of radiation on lung cancer cells was observed using CCK-8 and cell cloning experiments. The apoptotic effect of ononin combined with radiation on lung cancer cells was assessed using Hochester staining, flow cytometry, and WB assay. Additionally, WB and immunofluorescence analysis were conducted to investigate the influence of ononin on HIF-1α/VEGF pathway. Furthermore, Molecular Dynamics Simulation was employed to validate the targeted binding ability of ononin and HIF-1α. A lung cancer cell line was established to investigate the effects of knockdown and overexpression of HIF-1α. Subsequently, the experiment was repeated using tumor bearing nude mice and C57BL/6 mouse models in an in vivo study. Tumor volume was measured using a vernier caliper, while HE, immunohistochemistry, and immunofluorescence techniques were employed to observe the effects of ononin combined with radiation on tumor morphology, proliferation, and apoptosis. Additionally, Immunofluorescence was employed to examine the impact of ononin on HIF-1α/VEGF pathway in vivo, and its effect on liver function in mice was assessed through biochemistry analysis. RESULTS: At a concentration of 25 µM, ononin did not affect the proliferation of lung epithelial cells but inhibited the survival of lung cancer cells. In vitro experiments demonstrated that the combination of ononin and radiation could effectively inhibit the growth of lung cancer cells, induce apoptosis, and suppress the excessive activation of the Hypoxia inducible factor 1 alpha/Vascular endothelial growth factor pathway. In vivo experiments showed that the combination of ononin and radiation reduced the size and proliferation of lung cancer tumors, promoted cancer cell apoptosis, mitigated abnormal activation of the Hypoxia inducible factor 1 alpha pathway, and protected against liver function damage. CONCLUSION: This study provides evidence that the combination of AM and its small molecule ononin can enhance the sensitivity of lung cancer to radiation. Additionally, it has been observed that this combination can specifically target HIF-1α and exert its effects. Notably, ononin exhibits the unique ability to protect liver function from damage while simultaneously enhancing the tumor-killing effects of radiation, thereby demonstrating a synergistic and detoxifying role in tumor radiotherapy. These findings contribute to the establishment of a solid basis for the development of novel radiation sensitizers derived from traditional Chinese medicine.

Nickel Chain-Walking Catalysis: A Journey to Migratory Carboboration of Alkenes.

ConspectusChain-walking offers extensive opportunities for innovating synthetic methods that involve constructing chemical bonds at unconventional sites. This approach provides previously inaccessible retrosynthetic disconnections in organic synthesis. Through chain-walking, transition metal-catalyzed alkene difunctionalization reactions can take place in a 1,n-addition (n ≠ 2) mode. Unlike classical 1,2-regioselective difunctionalization reactions, there remains a scarcity of reports regarding migratory patterns. Moreover, the range of olefins utilized in these studies is quite limited.About five years ago, our research group embarked on a project aimed at developing valuable migratory difunctionalization reactions of alkenes through chain-walking. Our focus was on carboboration of alkenes utilizing nickel catalysis. The reaction commences with the migratory insertion of an olefin into a Ni-Bpin species. Subsequently, a thermodynamically stable alkyl nickel complex is generated through a chain-walking process. This complex then couples with a carbon-based electrophile, leading to the formation of an alkylboron compound. It is worth highlighting that the success of these transformations relies significantly on the utilization of a bisnitrogen-based ligand and LiOMe as a B2pin2 activator. Synthetically, these migratory carboboration reactions establish a robust platform for the rapid and efficient synthesis of a wide range of structurally diverse organoboron compounds, which are not facially accessed by conventional methods. The incorporation of a versatile boron group introduces a wealth of possibilities for subsequent diversifications, significantly enhancing the value of the resulting products and allowing for the creation of a broader range of valuable derivatives and applications.This Account provides a comprehensive overview of our research efforts and advancements in the field of migratory carboboration of unactivated alkenes using nickel catalysis. We begin by outlining the development of a series of 1,1-regioselective carboboration reactions of terminal alkenes. A significant focus is placed on the initial integration of boronate, which not only triggers the formation of thermodynamically stable metal species but also exerts control over remote stereochemistry in reactions involving substituted methylenecyclohexenes. Continuing our exploration, remarkable success is achieved in 1,3-regio- and cis-stereoselectivity when dealing with cyclic alkenes. Remarkably, nickel chain-walking catalysis enables heterocyclic alkenes to be viable coupling partners within our transformations. Moreover, it grants us the ability to achieve regioselectivity for cyclohexenes that was previously unattainable, thus expanding the horizons of regiochemical control in these reactions. Lastly, we present the evolution of ligand-modulated regiodivergent carboboration of allylarenes. By gaining insights into the underlying mechanisms driving regiodivergence, we lay a strong foundation for tackling challenges related to selecting specific sites in chain-walking reactions, especially when dealing with multiple stable factors. We anticipate that our findings, coupled with the mechanistic insights we've gained, will not only advance the realm of nickel chain-walking catalysis but also contribute to the broader understanding of selectivity control in reactions of this nature. This advancement will also catalyze the synthesis of intricate functional molecules, contributing to the creation of complex and valuable compounds in the realm of organic chemistry.

Kaempferol attenuates carbon tetrachloride (CCl4)-induced hepatic fibrosis by promoting ASIC1a degradation and suppression of the ASIC1a-mediated ERS.

BACKGROUND: Kaempferol is a flavonoid derived from the herb, Kaempferia galanga L., in addition to exhibiting a wide range of pharmacological properties, kaempferol is also an anti-inflammatory, anti-lipid metabolizing, and anti-oxidative stress agent. The underlying molecular mechanisms of its effects on vascular endothelial growth factor (VEGF) secretion and activation of hepatic stellate cells (HSCs) are yet unknown. Activated HSCs induces VEGF release and extracellular matrix (ECM) accumulation which are important factors in hepatic fibrosis. PURPOSE: Our aim is to explore how kaempferol may affect hepatic fibrosis and the mechanisms behind its effects. METHODS: The in vivo model was Sprague-Dawley rats induced with carbon tetrachloride (CCl4). Histological staining was used to observe histological features of the liver. The levels of (alanine aminotransferase) ALT and (aspartate aminotransferase) AST were detected by the corresponding kits. Platelet-derived growth factor (PDGF) was used to stimulate the HSC-T6 rat hepatic stellate cells. The mechanisms underlying this process were investigated using a variety of molecular approaches, including immunofluorescence, RT-qPCR, and western blotting. Moreover, intracellular Ca2+ were observed by laser confocal microscope. RESULTS: It was found that kaempferol significantly reduced the expression of ASIC1a, VEGF, α-SMA and Collagen-I proteins in a model of CCl4-induced hepatic fibrosis in rats. In HSC-T6, kaempferol inhibits activation of HSCs by decreasing expression of ASIC1a, eIF2α, p-eIF2α and ATF-4. Laser confocal fluorescence showed that kaempferol inhibited Ca2+ influx and reduced Ca2+ concentration around the endoplasmic reticulum. Molecular docking and cellular thermal shift assay (CETSA) results further indicated that kaempferol interacted with ASIC1a. We found that kaempferol may promote the degradation of ASIC1a and inhibited ASIC1a- mediated upregulation of ERS. CONCLUSION: The data from our in vivo experiments demonstrate that kaempferol effectively attenuates hepatic fibrosis. In vitro studies we further propose a novel mechanism of kaempferol against hepatic fibrosis which can interact with ASIC1a and promote ASIC1a degradation while inhibiting the activation and VEGF release of HSCs by suppressing the ASIC1a-eIF2α-ATF-4 signaling pathway.

Biocompatible Gallium Nanodots against Drug-Resistant Bacterial Pneumonia and Liver Abscess.

Resistant bacterial infection remains a severe public health threat, and conventional antibiotic drugs work poorly in effectively treating infectious diseases. Here, we developed gallium-based nanodots (Ga NDs), consisting of specific disruption of bacterial iron ability, to treat multidrug-resistant (MDR) Gram-negative bacteria-infected diseases. The Ga NDs significantly suppress the proliferation of two typical MDR bacteria strains (P. aeruginosa and ESBL E. coli) compared with clinically used antibacterial drugs, including penicillin and levofloxacin. Ga NDs could also disrupt the biofilms of these two bacterial strains. In P. aeruginosa infected pneumonia and ESBL E. coli infected acute liver abscess models, the Ga NDs enable substantial inhibition of bacterial growth and reduce the organs' inflammation that resulted in significant improvement of survival. Further, the Ga NDs demonstrated excellent biocompatibility and biosafety characteristics. Together, we believe that our gallium containing nanotherapeutics are expected to be developed into promising alternative therapies to combat drug-resistant bacterial infection.

A novel fasting regimen revealed protein reservation and complement C3 down-regulation after 14-day's continual dietary deprivation.

Objectives: The aim is to evaluate the effect of a novel 14-day fasting regimen on the balance between skeletal muscle and adipose tissue composition which might associate with inflammatory factors. Our analysis includes basic physical examinations, clinical laboratory analysis, bioelectrical impedance and biochemical analytic assessments of healthy volunteers. Methods: Eight healthy subjects were randomly selected from a pool of volunteers to undergo a continual dietary deprivation (CDD) regimen. Individuals were assigned to take Flexible Abrosia (FA, prebiotic combination) plus appropriate mineral supplement of potassium and magnesium at 3 mealtime every day to prevent potential injury from starved intestinal flora and avoid spasms of smooth muscle due to hunger. Physical and medical examinations were conducted and blood samples were collected at following timepoints: before CDD as self-control (0D), day 7 and day 14 during fasting, and 7-21days and/or 2~3mo after refeeding. Results: The combination of FA and mineral supplements significantly decreased self-reported physical response of starvation, with tolerable hunger-mediated sensations experienced during CDD. Bioelectrical and biochemical results indicated significant reduction in both muscle lean and fat mass on day 7. Meanwhile, markers related to fat composition consistently decreased during and after CDD. In addition, most biochemical marker levels, including serum proteins, reached their inflection points at the 7th day of CDD as compared to the control measurements. Levels of these factors started to show a relative plateau, or reversed direction upon the 14th day of CDD. The exceptions of above factors were myostatin and complement protein C3, which remained at lower concentrations in the blood throughout CDD, and were unable to fully recover toward baseline levels even after 3 months' refeeding. Conclusion: Our results indicated that human subjects undergoing prolonged dietary restriction were well protected by FA and mineral ions from gut injury or physical discomfort of starvation. Most factors showed a relative plateau response at the end of 14D-CDD. The muscle tissues were well preserved during prolonged fasting, and an improved protein/lipid ratio was observed. Upon refeeding, constant lower levels of myostatin and complement C3 were maintained after CDD implies a long-term beneficial effect in dealing with anti-aging and inflammation.

Neuregulin4 Acts on Hypothalamic ErBb4 to Excite Oxytocin Neurons and Preserve Metabolic Homeostasis.

Neuregulin 4 (Nrg4) is an adipose tissue-enriched secreted factor that modulates glucose and lipid metabolism. Nrg4 is closely associated with obesity and preserves diet-induced metabolic disorders. However, the specific mechanisms via which Nrg4 regulates metabolic homeostasis remain incompletely understood. Here, this work finds that the Nrg4 receptor, ErbB4, is highly expressed in the hypothalamus, and the phosphorylation of hypothalamic ErbB4 is reduced in diet-induced obesity (DIO) mice. Peripheral Nrg4 can act on ErbB4 via blood circulation and excite neurons in the paraventricular nucleus of hypothalamus (PVN). Central administration of recombinant Nrg4 protein (rNrg4) reduces obesity and related metabolic disorders by influencing energy expenditure and intake. Overexpression of ErbB4 in the PVN protects against obesity, whereas its knock down in oxytocin (Oxt) neuron accelerates obesity. Furthermore, Nrg4-ErbB4 signaling excites Oxt release, and ablation of Oxt neuron considerably attenuates the effect of Nrg4 on energy balance. These data suggest that the hypothalamus is a key target of Nrg4, which partially explains the multifaceted roles of Nrg4 in metabolism.

Review: Mechanisms and perspective treatment of radioresistance in non-small cell lung cancer.

Radiotherapy is the major treatment of non-small cell lung cancer (NSCLC). The radioresistance and toxicity are the main obstacles that leading to therapeutic failure and poor prognosis. Oncogenic mutation, cancer stem cells (CSCs), tumor hypoxia, DNA damage repair, epithelial-mesenchymal transition (EMT), and tumor microenvironment (TME) may dominate the occurrence of radioresistance at different stages of radiotherapy. Chemotherapy drugs, targeted drugs, and immune checkpoint inhibitors are combined with radiotherapy to treat NSCLC to improve the efficacy. This article reviews the potential mechanism of radioresistance in NSCLC, and discusses the current drug research to overcome radioresistance and the advantages of Traditional Chinese medicine (TCM) in improving the efficacy and reducing the toxicity of radiotherapy.

Potential molecular mechanism of Guiqi Baizhu Decoction in radiation-induced intestinal edema by regulating HIF-1a, AQP4 and Na+/K+-ATPase.

BACKGROUND: Guiqi Baizhu Decoction (GQBZD) has a good protective effect on radiation-induced intestinal edema (RIIE). However, the underlying molecular mechanisms need further elucidation. PURPOSE: To reveal the potential mechanism of RIIE and GQBZD treatment. METHODS: SD rats were irradiated with 6Gy X-ray to establish RIIE model. The general condition of the rats was observed; the dry/wet weight ratio of colon tissue was detected; the morphological changes of colon tissue were observed by HE staining; the expressions of ROS, HIF-1α and AQP4 in colon tissue were detected by confocal laser scanning; the expression of edema-related proteins was detected by Western blot. In addition, human colon epithelial cells (NCM460) was irradiated with 2Gy X-ray, and HIF-1α expression in NCM460 was knocked down by small interfering RNA (siRNA) transfection, and the activity of Na+/K+-ATPase was detected by enzyme activity kit; the ROS expression was detected by flow cytometer; the AQP4 expression was detected by laser confocal microscopy; and the expression of edema-related proteins were detected by Western blot. RESULTS: We found that after irradiation, the colon tissue of rats was significantly edema, mainly manifested as mucosal and submucosal edema, and the ultrastructure was reflected in the structural damage of nucleus and mitochondria. ROS, HIF-1α and AQP4 were significantly expressed, and Na+/K+-ATPase expression/activity was decreased. After the intervention of GQBZD, the edema of the colon tissue of the rats was improved, the expressions of ROS, HIF-1α and AQP4 were decreased, and the expression/activity of Na+/K+-ATPase was increased. CONCLUSION: Ionizing radiation (IR) can cause significant intestinal edema. AQP4 and Na+/K+-ATPase are the key factors of RIIE, which are regulated by ROS and HIF-1α. GQBZD can improve hypoxia and oxidative stress, regulate the expression of AQP4 and Na+/K+-ATPase, and achieve a protective effect on RIIE. This study is the first to reveal the mechanism of RIIE.

Pollen Typhae-Based Magnetic-Powered Microrobots toward Acute Gastric Bleeding Treatment.

Traditional Chinese herbal medicine (TCHM) is the naturally available pharmaceutical with millennia of evolution from ancient China, capable of a superior therapeutic index and minimized unwanted effects on the human body. This work presents a therapeutic microrobotic platform based on pollen typhae (PT), a typical type of TCHM, fabricated by coating porous PT microspheres with Fe3O4 nanoparticles (PT robots) via electrostatic adsorption. The PT robots exhibit effective and controllable motion in various biological media upon external magnetic control and, meanwhile, preserve the inherent hemostasis property of PT. The blood clotting capacity of PT robots is attributed to their stimulation of the endogenous blood coagulation pathway and platelets with increased counts, which could be further improved by their effective magnetic propulsion. The remote magnetic control also allows the manipulation of PT robots in mice stomach, inducing enhanced binding and prolonged retention of PT robots in stomach mucosa. Moreover, PT robots upon magnetic control show an enhanced hemostatic effect in treating the mice bearing acute gastric bleeding compared with other passive groups. This work offers a facile and feasible route to integrate TCHM with manmade micromachines possessing the innate curative features of TCHM. Such a design expanded the versatility of microrobots and can be generalized to vast types of TCHM for broader biomedical applications.

Engineering of bioactive metal sulfide nanomaterials for cancer therapy.

Metal sulfide nanomaterials (MeSNs) are a novel class of metal-containing nanomaterials composed of metal ions and sulfur compounds. During the past decade, scientists found that the MeSNs engineered by specific approaches not only had high biocompatibility but also exhibited unique physicochemical properties for cancer therapy, such as Fenton catalysis, light conversion, radiation enhancement, and immune activation. To clarify the development and promote the clinical transformation of MeSNs, the first section of this paper describes the appropriate fabrication approaches of MeSNs for medical science and analyzes the features and limitations of each approach. Secondly, we sort out the mechanisms of functional MeSNs in cancer therapy, including drug delivery, phototherapy, radiotherapy, chemodynamic therapy, gas therapy, and immunotherapy. It is worth noting that the intact MeSNs and the degradation products of MeSNs can exert different types of anti-tumor activities. Thus, MeSNs usually exhibit synergistic antitumor properties. Finally, future expectations and challenges of MeSNs in the research of translational medicine are spotlighted.

Role of phosphorous additives on nitrogen conservation and maturity during pig manure composting.

This study compared different types and addition amounts of phosphorous additives on nitrogen conservation and maturity during pig manure composting. Phosphogypsum and superphosphate were applied with the same amount of phosphorus (5% of the initial total nitrogen, molar basis) or weight (10% of initial dry matter) and compared to a control treatment without additives. Results show that phosphorous additives could effectively conserve nitrogen. Adding phosphogypsum could significantly reduce NH3 emission and total nitrogen loss, but increase N2O emission. Application of 10% superphosphate mitigated NH3 emissions and total nitrogen loss but inhibited the organic matter degradation and compost maturity. More importantly, with the addition of 5% initial total nitrogen (i.e., 2.5% dry matter), superphosphate could synchronously reduce NH3 and N2O emissions and improve compost quality by introducing additional nutrients into the compost. In comprehensive evolution of gaseous emissions, nitrogen loss, and compost maturity, superphosphate addition with 2.5% of initial dry matter was suggested to be used in practice.

Multistage-responsive clustered nanosystem to improve tumor accumulation and penetration for photothermal/enhanced radiation synergistic therapy.

Developing new strategies to overcome biological barriers and achieve efficient delivery of therapeutic nanoparticles (NPs) is the key to achieve positive therapeutic outcomes in nanomedicine. Herein, a multistage-responsive clustered nanosystem is designed to systematically resolve the multiple tumor biological barriers conflict between the enhanced permeability retention (EPR) effect and spatially uniform penetration of the nanoparticles. The nanosystem with desirable diameter (initial size of ~50 nm), which is favorable for long blood circulation and high propensity of extravasation through tumor vascular interstices, can accumulate effectively around the tumor tissue through the EPR effect. Then, these pH-responsive nanoparticles are conglomerated to form large-sized aggregates (~1000 nm) in the tumor under the acidic microenvironment, and demonstrated great tumor retention. Subsequently, the photothermal treatment disperses the aggregates to be ultrasmall gold nanoclusters (~5 nm), thereby improving their tumor penetration ability, and enhancing the radiotherapeutic effect by radiosensitizer. In 4T1 tumor model, this nanosystem shows great tumor accumulation and penetration, and the tumor growth and the lung/liver metastasis in particle/PTT/RT treated mice is significantly inhibited. As a photoacoustic/fluorescence imaging agent and PT/RT synergistic agent, this pH-/laser-triggered size multistage-responsive nanosystem displayes both great tumor accumulation and penetration abilities, and shows excellent potential in tumor therapy.

Auricular therapy for polycystic ovary syndrome: A protocol for a systematic review and meta-analysis.

BACKGROUND: This systematic review protocol aims to describe a meta-analysis to assess the effectiveness and safety of auricular therapy for patients with polycystic ovary syndrome (PCOS). METHODS: Randomized controlled trials of auricular therapy in treating PCOS will be searched in PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wan-Fang Database, and Chinese Scientific Journal Database. The primary outcome is the body mass index. The study selection, data extraction, and study quality evaluation will be performed independently by 2 researchers. A meta-analysis will be performed using RevMan V5.3 statistical software if possible; otherwise, descriptive analysis or subgroup analysis will be conducted. The quality of evidence for outcomes will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: This study will evaluate the effect and safety of auricular therapy in treating PCOS. CONCLUSIONS: The evidence we generated from the present study will provide more options for PCOS management in clinical practice. THE REGISTRATION DOI: 10.17605/OSF.IO/VBPSM.

Guiqi Baizhu Decoction Alleviates Radiation Inflammation in Rats by Modulating the Composition of the Gut Microbiota.

The gut microbiota is important in metabolism and immune modulation, and compositional disruption of the gut microbiota population is closely associated with inflammation caused by ionizing radiation (IR). Guiqi Baizhu decoction (GQBZD) is a medicinal compound used in traditional Chinese medicine with anti-inflammatory and antioxidation effects, especially in the process of radiotherapy. However, the effect of GQBZD on reducing the damage to the normal immune system in radiotherapy remains unclear. Here, we show that GQBZD reduces body weights, water intake, food intake, diarrhea level and quality of life score, and inflammation and enhances immunity function in rats treated with X-ray radiation. Meanwhile, our data indicate that GQBZD not only reverses IR-induced gut dysbiosis as indicated change of α-diversity and ß-diversity of microbiota, the composition of Desulfovibrio, Bacteroides, and Parabacteroides, except for Roseburia and Lachnoclostridium, but also maintains intestinal barrier integrity and promoting the formation of short-chain fatty acids (SCFAs). GQBZD can also reduce the level of phosphorylation P65 (p-P65). Our results demonstrate that GQBZD can significantly alleviate the inflammatory responses and improve the immune damage against IR, and may be used as prebiotic agents to prevent gut dysbiosis and radiation-related metabolic disorders in radiotherapy.

Astragalus polysaccharide inhibits radiation-induced bystander effects by regulating apoptosis in Bone Mesenchymal Stem Cells (BMSCs).

The purpose of this study was to investigate the effects of astragalus polysaccharides (APS) on the proliferation and apoptosis of bone marrow mesenchymal stem cells (BMSCs) induced by X-ray radiation-induced A549 cells bystander effect (RIBE), and to explore their mechanisms. In this study, APS increased the reduced cell proliferation rate induced by RIBE and inhibiting the apoptosis of bystander cells. In terms of mechanism, APS up-regulates the proteins Bcl-2, Bcl-xl, and down-regulates the proteins Bax and Bak, which induces a decrease in mitochondrial membrane potential, which induces the release of Cyt-c and AIF, which leads to caspase-dependent and caspase-independent pathway to cause apoptosis. In addition, we believe that ROS may be the main cause of these protein changes. APS can inhibit the generation of ROS in bystander cells and thus inhibit the activation of the mitochondrial pathway, further preventing cellular damage caused by RIBE.

pH-responsive silk fibroin-based CuO/Ag micro/nano coating endows polyetheretherketone with synergistic antibacterial ability, osteogenesis, and angiogenesis.

Polyetheretherketone has been widely used for bone defect repair, whereas failures may happen due to implant loosening and infection. Thus, PEEK implant with multi-function (osteogenesis, angiogenesis, and bacteria-killing) is essential to solve this problem. Herein, copper oxide microspheres (µCuO) decorated with silver nanoparticles (nAg) were constructed on porous PEEK surface via silk fibroin. In vitro studies highlighted the pH controlled release ability of this coating. It liberated a high dose of Cu2+ and Ag+ at low pH environment (pH 5.0), leading to 99.99% killing of planktonic bacteria and complete eradication of sessile bacteria, avoiding biofilm formation. Under physiological environment (pH 7.4), a lower amount of leaked metal ions induced promoted ALP production, collagen secretion, and calcium deposition, as well as NO production, which indicated potentiated osteogenesis and angiogenesis. In vivo results displayed the highest new bone volume around, and the appearance of new bone inside porous structure of, PEEK implant with this coating in rabbit tibia, signified the abilities of this coating to promote bone regeneration and osseointegration. Our study established solid support for implants with this coating to be a successful bone defect repair solution. STATEMENT OF SIGNIFICANCE: In this study, CuO/Ag micro/nano particles were incorporated into the porous surface of PEEK through polydopamine and silk fibroin layers. The design of this coating conferred pH-controlled release behavior to Cu2+ and Ag+. High dose of metal ions were released at pH 5.0, which presented synergistic antibacterial ability and killed 99.99% of planktonic bacteria. Low concentration of metal ions were controlled by this coating at physiological environment, which potentiated osteodifferentiation of Ad-MSC in vitro and led to complete integration of implant with bone tissue in vivo.

The Antiosteoporosis Effects of Yishen Bugu Ye Based on Its Regulation on the Differentiation of Osteoblast and Osteoclast.

Yishen Bugu Ye (YSBGY), a traditional Chinese medicine comprising 12 types of medicinal herbs, is often prescribed in China to increase bone strength. In this study, the antiosteoporotic effects of YSBGY were investigated in C57BL/6 mice afflicted with dexamethasone- (Dex-) induced osteoporosis (OP). The results showed that YSBGY reduced the interstitial edema in the liver and kidney of mice with Dex-induced OP. It also increased the number of trabecular bone elements and chondrocytes in the femur, promoted cortical bone thickness and trabecular bone density, and modulated the OP-related indexes in the femur and tibia of OP mice. It also increased the serum concentrations of type I collagen, osteocalcin, osteopontin, bone morphogenetic protein-2, bone morphogenetic protein receptor type 2, C-terminal telopeptide of type I collagen, and runt-related transcription factor-2 and reduced those of tartrate-resistant acid phosphatase 5 and nuclear factor of activated T cells in these mice, suggesting that it improved osteoblast differentiation and suppressed osteoclast differentiation. The anti-inflammatory effect of YSBGY was confirmed by the increase in the serum concentrations of interleukin- (IL-) 33 and the decrease in concentrations of IL-1, IL-7, and tumor necrosis factor-α in OP mice. Furthermore, YSBGY enhanced the serum concentrations of superoxide dismutase and catalase in these mice, indicating that it also exerted antioxidative effects. This is the first study to confirm the antiosteoporotic effects of YSBGY in mice with Dex-induced OP, and it showed that these effects may be related to the YSBGY-induced modulation of the osteoblast/osteoclast balance and serum concentrations of inflammatory factors. These results provide experimental evidence supporting the use of YSBGY for supporting bone formation in the clinical setting.

[Kinetic parameters and temperature sensitivity of soil nitrogen and phosphorus transforming enzymes in Robinia pseudoacacia plantations under different vegetation zones on the Loess Plateau, China]. / é»„åœŸé«˜åŽŸä¸åŒæ¤è¢«å¸¦äººå·¥åˆºæ§æž—åœŸå£¤æ°®ç£·è½¬åŒ–é ¶åŠ¨åŠ›å­¦å‚æ•°åŠå ¶æ¸©åº¦æ•æ„Ÿæ€§.

Soil enzymes are catalysts for organic matter decomposition, the kinetic characteristics of which are important indicators of the catalytic performance of enzymes, with important role in evalua-ting soil health quality. We examined the responses of soil enzyme kinetic parameters to temperature change and the variation characteristics of their temperature sensitivity (Q10) in Robinia pseu-doacacia plantation soil under three different vegetation zones on the Loess Plateau. The results showed that the potential maximum reaction rate (Vmax) and the half-saturation constant (Km) of alanine transaminase (ALT), leucine aminopeptidase (LAP) and alkaline phosphatase (ALP) all increased linearly with the increasing incubation temperature. The zonal regularity of forest zone > forest-steppe zone > steppe zone was presented in Vmax. The temperature sensitivity of Vmax(Q10(Vmax)) ranged from 1.14 to 1.62, and the temperature sensitivity of Km(Q10(Km)) ranged from 1.05 to 1.47, with both values being lower in forest-steppe zone than other vegetation zones. In low and high temperature regions, the variations of Q10 in different soil enzymes differed among vegetation zones. Results from redundancy analysis showed that Q10 had a significant correlation with environmental variables, especially soil nutrients, indicating that Q10 would be affected by other environmental factors besides temperature.

Laser-triggered aggregated cubic α-Fe2O3@Au nanocomposites for magnetic resonance imaging and photothermal/enhanced radiation synergistic therapy.

Theranostic nanoparticles (NPs) have recently generated substantial interest in translational cancer research due to their capabilities for multimodal diagnostic imaging and anti-cancer therapy. We herein developed cubic alpha-iron(III) oxide (α-Fe2O3) nanoparticles coated with ultrasmall gold nanoseeds, abbreviated as α-Fe2O3@Au, for the synergistic treatment of radiotherapy and photothermal therapy in breast cancer. The resultant NPs, with an average diameter of 49 nm, exhibited satisfactory biosafety profiles and provided tumor contrast in T2-weighted magnetic resonance (MR) imaging. The coating of ultrasmall Au nanoseeds exhibited strong absorption of near-infrared (NIR) laser that enabled to an efficacious photothermal therapy. It also sensitized radiotherapy, X-ray in this study, by generating large quantities of tumoricidal reactive oxygen species (ROS). Moreover, with the aid of NIR laser irradiation, the α-Fe2O3 substrate showed partial ablation and the Au NPs on its surface aggregated into a larger size (~13 nm), which has been proven to be the optimized size for radiotherapy. When tested in 4T1 murine breast cancer model, the α-Fe2O3@Au NPs significantly suppressed tumor growth (P < 0.01) when irradiated with a low-power laser (1.5 W/cm2 for 3 min) and an intermediate X-ray dose (6 Gy). Our results demonstrate that α-Fe2O3@Au, integrated with MRI, photothermal therapy, and radiosensitization, is a promising multifunctional theranostic nanomedicine for clinical applications.