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The rotary motion of the bit caused by the lateral force imbalance of the bit leads to premature failure of the bit, mainly because the side of the cutter makes contact with the rock and participates in breaking rock. The rotating motion of the bit causes the bit to form an irregular spiral bottom hole.A lot of research and experiments have been done to eliminate the cyclotron phenomenon. However, whether it is conventional PDC cutter or special-shaped PDC cutter single cutter rock breaking experiment simulation or laboratory experiment, it is based on the way of replacing circular cutting of cutter with linear scraping, and almost does not consider the radial scraping motion of cutter under circular motion, which is still different from the actual working state of the bit. Therefore, in order to further understand the rock breaking characteristics of the cutter under irregular or circular motion, it is necessary to carry out a single rock breaking study considering the combined circumferential and radial scraping motion.

Targeting the delivery of anti-cancer drugs to a tumor site is essential for effective treatment and to ensure minimal damage to healthy cells and tissues. In this work, a chitosan-based nanoplatform was constructed for combined photothermal therapy and chemotherapy of breast cancer. The pH-sensitive and biocompatible biopolymer chitosan (CS) was grafted with N-vinylcaprolactam (NVCL) and modified with biotin (Bio), imparting it with temperature sensitive property and also the ability for active targeting. The polymer self-assembled to give nanoparticles (NPs) loaded with indocyanine green (ICG) and doxorubicin (DOX). When the NPs are exposed to near-infrared (NIR) laser irradiation, ICG converts the light to heat, inducing a significant phase transition in the NPs and facilitating the release of the drug cargo. In addition, the solubility of chitosan is increased in the slightly acidic microenvironment of the tumor site, which also promotes drug release. A detailed analysis of the NPs both in vitro and in vivo showed that the carrier system is biocompatible, while the drug-loaded NPs are selectively taken up by cancer cells. Particularly when augmented with NIR irradiation, this leads to potent cell death in vitro and also in an in vivo murine xenograft model of breast cancer.

Intercropping cereals and legumes is practiced widely in the world for improving yields and economic benefits. Shorter legume crops in intercropping are shaded by taller cereals, substantially reducing legume growth and yield. Reducing shade in intercropping by shortening the plant height of cereals by seedling defoliation has been proposed as a practical approach to increase crop yields and land productivity. A two-year field experiment was conducted to investigate the effect of defoliation of cereal crops at seedling stage on the growth and yield of peanut (Arachis hypogaea L.) intercropped with corn (Zea mays L.) or millet (Setaria italica L.). In comparison with non-defoliation controls, defoliation reduced final plant height by 29 cm on average for corn and 18 cm for millet. Photosynthetically active radiation on peanut in intercropping systems with corn or millet intercropping was respectively 27.0% and 22.8% higher than those in controls, significantly improving the light environment of intercropped peanut. Net photosynthetic rates of peanut were on average 25.5% higher in corn and peanut intercropping and 19.6% higher in millet and peanut intercropping than those in non-defoliation controls. Total biomass of intercropped peanut increased owing to increased root growth. Across two years, yield of peanut intercropped with corn was 27.7% and with millet 32.8% higher than those of controls. Defoliation of cereal crops did not affect corn yield but significantly decreased millet yield by 24.5%. Our results suggest that applying seedling defoliation in intercropped corn could increase peanut yield without compromising corn yield in an intercropping system.

In the oil and gas drilling industry, cemented carbide teeth are one of the most widely used rock-breaking elements. In order to reveal the rock damage mechanism of tooth indentation, a series of tooth indentation experiments were conducted in this study, and an indentation simulation was also conducted as a supplement to the experiment. In the experiment, a new method to observe the inner damage status of the rock was put forward, i.e., utilizing the splitting action of the teeth to avoid unexpected rock damage that may affect the actual experiment results. The load-displacement curves and the damage status of the rock revealed that the wedge tooth was more efficient in fracturing and damaging the rock because the load requirement of the wedge tooth was lower, the narrow tooth crown generated larger specific stress in the rock; that rock-breaking advantage of the wedge tooth resulted from the occurrence of the compacted core and the tension stress generated by the core. According to the simulation results, the plastic strain in the intermediate area between the wedge teeth appeared more concentrated and increased faster, and the rock material beneath the wedge teeth was removed earlier than beneath the conical teeth, indicating that wedge teeth, disposed with proper spacing, can break rock more effectively than the conical teeth. The experiment and simulation results in this paper have proved the advantages of the wedge tooth in rock fracturing and damaging, which will provide technical support for the design and development for the drill bits applied in oil and gas drilling.

Background: Osteochondroma (OC) is one of the most common benign tumors of the long bones, but it rarely occurs in the maxillofacial skeleton. However, mandibular condylar OC often leads to severe facial deformity in affected patients, including facial asymmetry, deviation of the chin, and malocclusion. This study aimed to explore the clinical application of individualized 3D-printed templates to accurately and effectively treat condylar OC. Methods: A total of 8 patients with mandibular condylar OC were treated from July 2015 to August 2021. The enrolled patients (5 women and 3 men) had a median age of 27 years (range: 21–32 years). All patients exhibited symptoms of facial asymmetry and occlusal disorders preoperatively. The digital software used to virtually design the process consisted of three-dimensional reconstruction, 3D-cephalometry analysis, virtual surgery, individualized templates, and postoperative facial soft-tissue prediction. A set of 3D-printed templates (DOS and DOT) were used in all cases to stabilize the occlusion and guide the osteotomy. Then, pre- and post-operative complications, mouth opening, clinical signs, and the accuracy of the CT imaging analysis were all evaluated. All the measurement data were presented as means ± SD; Bonferroni and Tamhane T2 multiple comparison tests were used to examine the differences between the groups. Results: All patients healed uneventfully. None of the patients exhibited facial nerve injury at follow-up. In comparing the condylar segments with T0p and T1, the average deviation of the condylar segments was 0.5796 mm, indicating that the post-operative reconstructed condyles showed a high degree of similarity to the reconstruction results of the virtual surgical plan. Conclusions: Individualized 3D-printed templates simplified surgical procedures and improved surgical accuracy, proving to be an effective method for the treatment of patients with slight asymmetric deformities secondary to condylar OC.

Particles erosion wear always consist in the intersection of tee pipe, which is an inevitable problem. In order to obtain the erosion wear characteristics of two-phase flow tee pipe, several cases of different inlet diameters are investigated numerically in this paper. Euler-Lagrange method is adopted to describe the gas-solid two-phase flow and the finite volume method is adopted to solve the erosion results. Meshing O-type grids to obtain the reasonable boundary layer in ICEM CFD. By verifying and comparing the turbulence intensity and velocity of the six meshes, a reasonable finite element model is selected. Intersection, the severest erosion region, is the location where the gas flow direction changes. The inlet diameter determines the region of the impact particles directly hitting the wall. When the inlet diameter is smaller, the erosion of the intersection is severer. As the inlet velocity increases, both the erosion of the intersection and the outlet pipe become severer. However, there are only the erosion scars at the intersection are affected, with the increase of particle mass flow.

Currently MI repair approaches always exhibit low efficiency and do not match the clinical requirements. To provide an advanced engineering platform, an injectable hydrogel was developed to release OSM continuously and localized in the MI lesion.

Slag waste can be effectively used to produce coal–fired slag concrete (CSC), which has economic and environmental benefits. However, CSC used in engineering construction will eventually be subjected to damage. The purpose of this study is to investigate the mechanical characteristics and damage evolution behaviour of CSC specimens under a uniaxial compressive load using acoustic emission (AE) monitoring technology. Through uniaxial compression testing and AE monitoring, the stress–strain curve and AE characteristics of CSC specimens are obtained. Subsequently, a damage evolution model of the CSC specimens under a uniaxial compression load is constructed, and the damage evolution characteristics of the concrete are analysed. The results indicate that an increase in the ratio of the coal–fired slag mass to the cement mass results in a gradual reduction in the compressive strength of the CSC. Moreover, the maximum value of the cumulative energy count and cumulative ringing count of the AEs gradually increases while the damage degree gradually decreases. The damage evolution process for CSC can be divided into three stages: the initial damage formation stage, accelerated damage growth stage, and damage failure stage. The damage model, based on the AE cumulative ringing count, reasonably reflects the damage evolution process of the CSC specimens. The results of this study provide a reference for theoretical research and the engineering application of CSC.

The hypoxia of the tumor microenvironment (TME) often hinders the effectiveness of cancer treatments, especially O2-dependent photodynamic therapy (PDT). Methods: An integrated iridium oxide (IrO2)-manganese dioxide (MnO2) nanotheranostic agent was fabricated through bovine serum albumin (BSA)-based biomineralization of Ir3+ and Mn2+. BSA was first covalently modified with chlorin e6 (Ce6), and used to fabricate multifunctional BSA-Ce6@IrO2/MnO2 nanoparticles (NPs) for computed X-ray tomography (CT) and photoacoustic (PA) imaging-guided PDT and photothermal (PTT) therapy of cancer. Extensive in vitro and in vivo studies were performed. Results: The theranostic agent produced can relieve tumor hypoxia by the decomposition of endogenous H2O2 in cancer cells to oxygen. The oxygen generated can be exploited for improved PDT. Paramagnetic Mn2+ released from the NPs in the acidic TME permits magnetic resonance imaging (MRI) to be performed. The exceptional photothermal conversion efficiency (65.3%) and high X-ray absorption coefficient of IrO2 further endow the NPs with the ability to be used in computed CT and PA imaging. Extensive antitumor studies demonstrated that the BSA-Ce6@IrO2/MnO2 nanoplatform inhibits cancer cell growth, particularly after combined PTT and PDT. Systematic in vivo biosafety evaluations confirmed the high biocompatibility of the nanoplatform. Conclusion: This work not only provides a novel strategy for designing albumin-based nanohybrids for theranostic applications but also provides a facile approach for extending the biomedical applications of iridium-based materials.

Two-dimensional (2D) nanomaterials able to effectively absorb near-infrared (NIR) radiation have shown considerable potential as multifunctional platforms in the treatment of cancer. Here, we report a molybdenum dioxide (MoO

What is known and objective An increasing number of targeted drugs have been used to treat advanced or metastatic gastric cancer (GC) and gastroesophageal junction cancer (GEJC). However, the optimal treatment efficacy of these drugs is still controversial. The aims of this study are to systematically summarize the efficacy and safety of current targeted drugs for advanced or metastatic GC and GEJC. Methods PubMed, EmBase, Cochrane Library, Web of Science and ClinicalTrials were searched for double-blind randomized controlled trials (RCTs) on GC and GEJC up to December 2019. Additionally, we updated the literature search from Jan, 1, 2020 to September 30, 2021. Narrative and quantitative analysis were performed to analyse the efficacy and safety. STATA 15.1 was used to identify publication bias, and the SUCRA (surface under the cumulative ranking) curve was conducted to rank the treatments for each outcome. Results A total of 27 RCTs with 9295 GC and GEJC patients treated by 19 drugs were included. SUCRA showed that regorafenib was the most likely to improve patients' progression-free survival (96.4%), followed by apatinib (90.7%), nivolumab (82.4%), everolimus (76.5%) and pertuzumab (68.5%). Meanwhile, apatinib (92.4%) was most likely to improve overall survival, followed by nivolumab (87.9%), regorafenib (72.5%), olaparib (67.7%) and lapatinib (63.2%). Additionally, neutropenia, diarrhoea and fatigue were the most common adverse events caused by these drugs, followed by pain, nausea, decreased appetite, anaemia and vomiting. What is new and conclusion Regorafenib and nivolumab have higher efficacy and tolerability and are the most advantageous for advanced GC and GEJC. Moreover, apatinib has higher efficacy but lower tolerability. Everolimus and pertuzumab combined with chemotherapy have best secondary higher efficacy for progression-free survival and good tolerability. Lapatinib and olaparib combined with chemotherapy have moderate efficacy for overall survival and good tolerability.

Background Compared with random copolymers, block copolymerization is easier to prepare for nanoparticles with core-shell structure, and they will have better glucose sensitivity and higher insulin loading. Purpose In our study, insulin-loaded poly (3-acrylamidophenylboronic acid-block-N-vinyl caprolactam) p(AAPBA-b-NVCL) nanoparticles were successfully prepared and were glucose-sensitive, which could effectively lower the blood sugar levels within 72 hrs. Methods The polymer of p(AAPBA-b-NVCL) was produced by reversible addition-fragmentation chain transfer polymerization based on different ratios of 3-acrylamidophenylboronic acid (AAPBA) and N-vinylcaprolactam (NVCL), and its structure was discussed by Fourier transform infrared spectroscopy and 1H-nuclear magnetic resonance . Next, the polymer was manufactured into the nanoparticles, and the characteristics of nanoparticles were detected by dynamic light scattering, lower critical solution temperature, and transmission electron microscopy. After that, the cell and animal toxicity of nanoparticles were also investigated. Results The results demonstrated that p(AAPBA-b-NVCL) was successfully synthesized, and can be easily self-assembled to form nanoparticles. The new nanoparticles included monodisperse submicron particles, with the size of the nanoparticle ranged between 150 and 300nm and are glucose- and temperature-sensitive. Meanwhile, insulin can be easily loaded by p(AAPBA-b-NVCL) nanoparticles and an effective sustained release of insulin was observed when the nanoparticles were placed in physiological saline. Besides, MTT assay revealed that cell viability was more than 80%, and mice demonstrated no negative impact on blood biochemistry and heart, liver, spleen, lung, and kidney after intraperitoneal injection of 10 mg/kg/d of nanoparticles. This suggested that the nanoparticles were low-toxic to both cells and animals. Moreover, they could lower the blood sugar level within 72h. Conclusion Our research suggested that these p(AAPBA-b-NVCL) nanoparticles might have the potential to be applied in a delivery system for insulin or other hypoglycemic proteins.

In this study, we report a novel pH and temperature responsive paclitaxel-loaded drug delivery system based on chitosan and di(ethylene glycol) methyl ether methacrylate. This was functionalized with hyaluronic acid to permit active targeting of CD44-overexpressing human breast cancer cells. The resultant HA-CS-g-PDEGMA-PTX nanoparticles (NPs) have small and uniform sizes (˜170 nm), a high drug loading (13.6 ± 1.3%) and high encapsulation efficiency (76.2 ± 8.5%). Cell viability and confocal microscopy experiments demonstrated that the NPs could effectively target and kill MDA-MB-231 human breast cancer cells, but were much less toxic to healthy human umbilical vein endothelial cells. In vivo biodistribution studies in mice showed that the NPs accumulated in the tumor site, while free drug was distributed more widely and rapidly cleared from the body. Histopathological studies revealed that the NPs led to enhanced apoptosis in the tumor site, which resulted in reduced tumor growth. The NPs prepared in this work have great potential for the treatment of breast cancers, and further offer a platform with which to target other cancers.

Background Theranostics, elaborately integrating both therapeutic and diagnostic functions into a nanoplatform holds great potential for precision cancer medicine. Methods Herein, a biodegradable theranostic nanoplatform with hyperthermia-induced bubble ability for highly efficient ultrasound (US) imaging-guided chemo-photothermal therapy of breast tumors was developed. The prepared nanoparticles consisted of polydopamine (PDA)-modified hollow mesoporous organosilica nanoparticles (HMONs) with approximately 75 nm in diameter for doxorubicin (DOX) loading and perfluoropentane (PFP) filling. In addition, the pH-sensitive PDA coating served as both gatekeeper controlling DOX release and photothermal agent for inducing hyperthermia. Results Such nanoplatform (PDA@HMONs-DOX/PFP, PHDP) provides efficient loading (328 mg/g) and controllable stimuli-responsive release of DOX for chemotherapy. The incorporated disulfide bonds in the framework of HMONs endowed nanoparticles with intrinsic glutathione-responsive biodegradability and improved biocompatibility. Benefiting from the hyperthermia upon an 808-nm laser irradiation of PDA, the liquid-gas phase transition of the loaded PFP was induced, resulting in the generation of the nanobubbles, followed by the coalescence into microbubbles. This conversation could enhance the tumor cell uptake of nanoparticles, as well as intensify the US imaging signals. In addition, a synergistic therapeutic effect of our fabricated nanoplatform on cells/tumor growth effect has been systematically evaluated both in vitro and in vivo. Conclusion Therefore, such "all-in-one" PHDP nanoparticles with satisfactory biocompatibility and biodegradability, hyperthermia-induced bubble ability and simultaneous US imaging performance hold great potential for cancer nanotheranostics.

Two-dimensional (2D) nanomaterials able to effectively absorb near-infrared (NIR) radiation have shown considerable potential as multifunctional platforms in the treatment of cancer. Here, we repor...

In this study, a novel chitosan-based (CS) nanocarrier was developed for doxorubicin (DOX) and oleanolic acid (OA) co-delivery. CS was first functionalized with folic acid to allow selective uptake by cancer cells, and then subsequently with OA. The resultant copolymer self-assembled into nanoparticles (NPs) upon addition to water. These FA-CS-g-OA@DOX nanoparticles (NPs) had appropriate size (180 nm) and size distribution (PDI < 0.45) for tumor therapy, as well as a high drug-loading efficiency (15.6 % w/w DOX; 5.1% w/w OA) and pH-responsive release properties. In breast cancer MDA-MB-231 cells, more efficient uptake of FA-CS-g-OA@DOX NPs than of free DOX was observed by confocal laser scanning microscopy and flow cytometry. The in vitro cytotoxicity of FA-CS-g-OA@DOX NPs against MDA-MB-231 cells was higher than with free DOX and free OA, while the NPs were less harmful to healthy HUVEC cells. In vivo pharmacokinetic studies showed that FA-CS-g-OA@DOX NPs had a much longer circulation time than free DOX, while biodistribution results revealed that FA-CS-g-OA@DOX could actively target a MDA-MB-231 xenograft tumor in mice. The NPs are found to have apoptosis-enhancing and anti-proliferative capacities in vivo. The presence of OA in the formulation both sensitizes cancer cells to DOX and mitigates DOX-induced damage to healthy tissues. The FA-CS-g-OA@DOX NPs generated in this work hence have great potential for the treatment of multi-drug resistant breast cancers, and further offer a platform to target other cancers.

Ginsenoside Rg1 is the active ingredient of Chinese herbal medicine ginseng and sanqi, which has remarkable effects on anti-inflammation and anti-diabetes. In this study, we explored the molecular mechanism of ginsenoside Rg1 against diabetes in rat subjected to insulin resistance induced by high-fat and high-sugar (HFHS). Biochemical analysis revealed that ginsenoside Rg1 significantly decreased the serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, total cholesterol, triglyceride, low-density lipoprotein and increased the serum levels of high-density lipoprotein, which indicated ginsenoside Rg1 improved the extent of hepatic steatosis. Furthermore, ginsenoside Rg1 suppressed the expression of IL-1β, IL-6,TNF-α,NF-κB and G6Pase, however, p-Akt was up-regulated. These results suggested that ginsenosideRg1 improved insulin resistance through suppressing inflammatory response and glucose output, which may be a potential therapeutic strategy in protecting hepatic steatosis.

The fabrication of theranostic nanoplatforms which combine diagnostic and therapeutic functions have become an emerging approach for personal nanomedicine. Herein, a multifunctional nanoplatform consisting of A7R peptide (ATWLPPR) conjugated hollow mesoporous silica nanoparticles decorated with Ag2S nanodots (Ag2S@HMSs-A7R) has been developed as an efficient theranostic agent for simultaneous photoacoustic (PA) imaging and near-infrared fluorescence imaging (NIRF)-guided targeted chemotherapy and photothermal therapy against human breast cancer MDA-MB-231 cells. The design of Ag2S doped HMSs by in situ controlled growth of ultrasmall Ag2S nanodots in the mesopores of HMSs. The synthesized multifunctional nanoplatform exhibits high doxorubicin (DOX) loading capability (451 mg/g) and can be precisely controlled by glutathione (GSH), acidic environment and external laser irradiation. Thanks to the strong tunable NIR absorbance of Ag2S, the nanoplatform produce effective photoacoustic capacity and superb photothermal conversion under light irradiation, thereby exhibiting sufficient in vivo fluorescence and photoacoustic signals as well as desirable photothermal therapeutic performance. Importantly, A7R peptide can selectively bind the Neuropilin-1 (NRP-1) receptor which overexpressed by the MDA-MB-231 cells. The achieved Ag2S@HMSs-A7R possess ideal imaging capability for both PA and NIRF imaging in vivo, and the anti-tumor effect of Ag2S@HMSs(DOX)-A7R was studied in vitro and in vivo, showing remarkable synergistic chemo-photothermal effect (combination index, CI < 1). Over all, the strategy of utilizing triple-responsive nanocarriers presents a highly promising potential as an efficient method for cancer theranostics.