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Fire is a multiple and destructive disaster that usually results in great loss of life and property. Therefore, early detection of fire can help minimize mortality and reduce the risk to ecosystems and property. We propose a novel high-precision flame monitor, YOLOv5-CSF, that can monitor fires using existing monitoring equipment. Based on the YOLOv5 detector, we introduce a coordinate attention mechanism from the backbone network to obtain the relationship between flame position information and channel information in an efficient way which increase the feature expression of the backbone network. The swin transformer block is introduced in the neck network to expand the perceptual field of the network model and improve the flame feature extraction capability. The adaptive spatial feature fusion module is introduced in the head network to strengthen the multi-scale feature fusion of flame features and reduce false alarms. Compared with the original YOLOv5l, the average accuracy of the model is improved by 4.1%. Compared with seven other advanced flame monitors, the proposed algorithm has the highest average accuracy in the flame dataset and the proposed method is quite effective. [ABSTRACT FROM AUTHOR]

The impact between a sphere and flat surface plays a significant role in the granular handling process. A method is proposed to investigate the evolution of interfacial states for the sphere oblique impact with initial spin. Firstly, the sphere with irregular surface structures is applied, and the imprinted surfaces are recorded with a thin carbon paper. Then the interfacial characteristics are analyzed in cases of impact angle, contact material and drop height, etc. The geometrical parameters decrease exponentially with impact angle and include three main stages: plateau, slow decrease and sharp decrease. The motional ratio corresponds to slow increase, steady state and sharp increase. For the no pre-spin, it goes through five interfacial states with impact angle. Comparatively, the forward spin decreases the critical angle, and the backward spin decreases the number of states. Furthermore, the parameters increase linearly with drop height, while the effect on interfacial states is very little. [ABSTRACT FROM AUTHOR]

This study aimed to explore the underlying role and mechanism of LINC00313 in osteoarthritis (OA) progression. CHON-001 chondrocytes were treated with interleukin (IL)-1β to induce OA in vitro, and then transfected with LINC00313 overexpression plasmids (pcDNA-LINC00313) or small interfering RNA against tumor necrosis factor (TNF) receptor-associated factor 1 (si-TRAF1). Cell viability, apoptosis, levels of inflammatory cytokines tumor necrosis factor-α (TNF-α), IL-6 and IL-8, and expression of extracellular matrix (ECM) degradation related proteins in CHON-001 cells were determined. TRAF1 promoter methylation were was detected with methylation‐specific polymerase chain reaction (MSP) assay. Furthermore, a c-Jun N-terminal kinase (JNK) signaling activator was used to confirm whether the apoptosis signal-regulating kinase 1 (ASK1)/JNK signaling pathway was involved in the function of LINC00313/TRAF1 axis in chondrocytes. In addition, an OA mouse model was established and lentivirus LINC00313 overexpression vector (Lv-LINC00313) was injected, and then inflammatory cytokine levels, ECM protein expression, and pathological changes in cartilage tissues were detected. LINC00313 was downregulated and TRAF1 was upregulated in OA cartilage tissues. LINC00313 overexpression or TRAF1 silencing attenuated IL-1β-induced viability inhibition, apoptosis, inflammation and ECM degradation in CHON-001 cells. Moreover, LINC00313 inhibited TRAF1 expression through promoting DNA methyltransferase 1 (DNMT1) mediated promoter methylation. TRAF1 overexpression reversed the effects of LINC00313 on IL-1β-induced chondrocyte injury. LINC00313 overexpression inhibited the ASK1/JNK signaling pathway, and JNK activator reversed the effect. In addition, Lv-LINC00313 treatment alleviated cartilage tissue damage and cartilage matrix degradation in OA mice. LINC00313 alleviated OA progression through inhibiting TRAF1 expression and the ASK1/JNK signaling pathway. [ABSTRACT FROM AUTHOR]

Cycloxygenases (COXs) and matrix metalloproteinases (MMPs) in the tumor microenvironment (TME) are tightly related to the progression of cancers. Here, naproxen as a potent inhibitor of both COX and MMP was combined with platinum(IV) to construct hybrids as antitumor agents. Compound 2 with comparable or even superior activities to that of cisplatin, oxaliplatin, and carboplatin, great potential for reversing drug resistance, and superior tumor targeting properties was screened out as a lead compound. Moreover, compound 2 possessed potent tumor growth inhibition capability in vivo, which was comparable to that of oxaliplatin, and displayed rather lower side effects than the platinum(II) reference drugs. The naproxen platinum(IV) complex could easily undergo reduction and liberate the platinum(II) complex and naproxen as well as exert a multifunctional antitumor mechanism: (i) the liberated platinum(II) fragment would cause serious DNA injury; (ii) naproxen would inhibit COX-2 and decrease tumor-associated inflammation; and (iii) the naproxen platinum(IV) complex exhibited remarkable MMP-9 inhibition in tumor tissues. These antitumor functions can help reduce the growth and metastasis of malignancy. [ABSTRACT FROM AUTHOR]

Silicon is widely investigated as an advanced conversion-type anode material for lithium ion batteries due to the high theoretical capacity and natural abundance. However, the practical application is limited by the intrinsic poor conductivity and serious volume change. To promote the reaction kinetics and reversibility of Si electrode, core-shell structured Si@Fe 2 O 3 /C nanoparticles are fabricated employing metal-organic-frameworks as sacrificed template of Fe 2 O 3 -embedded carbon coating layer. The carbon layer not only boosts the conductivity of Si and Fe 2 O 3 nanoparticles but also accommodates their volume expansion during repeat lithiation/delithiation process. The metallic Fe(0) resulted from the lithiation process helps to improve the conductivity. As anode material for lithium ion batteries, Si@Fe 2 O 3 /C delivers high specific capacity (2941.8 mAh g−1 at 100 mA g−1), good cycling stability (680.7 mAh g−1 after 300 cycles at 1 A g−1) and good rate capability (423 mAh g−1 at 10 A g−1). Image 1 • Novel Si@Fe 2 O 3 /C composite was fabricated using Si@MIL-88-Fe as precursor. • Carbon coating improves the conductivity and cycling stability of the electrode. • Fe 2 O 3 helps to stable the SEI film and further improves the conductivity. • The Si@Fe 2 O 3 /C electrode delivers good lithium storage performance. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Bifunctional 7-hydroxycoumarin platinum(IV) complexes as antitumor agents. • Have much potential in overcoming cisplatin drug-resistance. • Antitumor mechanism was investigated. • Enhanced accumulation in whole cells and DNA. • Combination with HSA by noncovalent forces. Abstract A series of bi-functional 7-hydroxycoumarin platinum(IV) complexes were synthesized, characterized, and evaluated for antitumor activities. The 7-hydroxycoumarin platinum(IV) complexes display moderate to effective antitumor activities toward the tested cell lines and show much potential in overcoming drug resistance of platinum(II) drugs. In reducing microenvironment, the title compounds could be reduced to platinum(II) complex accompanied with two equivalents of coumarin units. By a unique mechanism, the 7-hydroxycoumarin platinum(IV) complex attacks DNA via the released platinum(II) compound, meanwhile it also inhibits the activities of cyclooxygenase by coumarin fragment. This action mechanism might be of much benefit for reducing tumor-related inflammation in the progress of inhibiting tumor proliferation and overcoming cisplatin resistance. The incorporation of 7-hydroxycoumarin leads to significantly enhanced platinum accumulation in both whole tumor cells and DNA. The HSA interaction investigation reveals that the tested coumarin platinum(IV) compound could effectively combine with HSA via van der Waals force and hydrogen bond. [ABSTRACT FROM AUTHOR]

The dielectric parameters of oil-immersed insulation paper, semi-conductive paper and mineral oil were measured at different temperature. The quantitative analysis about the influence of the equalizing cage density on the Inverted-type Oil-immersed Current Transformer (IOCT) electric field distribution was studied, and the temperature dependence of the insulation material dielectric parameters were taken into consideration. In high temperature conditions, the oil-paper damage of IOCT insulation system is generally not caused by electric breakdown but heat aging. The maximum electric field strength of oil-paper I is approximately reduced by 12.84%, and that of the oil-paper II is reduced by 0.35%, after the equalizing cage density is increased. The increasing of the equalizing cage density will be beneficial to the electric field equidistribution of the IOCT insulation system. [ABSTRACT FROM AUTHOR]

A new series of naphthalimide platinum(IV) compounds with dual DNA damage mechanism were designed, synthesized and evaluated for antitumor activities. The platinum(IV) compounds could combine with DNA and cause DNA damage via naphthalimide fragment. Then the platinum(II) complexes released in reductive microenvironment would cause remarkable secondary DNA lesions. Some title compounds exhibit good antitumor activities and are of great potential in overcoming the drug resistance of cisplatin. Furthermore, naphthalimide platinum(IV) complexes could effectively combine with HSA by electrostatic force, which would influence the drug distribution and bioactivities in vivo. Moreover, the accumulation of the tested platinum(IV) compounds in whole cells and DNA is remarkably enhanced in comparison with cisplatin and oxaliplatin. This article describes the design and synthesis of a new series of platinum(IV) compounds with dual DNA damage mechanism. Target compounds exhibited good antitumor activities and were of great potential in overcoming drug resistance. Moreover, they could effectively combine with HSA and further influence the drug distribution and bioactivities in vivo. [ABSTRACT FROM AUTHOR]

Abstract Naphthalimide platinum(IV) antitumor complexes with potential dual DNA damage mechanism were designed, synthesized and evaluated for antitumor activities. The incorporation of DNA targeted naphthalimide group to the platinum(IV) system exerts much positive impacts on their antitumor efficacy. The mechanism research reveals that the title compounds could interact with dsDNA in platinum(IV) form via the naphthalimide group and cause DNA lesion. The further reduction would release platinum(II) complexes and naphthalimide acids which would induce remarkable secondary damage to DNA. Furthermore, the naphthalimide platinum(IV) compounds could combine with human serum albumin via electrostatic force, which are favourable for their storage and transport in blood. Moreover, the title compounds exhibit higher accumulation in tumor cells, and exert lower toxic and higher safe properties than oxaliplatin in vivo. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

ATN‐type FeAPO‐39 molecular sieves with high iron content has been successfully synthesized under non‐solvent conditions, which is the first example of iron‐incorporated aluminophosphate with the ATN‐zeotype structure. The optimum synthetic conditions of this material were refined. It was found that the following synthetic conditions, i.e. a low P2O5/Al2O3 ratio, a high DPA/Al2O3 ratio (DPA: di‐n‐propylamine) and an elevated crystallization temperature, seemed to be more favorable for the non‐solvent synthesis of ATN phase. The composition and structural characteristics of resultant relatively pure FeAPO‐39 molecular sieves were intensively studied by XRD, FT‐IR, TG‐DTA, CHN elemental analysis, ICP‐AES, SEM, TEM, N2 physisorption, UV/Vis diffuse reflectance spectroscopy and Mössbauer spectroscopy analyses. The iron content and zeolite yield of FeAPO‐39 material were found to be as high as 5.56 wt.‐% and 82.6 %, respectively. The results of FT‐IR, TG‐DTA and CHN elemental analysis indicate that DPA molecules may co‐direct the synthesis of ATN zeolites along with additional structure‐directing agent NH4+ ions resulting from iron source. Owing to the specific structure‐directing role provided by iron source, the synthetic strategy presented here may find a potential application in the non‐solvent synthesis of other aluminosilicate and aluminophosphate zeolites with novel frameworks. The incorporation of iron into the framework of ATN‐zeotype structure was achieved in non‐solvent system. DPA molecules and additional NH4+ ions resulting from iron compound act as the SDA. [ABSTRACT FROM AUTHOR]

In the estimation of moisture content of the inverted-type oil-immersed current transformer (IOCT) insulation system, the interfacial polarization between oil-immersed insulation paper and semi-conductive paper should be considered. The classical model functions of frequency-domain dielectric spectroscopy (FDS) are no longer applicable. Therefore, the planar layered two-phase system model is applied in this paper. First, the FDS of oil-immersed paper and semi-conductive paper with certain moisture content is measured using Alpha-A broadband dielectric spectrometer. Then, the FDS of oil-immersed insulation paper is explained using the Havriliak–Negami (H–N) model function and the amendatory H–N model function considering that the dc conductance is used to explain the FDS of semi-conductive paper. The two functions are substituted into the planar layered two-phase system model. The model parameters are fit by means of least-squares technique. Finally, the numerical relationship between the chosen characteristic parameter and the moisture content of the IOCT insulation system is obtained by least-squares technique. In engineering, one can use the results considering the influence of interfacial polarization to estimate the moisture content of the IOCT insulation system. [ABSTRACT FROM AUTHOR]

Conjugates (A1–A5) of the Pt(iv) derivative (A6) with amino groups from peracetyl glucose, rhamnose and mannose with a propyl amino or ethyl amino linker at the reducing end were synthesized and exhibited significant therapeutic efficacy in tumour cells, especially for prostate cancer (PCa). The antitumor activities are greatly affected by glycosyl groups. Cytotoxic experiments in vitro indicated that the antitumor activities were increased by 5-fold when its Pt(iv) derivative was conjugated to S18 (IC50 = 4.82 ± 0.45 μM) and by 12-fold when conjugated to S21 (IC50 = 1.9 ± 0.67 μM). The mannose substituted Pt(iv) complexes A4 and A5 were also over an order of magnitude more potent towards HeLa, A549, MCF-7 and PC3 than cisplatin and oxaliplatin. Importantly, the glycosylated Pt(iv) derivatives A4 and A5 displayed potential safety for clinical therapeutic exposure with IC50 of 84 μM and 169 μM compared with cisplatin (IC50 = 8 μM) to 3T3. Cellular uptake and DNA platination are higher than cisplatin and oxaliplatin. ESI-MS analysis of A5 binding to 5′-dGMP revealed that bifunctional DNA lesions were formed. The antitumor activities in vivo showed that the MTD and LD50 for A4 and A5 are nearly 4-fold higher than that of oxaliplatin indicating the potential safety for the glycosylated Pt(iv) complexes. [ABSTRACT FROM AUTHOR]

Flame detection is critical to human society. Current flame detection methods have problems about huge model volume and large parameters. We proposed an improved YOLOv5-light that reduces the parameters while maintaining the same detection accuracy. First, we use the channel separation shuffling method to ensure the information exchange between channels and optimize the residual structure. Second, depthwise separable convolution is used as the downsampling module in the backbone network to reduce the model's parameters further. Finally, the Ghost module is used to improve the feature extraction module in the head network to reduce computational cost caused by ordinary convolution. The final experimental results show that the proposed YOLOv5-light network achieves detection accuracy similar to that of YOLOv5, with a 65.6% decrease in parameters and a model volume of only 34.8% of the latter. [ABSTRACT FROM AUTHOR]

A new series of glycosylated Pt(iv) complexes were designed, synthesized and evaluated for antitumor activities in vitro and in vivo. The incorporation of glycosyl groups to the Pt(iv) system has much influence on the antitumor abilities. Four lead compounds with activities comparable or even superior to cisplatin and oxaliplatin are screened out. These Pt(iv) complexes could be reduced to release Pt(ii) complexes and cause the death of tumour cells. The apoptosis-inducing properties of these compounds are similar to cisplatin. The accumulation of the glycosylated Pt(iv) complexes in cells and DNA is higher than cisplatin and oxaliplatin. The in vivo assay demonstrates that the tested compounds inhibit the growth of HepG2 tumors with low toxicity. [ABSTRACT FROM AUTHOR]

The influence of O 2 plasma treatment on the mesa-isolated region of AlGaN/GaN heterojunction field-effect transistors (HFETs) was studied. The etched surface of the undoped GaN layer was exposed to O 2 plasma generated by a plasma-enhanced chemical vapor deposition system. The current–voltage characteristics indicated that the current of the mesa-isolated region was strongly dependent on the treatment temperature. Treatment with O 2 plasma at 300 °C and 250 W for 15 min was confirmed to be the optimal condition, under which isolation current was reduced by four orders of magnitude and photovoltaic response was suppressed. The photoluminescence spectrum showed a decrease in the density of defects related to the yellow luminescence band and the occurrence of defects related to the blue luminescence band. X-ray photoelectron spectroscopy results showed the formation of Ga 2 O 3 and a possible defect of substitutional oxygen on the nitrogen site O N . AlGaN/GaN HFETs with an on/off drain current ratio of 1.73 × 10 7 were obtained, and the breakdown voltage of the mesa-isolated region increased from 171.5 to 467.2 V. [ABSTRACT FROM AUTHOR]

GaN MOSFETs were developed on an AlGaN/GaN heterostructure in which the drain and source ohmic contacts were fabricated on the AlGaN/GaN heterostructure, and the electron channel was formed on the GaN buffer layer by removing the AlGaN barrier layer. For devices with different types and sizes, discrepant field-effect mobilities were observed and the origins of the discrepancy were analyzed. One reason causing the discrepancy is the discrepancy of gate dimension between the design and fabrication. In devices with only mesa as the device isolation, the real channel width would be larger than the mesa width because a parallel channel might have formed in the isolation region just outside the device mesa. Boron ion implantation was found to be effective to cutoff the current path in the isolation region. Another reason causing the discrepancy is that the real channel length would be larger than the designed one owing to the lithography and gate dry recess process. To extract the correct mobility and effective channel length of the GaN MOSFET fabricated on AlGaN/GaN heterostructure with variation in the channel dimensions, several methods were proposed and compared basing on ring-type MOSFETs. [ABSTRACT FROM PUBLISHER]

An extra-large-pore aluminophosphate molecular sieve with -CLO topology was successfully synthesized in low-dosage ionic liquids (ILs) via a simplified ionothermal route, for which all raw materials were firstly mixed together, and then ground into homogeneous gels followed by high-temperature crystallization. A representative -CLO-type sample was characterized by XRD, SEM, N 2 physisorption, TG-DSC, CHN elemental analysis and liquid 13C NMR. The results indicate that the synthesis of -CLO topology is through the co-structure directing effect of the ionic liquid 1-ethyl-3-methylimidazolium bromide and diisopropylamine. Moreover, the optimum synthetic conditions of this material were refined. It was found that the appropriate crystallization temperature and time are 190 °C and 2 h, respectively. Owing to the facile preparation procedure and low consumption of ionic liquids, the newly synthesized extra-large-pore -CLO molecular sieve may find potential application in related areas. Image 104271 • –CLO molecular sieve was ionothermally synthesized in low-dosage ionic liquids. • A new synergistic template was found for the synthesis of –CLO material. • A facile preparation procedure was developed to synthesize –CLO material. [ABSTRACT FROM AUTHOR]

• Potent aminonaphthalimide platinum(IV) complex were designed and reported. • Displaying effective antitumor activities in vitro and in vivo. • Exhibiting a dual DNA damage mechanism to tumor cells. • Possessing much potential in overcoming drug resistance of cisplatin. A new aminonaphthalimide platinum(IV) complex was developed by incorporating aminonaphthalimide, a DNA intercalator, into the platinum(IV) system. This complex displayed potent antitumor activities against all tested tumor cell lines in vitro and showed great potential in overcoming drug resistance of cisplatin. Moreover, it remarkably inhibited the growth of CT26 xenografts in BALB/c mice without severe side effects in vivo. Then, the compound exhibited a dual DNA damage antitumor mechanism that it could interact with DNA in tetravalent form via the naphthalimide group to cause DNA lesion, and the further liberation of platinum(II) complex after reduction would induce remarkable secondary damage to DNA. Meanwhile, it caused cell apoptosis through an intrinsic apoptosis pathway by up-regulating the expression of caspase 3 and caspase 9. [ABSTRACT FROM AUTHOR]

[Display omitted] • Microwave assisted-extraction can be used as an effective method to increase the LPIs content. • LPIs using microwave assisted-extraction shows better functionalities. • Microwave assisted-extraction could increase the digestibility and degree of hydrolysis of LPIs. The impacts of microwave assisted-extraction (MAE) on the physicochemical characteristics, functionalities, and digestion behavior of Lactarius volemus (L. volemus) protein isolate (LPIs) was investigated. Compared with the conventional water bath assisted-extraction method (WAE), MAE significantly enhanced the extraction rate of LPIs by 30.00% and 47.98% at 20 and 60 min, respectively. Also, MAE unfolded the spatial structure of LPIs, promoting the transformation from ordered structure to disordered structure, exposing its hydrophobic groups and increasing free sulfhydryl content. In addition, LPIs obtained by MAE showed better solubility, emulsifying and foaming characteristics than that by WAE. MAE method can improve the digestibility and the degree of hydrolysis of LPIs compared to WAE, which were increased by 6.06% and 19.78% after 20 min extraction in the small intestine digestion, respectively. This study can provide a potential strategy to produce L. volemus protein isolate with high efficiency and quality. [ABSTRACT FROM AUTHOR]

Intramolecular catalytic hairpin assembly (intraCHA) has recently been developed. However, non-nucleic acid-initiated intraCHA is rarely explored. The only protein-initiated intraCHA depends on the unwarrantable binding affinity between protein and its aptamer, which generally results in limited initiation efficiency. Herein, a "repaired and initiated" intraCHA (RI-intraCHA) nanosystem was designed and its operation was reported for amplified imaging of DNA repair enzyme activity in live cells. 8-oxoguanine (8-OG) DNA glycosylase was selected as the model DNA repair enzyme. The RI-intraCHA nanosystem was constructed by linking a dsDNA (containing 8-OG sites and trigger strand), two hairpins to different vertexes of DNA tetrahedron. The nanosystem could independently enter into live cells in virtue of cell permeability of DNA tetrahedron. Upon repair action of endogenous 8-OG DNA glycosylase, intraCHA reaction in the nanosystem was initiated efficiently, generating amplified fluorescence signal. The nanosystem provided a detection limit of 0.2443 U/mL for 8-OG DNA glycosylase, which was lower than that of the reported imaging approaches. Furthermore, the nanosystem exhibited satisfactory biosafety and biostability, achieving amplified imaging of intracellular 8-OG DNA glycosylase activity. The designed RI-intraCHA nanosystem provided a promising tool for the research of basic biology of intracellular DNA repair enzymes as well as their clinic correlations. Schematic representation of the "repaired and initiated" intramolecular catalytic hairpin assembly (RI-intraCHA) nanosystem for amplified imaging the activity of intracellular 8-oxoguanine (8-OG) DNA glycosylase (a model DNA repair enzyme). [Display omitted] • "Repaired and initiated" intramolecular catalytic hairpin assembly system was showed. • The system depended on the repair action of 8-oxoguanine DNA glycosylase. • High efficient initiation of intramolecular catalytic hairpin assembly was achieved. • The system entered cells independently with satisfactory biosafety and biostability. • Amplified imaging intracellular 8-oxoguanine DNA glycosylase activity was realized. [ABSTRACT FROM AUTHOR]

The development of novel anticancer drugs with antiproliferative and antimetastatic activities is of great importance in the pharmaceutical field. Herein, a series of ligustrazine (LSZ) platinum(IV) complexes with chemotherapeutic and immunotherapeutic effects were designed, prepared and evaluated as antitumor agents for the first time. Complex 4 with potent antitumor activities both in vitro and in vivo was screened out as a candidate. Notably, it displays significantly more effective anti-metastatic activities than the platinum(II) drugs cisplatin and oxaliplatin. Mechanism detection discloses that it causes serious DNA damage and increases the expression of γ-H2AX and P53. Then, the apoptosis of tumor cells is promoted by activating the mitochondrial apoptotic pathway Bcl-2/Bax/caspase-3 and causing autophagy via modulating LC3-I/II and P62 expression. Furthermore, the immune therapeutic responses are significantly elevated by blocking HIF-1α, ERK 1/2 and COX-2 pathways to reduce PD-L1 expression, and further increasing CD3+ and CD8+ T cells to elevate T cell immunity in tumors. Tumor metastasis is blocked by the synergistic functions of DNA damage, hypoxia modulation and immune activation. [ABSTRACT FROM AUTHOR]

Plant fiber-reinforced polylactic acid (PLA) exhibits excellent mechanical properties and environmental friendliness and, therefore, has a wide range of applications. This study investigated the mechanical properties of three short plant fiber-reinforced PLA composites (flax, jute, and ramie) using mechanical testing and material characterization techniques (SEM, FTIR, and DSC). Additionally, we propose a methodology for predicting the mechanical properties of high-content short plant fiber-reinforced composite materials. Results indicate that flax fibers provide the optimal reinforcement effect due to differences in fiber composition and microstructure. Surface pretreatment of the fibers using alkali and silane coupling agents increases the fiber–matrix interface contact area, improves interface performance, and effectively enhances the mechanical properties of the composite. The mechanical properties of the composites increase with increasing fiber content, reaching the highest value at 40%, which is 38.79% higher than pure PLA. However, further increases in content lead to fiber agglomeration and decreased composite properties. When the content is relatively low (10%), the mechanical properties are degraded because of internal defects in the material, which is 40.42% lower than pure PLA. Through Micro-CT technology, the fiber was reconstructed, and it was found that the fiber was distributed mainly along the direction of injection molding, and the twin-screw process changes the shape and length of the fiber. By introducing the fiber agglomeration factor function and correcting the Halpin-Tsai criterion, the mechanical properties of composite materials with different contents were successfully predicted. Considering the complex stress state of composite materials in actual service processes, a numerical simulation method was established based on transversely isotropic material using the finite element method combined with theoretical analysis. The mechanical properties of high-content short plant fiber-reinforced composite materials were successfully predicted, and the simulation results showed strong agreement with the experimental results. [ABSTRACT FROM AUTHOR]

Summary: Interleukin‐35 (IL‐35) is a recently identified heterodimeric cytokine in the IL‐12 family. It consists of an IL‐12 subunit α chain (P35) and IL‐27 subunit Epstein–Barr virus‐induced gene 3 (EBI3) β chain. Unlike the other IL‐12 family members, it signals through four unconventional receptors: IL‐12Rβ2–IL‐27Rα, IL‐12Rβ2–IL‐12Rβ2, IL‐12Rβ2–GP130, and GP130–GP130. Interleukin‐35 signaling is mainly carried out through the signal transducer and activator of transcription family of proteins. It is secreted not only by regulatory T (Treg) cells, but also by CD8+ Treg cells, activated dendritic cells and regulatory B cells. It exhibits immunosuppressive functions distinct from those of other members of the IL‐12 family; these are mediated primarily by the inhibition of T helper type 17 cell differentiation and promotion of Treg cell proliferation. Interleukin‐35 plays a critical role in several immune‐associated diseases, such as autoimmune diseases and viral and bacterial infections, as well as in tumors. In this review, we summarize the structure and function of IL‐35, describe its role in immune‐related disorders, and discuss the mechanisms by which it regulates the development and progression of diseases, including inflammatory bowel disease, collagen‐induced arthritis, allergic airway disease, hepatitis, and tumors. The recent research on IL‐35, combined with improved techniques of studying receptors and signal transduction pathways, allows for consideration of IL‐35 as a novel immunotherapy target. [ABSTRACT FROM AUTHOR]

Abstract Iron-containing aluminophosphate molecular sieve with LEV topology (Fe-LEV molecular sieve) has been successfully synthesized by a microwave-assisted ionothermal method in low-dosage of eutectic mixture solvent, which is the first example of Fe incorporated aluminophosphates with the LEV-zeotype structure. The optimum synthetic conditions of this material were refined. The structure and morphology of a representative Fe-LEV sample, as well as the structure directing effect of eutectic mixture were thoroughly analyzed by various techniques including XRD, 27Al and 31P MAS NMR, ICP-AES, DR UV-Vis, ESR, XPS, N 2 adsorption/desorption, NH 3 -TPD, SEM, TEM, EDX, CHN elemental analysis, TG-DTA and FT-IR spectra. It was found that the combined effect of the starting precursor and a suitable structure-directing agent yielded an appropriate crystallization system of Fe-LEV molecular sieve, for which choline cations and intact tetraethylammonium bromide molecules were identified to be the structure-directing agents. The calcined Fe-LEV molecular sieve exhibits higher specific surface area and iron content, as well as a medium acidity and special hierarchical structure with both micropores and mesopores, implying that these zeolitic materials have a great potential in some industrially relevant applications. Graphical abstract Image 1 Highlights • The incorporation of iron into the framework of LEV-zeotype structure was achieved. • Fe-LEV zeolite was synthesized by microwave irradiation in low-dosage of eutectic mixture. • Choline cations and tetraethylammonium bromide molecules act as the SDAs. • Fast synthesis of Fe-LEV zeolite was achieved within 20 min. [ABSTRACT FROM AUTHOR]

DC bias in power transformers leads to strong core saturation and thus nonlinearly inferior operation. This paper analyzes the ability of power transformers to withstand the dc bias by novel analytical criteria. The proposed criteria are obtained from the nonlinear equivalent circuit, which considers the effects of nonlinear inductances. The validity of the proposed analytical criteria is verified by the finite-element analysis results and experimental results, which indicates that the proposed analytical criteria are effective to evaluate the ability to withstand the dc bias of power transformers. [ABSTRACT FROM AUTHOR]

Years of outbreaks of woody canker (Cryptosphaeria pullmanensis) in the United States, Iran, and China have resulted in massive economic losses to biological forests and fruit trees. However, only limited information is available on their distribution, and their habitat requirements have not been well evaluated due to a lack of research. In recent years, scientists have utilized the MaxEnt model to estimate the effect of global temperature and specific environmental conditions on species distribution. Using occurrence and high resolution ecological data, we predicted the spatiotemporal distribution of C. pullmanensis under twelve climate change scenarios by applying the MaxEnt model. We identified climatic factors, geography, soil, and land cover that shape their distribution range and determined shifts in their habitat range. Then, we measured the suitable habitat area, the ratio of change in the area of suitable habitat, the expansion and shrinkage of maps under climate change, the direction and distance of range changes from the present to the end of the twenty-first century, and the effect of environmental variables. C. pullmanensis is mostly widespread in high-suitability regions in northwestern China, the majority of Iran, Afghanistan, and Turkey, northern Chile, southwestern Argentina, and the west coast of California in the United States. Under future climatic conditions, climate changes of varied intensities favored the expansion of suitable habitats for C. pullmanensis in China. However, appropriate land areas are diminishing globally. The trend in migration is toward latitudes and elevations that are higher. The estimated area of possible suitability shifted eastward in China. The results of the present study are valuable not only for countries such as Morocco, Spain, Chile, Turkey, Kazakhstan, etc., where the infection has not yet fully spread or been established, but also for nations where the species has been discovered. Authorities should take steps to reduce greenhouse gas emissions in order to restrict the spread of C. pullmanensis. Countries with highly appropriate locations should increase their surveillance, risk assessment, and response capabilities. [ABSTRACT FROM AUTHOR]

To develop new chemotherapeutics with anti-metastasis properties, a series of multi-specific niflumic acid (NFA) platinum(IV) complexes with DNA damage, inflammation inhibition, immunity activation, and angiogenesis suppression mechanisms were designed, synthesized and evaluated as novel antitumor agents. The dual NFA platinum(IV) complex with a cisplatin core showed promising antitumor activities both in vitro and in vivo with lower toxicity than platinum(II) drugs and displayed attractive anti-metastasis performance. It caused serious DNA damage and further elevated the expression of γ-H2AX. Furthermore, it promoted apoptosis by activating the mitochondrial apoptotic pathway and autophagy of tumor cells. Moreover, immune response in tumors was significantly improved by increasing CD3+, CD4+ and CD8+ T infiltrating cells. Subsequently, the pathway ERK/HIF-1α/VEGFA associated with angiogenesis was suppressed by the reduced inflammation and elevated immune response, and the density of microvessels marked by CD34 was significantly reduced in tumors. Accordingly, the multi-specific NFA platinum(IV) complexes have great potential to be developed as novel anti-proliferative and anti-metastatic drugs. [ABSTRACT FROM AUTHOR]

An 11-story high-rise building with a shear-wall structure utilized a raft foundation based on a deep alluvial deposit. After structure completion, the building tilted beyond acceptable limits. This paper presents the investigation, settlement analysis, building rectification, and foundation remediation. The purpose of this study is to provide a common method of addressing similar problems and propose two formulas to guide design. First, through site investigation and settlement reanalysis, it was determined that the large settlement and building eccentricity accounted for the building tilt. Second, underexcavation was used for the side with less subsidence to address the building differential settlement, and precast micropiles were driven into the foundation to improve foundation safety. Finally, two formulas for underexcavation were proposed to apply to general rectification projects. A simplified analysis method was adopted for formula derivation. In accordance with the force balance in the foundation soil before and after underexcavation, the preferable hole spacing could be expressed as a multiple of the hole diameter, i.e., λ=K/(K−1) , which mainly depends on the safety factor of the bearing capacity of the foundation soil. Assuming that the extraction volume of soil equals the forced settlement volume for inclination correction, the diameter of the hole is obtained, i.e., d=4λs/π , which mainly depends on the proposed forced settlement. The key parameters were verified by the case history. The case history and practical design method provide a framework for projects experiencing differential settlement. Buildings sometimes incline. Reasons for the inclination are various, such as severe foundation settlement, surrounding underground construction, neighboring foundation pit excavation, and underground water drainage. Underexcavation is a cost-effective and "soft" method of rectifying buildings. It is suitable for buildings with shallow foundations. This paper presents a case history, and theoretical formulas for underexcavation design are proposed. In the case study, the methods of investigating and analyzing building inclination and the technology of inclination correction can provide valuable references for similar projects. The theoretical formulas can provide the key parameters of limit hole spacing and hole diameter for a correction design and enable a designer to quickly give a correction scheme for general conditions. For specific projects, appropriate adjustments should be made according to geotechnical conditions, the surrounding environment, and the suitability of construction. Notably, even with the formulas to guide design and construction, in view of the complexity of geological issues, close monitoring is still essential. [ABSTRACT FROM AUTHOR]

To develop new anti-metastasis chemotherapeutic drugs, a series of flurbiprofen (FLP) and zaltoprofen (ZTP) platinum(IV) complexes targeting COX-2, PD-L1 and DNA was prepared and investigated. Complex 2 with dual FLP ligands displays promising antitumor activities in vitro and exhibits much potential in overcoming drug resistance. More importantly, the antitumor evaluation in vivo demonstrates that complex 2 possesses promising inhibition of cancer growth and metastasis simultaneously. Further investigation of the mechanism revealed the multi-specific antitumor function of complex 2. It exerts remarkable DNA damage after reduction to platinum(II) complex, and up-regulates the expression of p53 and γ-H2AX. Then, complex 2 promotes mitochondria-mediated apoptosis effectively by activating the Bcl-2/Bax/caspase3 pathway. Furthermore, inflammation in tumor tissues is restrained by the suppression of enzymes COX-2, MMP-9, NLRP3 and caspase1, which would favor the inhibition of tumor metastasis. Moreover, compound 2 boosts T-cell immunity by restraining PD-L1 expression, and further improving the density of CD3+ and CD8+ T cells in tumor tissues. [ABSTRACT FROM AUTHOR]

[Display omitted] • The binding between BLG and ECG/PIC followed the trend of pH 8.5 > pH 6.0 > pH 4.0. • ECG and PIC were competitively bound to BLG in the ternary system. • The β-sheet or D h of (BLG + PIC) + ECG in ternary systems at pH 6.0 was the smallest. • pH and BLG influenced the synergistic antioxidant effect between ECG and PIC. • ECG or PIC was the most stable in the (BLG + PIC) + ECG system at pH 6.0. (−)-Epicatechin gallate (ECG) and piceatannol (PIC) are commonly polyphenols with excellent biological activities. β-Lactoglobulin (BLG) is a food-grade globule protein and its morphologies are sensitive to pH. This study used experimental and computational methods to determine the interaction of single or combined ECG and PIC with BLG at different pHs. The static quenching process was determined through fluorescence and ultraviolet–visible spectroscopy. Compared with ECG, PIC could significantly bind to BLG with higher affinity. Their binding affinity for BLG with different morphologies followed the tendency of monomer > dimer > tetramer. The negative contribution of van der Waals forces, electrostatic interactions, and hydrogen bonds to Δ H o exceeded the positive contribution of hydrophobic interactions in the spontaneous and exothermic process. The reduced binding affinity in the ternary systems demonstrated the competitive binding between ECG and PIC on BLG, and the hinder effect of ECG or PIC was enhanced with increasing pH. Molecular docking studies revealed the same binding sites of ECG and PIC on various conformations of BLG and identical driven forces as thermodynamic results. Tryptophan and tyrosine were the main participators in the BLG + ECG and BLG + PIC systems, respectively. The conformational changes in the binary and ternary systems could be ascertained through synchronous fluorescence, circular dichroism, and dynamic light scattering. Furthermore, the effects of pH and BLG encapsulation on the antioxidant capacity and stability of ECG or PIC were also implemented. ECG or PIC was the most stable in the (BLG + PIC) + ECG system at pH 6.0. This study could clarify the interaction mechanism between ECG/PIC and BLG and elucidate the pH effect on their binding information. The results will provide basic support for their usage in food processing and applications. [ABSTRACT FROM AUTHOR]

Background clinical trials dedicated to the older patients with cancer are essential to help to define optimal cancer therapy for this rapidly growing population. Our study aimed to analyse the characteristics and the evolution of older-patient-specific oncological trials registered in ClinicalTrials.gov. Methods a dataset of 61,120 oncological trials registered in ClinicalTrials.gov between 2000 and 2019 was downloaded. Characteristics of older-patient-specific trials were compared with characteristics of age-unspecified trials. Chronological shifts in older-patient-specific trials were also analysed. Results of the 49,273 interventional trials eligible for analysis, only 490 (1.0%) were older-patient-specific. More than half of the older-patient-specific trials were phase 2 and enrolled less than 100 patients. Compared with age-unspecified trials, older-patient-specific trials were less likely to be funded by industry (26.9 vs 37.1%), and more likely to be conducted in Europe (44.5 vs 28.3%). During the two time periods between 2000 and 2009, and 2010 and 2019, the proportion of supportive care-oriented trials increased from 1.9 to 13.9%. Concerningly, the use of clinically meaningful end points in older patients such as disease-specific survival, patient-reported outcomes and functional status as a primary end point was uncommon (0.4, 8.1 and 7.3%, respectively). There was no correlation between the number of trials for a given cancer type and relative incidence and mortality. 196/490 (40.0%) of the trials were conducted for patients with haematological cancer. Conclusion our study helps us to better understand the current state of older-patient-specific oncological trials and provide insights for future development, resulting in the improvement of the care of older patients with cancer. [ABSTRACT FROM AUTHOR]

This study developed co-loaded vitamin B 12 (vitB 12) and D 3 (vitD 3) solid microcapsules using W 1 /O/W 2 emulsions, followed by spray-drying. The effects of four polysaccharide-based gels as co-encapsulants on the microcapsules' morphological characteristics, encapsulation efficiency, storage stability, and gastrointestinal simulation were explored. The electrostatic bonding with chitosan in W 1 and multilayer protection from the W 1 /O/W 2 structure cause the high encapsulation efficiency of vitB 12 (88.3 ± 0.8%–92.7 ± 1.1%). Further, adding polysaccharides into W 2 improved the particle integrity of the dried powders and enhanced the retention rate and encapsulation efficiency of vitamins. Stability testing revealed that the encapsulation matrix incorporating sodium carboxymethylcellulose provided the best protection for vitB 12 (plateau values of 97.8 and 95.8% at 25 and 40 °C, respectively) and lower degradation rates for vitD 3 (decay constants k D of 0.26 and 0.49%/day). The formulation containing sodium alginate exhibited a controlled release of core components under simulated gastric conditions and the highest cumulative release (91.1 ± 5.3% vitB 12 and 81.9 ± 3.6% vitD 3) under simulated intestinal conditions. Our study suggests that the co-encapsulation strategy using the W 1 /O/W 2 structure and spray-drying can be utilised to obtain good commercial products containing hydrophilic and lipophilic components, and polysaccharides as co-encapsulants can effectively regulate the chemical stability and release behaviour of the encapsulated components. [Display omitted] • Vitamin B 12 and D 3 co-loaded emulsions and their dry microcapsules are prepared. • Four polysaccharide-based gels are used as co-encapsulants. • Multilayer protection improved the encapsulation efficiency of vitamins. • Polysaccharide-based gels enhance the microencapsulated particle integrity. • CMC and SA improve chemical stability and controlled release of vitamins. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pneumonia infection is associated with high rates of hospitalization and mortality and this has placed healthcare systems under strain. Our study provides a novel method for the progress prediction, clinical treatment and prognosis of NCP, and has important clinical value for timely treatment of severe NCP patients. To summarize the clinical features and severe illness risk factors of the patients with novel coronavirus pneumonia (NCP), in order to provide support for the progression prediction, clinical treatment and prognosis of NCP patients. A total of 196 NCP patients treated in our hospital from January 25, 2020 to June 21, 2020 were divided into the severe group and the mild group. The clinical features of the two groups were analyzed and compared. The risk factors were explored by using multivariate logistic regression, and the receiver operating characteristic (ROC) curve was obtained. The correlations of the risk factors with the prognosis of NCP were investigated combined with the lung function test. The primary clinical symptoms of 196 cases of NCP included fever in 167 cases (85.2%) and cough in 121 cases (61.73%). The chest computed tomography (CT) scans of the 178 cases (90.81%) showed a typical ground-glass opacification. In 149 cases, the lymphocyte count was decreased, while the levels of creatine kinase (CK), lactate dehydrogenase (LDH), c-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and D-dimer (D-D) increased. 44 cases (22.45%) were found to be severely ill. The multivariate logistic regression analysis demonstrated that age, underlying disease, length of hospital stay, body mass index (BMI), LDH, chest CT visual score, absolute lymphocyte count (ALC) and CRP were risk factors for severe [ABSTRACT FROM AUTHOR]

Background: Walnut anthracnose caused by Colletotrichum gloeosporioides (Penz.) Penz. and Sacc. is an important walnut production problem in China. Although the long non-coding RNAs (lncRNAs) are important for plant disease resistance, the molecular mechanisms underlying resistance to C. gloeosporioides in walnut remain poorly understood. Results: The anthracnose-resistant F26 fruits from the B26 clone and the anthracnose-susceptible F423 fruits from the 4–23 clone of walnut were used as the test materials. Specifically, we performed a comparative transcriptome analysis of F26 and F423 fruit bracts to identify differentially expressed LncRNAs (DELs) at five time-points (tissues at 0 hpi, pathological tissues at 24 hpi, 48 hpi, 72 hpi, and distal uninoculated tissues at 120 hpi). Compared with F423, a total of 14,525 DELs were identified, including 10,645 upregulated lncRNAs and 3846 downregulated lncRNAs in F26. The number of upregulated lncRNAs in F26 compared to in F423 was significantly higher at the early stages of C. gloeosporioides infection. A total of 5 modules related to disease resistance were screened by WGCNA and the target genes of lncRNAs were obtained. Bioinformatic analysis showed that the target genes of upregulated lncRNAs were enriched in immune-related processes during the infection of C. gloeosporioides, such as activation of innate immune response, defense response to bacterium, incompatible interaction and immune system process, and enriched in plant hormone signal transduction, phenylpropanoid biosynthesis and other pathways. And 124 known target genes for 96 hub lncRNAs were predicted, including 10 known resistance genes. The expression of 5 lncRNAs and 5 target genes was confirmed by qPCR, which was consistent with the RNA-seq data. Conclusions: The results of this study provide the basis for future functional characterizations of lncRNAs regarding the C. gloeosporioides resistance of walnut fruit bracts. [ABSTRACT FROM AUTHOR]

The design of novel platinum(IV) complexes with mitochondria injury competence, besides the DNA damage mechanism, is a promising way to develop new platinum drugs. Herein, dihydro-2-quinolone (DHQLO) as a mitocan was incorporated into the platinum(IV) system for the first time to prepare a new series of DHQLO platinum(IV) compounds. Complex 1b could effectively inhibit the proliferation of tumor cells in vitro and in vivo. It accumulated at higher levels in both whole cells and DNA, and easily underwent intercellular reduction to release platinum(II) and DHQLO moieties. The released platinum(II) complex caused serious DNA damage by covalent conjunction with the DNA duplex, and remarkably increased the expression of the γ-H2AX protein. Moreover, 1b also caused serious mitochondria injury to induce mitochondrial membrane depolarization and increase ROS generation. Such actions upon DNA and mitochondria activate the p53 apoptotic pathway synergetically in tumor cells by upregulating the protein p53 and apoptotic proteins caspase9 and caspase3, which efficiently promoted the apoptotic death of tumor cells. Compound 1b with such synergic mechanism exhibited great potential in reversing cisplatin resistance and improving antitumor efficacies. [ABSTRACT FROM AUTHOR]

Combinatorial chemo-photodynamic therapy is regared as effective cancer therapy strategy, which could be realized via multiple nano-drug delivery system. Herein, novel high payload nanoparticles stabilized by amphiphilic block polymer cholesterol-b-poly(ethylene glycol) (PEG)2000 (Chol-PEG2000) were fabricated for loading chemotherapeutic drug 10-hydroxycamptothecin (HCPT) and photosensitizer chlorin e6 (Ce6). The obtained HCPT/Ce6 NPs showed uniform rod-like morphology with a hydration diameter of 178.9 ± 4.0 nm and excellent stability in aqueous solution. HCPT and Ce6 in the NPs displayed differential release profile, which was benefit for preferentially exerting the photodynamic effect and subsequently enhancing the sensitivity of the cells to HCPT. Under laser irradiation, the NPs demonstrated fantastic in vitro and in vivo anticancer efficiency due to combinational chemo-photodynamic therapy, enhanced cellular uptake effectiveness, and superb intracellular ROS productivity. Besides, the NPs were proved as absent of systemic toxicity. In summary, this nanoparticle delivery system could be hopefully utilized as effective cancer therapy strategy for synergistically exerting combined chemo-photodynamic therapy in clinic. [ABSTRACT FROM AUTHOR]

Nickel phosphides are considered to be a promising lithium storage host due to their high theoretical capacities. However, the volume change during the charge–discharge process and inherent poor reaction kinetics limit their electrochemical performance. To solve these problems, Ni/Ni2P heterostructures encapsulated in 3D porous carbon networks are fabricated. The macro/micro-pores-rich carbon networks are in situ constructed via a freeze-drying method and subsequent pyrolysis route using NaCl as a template. In the following phosphorization process, Ni/Ni2P nanoparticles are homogenously embedded in the carbon matrix. When used as anodes for lithium ion batteries, the Ni/Ni2P/porous carbon networks deliver high discharge capacity, good cycling stability as well as good rate performance. It is believed that metallic Ni and porous carbon networks significantly improve the conductivity of electrodes. Moreover, the 3D conductive matrix can not only alleviate the volume change, but also prevent the aggregation and pulverization of Ni2P nanoparticles during the charge–discharge process. [ABSTRACT FROM AUTHOR]

Abstract A series of new 4-hydroxycoumarin platinum(IV) complexes were designed, synthesized and evaluated as antitumor agents. All the title compounds display moderate to effective antitumor activities toward the tested cell lines and two prominent compounds were screened out with activities comparable to cisplatin and oxaliplatin. The mechanism investigation demonstrates that the platinum(IV) compounds could be reduced to bivalence and exert significant genotoxicity to tumor cells. Meanwhile the coumarin moiety endows the title compounds with cyclooxygenase inhibitory competence which might favour the reduction of tumor-related inflammation and further influence tumor proliferation. The coumarin platinum(IV) complex could effectively induce apoptosis of SKOV-3 cells through up-regulating the expression of caspase3 and caspase9. Furthermore, the conversion of platinum(II) drugs to platinum(IV) form via the conjunction with 4-hydroxycoumarin enhances the drug uptake in whole cells and DNA simultaneously. Moreover, the 4-hydroxycoumarin platinum(IV) complex could combine with human serum albumin via van der Waals force and hydrogen bond, which would influence their transport and bioactivities in vivo. Graphical abstract New 4-hydroxycoumarin platinum(IV) hybrids were designed, synthesized and evaluated as antitumor agents. The platinum(IV) core could be reduced to bivalence and display significant genotoxicity. Meanwhile the coumarin group endows the title compounds with cyclooxygenase inhibitory competence which would favour of reducing tumor-related inflammation and further influencing tumor proliferation. Unlabelled Image Highlights • Development of 4-hydroxycoumarin platinum(IV) hybrids as antitumor agents • Antitumor activities were evaluated and the action mechanism was investigated. • Active apoptotic pathway by up-regulating the expression of caspase3 and caspase9 • Exert higher accumulation in both whole cells and DNA than platinum(II) drugs • Combine with human serum albumin effectively by noncovalent forces [ABSTRACT FROM AUTHOR]

[Display omitted] • A DNA tetrahedron linked with the targeting aptamer MUC1 (MUC1-TD) was constructed. • Daunorubicin (DAU) and acridine orange (AO) intercalatively bound to MUC1-TD. • The presence of AO in the ternary system weakened the binding of DAU to MUC1-TD. • The combined DAU and AO had a synergistic cytotoxicity on drug-resistant cells. • The loading of MUC1-TD augmented the cytotoxic effects of DAU and AO. Chemotherapy–phototherapy (CTPT) combination drugs co-loaded by targeted DNA nanostructures can achieve controlled drug delivery, reduce toxic side effects and overcome multidrug resistance. Herein, we constructed and characterized a DNA tetrahedral nanostructure (MUC1-TD) linked with the targeting aptamer MUC1. The interaction of daunorubicin (DAU)/acridine orange (AO) alone and in combination with MUC1-TD and the influence of the interaction on the cytotoxicity of the drugs were evaluated. Potassium ferrocyanide quenching analysis and DNA melting temperature assays were used to demonstrate the intercalative binding of DAU/AO to MUC1-TD. The interactions of DAU and/or AO with MUC1-TD were analyzed by fluorescence spectroscopy and differential scanning calorimetry. The number of binding sites, binding constant, entropy and enthalpy changes of the binding process were obtained. The binding strength and binding sites of DAU were higher than those of AO. The presence of AO in the ternary system weakened the binding of DAU to MUC1-TD. In vitro cytotoxicity studies demonstrated that the loading of MUC1-TD augmented the inhibitory effects of DAU and AO and the synergistic cytotoxic effects of DAU + AO on MCF-7 cells and MCF-7/ADR cells. Cell uptake studies showed that the loading of MUC1-TD was beneficial in promoting the apoptosis of MCF-7/ADR cells due to its enhanced targeting to the nucleus. This study has important guiding significance for the combined application of DAU and AO co-loaded by DNA nanostructures to overcome multidrug resistance. [ABSTRACT FROM AUTHOR]

With the ever-growing development of information technology, the education sector has adopted advanced technologies to improve this field. Various procedures based on human–computer interaction (HCI) can be applied to enhance the efficiency of interaction between humans and computers, especially in education. Active learning is one of the major technological fields that improve the usability of active learning. The implementation of HCI approaches such as project-based learning (PBL), active learning classrooms (ALCs), and multi-user virtual environments (MUVE) can improve students' learning capabilities and teachers' teaching skills, making education more effective. After studying different applications of HCI in active learning, this study aims to extract common features and identify the most efficient ones. For the evaluation process, we presented two techniques: Criteria Importance Through Inter Correlation (CRITIC) and Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) to select the most effective HCI approach among various options. We chose nine criteria along with ten alternatives and ranked them based on their performance scores. For assigning weights to criteria, we utilized the CRITIC strategy, while the TOPSIS technique was applied to rank the alternatives. In the proposed study, we identified that the alternative with the highest performance score is placed in first place, while the alternative with the worst performance score is placed at the bottom. The study concluded that the most efficient and effective approach was selected among various options, which can be used as a suggestion for decision-related issues and future directions. [ABSTRACT FROM AUTHOR]

Herein, cyclosporine A loaded liposomes (CsA-Lips) were fabricated aimed at improving the biocompatibility of the ophthalmic formulation and getting rid of the direct contact of ocular tissues with irritant excipients. Response surface methodology was exploited in order to investigate the influence of miscellaneous factors on the key characteristics of CsA-Lips. Ratio of EPC:CsA, ratio of EPC:Chol, and stirring speed were selected as the independent variables, while size, drug-loading content (DL), and drug-loading content (DL) loss rate were applied as the response variables. In case of the maximal lack-of-fit p-value and minimum sequential p-value, quadratic model was regarded as the fittest model to analyze the data. The correlation of independent variables with response variables was described by three-dimension surface figures. Optimized formulation for CsA-Lips was obtained with ratio of EPC:CsA set as 15, ratio of EPC:Chol set as 2, and stirring speed set as 800 rpm. The particle size of CsA-Lips was 129.2 nm after optimalization while their TEM images exhibited spherical unilamellar vesicles with clearly shell-core structure. CsA released more rapidly from CsA-Lips in comparison with self-made emulsion and Restasis®. Besides, minimum cytotoxicity of CsA-Lips was perceived via both MTT method and LDH method, indicating the excellent compatibility of the ophthalmic formulation. Simultaneously, CsA-Lips showed enhanced nonspecific internalization in the cytoplasm with a time-dose-dependent manner. In conclusion, CsA-Lips could be adhibited as the hopeful ophthalmic drug delivery system clinically for dry eye syndrome (DES). [Display omitted] • Cyclosporin A liposomes were fabricated via ethanol injection method. • Response surface methodology was exploited to advance the formulation. • Cyclosporin A liposomes exhibited excellent colloidal stability. • Cyclosporin A liposomes possessed superb cellular uptake efficiency. • Cyclosporin A liposomes displayed fantastic in vitro compatibility and safety. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel method to enhance the electrochemical response sensitivity of graphene-modified screen-printed carbon electrode (G/SPCE) with polypyrrole nanosheets is proposed. • The sensitivity mechanism was investigated at the molecular level by experimental characterization and density functional theory calculations. • The increased dimensionality of reactive interface by PPy is the key to enhance response sensitivity of G/SPCE. • The response sensitivity of graphene to PF molecule is greatly enhanced by the synergistic effect generated of PPy and graphene. Here, a novel method to enhance the electrochemical properties of graphene-modified screen-printed carbon electrode (G/SPCE) with polypyrrole (PPy) nanosheets is proposed. The mechanism of improving the electrochemical sensitivity of G/SPCE was investigated at the molecular level. G/SPCE was modified with PPy nanosheets synthesized by oxidative polymerization to improve its electrochemical properties. The cyclic voltammetry (CV) and differential pulse voltammetry (DPV) response of PPy-modified G/SPCE (PPy/G/SPCE) to K 3 [Fe(CN) 6 ] (PF) were tested experimentally. The results show that the oxidation current sensitivity of G/SPCE to PF after PPy nanosheets modification increased from 11.12 μA·mM−1 to 12.91 μA·mM−1 in CV response, and from 8.44 μA·mM−1 to 10.72 μA·mM−1 in DPV response. The effective reaction area of PPy/G/SPCE was found to be increased by scanning electron microscopy. And the functional group C O/C O in PPy/G/SPCE, acting as a catalyst for the redox reaction of PF, was also found to be improved by X-ray photoelectron spectroscopy. Furthermore, the adsorption energy, electron transfer and density of states changes of PF molecule on pure and PPy-modified graphene were analyzed based on density functional theory calculation. The calculation results show that the adsorption energy and electron transfer of PPy-modified graphene to PF molecule are significantly increased. The response sensitivity of graphene to PF molecule is greatly enhanced by the synergistic effect generated of PPy and graphene. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the therapeutic effects and mechanisms of hyperbaric oxygen (HBO) treatment on rats following spinal cord injury (SCI).Methods: A total of 45 Sprague-Dawley (SD) rats were randomly divided into three groups. Sham-SCI group was surgically exposed but not subjected to the SCI procedure. SCI-control group was administered SCI and treated with regular air. SCI-HBO group was administered SCI and HBO treatment. Neuromotor functions were examined using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and the inclined plane assessment at before SCI (baseline) and after SCI. Superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels were measured.Results: Starting from Day 1 after SCI but except Day 2, the SCI-HBO group has significantly higher BBB scores than the SCI-control group. After SCI, the maximum inclination angles at which rats could maintain were significantly lower in both SCI groups. But the maximum angles were significantly bigger for the rats in the SCI-HBO group than those on the SCI-control group at 5, 10 and 20 days after SCI. SOD activities in SCI-HBO rats were significantly higher and MDA levels were significantly lower than in SCI-control rats, at two and five days after SCI. There was also less cystic degeneration of spinal cord in SCI-HBO rats, compared to SCI-control rats.Conclusions: These results suggest that HBO treatment has a therapeutic value in treating SCI. Increased oxygen free radical scavenging and reduced lipid oxidation may be one of the mechanisms. [ABSTRACT FROM AUTHOR]

Benzoates as toxic intermediate are naturally produced by fungal intracellular metabolism, and CYP53 can specific transform the substrates. In the study, we constructed the CYP53 homology model and analyzed the corresponding active region. At the same time, the molecular docking and the structure-based pharmacophore model (SBP) were performed to explore the bind mode of representative CYP53 inhibitors. On the basis, a series of phenylpyridines derivatives were designed as novel CYP53 inhibitors, and their molecular structures were synthesized and evaluated. Compared with the positive control groups, their antifungal activity showed the obvious upward trend. In particular, target compounds (13a, 15b) possessed the excellent biological activity against pathogenic fungi and drug-resistant fungi in vivo and in vitro. The preliminary action mechanism has confirmed that target compounds could inhibit CYP53 activity, and block the metabolism of toxic intermediates (Benzoates). This further induced the accumulation of reactive oxygen species (ROS) through the pattern of mitochondrial depolarization, which eventually caused fungal lysis and death. In summary, the study provided the reasonable computational models, and effectively guided the generation of novel CYP53 antifungal inhibitors. [Display omitted] • The binding modes of CYP53 inhibitors were systematically analyzed. • Novel compounds were designed based on the characteristics of CYP53 active site. • Target compounds (13a, 15b) showed the excellent antifungal activity in vivo and in vitro. • The action mechanism of target compounds (13a, 15b) was confirmed in the study. [ABSTRACT FROM AUTHOR]

Herein, novel laser-responsive multi-functional nanoparticles (NPs-Lip@PTX/CyA/Ce6) were fabricated with bovine serum albumins (BSA) based nanoparticles, which simultaneously carried chemotherapeutic drug paclitaxel (PTX) and P-gp inhibitor cyclosporin A (CyA), as core and photosensitizer agent Chlorin e6 (Ce6) loaded Tf-modified liposomal bilayer as shell. NPs-Lip@PTX/CyA/Ce6 exhibited apparent core-shell structure morphology with particle size of 160.9 ± 1.7 nm and zeta potential of − 26.7 ± 0.6 mV, indicating their excellent stability in aqueous solution. Besides, NPs-Lip@PTX/CyA/Ce6 possessed laser-responsive release profiles upon laser irradiation at specific wavelength, which was favor to exert efficient combinatorial chemo-photodynamic therapy and effectively reverse the multiple drug resistance (MDR). Under laser irradiation, as expected, NPs-Lip@PTX/CyA/Ce6 demonstrated superb intracellular ROS productivity and fantastic in vitro and in vivo anti-cancer therapy effect but absent of systemic toxicity. In conclusion, the nano-drug delivery system would be prospectively applied in clinic as resultful therapeutic tactic for investing compositional chemo-photodynamic therapy synergistically. [Display omitted] • Novel laser-responsive multi-functional NPs-Lip@PTX/CyA/Ce6 were fabricated. • NPs-Lip showed apparent core-shell structure morphology and excellent stability. • NPs-Lip possessed laser-responsive release profiles. • NPs-Lip exhibited superb cellular 1O 2 productivity and uptake efficiency. • NPs-Lip displayed fantastic antitumor efficacy but absent of systemic toxicity. [ABSTRACT FROM AUTHOR]

[Display omitted] • • The binding of mithramycin dimers to DNA nanotrains (AS1411NTrs) was investigated. • • The effect of Mg2+, Zn2+, and Mn2+ on the binding was compared. • • The binding parameters were correlated with drug loading, release and cytotoxicity. • • High drug loading, sustained release and specific targeting were confirmed. Self-assembled DNA nanostructures, as a novel type of nano-biomaterials, are widely used for smart and targeted drug delivery due to their precise structures and versatile functions. The binding affinity of drugs to DNA nanostructures plays an important role in drug loading, release and efficacy. The interaction of mithramycin (MTR) with AS1411-tethered DNA nanotrains (AS1411NTrs) in the presence of different divalent metal ions (Mg2+, Zn2+, and Mn2+) was studied by fluorescence spectroscopy, differential scanning calorimetry and viscosity measurement. The binding mode between the MTR dimers and AS1411NTrs was determined by viscosity experiment and melting temperature measurement. The thermodynamic parameters of the binding process (binding stoichiometry, binding constant, enthalpy change, entropy change and Gibbs free energy change) were determined by fluorescence spectroscopy and differential scanning calorimetry, and the effect of different metal ions on the binding was compared. The release of the MTR dimers loaded by AS1411NTrs in the absence and presence of DNase I was analyzed. The in vitro cytotoxicity of the MTR dimers to HepG2 cancer cells and L02 normal cells and their intracellular uptake efficiency were evaluated. The binding parameters were correlated with the loading, release and cytotoxicity of the MTR dimers. These studies showed that AS1411NTrs had high drug loading and sustained release effect on (MTR) 2 Mg2+, (MTR) 2 Zn2+ and (MTR) 2 Mn2+. This drug loading system improved the lethality to cancer cells and reduced the side effects on normal cells. This study may provide a theoretical basis for the clinical application of MTR loaded by DNA nanostructures. [ABSTRACT FROM AUTHOR]

Combined chemo-photodynamic therapy strategy is regarded as a potential strategy for advanced cancer treatments. Herein, novel high payload 7-ethyl-10-hydroxycamptothecin (SN38)/chlorin e6 (Ce6) NPs based on the collaborative assembly of the pre-obtained SN38–Ce6 complex and biocompatible amphiphilic block polymer DSPE-PEG 2000 were successfully constructed. The self-assembly mechanism of the NPs was corporately disclosed as static quenching resulted from complex formation between DSPE-PEG 2000 and the pre-acquired SN38–Ce6 complex via fluorescence quenching experiment. The high payload SN38/Ce6 NPs exhibited uniform rod-like morphology with a hydrodynamic radius of about 200 nm, a zeta potential of around −25 mV, and excellent storage stability. The high payload NPs showed efficient singlet oxygen generation capacity both in tube and in murine mammary carcinoma (4T1) cells under laser irradiation. Moreover, the in vitro cytotoxicity and in vivo antitumor efficacy of the NPs (with laser) against 4T1 cell lines model were proved to be statistically significant compared to CPT-11 injection and single-drug NPs due to synergistic chemo-photodynamic therapy and high cellular uptake efficiency. Meanwhile, the systemic toxicity of the NPs was basically absent. Conclusively, the high payload dual-functional nanoparticles could be served as a promising strategy for cancer treatment in clinic. Image 1 • High payload SN38/Ce6 NPs were fabricated for synergistic chemo-PDT therapy. • The self-assembly of the NPs was static quenching process. • The NPs possessed superior 1O 2 generation capacity in tube and in cells. • The NPs exhibited excellent in vitro/in vivo antitumor efficacy. • The NPs were absent of systemic toxicity. [ABSTRACT FROM AUTHOR]

DNA nanostructures-based chemotherapy-phototherapy (CTPT) combination therapy can achieve targeted release and effectively overcome multidrug resistance (MDR). The therapeutic effect of CTPT combination drugs loaded in DNA nanostructures is related to the interactions among them. Herein, based on our previous research on AS1411NTrs loading with a single drug of DOX, the interactions between a single drug (toluidine blue O, TBO) or combination drugs (doxorubicin and toluidine blue O, DOX + TBO) and AS1411 aptamer-tethered DNA nanotrains (AS1411NTrs) were investigated. By fluorescence spectroscopy and isothermal titration calorimetry technique, the corresponding thermodynamic parameters were obtained, including the number of binding sites, binding constant, enthalpy change and entropy change. By combining with the differential scanning calorimetry and ferrocyanide ion quenching analysis, the binding mode-thermodynamic parameters were correlated. In addition, the effect of the binding affinity of DOX and TBO to AS1411NTrs on the drugs release rate was studied. Finally, the in vitro cytotoxicity and confocal laser scanning microscopy imaging of AS1411NTrs + TBO + DOX was investigated. The results showed that this drug delivery system could increase its in vitro cytotoxicity and overcome drug resistance in DOX-resistant human breast cancer cells (MCF-7/ADR). The work would provide important information for the combination therapy of DOX and TBO to overcome MDR effectively. Unlabelled Image • Doxorubicin (DOX) and toluidine blue O (TBO) were intercalated into DNA nanotrains. • The binding affinity of DOX with DNA nanotrains was stronger than that of TBO. • The addition order of DOX and TBO could affect the stability of DNA nanotrains. • Due to the stronger binding to DNA nanotrains, DOX released more slowly than TBO. • DOX + TBO combination drugs loaded in DNA nanotrains could overcome drug resistance. [ABSTRACT FROM AUTHOR]