Nanobubble-mediated co-delivery of siTRIM37 and IR780 for gene and sonodynamic combination therapy against triple negative breast cancer.

Gene therapy often fails due to enzyme degradation and low transfection efficiency, and single gene therapy usually cannot completely kill tumor cells. Several studies have reported that TRIM37 plays a significant role in promoting the occurrence and development of triple negative breast cancer (TNBC). Herein, we constructed siTRIM37 and IR780 co-loaded nanobubbles (NBs) to achieve the combination of gene therapy and sonodynamic therapy (SDT) against TNBC. On the one hand, ultrasound irradiation causes siRNA@IR780 NBs rupture to produce ultrasound targeted nanobubble destruction (UTND) effect, which promotes the entry of IR780 and siTRIM37 into cells, increasing the local concentration of IR780 and gene transfection efficiency. On the other hand, under the stimulation of ultrasound, IR780 generates reactive oxygen species (ROS) to kill TNBC cells. Mechanism studies reveal thatTRIM37 is an anti-apoptotic gene in TNBC, and inhibiting TRIM37 expression can induce cell death through the apoptotic pathway. And the combination of siTRIM37 and SDT can aggravate the degree of apoptosis to increase cell death. Therefore, siRNA@IR780 NBs-mediated combination therapy may provide a new treatment approach for TNBC in the future. .

TME-Responsive Nanoplatform with Glutathione Depletion for Enhanced Tumor-Specific Mild Photothermal/Gene/Ferroptosis Synergistic Therapy.

Background: Triple negative breast cancer (TNBC) is one of the worst prognosis types of breast cancer that urgently needs effective therapy methods. However, cancer is a complicated disease that usually requires multiple treatment modalities. Methods: A tumor microenvironment (TME)-responsive PFC/TRIM37@Fe-TA@HA (abbreviated as PTFTH) nanoplatform was constructed by coating Fe3+ and tannic acid (TA) on the surface of TRIM37-siRNA loaded phase-transition perfluorocarbon (PFC) nanodroplets and further modifying them with hyaluronic acid (HA) to achieve tumor-specific mild photothermal/gene/ferroptosis synergistic therapy (MPTT/GT/ Ferroptosis) in vitro. Once internalized into tumor cells through CD44 receptor-mediated active targeting, the HA shell of PTFTH would be preliminarily disassembled by hyaluronidase (HAase) to expose the Fe-TA metal-phenolic networks (MPNs), which would further degrade in response to an acidic lysosomal environment, leading to HAase/pH dual-responsive release of Fe3+ and PFC/TRIM37. Results: PTFTH showed good biocompatibility in vitro. On the one hand, the released Fe3+ could deplete the overexpressed glutathione (GSH) through redox reactions and produce Fe2+, which in turn converts endogenous H2O2 into highly cytotoxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT). On the other hand, the local hyperthermia generated by PTFTH under 808 nm laser irradiation could not only improve CDT efficacy through accelerating the Fe2+-mediated Fenton reaction, but also enhance TRIM37-siRNA delivery for gene therapy (GT). The consumption of GSH and accumulation of •OH synergistically augmented intracellular oxidative stress, resulting in substantial tumor cell ferroptosis. Moreover, PTFTH possessed outstanding contrast enhanced ultrasound (CEUS), photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) ability. Conclusion: This PTFTH based multiple-mode therapeutic strategy has successfully achieved a synergistic anticancer effect in vitro and has the potential to be translated into clinical application for tumor therapy in future.

Insights into the Injectivity and Propagation Behavior of Preformed Particle Gel (PPG) in a Low-Medium-Permeability Reservoir.

Heterogeneous phase combined flooding (HPCF) has been a promising technology used for enhancing oil recovery in heterogeneous mature reservoirs. However, the injectivity and propagation behavior of preformed particle gel (PPG) in low-medium-permeability reservoir porous media is crucial for HPCF treatment in a low-medium-permeability reservoir. Thus, the injectivity and propagation behavior of preformed particle gel in a low-medium-permeability reservoir were systematically studied by conducting a series of sand pack flooding experiments. The matching factor (δ) was defined as the ratio of the average size of PPG particles to the mean size of pore throats and the pressure difference ratio (ß) was proposed to characterize the injectivity and propagation ability of PPG. The results show that with the increase in particle size and the decrease in permeability, the resistance factor and residual resistance factor increase. With the increase in the matching factor, the resistance factor and residual resistance factor increase. The higher the resistance factor and residual resistance factor are, the worse the injectivity of particles is. By fitting the relationship curve, PPG injection and propagation standards were established: when the matching coefficient is less than 55 and ß is less than 3.4, PPG can be injected; when the matching coefficient is 55-72 and ß is 3.4-6.5, PPG injection is difficult; when the matching coefficient is greater than 72 and ß is greater than 6.5, PPG cannot be injected Thus, the matching relationship between PPG particle size and reservoir permeability was obtained. This research will provide theoretical support for further EOR research and field application of heterogeneous phase combined flooding.

A leak K+ channel TWK-40 sustains the rhythmic motor program.

Leak potassium (K+) currents, conducted by two-pore domain K+ (K2P) channels, are critical for the stabilization of the membrane potential. The effect of K2P channels on motor rhythm remains enigmatic. We show here that the K2P TWK-40 contributes to the rhythmic defecation motor program (DMP) in Caenorhabditis elegans. Disrupting TWK-40 suppresses the expulsion defects of nlp-40 and aex-2 mutants. By contrast, a gain-of-function (gf) mutant of twk-40 significantly reduces the expulsion frequency per DMP cycle. In situ whole-cell patch clamping demonstrates that TWK-40 forms an outward current that hyperpolarize the resting membrane potential of dorsorectal ganglion ventral process B (DVB), an excitatory GABAergic motor neuron that activates expulsion muscle contraction. In addition, TWK-40 substantially contributes to the rhythmic activity of DVB. Specifically, DVB Ca2+ oscillations exhibit obvious defects in loss-of-function (lf) mutant of twk-40. Expression of TWK-40(gf) in DVB recapitulates the expulsion deficiency of the twk-40(gf) mutant, and inhibits DVB Ca2+ oscillations in both wild-type and twk-40(lf) animals. Moreover, DVB innervated enteric muscles also exhibit rhythmic Ca2+ defects in twk-40 mutants. In summary, these findings establish TWK-40 as a crucial neuronal stabilizer of DMP, linking leak K2P channels with rhythmic motor activity.

Nanoparticle-Based Drug Delivery Systems for Enhancing Bone Regeneration.

The treatment of bone defects has been a long-standing challenge in clinical practice. Among the various bone tissue engineering approaches, there has been substantial progress in the development of drug delivery systems based on functional drugs and appropriate carrier materials owing to technological advances in recent years. A large number of materials based on functional nanocarriers have been developed and applied to improve the complex osteogenic microenvironment, including for promoting osteogenic activity, inhibiting osteoclast activity, and exerting certain antibacterial effects. This Review discusses the physicochemical properties, drug loading mechanisms, advantages and disadvantages of nanoparticles (NPs) used for constructing drug delivery systems. In addition, we provide an overview of the osteogenic microenvironment regulation mechanism of drug delivery systems based on nanoparticle (NP) carriers and the construction strategies of drug delivery systems. Finally, the advantages and disadvantages of NP carriers are summarized along with their prospects and future research trends in bone tissue engineering. This Review thus provides advanced strategies for the design and application of drug delivery systems based on NPs in the treatment of bone defects.

Dual-functional thermosensitive hydrogel for reducing infection and enhancing bone regeneration in infected bone defects.

The contamination of bone defects is a serious therapeutic problem. The treatment of infected bone defects involves rigorous infection control followed by bone reconstruction. Considering these two processes, the development of biomaterials possessing antibacterial and osteogenic properties offers a promising approach for the treatment of infected bone defects. In this study, a dual-functional, thermosensitive, and injectable hydrogel composed of chitosan (CS), quaternized CS (QCS), and nano-hydroxyapatite (nHA) was designed, and the ratio of CS to QCS in the hydrogel was optimized to enhance the antibacterial efficacy of CS while reducing the cytotoxicity of QCS. In vitro studies demonstrated that the hydrogel with an 85 %:15 % ratio of CS to QCS exhibited excellent biocompatibility and antibacterial properties while also possessing suitable mechanical characteristics and degradability. The incorporation of nHA into the hydrogel enhanced MC3T3-E1 proliferation and osteogenic differentiation. Moreover, this hydrogel demonstrated superior in vivo therapeutic effectiveness in a rabbit model of infected bone defect. In summary, this study provides a promising material design and a comprehensive one-step treatment strategy for infected bone defects.

Dual-functional 3D-printed porous bioactive scaffold enhanced bone repair by promoting osteogenesis and angiogenesis.

The treatment of bone defects is a difficult problem in orthopedics. The excessive destruction of local bone tissue at defect sites destroys blood supply and renders bone regeneration insufficient, which further leads to delayed union or even nonunion. To solve this problem, in this study, we incorporated icariin into alginate/mineralized collagen (AMC) hydrogel and then placed the drug-loaded hydrogel into the pores of a 3D-printed porous titanium alloy (AMCI/PTi) scaffold to prepare a bioactive scaffold with the dual functions of promoting angiogenesis and bone regeneration. The experimental results showed that the ACMI/PTi scaffold had suitable mechanical properties, sustained drug release function, and excellent biocompatibility. The released icariin and mineralized collagen (MC) synergistically promoted angiogenesis and osteogenic differentiation in vitro. After implantation into a rabbit radius defect, the composite scaffold showed a satisfactory effect in promoting bone repair. Therefore, this composite dual-functional scaffold could meet the requirements of bone defect treatment and provide a promising strategy for the repair of large segmental bone defects in clinic.

Anthropogenic multipollutant input to the offshore South China Sea.

The remote region of the South China Sea (SCS), situated far from urban mainland areas, is commonly perceived to experience minimal pollution. However, this may evolve into a considerably polluted region owing to increasing anthropogenic pollutants. In this study, we employ a multidisciplinary approach to analyze the surface sediments collected from the offshore area of the southern SCS. Our aim is to explore potential anthropogenic pollutants, their interactions, and the related controlling factors. This research endeavors to enhance our understanding of the current pollution status in the SCS and help making relevant policy management decisions. Comparison with previous reports reveals that now, the area is more extensively and increasingly contaminated by petroleum hydrocarbons and heavy metals (Cd and As) than before. For the first time, we report the recognition of coprostanol and long-chain alkyl mid-chain ketones, unveiling the noticeable incorporation of sewage fecal matter and biomass burning into offshore sediments. Moreover, sedimentary multipollutants (except ketones) exhibit strong correlations with terrestrial elements and fine-sized particles, displaying a roughly high-west/low-east spatial variability in pollutant accumulation or enrichment. These signatures evidently demonstrate the major impact of river discharges (e.g., the Mekong River to the west and the Pearl and Red Rivers to the north) on the SCS. They have hydrodynamic effects on the subsequent basin-wide dispersal of pollutants, driven by monsoon-induced large- and regional-scale currents. The different behavior of burning-related ketones may be partly due to their aerosol form, leading to atmospheric transportation. Because anthropogenic multipollutants pose compounded threats, exacerbating oceanic warming and acidification to marine ecosystems such as the widespread coral reefs in the southern SCS, scientific management of urban emissions is required to mitigate ecosystem degradation in the Anthropocene era.

Protocol for near-infrared optogenetics manipulation of neurons and motor behavior in C. elegans using emissive upconversion nanoparticles.

In deep tissue, optogenetics faces limitations with visible light. Here, we present a protocol for near-infrared (NIR) optogenetics manipulation of neurons and motor behavior in Caenorhabditis elegans using emissive upconversion nanoparticles (UCNPs). We describe steps for synthesizing and modifying UCNPs. We then detail procedures for regulating neurons using these UCNPs in the model organism C. elegans. Using NIR light allows for superior tissue penetration to manipulate neuronal activities and locomotion behavior. For complete details on the use and execution of this protocol, please refer to Guo et al.,1 Ao et al.,2 and Zhang et al.3.

Establishment of protoplasts transient expression system in Pinellia ternata (Thunb.) Breit.

OBJECTIVE: In this study, we established an efficient and rapid transient expression system in the protoplasts of Pinellia ternata (Thunb.) Breit. (P. ternata). RESULTS: The protoplasts of P. ternata were prepared from plant leaves as the source material by digesting them with the combination of 20 g·l-1 cellulase and 15 g·l-1 macerozyme for 6 h. Based on the screening of PEG concentration, the conditions for PEG-mediated protoplast transformation were improved, and the highest transformation efficiency was found for 40% PEG 4000. Furthermore, we used the subcellular protein localization technique in P. ternata protoplasts to allow further validation of transient expression system. CONCLUSIONS: We present the method that can be applicable for studying both gene verification and expression in P. ternata protoplasts, thus allowing for engineering the improved varieties of P. ternata through molecular plant breeding techniques. This method can also be widely applicable for analyzing protein interactions, detecting promoter activity, for somatic cell fusion in plant breeding, as well as for other related studies.

Functionalized Decellularized Bone Matrix Promotes Bone Regeneration by Releasing Osteogenic Peptides.

The decellularized bone matrix (DCB) provides a promising bone substitute for the treatment of bone defects because of its similar biochemical, biophysical, and mechanical properties to normal bone tissue. However, the decellularized procedure also greatly reduced its osteogenic induction activity. In this study, peptides derived from the knuckle epitope of bone morphogenetic protein-2 were incorporated into the thermo-sensitive hydrogel poloxamer 407, and the peptide-loaded hydrogel was then filled into the pores of DCB to construct a functionalized scaffold with enhanced osteogenesis. In vitro studies have shown that the functionalized DCB scaffold possessed appropriate mechanical properties and biocompatibility and exhibited a sustained release profile of osteogenic peptide. These performances critically facilitated cell proliferation and cell spreading of bone marrow mesenchymal stem cells and upregulated the expression of osteogenic-related genes by activating the Smad/Runx2 signaling pathway, thereby promoting osteogenic differentiation and extracellular matrix mineralization. Further in vivo studies demonstrated that the functionalized DCB scaffold accelerated the repair of critical radial defects in rabbits without inducing excessive graft-related inflammatory responses. These results suggest a clinically meaningful strategy for the treatment of large segmental bone defects, and the prepared osteogenic peptide modified composite DCB scaffold has great application potential for bone regeneration.

Preparation of Bi2O3-YSZ and YSB-YSZ Composite Powders by a Microemulsion Method and Their Performance as Electrolytes in a Solid Oxide Fuel Cell.

Bi2O3 is a promising sintering additive for YSZ that not only decreases its sintering temperature but also increases its ionic conductivity. However, Bi2O3 preferably grows into large-sized rods. Moreover, the addition of Bi2O3 induces phase instability of YSZ and the precipitation of monoclinic ZrO2, which is unfavorable for the electrical property. In order to precisely control the morphology and size of Bi2O3, a microemulsion method was introduced. Spherical Bi2O3 nanoparticles were obtained from the formation of microemulsion bubbles at the water-oil interface due to the interaction between the two surfactants. Nanosized Bi2O3-YSZ composite powders with good mixing uniformity dramatically decreased the sintering temperature of YSZ to 1000 °C. Y2O3-stabilized Bi2O3 (YSB)-YSZ composite powders were also fabricated, which did not affect the phase of YSZ but decreased its sintering temperature. Meanwhile, the oxygen vacancy concentration further increased to 64.9% of the total oxygen with the addition of 5 mol% YSB. In addition, its ionic conductivity reached 0.027 S·cm-1 at 800 °C, one order of magnitude higher than that of YSZ. This work provides a new strategy to simultaneously decrease the sintering temperature, stabilize the phase and increase the conductivity of YSZ electrolytes.

Antibacterial peptides-loaded bioactive materials for the treatment of bone infection.

Bacterial bone infection in open fractures is an urgent problem to solve in orthopedics. Antimicrobial peptides (AMPs), as a part of innate immune defense, have good biocompatibility. Their antibacterial mechanism and therapeutic application against bacteria have been widely studied. Compared with traditional antibiotics, AMPs do not easily cause bacterial resistance and can be a reliable substitute for antibiotics in the future. Therefore, various physical and chemical strategies have been developed for the combined application of AMPs and bioactive materials to infected sites, which are conducive to maintaining the local stability of AMPs, reducing many complications, and facilitating bone infection resolution. This review explored the molecular structure, function, and direct and indirect antibacterial mechanisms of AMPs, introduced two important AMPs (LL-37 and ß-defensins) in bone tissues, and reviewed advanced AMP loading strategies and different bioactive materials. Finally, the latest progress and future development of AMPs-loaded bioactive materials for the promotion of bone infection repair were discussed. This study provided a theoretical basis and application strategy for the treatment of bone infection with AMP-loaded bioactive materials.

Research Progress of Nanomedicine-Based Mild Photothermal Therapy in Tumor.

With the booming development of nanomedicine, mild photothermal therapy (mPTT, 42-45°C) has exhibited promising potential in tumor therapy. Compared with traditional PTT (>50°C), mPTT has less side effects and better biological effects conducive to tumor treatment, such as loosening the dense structure in tumor tissues, enhancing blood perfusion, and improving the immunosuppressive microenvironment. However, such a relatively low temperature cannot allow mPTT to completely eradicate tumors, and therefore, substantial efforts have been conducted to optimize the application of mPTT in tumor therapy. This review extensively summarizes the latest advances of mPTT, including two sections: (1) taking mPTT as a leading role to maximize its effect by blocking the cell defense mechanisms, and (2) regarding mPTT as a supporting role to assist other therapies to achieve synergistic antitumor curative effect. Meanwhile, the special characteristics and imaging capabilities of nanoplatforms applied in various therapies are discussed. At last, this paper puts forward the bottlenecks and challenges in the current research path of mPTT, and possible solutions and research directions in future are proposed correspondingly.

In-situ growth of 3D hierarchical γ-FeOOH/Ni3S2 heterostructure as high performance electrocatalyst for overall water splitting.

Obtaining efficient, stable, and low-cost electrocatalysts is the key to realizing large-scale water splitting. In this work, three-dimensional (3D) hierarchical γ-iron oxyhydroxide (γ-FeOOH)/Ni3S2 electrocatalyst on Ni foam is constructed for electrochemical overall water splitting. The 3D γ-FeOOH/Ni3S2 heterostructure can effectively enhance active sites and charge transfer capability, also the heterostructure can benefit electronic effect at the interfaces and synergistic effect of multiple components. Therefore, the γ-FeOOH/Ni3S2 exhibits excellent electrocatalytic activity with low overpotentials of 279 mV at 50 mA⋅cm-2 for oxygen evolution reaction and 92 mV at 10 mA⋅cm-2 for hydrogen evolution reaction, respectively. In addition, only a potential of 1.66 V is needed to attain 10 mA⋅cm-2 for the overall water splitting. In particular, the γ-FeOOH/Ni3S2 exhibits long-term stability for 120 h at 10 mA⋅cm-2 without significant degradation. This work provides a valuable idea for obtaining low-cost and high performance bifunctional electrocatalysts for water splitting.

Characteristics and Functional Application of Cellulose Fibers Extracted from Cow Dung Wastes.

The widespread use of petroleum-based products has led to increasing environmental and ecological problems, while the extraction and application of various natural cellulose fibers have received increasing attention. This research focuses on the extraction of cellulose fibers from cow dung using different treatments: hot water, hydrogen peroxide (H2O2), sodium hydroxide (NaOH) and potassium hydroxide (KOH) boilings, as well as a selection of the best quality cow dung fibers for papermaking with quality control. The study's objective is to find a sustainable method to extract as much material as possible from renewable biomass feedstock. The results show that the best extraction rate is obtained by KOH boiling with 42% cellulose fibers extracted. Corresponding handmade paper has a burst index of 2.48 KPam2/g, a tear index of 4.83 mNm2/g and a tensile index of 26.72 Nm/g. This project expands the sources of natural cellulose fibers to an eco-friendly and sustainable one and opens up new applications for cow dung.

Research progress of L-aspartate-α-decarboxylase and its isoenzyme in the ß-alanine synthesis.

Driven by the massive demand in recent years, the production of ß-alanine has significantly progressed in chemical and biological ways. Although the chemical method is relatively mature compared to biological synthesis, its high cost of waste disposal and environmental pollution does not meet the environmental protection standard. Hence, the biological method has become more prevalent as a potential alternative to the chemical synthesis of ß-alanine in recent years. As a result, the aspartate pathway from L-aspartate to ß-alanine (the most significant rate-limiting step in the ß-alanine synthesis) catalyzed by L-aspartate-α-decarboxylase (ADC) has become a research hotspot in recent years. Therefore, it is vital to comprehensively understand the different enzymes that possess a similar catalytic ability to ADC. This review will investigate the exploratory process of unique synthesis features and catalytic properties of ADC/ADC-like enzymes in particular creatures with similar catalytic capacity or high sequence homology. At the same time, we will discuss the different ß-alanine production methods which can apply to future industrialization.

Application of bioactive metal ions in the treatment of bone defects.

The treatment of bone defects is an important problem in clinical practice. The rapid development of bone tissue engineering (BTE) may provide a new method for bone defect treatment. Metal ions have been widely studied in BTE and demonstrated a significant effect in promoting bone tissue growth. Different metal ions can be used to treat bone defects according to specific conditions, including promoting osteogenic activity, inhibiting osteoclast activity, promoting vascular growth, and exerting certain antibacterial effects. Multiple studies have confirmed that metal ions-modified composite scaffolds can effectively promote bone defect healing. By studying current extensive research on metal ions in the treatment of bone defects, this paper reviews the mechanism of metal ions in promoting bone tissue growth, analyzes the loading mode of metal ions, and lists some specific applications of metal ions in different types of bone defects. Finally, this paper summarizes the advantages and disadvantages of metal ions and analyzes the future research trend of metal ions in BTE. This article can provide some new strategies and methods for future research and applications of metal ions in the treatment of bone defects.

Dual-functional composite scaffolds for inhibiting infection and promoting bone regeneration.

The treatment of infected bone defects is an intractable problem in orthopedics. It comprises two critical parts, namely that of infection control and bone defect repair. According to these two core tasks during treatment, the ideal approach of simultaneously controlling infection and repairing bone defects is promising treatment strategy. Several engineered biomaterials and drug delivery systems with dual functions of anti-bacterial action and ostogenesis-promotion have been developed and demonstrated excellent therapeutic effects. Compared with the conventional treatment method, the dual-functional composite scaffold can provide one-stage treatment avoiding multiple surgeries, thereby remarkably simplifying the treatment process and reducing the treatment time, overcoming the disadvantages of conventional bone transplantation. In this review, the impaired bone repair ability and its specific mechanisms in the microenvironment of pathogen infection and excessive inflammation were analyzed, providing a theoretical basis for the treatment of infectious bone defects. Furthermore, we discussed the composite dual-functional scaffold composed of a combination of antibacterial and osteogenic material. Finally, a series of advanced drug delivery systems with antibacterial and bone-promoting capabilities were summarized and discussed. This review provides a comprehensive understanding for the microenvironment of infectious bone defects and leading-edge design strategies for the antibacterial and bone-promoting dual-function scaffold, thus providing clinically significant treatment methods for infectious bone defects.