To address the issue of electrochemical sensors being susceptible to fouling interference in complex food matrices, this work proposed a high-performance antifouling aptasensor based on a triblock zwitterionic copolymer and a gold nanostars (Au NSs) conductive substrate. Through precise control over the composition of two zwitterionic monomers [2-methacryloyloxyethyl phosphorylcholine (MPC) and carboxybetaine methacrylate (CBMA)] and N, N'-diacryloylcystamine (BAC, a disulfide-containing cross-linker), the triblock zwitterionic copolymer [p(MPC9-co-CBMA1)-BAC] was prepared via free-radical polymerization. The thiol groups derived from BAC in the copolymer facilitated its stable anchoring onto Au NSs, and the carboxyl groups of CBMA enabled the covalent immobilization of amino-functionalized aptamer, affording dual functions of surface anchoring and aptamer immobilization. Antifouling performance of the aptasensor was validated in different simulated solutions (signal suppression as low as 0.26%) and real food samples (2.3% after 2.5 h). The fabricated aptasensor supported the sensitive quantification of chloramphenicol (CAP) with a linear range of 0.005-500 ng/mL and a limit of detection (LOD) as low as 0.09 pg/mL. Notably, recoveries for spiked honey and milk powder samples ranged from 94.4% to 106.4% with only dilution treatment, showing favorable accuracy and application potential of the strategy. This work provided an effective approach to reduce interference from complex food matrices in electrochemical sensing.

Radiation-induced skin injury (RISI) is one of the major complications of tumor radiotherapy, and remains clinically unaddressed due to insufficient wound healing and high infection risks. To address this clinical challenge, this study developed a novel multifunctional composite material based on a DNA hydrogel. This material innovatively integrates polydopamine-modified graphene oxide (PDA@GO) and fibroblast growth factor 2 (FGF2) into a DNA hydrogel matrix, achieving integrated therapeutic effects in radioprotection and tissue repair. Specifically, PDA@GO, with its excellent free radical scavenging ability, effectively eliminates excessive reactive oxygen species (ROS) in the wound microenvironment. Meanwhile, the unique three-dimensional porous network structure of the DNA hydrogel acts as an ideal sustained-release carrier for FGF2, significantly enhancing its bioavailability. Both in vitro and in vivo experiments demonstrated that this composite material demonstrates excellent biocompatibility, anti-inflammatory properties, and radioprotective performance. Compared with similar radioprotective agents and conventional clinical treatments, the FGF2-PDA@GO/DG hydrogel showed significant advantages in promoting wound healing and alleviating radiation-caused damage. These results support an encouraging biomaterial-based strategy for treating radiation-induced skin injury.

Given the inherent limitations of current nano-based antimicrobial materials, including their restricted broad-spectrum efficacy and challenges in practical application, it is essential to develop an innovative therapeutic platform that effectively alleviates these shortcomings. Herein, inspired by the cryptic antimicrobial properties of natural marine mussels, an o-dihydroxybenzene-based covalent organic framework (TAPT-2,3DHA-COF) is successfully synthesized, which exhibits potent broad-spectrum antibacterial activity through the auto-oxidative release of antibacterial agents. At the minimum inhibitory concentrations (MICs), potent antibacterial effects (> 90% inhibition) are observed against six common and even resistant bacterial strains, including Staphylococcus aureus (1024 mu g mL(-1)), Escherichia coli (512 mu g mL(-1)), Pseudomonas aeruginosa (256 mu g mL(-1)), methicillin-resistant Staphylococcus aureus (MRSA; 1024 mu g mL(-1)), etc. Encouraged by the aforementioned excellent performance, a hybrid acrylamide hydrogel covalent organic framework (Gel@COF) is constructed, which combines the advantages of both components, including robust antibacterial activity, mechanical stability, and biocompatibility. Notably, the potent healing-promoting capability of Gel@COF is demonstrated in diabetic mice models with MRSA-infected wounds, achieving an impressive wound healing rate of 99.62%. This work not only broadens the application of COFs in the field of antimicrobials but also provides a new strategy for developing advanced anti-infective materials in the future.

Vancomycin is a natural glycopeptide antibiotic produced by Streptomyces species. It is primarily employed to treat infections caused by drug-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA). However, the therapeutic concentration range of vancomycin is narrow, necessitating therapeutic drug monitoring (TDM). Currently, the commonly used vancomycin detection methods face challenges such as high equipment costs, complex operations, lengthy processing times, and poor reproducibility. To overcome these limitations, we developed a CRISPR-enhanced fluorescent (CEF) aptasensor for efficient and accurate detection of vancomycin, using signal amplification to provide critical support for TDM. In the presence of vancomycin, its specific binding to the aptamer exposes the primer strand, which is part of the self-assembled DNA tetrahedron, thereby initiating the RCA process. The product subsequently activates Cas12a, causing it to trans-cleave the signal probe ssDNA-FQ, which is modified by Cy3 and BHQ2. The fluorophore will move away from the quencher, thereby restoring fluorescence and generating a significantly amplified fluorescent signal, achieving highly sensitive detection of vancomycin. The constructed biosensor exhibits good linear response in the target concentration range of 1 fM to 10 nM, with a detection limit of 164 aM. This novel biosensor holds great promise for the accurate detection of low-abundance biomarkers like vancomycin, which is crucial for ensuring optimal dosing and preventing adverse effects such as nephrotoxicity. Moreover, the simplicity, rapidity, and costeffectiveness of this aptasensor make it an ideal candidate for therapeutic drug monitoring and clinical diagnostics.

BACKGROUND:Kanamycin is an antibiotic that can easily cause adverse side effects if used improperly. Due to the extremely low concentrations of kanamycin in food, quantitative detection of kanamycin becomes a challenge. As one of the DNA self-assembly strategies, entropy-driven strand displacement reaction (EDSDR) does not require enzymes or hairpins to participate in the reaction, which greatly reduces the instability of detection results. Therefore, it is a very beneficial attempt to construct a highly sensitive and specific fluorescence detection method based on EDSDR that can detect kanamycin easily and quickly while ensuring that the results are effective and stable. RESULTS:We created an enzyme-free fluorescent aptamer sensor with high specificity and sensitivity for detecting kanamycin in milk by taking advantage of EDSDR and the high specific binding between the target and its aptamer. The specific binding can result in the release of the promoter chain, which then sets off the pre-planned EDSDR cycle. Fluorescent label modification on DNA combined with the fluorescence quenching-recovery mechanism gives the sensor impressive fluorescence response capabilities. The research results showed that within the concentration range of 0.1 nM-50 nM, there was a good relationship between the fluorescence intensity of the solution and the concentration of kanamycin. Specificity experiments and actual sample detection experiments confirmed that the biosensor could achieve highly sensitive and specific detection of trace amounts of kanamycin in food, with a detection limit of 0.053 nM (S/N = 3). SIGNIFICANCE:To our knowledge, this is the first strategy to combine EDSDR with fluorescence to detect kanamycin in food. Accurate results can be obtained in as little as 90 min with no enzymes or hairpins involved in the reaction. Furthermore, our enzyme-free biosensing method is straightforward, highly sensitive, and extremely specific. It has many possible applications, including monitoring antibiotic residues and food safety.

Background: MicroRNAs play an important role in regulating cell function and gene expression. Early prevention and clinical diagnosis of diseases have high requirements for high-sensitivity detection of microRNAs. Due to the limitations of tedious operation and large sample size, miRNA with small molecular weight and low expression abundance cannot be accurately detected in traditional miRNA detection. To improve the sensitivity and accuracy of detection, we established a novel biosensor based on nucleic acid circuit of signal amplification, which converted miRNA recognition into a fluorescence signal for amplification.Results: We designed a biosensor based on an exponential amplification reaction with cascaded HCR and DNAzyme nucleic acid circuit (named E-NOF biosensor) by amplicon sub-fragments to trigger the construction of fluorescence nano-orbitals (NOF), which could be used to detect miRNA ultrasensitively. By modifying two fluorophores (Cy3 and Cy5) on the chain of constructing nano-orbitals, when the amplicon triggered the construction of nano-orbitals, fluorescence resonance energy transfer (FRET) occurred between Cy3 and Cy5, and then two fluorescence signals with different trends could be observed. Therefore, through the ratio of the two signals, we could quantitatively and quickly detect the miRNA from 1 fM to 100 nM, and the E-NOF biosensor detection limit was as low as 0.129 fM. Furthermore, the HCR nucleic acid circuit cascaded with DNAzyme could enrich the fluorophores on the nano-orbitals and significantly enhance the fluorescence signal by accelerating the reaction rate.Significance: According to our understanding, the E-NOF biosensor is the first strategy to cascade EXPAR with HCR and DNAzyme nucleic acid circuit for miRNA-1246 detection. Accurate results can be obtained in only 120 min. Compared with the traditional HCR system, the sensitivity of the new E-NOF biosensor is increased by 1 x 109 times. Furthermore, the biosensor can also detect biomarkers in human serum samples. It has great potential in miRNA detection and identification.

为了揭示不同大孔隙参数取值条件下边坡水分场的变化规律,利用2个耦合的Richards方程描述大孔隙流,并联合运动波方程,建立坡面径流与大孔隙流耦合模型;基于有限元软件COMSOL的偏微分方程接口,实现所建立耦合模型的数值求解,并自行设计室内模型试验,验证数值结果,分析不同大孔隙参数对体积含水率和坡面积水深度的影响.结果表明:COMSOL软件的偏微分方程接口可以实现所建立耦合模型的数值求解,相比于无大孔隙坡面,考虑大孔隙时水分入渗深度明显更大;边坡饱和区深度与湿润锋深度均随大孔隙域占比的增大而增大,均随大孔隙域与基质域导水系数之比与经验参数的增大而减小;当降雨历时为30 min时,坡面积水深度区分度最大,表现在随着大孔隙域占比的增大而减小,均随大孔隙域与基质域导水系数之比和经验参数的增大而增大;3种大孔隙参数按照对边坡水分场影响程度由大到小的顺序为大孔隙域占比、经验参数、大孔隙域与基质域导水系数之比.

Parsing the intricate interplay between gut microbiota, gene modulation, and host metabolism remains challenging. Wang et al. employed diverse methods to uncover how the gut microbiota reshapes intestinal lipid metabolism through the lncRNA Snhg9, underscoring the value of systems biology approaches in dissecting host-microbiome relationships involved in metabolic disorders.

Many organics are dangerous to environment as well as precise electronic devices. Detection of organics is a big challenge due to huge amount of species of organic materials. This is because specific fluorescence probe is needed in order to detect a kind of specific organic material. This make it impossible to develop specific fluorescence probe for each kind of organic material. As a result, development of an all-purpose fluorescence probe which is high sensitive to different types of organics is of crucial importance. In this work, we report an all-purpose up-conversion fluorescence probe for high sensitive detection of different species of organic materials. Surface functional groups –COOH, which help to alter electrons transition (alter emission intensity ratio I348/364) of rare earth materials doped upconversion micro-particles (UCMPs), are key to the all –purpose upconversion fluorescence probe. Intensity response of I348/364 is detected to be as low as 3*10-10 and 8*10-10 g to water and oil by a single excitation, respectively. As a result, residue chemicals on a piece of paper can be detected by this upconversion fluorescence probe after a finger touched the paper. High sensitive detection of different species of organic materials are also demonstrated in this work. This findings significantly pave the way of all-purpose sensors development.

Therapeutic metallodrugs have gained substantial success in cancer treatment and also motivate the active exploration of metallodrugs for cancer theranostics. However, it remains a challenge to engineer metallodrugs with desired therapy efficacy and safety because of their frequent in vivo limited bioavailability and off-target delivery. Herein, an efficient strategy to design vanadium nanodrugs (VNDs) with cancer-specific theranostic capability for visualizing/treating in vivo mice tumors, is developed. The VNDs are controllably constructed via a non-covalent coordination triggered self-assembly strategy, which allows the general synthesis of diverse nanoscale metallodrugs. Significantly, the VNDs exert an approximately tenfold enhancement of therapy efficacy in comparison with vanadium compounds and the clinically used cisplatin due to their improved bioavailability and multiple pathways-mediated tumor-selective therapy. Moreover, the VNDs feature intense near-infrared (NIR) absorption and undergo specific disassembly in the tumor microenvironment, thus enabling tumor-specific molecular imaging by the turn-on NIR fluorescence of embedded labels upon disassembly. Hence, the vanadium nanoprodrugs propose a new paradigm for in vivo tumor-selective therapy and imaging and may propel the design of effective anticancer metallodrugs.

Gas therapy has emerged as a forceful strategy for augmenting the effects of chemotherapeutic drugs against cancer cells. However, it remains extremely challenging to effectively deliver gas into tissues of interest and unravel its underlying mechanisms. Herein, we designed a near-infrared (NIR) light-switchable nitric oxide (NO) delivery nanosystem for high-efficacy multidrug resistance (MDR) reversal in cancer therapy based on a yolk-shell upconverting nanoparticles@magnesium silica (UCNP@MgSiO3). The internal hollow cavity and flower-like mesoporous shell of UCNPs@MgSiO3 not only enabled a significantly high encapsulation capacity for the NO precursor (BNN6) and doxorubicin (DOX) but also allowed the enhanced cellular uptake, resulting in NIR-triggered NO generation and low pH-triggered DOX release in cancer cells. Mechanistically, intracellular NO can downregulate the drug efflux-related P-glycoprotein and adenosine 5'-triphosphate-binding cassette transporters, thereby increasing the DOX accumulation in the cell nuclei. Such combination therapy of NO and DOX induced the apoptosis of MDR cells and completely inhibited in vivo MDR tumor growth. We further elucidated the therapy mechanism via proteomic profiling, showcasing the downregulation of the ubiquitin-proteasome pathway and nuclear factor kappa-B signaling pathway in the NO-treated MDR cells. Therefore, our findings develop a promising nanoscale gas/drug delivery paradigm for fighting MDR tumors and providing molecular insights into cancer therapy.

The design of bright NIR-II luminescent nanomaterials that enable efficient labelling of proteins without disturbing their physiological properties in vivo is challenging. We developed an efficient strategy to synthesize bright NIR-II gold nanoclusters (Au NCs) protected by biocompatible cyclodextrin (CD). Leveraging the ultrasmall size of Au NCs (<2 nm) and strong macrocycle-based host–guest chemistry, the as-synthesized CD-Au NCs can readily label proteins/antibodies. Moreover, the labelled proteins/antibodies enable highly efficient in vivo tracking during blood circulation, without disturbing their biodistribution and tumor targeting ability, thus leading to a sensitive tumor-targeted imaging. CD-Au NCs are stable in the harsh biological environment and show good biocompatibility and high renal clearance efficiency. Therefore, the NIR-II biolabels developed in this study provide a promising platform to monitor the physiological behavior of biomolecules in living organisms.

MicroRNAs play a crucial role in regulating gene expression and cellular function. Reliable detection of miRNA is highly demanded in clinical diagnosis and therapy. Herein, we designed a structure-convertible DNA switch and constructed a novel switch-conversional ratiometric fluorescence biosensor (SCRF biosensor) for highly sensitive miRNA detection by the use of amplicon fragments to convert the structure of the switch. The DNA switch was a sophisticated designed single-strand DNA with a stem-loop structure and modified with two fluorophores (Cy3 and Cy5) and one quencher at specific sites of the switch. Amplicon fragments (c*) were produced by an exponential amplification reaction. When the c* hybridized to the loop of a DNA switch, the structure of the switch would convert, and fluorescence resonance energy transfer occurred between Cy5 and Cy3. Then two fluorescence signals with different trends would be observed. As a result, by the ratio of the two signals, we can quantitatively and quickly detect the target miRNA with the concentration range from 100 fM to 100 nM and the excellent detection limit down to 70.9 fM, providing this new SCRF biosensor broad application prospects.

通过对李坊重晶石矿床重晶石的Sr同位素分析,探讨钡的物质来源.结果显示,重晶石的Rb含量为2.70×10-6～13.41×10-6,Sr含量为520.40×10-6～2166.00×10-6,87Rb/86Sr比值低,87Sr/86Sr比值介于0.71081～0.71180之间,平均值为0.71126,高于同时期海水锶的87 Sr/86 Sr比值,低于壳源锶的87 Sr/86 Sr平均值,表明重晶石的锶来自海水锶与壳源锶的混合.示踪结果显示重晶石的钡主要来源于下伏地层,并暗示基底属于大陆型地壳.

The establishment of analytical methods with superior sensitivity, selectivity, accuracy, and stability, as well as ultralow detection limits inspired a broad range of research enthusiasm. In this work, we developed an electrochemical method for detecting mercury ions using metallic 1T-MoS2 nanosheets, which was firstly fabricated using phase engineering strategy and then exfoliated. Remarkably promoted sensitivity and significantly lowered limits of detection (LODs) were achieved due to the dramatically reduced charge transfer resistance of 1T-MoS2 nanosheets compared with that of the semiconducting 2H-MoS2 nanoflakes. After electrode modification and optimization, working curves for both two materials were obtained. Astonishingly, the LODs of 1T-MoS2 modified glassy carbon electrodes (GCEs) was calculated to be 1.54 x 10(-19) M (D-L = 3 sigma/k), which was six orders of magnitude lower than that of 2H-MoS2 (1.46 x 10(-13) M). And 1T-MoS2-based electrochemical detection method also exhibited superior selectivity towards other ten ions selected because of the high affinity between Hg and S. The stability and reproducibility of the new method was impressive as well, and the recovery rates using spiked real water samples were all in the range of 99.8-101.2% due to the superb sensitivity. All results proved that the metallic 1T-MoS2 nanosheets a promising material for electrochemical detection of mercury ions. (c) 2020 Elsevier Ltd. All rights reserved.

福建李坊大型重晶石矿床围岩中发育层状硅质岩,为了研究硅质岩的成因,本文对14件硅质岩样品进行了硅、氧同位素分析.结果 表明:δ(30 Si)分布范围为-0.3×10-3～+0.1×10-3,平均值为-0.1×10-3;δ(18O)分布范围为10.6×10-3～18.9×10-3,平均值为14.7×10-3.基于该层状硅质岩的δ(30Si)和δ(18O)分布范围特征,结合野外地质调查研究工作的认识,该硅质岩应为原生沉积成因,二氧化硅来源于热水沉积;根据燧石-海水氧同位素地质温度计估算石英的形成温度为100.2℃-198.7℃,平均值为146.0℃,即该硅质岩形成于热水沉积,暗示李坊重晶石矿床形成于热水沉积作用.

Nucleic acid nanoswitches have a status that cannot be ignored in the field of biosensing due to the excellent biocompatibility and flexibility of design. In our current research, we have constructed a new electrochemical platform based on self-assembled pH-sensitive continuous circular DNA nanoswitch for miRNA-21 detection. We elaborately designed an inside ring probe (IRP) which could form a circle when complemented with an outside ring probe (ORP). Under the weakly acidic condition, IRPs and ORPs are self-assembled into continuous annular DNA, meanwhile, the nanoswitch is activated. However, if it is not a weakly acidic environment with a pH equal to 6, these circles are separated and the nanoswitch cannot be triggered. Therefore, the biosensor doesn't work. Only when the pH is 6, can the nanoswitch be activated. Consequently, a large number of RuHex will accumulate on the continuous annular DNA, which leads to highly sensitive detection of miRNA-21, with concentration ranged from 10-15 to 10-8 M and limit of detection down to 0.84 fM. More importantly, this nanoswitch-based biosensor can directly detect the target microRNA in human serum without pretreatment. Therefore, the proposed novel electrochemical DNA nanoswitch will have broad application prospects in biomarker detection and clinical diagnosis.

Even though black phosphorus (BP) has exhibited outstanding capabilities in biomedical, physical, and energy fields, the issues of degradation under ambient conditions and unreactive functional interface limit its further application. There are numerous methodologies utilized to prevent BP degradation; however, these methods usually generate further problems and normally do not involve alterations to the chemically inert BP. Herein, for the first time, we propose a simple and efficient strategy to prepare and modify BP nanosheets (p-BPNSs) by employing aromatic 1-pyrenylbutyric acid through a noncovalent π-π stacking interaction. This strategy not only adopts a novel strategy for enhancing the stability of BPNSs but also paves a convenient way to anchor other active biomolecules such as a targeting effect to extend the biomedical applications of BPNSs. The modified p-BPNSs exhibit enhanced physical and chemical stabilities as well as rich carboxyl groups for further modification. In this work, RGD-modified p-BPNSs exhibit targeted photothermal therapy ability against cancer in both in vitro and in vivo studies, owing to anchoring of arginine-glycine-aspartic acid (RGD) tripeptides, which could target nanosheets into the tumor site through systematic circulation. Consequently, this work not only provides a new concept for modifying and protecting the BP but also opens a novel window for extending the biomedical application of BP by surface engineering.

With the development of clinical medicine-related technologies, the detection of cancer biomarkers has become an essential method for cancer diagnosis. DNA self-assembly is a valuable approach to monitor low-abundance miRNA. Herein, we report a novel DNA jungle biosensor for target-induced enzyme-free and label-free ultrasensitive detection of miRNA-21 in biological samples. The method consists of two parts. The target catalyzes the assembly of the hairpin to form the backbone of the DNA jungle, and the auxiliary probes hybridize to form branches freely and undirectedly. The DNA jungle can be self-assembled seeded from a single target initiator, affording the potential for screening a single target molecule. Vitro assays show that the DNA jungle offers very high amplification efficiency and specificity, with a direct detection limit of 1 aM. This DNA jungle strategy can provide a useful platform for low-abundance biomarker detection for cell biology and diagnostics.