Latest ArticlesIn this article, we used the self-excitation and self-inductance characteristics of polyvinylidene fluoride (PVDF) piezoelectric materials, combined with the powerful signal processing and calculation analysis capabilities of integrated circuits, for the first time to explore a set of microcantilever sensor "readout system" without additional driver (self-driving) and can realize self-sensing external signal (self-sensing). It was successfully applied to the unlabeled detection of avian influenza virus (AIV) H9N2. The specific force of the antigen-antibody complexes on the surface of the microcantilever leads to the change of the stress of the cantilever, which drives the constructed detection device, and does not require an additional excitation source to drive it, that is, the self-driving part. At the same time, due to the movement of piezoelectric charges in the film caused by the positive piezoelectric effect of the PVDF film, self-inductive charges are generated on the surface of the sensor dielectric. The charge signal is converted into a voltage signal, and the sensing part is completed, that is, self-sensing. The immunosensor has a linear range of 100-1000 ng/mL with a detection limit of 2.9 ng/mL. The method will also open up a new avenue for the detection of other analytes based on antigen-antibody responses.
Developing efficient electrocatalysts for hydrogen evolution reaction (HER) is of great importance in contemporary water electrolysis technology. Here, a novel hierarchically sea urchin-like electrocatalyst (Mo4O11-MoS2-VO2) is synthesized by hydrothermal deposition and post-annealing strategy. The optimized electrocatalyst behaves as a high active hydrogen evolution electrode in 0.5 mol/L H2SO4. This electrode needs overpotential of only 43 mV to achieve 10 mA/cm2 with a Tafel slope of 37 mV/dec and maintains its catalytic activity for at least 36 h. Better than most previously reported non-noble metal electrocatalysts anchored on carbon cloth. It is worth mentioning that the hierarchical sea urchin-like structure promotes the redistribution of electrons and provides more catalytic active sites. This strategy shows a way for the construction of inexpensive non-noble metal electrocatalysts in the future.
Recent developments in the utilization of microfluidic chips (MFCs) have shown their potential utility in multiphase organic synthesis by enabling efficient organic reactions in flow chemistry. However, MFCs technology has been wandering in the laboratory of small dose synthetic routes, which is limited to the level of "tiny" fluid flux. To address this issue, we herein report the first case of the chips with high-throughput 3D channels produced by femtosecond laser being used to create a time-saving, cost-effective and risk-free approach suitable for large-scale flow synthesis. Several multiphase reactions have been successfully prepared on demand in our designed flow synthesis system containing 3D MFCs: 1) benzyl alcohol was converted to benzaldehyde in 3 min with a yield of 97.50% by liquid-liquid two-phase transfer catalytic oxidation; 2) organozinc reagents and α-cyano carbonyl carbon compounds were synthesized by solid-liquid two-phase metal insertion reaction in 7 min, and the yield was up to 100%; 3) benzoic acid was synthesized by gas-liquid two-phase carboxylation reaction in 2.8 s with a yield of 96%. Significant gains in production rate result from the effective scaling of flow reactors from microliters per hour in MFCs to intermediate milliliters per minute without affecting mass transport performance. Meanwhile, our 3D MFCs show excellent mass and heat transfer efficiency in large-scale industrial units, breaking through the bottleneck in this field. As a result, it is possible to imagine the creation of a new, streamlined flow synthetic technique via MFCs for green multiphase organic synthesis.
Cognitive impairment often occurs after post traumatic brain injury. In addition, recovery of cognitive impairment is largely dependent on spontaneous repair and the severity of secondary insult. The tetrahedral framework nucleic acid is a novel nanostructure has been shown to have a positive biological effect in promoting regeneration and anti-inflammation. To explore the treatment effect of tetrahedral framework nucleic acids for cognitive impairment recovery post traumatic brain injury, we established a mouse model of traumatic brain injury and verified the efficacy of tetrahedral framework nucleic acids in promoting cognitive impairment recovery post traumatic brain injury. The results show that the tetrahedral framework nucleic acids promoted the recovery of post-traumatic cognitive function by enhancing the proliferation of endogenous neural stem cells. Besides, tetrahedral framework nucleic acids modulated the neuroinflammatory response in the acute phase by inhibiting excessive astrocyte and microglial activation. Taken together, the results of the study indicate tetrahedral framework nucleic acids for treatment of cognitive impairment post traumatic brain injury.
The clinical efficacy of chemotherapeutic drugs is hindered by their poor aqueous solubility, low bioavailability and severe side effects. In recent years, polymeric nanocarriers have been used for drug delivery to improve the efficacy of many chemotherapeutics. In this study, a series of biodegradable phenylalanine-based poly(ester amide) (Phe-PEA) with tunable molecular weights (MWs) were synthesized to systematically investigate the relationship between the polymer MW and the efficacy of the corresponding polymeric nanoparticles (NPs). The results indicated that a range of polymers with different MWs can be obtained by varying the monomer ratio or reaction time. Doxorubicin (DOX), a classic clinical lymphoma treatment strategy, was selected as a model drug. The loading capacity and stability of the higher MW polymeric NPs were superior to those of the lower MW ones. Moreover, in vitro and in vivo data revealed that high MW polymeric NPs had better anticancer efficacy against lymphoma and higher biosafety than low MW polymeric nanoparticles and DOX. Therefore, this study suggests the importance of polymer MW for drug delivery systems and provides valuable guidance for the design of enhanced polymeric drug carriers for lymphoma treatment.
Liquid chromatography tandem mass spectrometry (LC-MS/MS) plays an important role in clinical diagnostics. Although LC-MS/MS is superior in terms of accurately quantifying molecules in complex matrices, instrument footprint, operation and maintenance complexity also hinder its expansion as the analytical technique of choice. In this study, a compact LC-MS instrument was developed, in which an assembled liquid chromatograph was coupled with a miniature ion trap mass spectrometer. The overall instrument has a footprint of 69 cm × 31 cm × 31 cm, and it requires no gas supply as well as minimum maintenance. Furthermore, the use of LC-MS is in accord with conventional clinical diagnostic protocols, and the choice of ion trap offers tandem MS performance. The results showed that the use of LC could improve both mixture analysis capability and detection sensitivity of the miniature mass spectrometer. After optimization, feasibility of this instrument in clinical practice was demonstrated by the quantitation of four widely used immunosuppressants in blood samples. Relatively good linearities were obtained, which spanned the reference ranges of effective therapeutic concentrations of each immunosuppressant. Intra-day and inter-day accuracy and precision of analytical method were also assessed. This work showed that a compact LC-MS instrument could be used in clinical diagnosis, either to replace conventional lab-scale instruments or to be used in POCT applications.
This study reports several modification strategies to optimize and enhance the performance of two-dimensional (2D) metal organic frameworks (MOFs)-derived catalysts in peroxydisulfate (PDS) activation. The raw 2D Ni-MOF and 2D Ni-Fe-MOF without modification show poor catalytic activities for PDS activation and high metal ion leaching. The carbonization of 2D MOF can increase the activity of the catalyst but cannot solve the metal leaching problem. The further acid treatment of carbonization products can further improve the catalytic activity and decrease the metal ion leaching. The in-situ growth of 2D MOF on graphene oxide (GO) support with subsequent carbonization and acid treatment offers the best performance in PDS activation for organic pollutant removal with low metal ion leaching. Compared with other PDS systems, the Ni-Fe-C-acid/GO system displays much lower catalyst and PDS dosages for p-chloroaniline degradation. This study presents new insights in the modification strategies of 2D MOF-based catalysts in PDS activation.
Metastatic breast cancer (MBC) is one of the most common and knotty diseases in female population which could place them in a life-threatening condition. For malignant proliferation and migration, cancer cells require a large amount of glucose and energy to meet the demand of rapid metabolism. Hence, efficiently diminishing the utilization of energy substances by cancer cells is emerging as validated therapeutic strategies for cancer therapy. Herein, a nanoplatform with dual-inhibition of glucose uptake and oxidative phosphorylation (OXPHOS) was designed, which consisted of albendazole (ABZ) and atovaquone (ATO) by simple carrier-free self-assembling. The introduction of ABZ could evidently decrease glucose uptake to reduce the main "energy fuel" of cancer cells. Meanwhile, as a blocker of OXPHOS, ATO would reduce adenosine triphosphate (ATP) production and ameliorate hypoxia microenvironment by suppressing mitochondrial respiratory chain. Under such dual inhibition of energy metabolism, AA NPs exerted synergistic energy exhaustion effect and outstanding hypoxia improvement function, efficiently inhibiting tumor growth and metastasis. This research not only illustrates the feasibility of energy metabolism therapy by co-inhibiting glucose uptake and OXPHOS, but also provides an ingenious tactic to diminish metastasis during MBC treatment
Caproate, produced by microbial chain elongation process, is potential to replace the diversified fossil-based products, contributing to carbon neutrality. However, its production performance is far from industrial application, so the cost-effective enhancement measures are highly needed. This study confirmed powdered activated carbon (PAC) has a significant effect on enhancing caproate production performance. The production, yield, and selectivity of caproate were improved by more than 1-fold by the optimized PAC dosage of 15 g/L, comparing with control. Mechanism investigation from a new visual angle showed that PAC accelerated ethanol oxidation to generate acetyl-CoA, and simultaneously boosted the efficiency of reverse β oxidation (RBO) by promoting the timely reaction of butyrate and acetyl-CoA to synthesis caproate. The addition of PAC also shifted the microbial community by enriching more caproate-producing bacteria but eliminating irrelevant ones. Furthermore, metagenomic analysis revealed that PAC effectively up-regulated the functional genes encoding key enzymes responsible for ethanol oxidation and RBO pathway, which was the root cause for the improved caproate production. This study presented the intrinsic insights into the mechanism of PAC promoting caproate generation, laying a foundation to the scale production of caproate.
Cyclin-dependent kinases (CDKs) have become potential targets for treating various diseases, especially cancer. Compound iCDK9 is an excellent and selective CDK9 inhibitor, but its major limitation is the potential toxicity and poor understanding of the underlying mechanism. The PROTAC (proteolysis targeting chimera) degraders of bioactive molecules can significantly induce in vitro and in vivo degradation of their target protein with high selectivity and effectively reduce the dose-limiting toxicity of small molecule drugs. Therefore, we designed and synthesized the bifunctional PROTAC molecules of iCDK9, being used for identifying its previously unknown target and revealing the underlying pharmacological mechanism. The PROTAC bifunctional molecule CD-5 could selectively and significantly degrade CDK9 with low cell toxicity. Therefore, we selected CD-5 as a chemical prober in the SILAC quantitative proteomic analysis, which disclosed that CD-5 could enormously lessen the lysine acetyltransferase KAT6A. Furthermore, KAT6A degradation induced by CD-5 repressed the levels of H3K14Ac and H3K23Ac. Lastly, the streptavidin immunoprecipitation (IP) assay confirmed a direct interaction between KAT6A and iCDK9. Collectively, our results uncover that KAT6A is a potential non-kinase target of iCDK9. Notably, this study also demonstrates that the PROTAC-SILAC strategy is an alternative approach for cellular target identification of bioactive molecules.
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