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5-formylcytidine (f5C) is a unique post-transcriptional RNA modification found in mRNA and tRNA at the wobble site, playing a crucial role in mitochondrial protein synthesis and potentially contributing to the regulation of translation. Recent studies have unveiled that the f5C modifications may drive mitochondrial mRNA translation to power cancer metastasis. Accurate identification of f5C sites is essential for further unraveling their molecular functions and regulatory mechanisms, but there are currently no computational methods available for predicting their locations. In this study, we introduce an innovative ensemble approach, successfully enabling the computational recognition of Saccharomyces cerevisiae f5C. We conducted a comprehensive model selection process that involved multiple basic machine learning and deep learning algorithms such as recurrent neural networks, convolutional neural networks and Transformer-based models. Initially trained only on sequence information, these individual models achieved an AUROC ranging from 0.7104 to 0.7492. Through the integration of 32 novel domain-derived genomic features, the performance of individual models has significantly improved to an AUROC between 0.7309 and 0.8076. To further enhance accuracy and robustness, we then constructed the ensembles of these individual models with different combinations. The best performance attained by our ensemble models reached an AUROC of 0.8391. Shapley additive explanations were conducted to explain the significant contributions of genomic features, providing insights into the putative distribution of f5C across various topological regions and potentially paving the way for revealing their functional relevance within distinct genomic contexts. A freely accessible web server that allows real-time analysis of user-uploaded sites can be accessed at: www.rnamd.org/Resf5C-Pred.

Abstract Background Unintentional injuries is the leading cause of death in children aged 6–18 in China. Previous studies on the association between the guardians’ educational levels and unintentional injuries in children have been inconclusive, and it remains unclear among the Chinese population. Therefore, this study aimed to identify the association between guardians’ educational levels and unintentional injuries in children aged 6–18 in Shenzhen, China. Methods This cross-sectional study enrolled 9,903 children aged 6–18 in Shenzhen in 2020 using a multistage cluster sampling method. Information on the children and guardians were collected, and unintentional injuries in the past year was examined by using two nested questions. Logistic regression analyses were used to test the association between the guardians’ educational levels and unintentional injuries in children aged 6–18, and the crude odds ratios (ORs) and adjusted ORs with 95% confidence intervals (95% CI) were calculated. Results 275 of the 9,903 children reported experiencing at least one unintentional injuries in the past year, and the weighted incidence of unintentional injuries was 6.3% (95% CI: 5.8–6.8%) in children aged 6–18 in Shenzhen, China. The incidence of unintentional injuries differed significantly in the guardians’ education levels (P

Abstract The photo‐enzyme coupling system (PECS) holds immense potential in “green” biomanufacturing, encompassing the realms of pharmaceuticals, fuels, and carbon sequestration. Nevertheless, the intricate nature of enzymes' structures significantly impedes the seamless integration of multiple enzymes in a precise, tandem fashion, with exact control over their distribution, posing a formidable challenge. Herein, it has devised a mesoporous csq‐type metal organic framework (Zr‐MOF) from meso‐tetrakis‐(4‐((phenyl)ethynyl)benzoate)porphyrin (Por‐PTP) and Zr6(μ3‐O)4(μ3‐OH)4(OH)4(H2O)4) nodes (Zr6 clusters), featuring intricate hierarchical hexagonal (5.8 nm) and triangular (2.9 nm) channels, enabling the simultaneous encapsulation of Formate dehydrogenase from Candida boidinii (CbFDH) and ferredoxin‐NADP+ reductase (FNR) via a spatiotemporally controlled strategy for cofactor‐dependent photoenzymatic carbon dioxide (CO2) conversion. Upon illumination, photoexcited electrons originating from the Zr‐MOF frameworks migrate to the adjacent FNR for cofactor NADH regeneration, which is then harnessed by proximal CbFDH for CO2 fixation. Concurrently, the resulting holes are neutralized by AA for system recovery. The results demonstrated the confinement of tandem enzymes within MOF channels significantly enhanced the performance of multi‐enzyme cascade pathways as well as augmenting the local NAD+/NADH, which leading to a further improvement in the efficiency of tandem biocatalytic formic acid generation (55 mm) from CO2. Crucially, the photo‐enzyme‐coupled factories exhibited remarkable stability alongside exceptional recyclability, attributed to the preservation of MOF skeletons.

Gannan is the largest navel orange production area in China. Most studies have primarily focused on the effects of either soil or topographic factors on the quality of navel oranges. However, there has been a lack of research exploring the relationship between navel orange quality and multiple environmental factors (meteorological, topographic, and soil). This study focused on Gannan navel oranges, selecting standard orchards in the core navel orange-producing area as the research region. It employed the Partial Least Squares Regression (PLSR) method to investigate the extent of the impact of environmental factors on fruit quality. The results indicated that the effect of soil factors on fruit shape and fruit flavor was greater than that of meteorological and topographic factors in the Gannan area. And the fruit peel is more uniformly influenced by environmental factors. Based on the degree of impact of various environmental factors, multiple regression equations for fruit quality have been established to identify the optimal conditions conducive to the comprehensive development of Gannan navel oranges. These findings help determine the optimal planting areas for Gannan navel oranges, providing practical evidence for the future development of navel oranges.

Human beings are living longer than ever before and aging is accompanied by an increased incidence of motor deficits, including those associated with the neurodegenerative conditions, Parkinson's disease (PD) and Huntington's disease (HD). However, the biological correlates underlying this epidemiological finding, especially the functional basis at the synapse level, have been elusive. This study reveals that motor skill performance examined via rotarod, beam walking and pole tests is impaired in aged mice. This study, via electrophysiology recordings, further identifies an aging-related reduction in the efficacy of inhibitory synaptic transmission onto dorsolateral striatum (DLS) indirect-pathway medium spiny neurons (iMSNs), i.e., a disinhibition effect on DLS iMSNs. In addition, pharmacologically enhancing the activity of DLS iMSNs by infusing an adenosine A2A receptor (A2AR) agonist, which presumably mimics the disinhibition effect, impairs motor skill performance in young mice, simulating the behavior in aged naïve mice. Conversely, pharmacologically suppressing the activity of DLS iMSNs by infusing an A2AR antagonist, in order to offset the disinhibition effect, restores motor skill performance in aged mice, mimicking the behavior in young naïve mice. In conclusion, this study identifies a functional inhibitory synaptic plasticity in DLS iMSNs that likely contributes to the aging-related motor skill deficits, which would potentially serve as a striatal synaptic basis underlying age being a prominent risk factor for neurodegenerative motor deficits.

Abstract Background Opioid crisis has become a global concern, but whether physical activity (PA) can effectively reduce prescription opioid use remains unclear. The study aimed to examine the relationship of different domains of PA (e.g., occupation-related PA [OPA], transportation-related PA [TPA], leisure-time PA [LTPA]) with prescription opioid use and duration of prescription opioid use. Methods This cross-sectional study was conducted on 27,943 participants aged ≥ 18 years from National Health and Nutrition Examination Survey (NHANES, 2007– March 2020). We examined the relationship of different domains of PA with prescription opioid use and duration of prescription opioid use using multivariable logistic regression. Stratified analysis and a series of sensitivity analysis were used to elevate robustness. All analyses were conducted using appropriate sampling weights. Results Of the 27,943 participants, the mean age was 45.10 years, with 14,018 [weighted, 50.0%] females and 11,045 [weighted, 66.0%] non-Hispanic White. After multivariable adjustment, inverse associations between PA and prescription opioid use were observed for sufficient (≥ 150 min/week) total PA (OR,0.68 95%CI [0.56–0.81]), TPA (OR,0.73 95%CI [0.58–0.92]), and LTPA (OR,0.60 95%CI [0.48–0.75]) compared with insufficient PA(

GL-V9, a derivative of wogonin, has shown potent antitumor effects in various cancers, yet its impact on chronic myeloid leukemia (CML) remains unexplored. In this study, we found that GL-V9 significantly decreased the viability of CML cells. Annexin V/PI staining demonstrated that GL-V9 induced apoptosis in a concentration-dependent manner. The JC-1 assay indicated a significant reduction in mitochondrial membrane potential (ΔΨm) in cells treated with GL-V9. Additionally, GL-V9 altered reactive oxygen species (ROS) levels in CML cells. Through transcriptomic sequencing and Western blot analysis, we further revealed that GL-V9 activated the MAPK pathway. These results suggest that GL-V9 is a promising therapeutic candidate for CML.

Abstract Plant chloroplasts have a highly compartmentalized interior, essential for executing photocatalytic functions. However, the construction of a photocatalytic reaction compartment similar to chloroplasts in inorganic–biological hybrid systems (IBS) has not been reported. Drawing inspiration from the compartmentalized chloroplast and the phenomenon of liquid–liquid phase separation, herein, a new strategy is first developed for constructing a photocatalytic subcellular hybrid system through liquid–liquid phase separation technology in living cells. Photosensitizers and in vivo expressed hydrogenases are designed to coassemble within the cell to create subcellular compartments for synergetic photocatalysis. This compartmentalization facilitates efficient electron transfer and light energy utilization, resulting in highly effective H2 production. The subcellular compartments hybrid system (HM/IBSCS) exhibits a nearly 87‐fold increase in H2 production compared to the bare bacteria/hybrid system. Furthermore, the intracellular compartments of the photocatalytic reactor enhance the system's stability obviously, with the bacteria maintaining approximately 81% of their H2 production activity even after undergoing five cycles of photocatalytic hydrogen production. The research brings forward visionary prospects for the field of semi‐artificial photosynthesis, offering new possibilities for advancements in areas such as renewable energy, biomanufacturing, and genetic engineering.

With a gradual increase in breast cancer incidence and mortality rates and an urgent need to improve patient prognosis and cosmetology, magnetic resonance imaging (MRI)-guided radiofrequency ablation (RFA) therapy has attracted wide attention as a new treatment method for breast cancer. MRI-RFA results in a higher complete ablation rate and extremely low recurrence and complication rates. Thus, it may be used as an independent treatment for breast cancer or adjuvant to breast-conserving surgery to reduce the extent of breast resection. Furthermore, with MRI guidance, accurate control of RFA can be achieved, and breast cancer treatment can enter a new stage of minimally invasive, safe, and comprehensive therapy. With progress in MR thermometry technology, the applications of MRI are expected to broaden.

Summary: The NLRP3 inflammasome plays a pivotal role in various chronic inflammation-driven human diseases. However, no drugs specifically targeting NLRP3 inflammasome have been approved by the Food and Drug Administration (FDA) of the United States. In our current study, we showed that dimethyl fumarate (DMF) efficiently suppressed the activation of the NLRP3 inflammasome induced by multiple agonists and covalently modified Cys673 of NLRP3, thereby impeding the interaction between NLRP3 and NEK7. The inhibitory effect of DMF was nullified by anaplerosis of the Cys673 mutant (but not the wild-type) NLRP3 in Nlrp3−/− THP-1 cells. In vivo experiments, DMF demonstrated protective effects in the dextran sodium sulfate (DSS)-induced ulcerative colitis of WT mice, but not in Nlrp3−/− mice. In summary, our study identified DMF as a direct covalent inhibitor of NLRP3 and a potential candidate for the treatment of NLRP3 inflammasome-mediated diseases.

The fragility curve expresses the probability that an asset exceeds some serviceability state for a given level of environmental perturbation or other loadings. It is an important component in the quantitative risk analysis and resilience evaluation of infrastructure exposed to natural hazards. Incidences of over-settlement of embankments are increasingly reported due to more intense and longer-duration rainfall events. This paper develops fragility curves for the rainfall-induced embankment settlement. For this purpose, an embankment incorporating enhanced seepage and displacement analysis within unsaturated soil conditions is modelled based on a reported case history. A Monte Carlo simulation is used for rainfall infiltration and embankment deformation analysis under various rainfall scenarios. Probability values are obtained to achieve three levels of damage states in terms of road embankment settlement. The parametric analysis produces the exceedance probability curves for various rainfall intensities, saturated permeabilities and embankment slope angles. This work offers an efficient tool for assessing fragility to rainfall-induced excessive settlement of embankments.

The safety and stability of tunnel construction are paramount concerns in tunnel engineering. Traditionally, the assessment of tunnel stability involves evaluating whether tunnel displacement and deformation velocities exceed acceptable thresholds, using specifications and analogical reasoning. However, standardized cautionary indicators often lack adaptability and can result in unnecessary reinforcement and increase economic costs. This study presents a method for determining limit displacement and deformation velocities based on tunnel deformation limit states. Based on the finite difference method, which considers the quality of surrounding rock mass and tunnel geometric configuration, a parametric analysis of these velocities is presented. The vault settlement, relative spandrel displacement, relative hance displacement, and deformation velocity are investigated to establish the thresholds for displacement and deformation velocities. Furthermore, a sensitivity analysis using a multivariate adaptive spline regression model is performed to measure the parameter effects on the early allowance values. Finally, a response surface method is developed to estimate the indicators in order to provide criteria for assessing and warning about surrounding rock stability. The obtained results show that the proposed limit state analysis method is effective for providing a standardized criterion for tunnel excavation, and the sensitivity analysis indicates tunnel depth as the most influential factor on tunnel reliability.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is pivotal in immunotherapy. Several agonists and inhibitors of the cGAS-STING pathway have been developed and evaluated for the treatment of various diseases. The agonists aim to activate STING, with cyclic dinucleotides (CDNs) being the most common, while the inhibitors aim to block the enzymatic activity or DNA binding ability of cGAS. Meanwhile, non-CDN compounds and cGAS agonists are also gaining attention. The omnipresence of the cGAS-STING pathway in vivo indicates that its overactivation could lead to undesired inflammatory responses and autoimmune diseases, which underscores the necessity of developing both agonists and inhibitors of the cGAS-STING pathway. This review describes the molecular traits and roles of the cGAS-STING pathway and summarizes the development of cGAS-STING agonists and inhibitors. The information is supposed to be conducive to the design of novel drugs for targeting the cGAS-STING pathway.

A series of novel 9-O-substituted-13-octylberberine derivatives were designed, synthesised and evaluated for their anti-hepatocellular carcinoma (HCC) activities. Compound 6k showed the strongest activity against three human hepatoma cells including HepG2, Sk-Hep-1 and Huh-7 cells with IC50 values from 0.62 to 1.69 μM, which were much superior to berberine (IC50 >50 μM). More importantly, 6k exhibited lower cytotoxicity against normal hepatocytes L-02 with good lipid-water partition properties. The mechanism studies revealed that 6k caused G2/M phase arrest of the cell cycle, stabilised G-quadruplex DNA, and induced apoptosis via a mitochondrial apoptotic pathway. Finally, the in vivo anti-HCC activity of 6k was validated in the H22 liver cancer xenograft mouse model. Collectively, the current study would provide a new insight into the discovery of novel, safe and effective anti-HCC agents.

In the face of multiple challenges in stabilizing economic growth, improving people's living quality, and limiting the total amount of CO2 emissions, firstly, this study analyzes the incentive and optimization policies of scientific and technological (S&T) talents from four aspects: incentive, cultivation, flow, and evaluation. Moreover, practical suggestions are put forward. Secondly, an optimization model of China's low-carbon economy (LCE) is implemented. The Matlab software can be adopted to solve the economic output of each department in the expected year and obtain the overall economic indicators for 2017 and 2022. Finally, the output influence and CO2 emission influence of each industry are analyzed. The research results are as follows. (1) From the viewpoint of public health (PH), the countermeasures and suggestions of the S&T talents policy mainly include four parts: building a complete S&T talents policy system, expanding the coverage group of the policy, strictly implementing the policy of evaluating S&T talents, and improving the guarantee mechanism of relevant talents introduction policy. (2) In 2017, the primary industry, agriculture, forestry, animal husbandry, and fishery, accounted for 5.33%; the secondary industry, the energy sector accounted for 72.04%, and the tertiary industry (service industry) accounted for 22.63%. In 2022, the primary, secondary, and tertiary industry accounted for 6.09%, 68.44%, and 25.47%. (3) From the perspective of the industrial influence coefficient, the coefficient of all sectors is stable during 2017–2022. From the standpoint of CO2 emission, China's total CO2 emission shows rapidly increasing trend during the same period. This study has vital practical significance and theoretical value for realizing the sustainable development (SH) and transformation of the LCE.

Abstract Background T cell malignancies proliferate vigorously, are highly dependent on lysosomal function, with limited therapeutic options. Deregulation of lysosomal structure and function has been confirmed to be a key role in the treatment of hematologic malignant disease. Methods Cell counting kit 8 and Annexin V/PI staining were used to assess the cell viability and apoptosis rate. Flow cytometry, liquid chromatography mass spectrometry, immunofluorescence and western blot were performed to detect the effect on lysosomes. Drug affinity responsive target stability, molecular docking and cellular thermal shift assay were employed to confirm the target protein of V8 on lysosomes. A xenograft model was constructed in NOD/SCID mice to assess the effect and mechanism. Results V8, a new lysosomotropic compound, could be rapidly trapped by lysosomes and accumulation in lysosomes, contributing to lysosomal‐dependent cell death by evoking lysosomal membrane permeabilization (LMP), accompanied with disrupted lysosome and autophagic flux. Mechanistically, heat shock protein 70 (HSP70) was identified as the binding target of V8 in lysosome. As a downstream effect of targeting HSP70, enzymatic activity of acid sphingomyelinase (ASM) was inhibited, which induced disturbance of lipid metabolism, instability of lysosomal membrane, and leakage of cathepsin B and D, leading to LMP‐mediated cell death. In vivo study showed V8 well controlled the growth of the tumour and confirmed lysosomal cell death induced by V8. Conclusions Collectively, this study suggests targeting lysosomal HSP70‐ASM axis by V8 illustrates the great value of drug therapy for T cell malignancies and the unlimited potential of lysosomal targeting for cancer therapy.

Accurate determination of extra-cellular pH (pHe) and intra-cellular pH (pHi) is important to cancer diagnosis and treatment because tumor cells exhibit a lower pHe and a slightly higher pHi than normal cells. In this work, the characteristic absorption of water in the near-infrared (NIR) region was utilized for the determination of pHe and pHi. Dulbecco’s modified eagle medium (DMEM) and bis (2-ethylhexyl) succinate sodium sulfonate reverse micelles (RM) were employed to simulate the extra- and intra-cellular fluids, respectively. Continuous wavelet transform (CWT) was used to enhance the resolution of the spectra. Quantitative models for pHe and pHi were established using partial least squares (PLS) regression, producing relative errors of validation samples in a range of −0.74–2.07% and −1.40–0.83%, respectively. Variable selection was performed, and the correspondence between the selected wavenumbers and water structures was obtained. Therefore, water with different hydrogen bonds may serve as a good probe to sense pH within biological systems.

The integrity of lysosomes is of vital importance to survival of tumor cells. We demonstrated that LW-218, a synthetic flavonoid, induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization in hematological malignancy. LW-218-induced lysosomal damage and lysosome-dependent cell death were mediated by cathepsin D, as the lysosomal damage and cell apoptosis could be suppressed by depletion of cathepsin D or lysosome alkalization agents, which can alter the activity of cathepsins. Lysophagy, was initiated for cell self-rescue after LW-218 treatment and correlated with calcium release and nuclei translocation of transcription factor EB. LW-218 treatment enhanced the expression of autophagy-related genes which could be inhibited by intracellular calcium chelator. Sustained exposure to LW-218 exhausted the lysosomal capacity so as to repress the normal autophagy. LW-218-induced enlargement and damage of lysosomes were triggered by abnormal cholesterol deposition on lysosome membrane which caused by interaction between LW-218 and NPC intracellular cholesterol transporter 1. Moreover, LW-218 inhibited the leukemia cell growth in vivo. Thus, the necessary impact of integral lysosomal function in cell rescue and death were illustrated.

Abstract Background The positive transcription elongation factor b (P-TEFb) kinase activity is involved in the process of transcription. Cyclin-dependent kinase 9 (CDK9), a core component of P-TEFb, regulates the process of transcription elongation, which is associated with differentiation and apoptosis in many cancer types. Wogonin, a natural CDK9 inhibitor isolated from Scutellaria baicalensis. This study aimed to investigate the involved molecular mechanisms of wogonin on anti- chronic myeloid leukemia (CML) cells. Materials and methods mRNA and protein levels were analysed by RT-qPCR and western blot. Flow cytometry was used to assess cell differentiation and apoptosis. Cell transfection, immunofluorescence analysis and co-immunoprecipitation (co-IP) assays were applied to address the potential regulatory mechanism of wogonin. KU-812 cells xenograft NOD/SCID mice model was used to assess and verify the mechanism in vivo. Results We reported that the anti-CML effects in K562, KU-812 and primary CML cells induced by wogonin were regulated by P-TEFb complex. We also confirmed the relationship between CDK9 and erythroid differentiation via knockdown the expression of CDK9. For further study the mechanism of erythroid differentiation induced by wogonin, co-IP experiments were used to demonstrate that wogonin increased the binding between GATA-1 and FOG-1 but decreased the binding between GATA-1 and RUNX1, which were depended on P-TEFb. Also, wogonin induced apoptosis and decreased the mRNA and protein levels of MCL-1 in KU-812 cells, which is the downstream of P-TEFb. In vivo studies showed wogonin had good anti-tumor effects in KU-812 xenografts NOD/ SCID mice model and decreased the proportion of human CD45+ cells in spleens of mice. We also verified that wogonin exhibited anti-CML effects through modulating P-TEFb activity in vivo. Conclusions Our study indicated a special mechanism involving the regulation of P-TEFb kinase activity in CML cells, providing evidences for further application of wogonin in CML clinical treatment. Video Abstract

Abstract It is widely accepted that lysosomes are essential for cell homeostasis, and autophagy plays an important role in tumor development. Here, we found FV-429, a synthetic flavonoid compound, inhibited autophagy flux, promoted autophagosomes accumulation, and inhibited lysosomal degradation in T-cell malignancies. These effects were likely to be achieved by lysosomal dysregulation. The destructive effects of FV-429 on lysosomes resulted in blockage of lysosome-associated membrane fusion, lysosomal membrane permeabilization (LMP), and cathepsin-mediated caspase-independent cell death (CICD). Moreover, we initially investigated the effects of autophagy inhibition by FV-429 on the therapeutic efficacy of chemotherapy and found that FV-429 sensitized cancer cells to chemotherapy agents. Our findings suggest that FV-429 could be a potential novel autophagy inhibitor with notable antitumor efficacy as a single agent.

Under the background of mass entrepreneurship and innovation, innovative entrepreneurship research is urgently needed for entrepreneurs. The aim was to explore the innovative entrepreneurship consciousness of new entrepreneurs. First, the regional competitive advantage theory is discussed. The research method of questionnaire survey is combined with statistical analysis to obtain relevant research data. Quantitative standards are used to measure the impact of regional advantages and policy support on entrepreneurs’ innovation and entrepreneurship. The policy content analysis and questionnaire survey are applied to discuss the impact of regional competitive advantage, educational psychology, innovation and entrepreneurship policy, and entrepreneurs’ innovation consciousness. Meantime, the policies related to entrepreneurs’ innovation and entrepreneurship are further explored. The results show that the proportions of young entrepreneurs suffering anxiety and depression are 29.4 and 27.5%, respectively, which are significantly higher than the national average. Besides, in the test, F=23.11, p

Western-style pork products have attracted many modern urban consumers, and these products have rapidly entered the Chinese market. The current hazard analysis of processed meat products mainly focuses on processing hazards (PAHs, microorganisms, and food additives), with less attention to veterinary drug residues. According to the survey results, the residues of antimicrobial drugs (sulfonamides and quinolones) in pork and its products in China are a severe problem, which may cause metabolic reactions, toxic effects, or enhance drug resistance. This study applied a modified QuEChERS method combined with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MSMS) to develop a rapid and sensitive method for determining antimicrobial drugs in bacon and ham was successfully evaluated methodologically by EU 2002/657/EC. This study used a three-level, three-factor Box–Behnken design (BBD) to optimize the QuEChERS method by response surface methodology. The excellent linearity of the calibration curve was shown in the corresponding concentration range with a coefficient of determination greater than 0.99. The values of decision limit (CCα) and detection capability (CCβ) were in the range of 10.9–31.3 μg/kg and 11.8–52.5 μg/kg, respectively. The method successfully detected two trace levels of antimicrobial drugs in commercially available samples, including sulfadiazine and moxifloxacin.

Nanoparticles (NPs) have been widely used as target delivery vehicles for therapeutic goods; however, compared with inorganic and organic nanomaterials, protein nanomaterials have better biocompatibility and can self-assemble into highly ordered cage-like structures, which are more favorable for applications in targeted drug delivery. In this review, we concentrate on the typical protein cage nanoparticles drugs encapsulation processes, such as drug fusion expression, diffusion, electrostatic contact, covalent binding, and protein cage disassembly/recombination. The usage of protein cage nanoparticles in biomedicine is also briefly discussed. These materials can be utilized to transport small molecules, peptides, siRNA, and other medications for anti-tumor, contrast, etc.

A method for the simultaneous screening of 258 pesticide residues in silage using modified QuEChERS combined with liquid chromatography (LC)- and gas chromatography (GC)- quadrupole-Orbitrap mass spectrometry (Q-Orbitrap/MS) has been developed. After hydration, the silage was homogenized with a 1% acetic acid–acetonitrile solution, and the extract was purified using C18, PSA, and anhydrous magnesium sulfate. Finally, the sample was detected using LC/GC-Q-Orbitrap/MS, and quantified using an external standard method. The results showed that 258 pesticides had an excellent linear relationship in the range of 0.1–50 μg L−1, and that the coefficients of determination (R2) were more than 0.99. The screening detection limit (SDL) of silage was in the range of 0.5–50 μg kg−1, and the limit of quantitation (LOQ) was in the range of 1–50 μg kg−1. The accuracy and precision of the method were verified at the spiked levels of 1-, 2- and 10-times LOQ, and the recovery of 258 pesticides was in the range of 66.5–119.8%, with relative standard deviations (RSDs) of less than 20% (n = 6). This method was simple, rapid, and reliable, and could be applied to screen and quantify multi-pesticide residues in silage.

Abstract Background Although targeting histone deacetylases (HDACs) may be an effective strategy for core binding factor‐acute myeloid leukemia (CBF‐AML) harboring t(8;21) or inv(16), HDAC inhibitors are reported to be limited by drug‐resistant characteristic. Our purpose is to evaluate the anti‐leukemia effects of Baicalein on CBF‐AML and clarify its underlying mechanism. Methods Enzyme activity assay was used to measure the activity inhibition of HDACs. Rhodamine123 and RT‐qPCR were employed to evaluate the distribution of drugs and the change of ATP‐binding cassette (ABC) transporter genes. CCK8, Annexin V/PI, and FACS staining certified the effects of Baicalein on cell growth, apoptosis, and differentiation. Duolink and IP assay assessed the interaction between HDAC‐1 and ubiquitin, HSP90 and AML1‐ETO, and Ac‐p53 and CBFβ‐MYH11. AML cell lines and primary AML cells‐bearing NOD/SCID mice models were used to evaluate the anti‐leukemic efficiency and potential mechanism of Baicalein in vivo. Results Baicalein showed HDAC‐1/8 inhibition to trigger growth suppression and differentiation induction of AML cell lines and primary AML cells. Although the inhibitory action on HDAC‐1 was mild, Baicalein could induce the degradation of HDAC‐1 via ubiquitin proteasome pathway, thereby upregulating the acetylation of Histone H3 without promoting ABC transporter genes expression. Meanwhile, Baicalein increased the acetylation of HSP90 and lessened its connection to AML1/ETO, consequently leading to degradation of AML1‐ETO in t(8;21)q(22;22) AML cells. In inv(16) AML cells, Baicalein possessed the capacity of apoptosis induction accompanied with p53‐mediated apoptosis genes expression. Moreover, CBFβ‐MYH11‐bound p53 acetylation was restored via HDAC‐8 inhibition induced by Baicalein contributing the diminishing of survival of CD34+ inv(16) AML cells. Conclusions These findings improved the understanding of the epigenetic regulation of Baicalein, and warrant therapeutic potential of Baicalein for CBF‐AML.

In this research, the probability matrix factorization (PMF) algorithm was introduced to optimize the deep neural network algorithm model with the purpose of studying the application value of personality development theory and deep learning neural network in college students’ entrepreneurship psychological education courses. Based on the personality development theory, a recommendation algorithm system for entrepreneurial projects under optimized deep neural network was established. A total of 518 college students from several universities were divided into an experimental group and a control group, with 259 students in each group. In addition to the normal courses of entrepreneurship psychology education, students in the experimental group were taught the entrepreneurship project recommendation system based on the optimized deep neural network designed in this research, while students in the control group were taught entrepreneurship psychology education normally. The intervention effect before and after entrepreneurship education was evaluated by the questionnaire of college students’ entrepreneurial intention and college students’ entrepreneurial mental resilience scale. The results demonstrate that the system recall rate and accuracy based on the algorithm in this research have been significantly higher than that of PMF algorithm and deep belief network (DBN) algorithm, and the difference is statistically significant (p < 0.05); the mean square error (MSE) of the proposed algorithm is significantly smaller than that of PMF algorithm and DBN algorithm, and the difference is statistically significant (p < 0.05); the improvement of entrepreneurial toughness, entrepreneurial strength, optimism, entrepreneurial possibility, and behavioral tendency of the experimental group after the test was significantly higher than that of the control group (p < 0.05). Therefore, compared with traditional algorithms, the proposed method for entrepreneurial projects based on the theory of personality development and the optimized deep neural network shows better performance, and it can effectively improve the entrepreneurial intention and psychological resilience of college students.

ABSTRACT: To effectively assess the extent of the mycotoxin contamination of grapes, a method was developed to analyze 22 mycotoxins by ultra-high-performance liquid chromatography coupled with quadrupole/orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS). Samples were extracted and purified using the QuEChERS (quick, easy, cheap, effective, rugged, and safe) procedure. The extracts were separated on a BEH Shield C18 column (100 mm × 2.1 mm, 1.7 μm), using methanol and water with 0.1% formic acid solution and 2 mmol/L ammonium acetate as the mobile phases. The quantification was performed according to a matrix-matched external standard method. There was a good linear relationship within the respective mass concentration ranges of 22 mycotoxins; the correlation coefficients were not less than 0.998 1. The limit of quantification was 0.3–10.0 μg/kg. Mycotoxin recovery ranged from 68.6% to 109.0%, with a relative standard deviation of 1.28%–12.80%. The method is simple, rapid, highly sensitive, and accurate, making it useful for screening grapes for common and emerging mycotoxins.