[Optimization of prediction model for personalized water pills based on semantic analysis of traditional Chinese medicine materials].

This study aims to optimize the prediction model of personalized water pills that has been established by our research group. Dioscoreae Rhizoma, Leonuri Herba, Codonopsis Radix, Armeniacae Semen Amarum, and calcined Oyster were selected as model medicines of powdery, fibrous, sugary, oily, and brittle materials, respectively. The model prescriptions were obtained by uniform mixing design. With hydroxypropyl methylcellulose E5(HPMC-E5) aqueous solution as the adhesive, personalized water pills were prepared by extrusion and spheronizaition. The evaluation indexes in the pill preparation process and the multi-model statistical analysis were employed to optimize and evaluate the prediction model of personalized water pills. The prediction equation of the adhesive concentration was obtained as follows: Y_1=-4.172+3.63X_A+15.057X_B+1.838X_C-0.997X_D(adhesive concentration of 10% when Y_1<0, and 20% when Y_1>0). The overall accuracy of the prediction model for adhesive concentration was 96.0%. The prediction equation of adhesive dosage was Y_2=6.051+94.944X_A~(1.5)+161.977X_B+70.078X_C~2+12.016X_D~(0.3)+27.493X_E~(0.3)-2.168X_F~(-1)(R~2=0.954, P<0.001). Furthermore, the semantic prediction model for material classification of traditional Chinese medicines was used to classify the materials contained in the prescription, and thus the prediction model of personalized water pills was evaluated. The results showed that the prescriptions for model evaluation can be prepared with one-time molding, and the forming quality was better than that established by the research group earlier. This study has achieved the optimization of the prediction model of personalized water pills.

[Intelligent material classification of traditional Chinese medicine based on semantic analysis].

A method for material classification of traditional Chinese medicines based on the physical properties of powder has been established by our research group. This method involves pre-treatment of traditional Chinese medicine decoction pieces, powder preparation, and determination of physical properties, being cumbersome. In this study, the word segmentation logic of semantic analysis was adopted to establish the thesaurus and local standardized semantic word segmentation database with the macroscopic and microscopic characteristics of 36 model traditional Chinese medicines as the basic data. The physical properties of these medicines have been determined and the classification of these medicines is clear in the cluster analysis. A total of 55 keywords for powdery, fibrous, sugary, oily, and brittle materials were screened by association rules and the set inclusion and exclusion criteria, and the weights of the keywords were calculated. Furthermore, the algorithms of the keyword matching scores and the computation rules of the single or multiple material classification were established for building the intelligent model of semantic analysis for the material classification. The semantic classification results of the other 35 TCMs except Pseudostellariae Radix(multi-material medicine) agreed with the clustering results based on the physical properties of the powder, with an agreement rate of 97.22%. In model validation, the prediction results of semantic classification of traditional Chinese medicines were consistent with the clustering results based on the physical properties of powder, with an agreement rate of 83.33%. The results showed that the method of material classification based on semantic analysis was feasible, which laid a foundation for the development of intelligent decision-making technology for personalized traditional Chinese medicine preparations.

Imbalanced and Unchecked: The Role of Metal Dyshomeostasis in Driving COPD Progression.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterized by persistent inflammation and oxidative stress, which ultimately leads to progressive restriction of airflow. Extensive research findings have cogently suggested that the dysregulation of essential transition metal ions, notably iron, copper, and zinc, stands as a critical nexus in the perpetuation of inflammatory processes and oxidative damage within the lungs of COPD patients. Unraveling the intricate interplay between metal homeostasis, oxidative stress, and inflammatory signaling is of paramount importance in unraveling the intricacies of COPD pathogenesis. This comprehensive review aims to examine the current literature on the sources, regulation, and mechanisms by which metal dyshomeostasis contributes to COPD progression. We specifically focus on iron, copper, and zinc, given their well-characterized roles in orchestrating cytokine production, immune cell function, antioxidant depletion, and matrix remodeling. Despite the limited number of clinical trials investigating metal modulation in COPD, the advent of emerging methodologies tailored to monitor metal fluxes and gauge responses to chelation and supplementation hold great promise in unlocking the potential of metal-based interventions. We conclude that targeted restoration of metal homeostasis represents a promising frontier for ameliorating pathological processes driving COPD progression.

Phosphorylation of IDH1 Facilitates Progestin Resistance in Endometrial Cancer.

The progestin regimen is one of the main therapeutic strategies for women with endometrial cancer who undergo conservative management. Although many patients respond well to initial therapy, progestin-refractory disease inevitably emerges, and the molecular basis underlying progestin resistance has not been comprehensively elucidated. Herein, they demonstrated progestin results in p38-dependent IDH1 Thr 77 phosphorylation (pT77-IDH1). pT77-IDH1 translocates into the nucleus and is recruited to chromatin through its interaction with OCT6. IDH1-produced α-ketoglutarate (αKG) then facilitates the activity of OCT6 to promote focal adhesion related target gene transcription to confer progestin resistance. Pharmacological inhibition of p38 or focal adhesion signaling sensitizes endometrial cancer cells to progestin in vivo. The study reveals p38-dependent pT77-IDH1 as a key mediator of progestin resistance and a promising target for improving the efficacy of progestin therapy.

Preparation of a long-lasting tablet of spinosad microspheres and its residual insecticidal efficacy against the yellow fever mosquito, Aedes aegypti (Diptera: Culicidae) larvae.

BACKGROUNDS: In order to provide a long-lasting formulation for spinosad (SP) targeting larval stages of Aedes aegypti (Linnaeus) and others alike, a SP tablet was developed based on microspheres, using polylactic acid as inside coating material. The microspheres were encapsulated using polyethylene glycol and 1-hexadecanol to form a sustained-release SP tablet. Micromorphology, active ingredient loading, structure identification, photolysis resistance and biological activity were evaluated in this report. RESULTS: (i) The SP microspheres had an average particle size of 6.16 ± 2.28 µm, low adhesion and good dispersion as evaluated by scanning electron microscopy and morphology. (ii) The average active ingredient loading and encapsulation of SP microspheres were 32.80 ± 0.74% and 78.41 ± 2.22%, respectively. (iii) The chemical structure of encapsulated SP was confirmed by Fourier transform infrared and 1H-nuclear magnetic resonance. (iv) The photostability of the microspheres and the tablets were evaluated. The results showed that DT50 (time required to dissipate 50% of the mass originally present) of SP was 0.95 days in microspheres and 6.94 days in tablets. (v) The long-term insecticidal activity of SP tablets was investigated, and the tablet had a long-lasting activity against the mosquito larvae, showing 100% larval mortality for 63 days. CONCLUSIONS: The study provided a new long-lasting formulation of SP, which displayed good efficacy in the control of Ae. aegypti larvae. © 2024 Society of Chemical Industry.

Multifunctional Cellulose Nanocrystals Electrolyte Additive Enable Ultrahigh-Rate and Dendrite-Free Zn Anodes for Rechargeable Aqueous Zinc Batteries.

The design of aqueous zinc (Zn) chemistry energy storage with high rate-capability and long serving life is a great challenge due to its inhospitable coordination environment and dismal interfacial chemistry. To bridge this big gap, herein, we build a highly reversible aqueous Zn battery by taking advantages of the biomass-derived cellulose nanocrystals (CNCs) electrolyte additive with unique physical and chemical characteristics simultaneously. The CNCs additive not only serves as fast ion carriers for enhancing Zn2+ transport kinetics but regulates the coordination environment and interface chemistry to form dynamic and self-repairing protective interphase, resulting in building ultra-stable Zn anodes under extreme conditions. As a result, the engineered electrolyte system achieves a superior average coulombic efficiency of 97.27 % under 140 mA cm-2, and steady charge-discharge for 982 h under 50 mA cm-2, 50 mAh cm-2, which proposes a universal pathway to challenge aqueous Zn chemistry in green, sustainable, and large-scale applications.

Introducing the Reversible Reaction of CO2 with Diamines into Nonisocyanate Polyurethane Synthesis.

Nonisocyanate polyurethanes (NIPUs) are considered greener alternatives to traditional polyurethanes, and the preparation of NIPUs considerably depends on the design and synthesis of suitable monomers. Herein, we propose a toolbox for in situ capturing and conversion of CO2 into α,ω-diene-functionalized carbamate monomers by taking advantage of the facile reversible reaction of CO2 with diamines in the presence of organic superbases. The activation of CO2 into carbamate intermedia was demonstrated by NMR and in situ FTIR, and the optimal conditions to prepare α,ω-diene-functionalized carbamate monomers were established. Thiol-ene and acyclic diene metathesis (ADMET) polymerization of these monomers under mild conditions yielded a series of poly(thioether urethane)s and unsaturated aromatic-aliphatic polyurethanes with high yield and glass transition temperatures ranging from -26.8 to -1.1 °C. These obtained NIPUs could be further modified via postpolymerization oxidation or hydrogenation to yield poly(sulfone urethane) and saturated polyurethane with tunable properties.

Dual-Proton Conductor for Fuel Cells with Flexible Operational Temperature.

The properties of proton conductors determine the operating temperature range of fuel cells. Typically, phosphoric acid (PA) proton conductors exhibit excellent proton conductivity owing to their high proton dissociation and self-diffusion abilities. However, at low temperatures or high current densities, water-induced PA loss causes rapid degradation of cell performance. Maintaining efficient and stable proton conductivity within a flexible temperature range can significantly reduce the start-up temperature of PA-doped proton exchange membrane fuel cells. In this study, a dual-proton conductor composed of an organic phosphonic acid (ethylenediamine tetramethylene phosphonic acid, EDTMPA) and an inorganic PA is developed for proton exchange membranes. The proposed dual-proton conductor can operate within a flexible temperature range of 80-160 °C, benefiting from the strong interaction between EDTMPA and PA, and the enhanced proton dissociation. Fuel cells with the EDTMPA-PA dual-proton conductor showed excellent cell stability at 80 °C. In particular, under the high current density of 1.5 A cm-2 at 160 °C, the voltage decay rate of the fuel cell with the dual-proton conductor is one-thousandth of that of the fuel cell with PA-only proton conductor, indicating excellent stability.

Discovery of a Highly Potent and Selective MYOF Inhibitor with Improved Water Solubility for the Treatment of Gastric Cancer.

Myoferlin (MYOF) mediates the growth and metastasis of various cancers as an emerging therapeutic target by regulating exocytosis and endocytosis. However, the previously reported MYOF inhibitor, 6y, failed to be a favorable candidate agent due to its poor physicochemical properties, such as water solubility, in preclinical studies. Naturally, a novel range of MYOF inhibitors was synthesized and optimized based on the lead compound 6y. The optimal compound HJ445A potently repressed the proliferation of gastric cancer cells with IC50 values of 0.16 and 0.14 µM in MGC803 and MKN45, respectively. Moreover, HJ445A bound to the MYOF-C2D domain with a KD of 0.17 µM, and HJ445A prevented the migration of gastric cancer cells by reversing the epithelial-mesenchymal transition (EMT) process and inhibited the colony formation of the MKN45 cells in a concentration-dependent manner. Notably, the water solubility of HJ445A was significantly improved compared to 6y, with about 170-fold enhancement. Additionally, HJ445A also demonstrated superior antitumor efficacy in vivo.

Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC.

Inflammasome activity is important for the immune response and is instrumental in numerous clinical conditions. Here we identify a mechanism that modulates the central Caspase-1 and NLR (Nod-like receptor) adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD). We show that the function of ASC in assembling the inflammasome is controlled by its modification with SUMO (small ubiquitin-like modifier) and identify that the nuclear ZBTB16 (zinc-finger and BTB domain-containing protein 16) promotes this SUMOylation. The physiological significance of this activity is demonstrated through the reduction of acute inflammatory pathogenesis caused by a constitutive hyperactive inflammasome by ablating ZBTB16 in a mouse model of Muckle-Wells syndrome. Together our findings identify an further mechanism by which ZBTB16-dependent control of ASC SUMOylation assembles the inflammasome to promote this pro-inflammatory response.

CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis.

Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and mediates hyperactivation of human and mouse platelets through the p38 MAPK-NF-κB signaling pathway. Conversely, the pharmacological blockade of CD36 or p38 notably attenuates human platelet activation induced by the E protein. Similarly, the genetic deficiency of CD36, as well as the pharmacological inhibition of p38 in mice, significantly diminishes E protein-induced platelet activation and thrombotic events. Together, our study reveals a critical role for the CD36-p38 axis in E protein-induced platelet hyperactivity, which could serve as an actionable target for developing therapies against aberrant thrombotic events related to the severity and mortality of COVID-19.

[Classification optimization of traditional Chinese medicine materials based on additive physical properties of powder].

According to the method of predicting the physical properties of oily powder based on the additive physical properties of Chinese medicinal powder, Dioscoreae Rhizoma and calcined Ostreae Concha with high sieve rate and good fluidity were mixed and crushed with Persicae Semen, Platycladi Semen, Raphani Semen, Ziziphi Spinosae Semen, and other typical oily materials with high fatty oil content in proportion to obtain 23 mixed powders. Fifteen physical properties such as bulk density, water absorption, and maximum torque force were measured, and the physical properties of typical oily powders were predicted. When the mixing and grinding ratio was in the range of 5∶1-1∶1, the r value in the correlation equation between the weighted average score of the mixed powder and the powder proportion ranged from 0.801 to 0.986, and the linearity was good, indicating that the method of predicting the physical properties of oily powder based on the additive physical properties of traditional Chinese medicine(TCM)powder was feasible. The results of cluster analysis showed that the classification boundaries of the five kinds of TCM materials were clear, and the similarity of the physical fingerprints of powdery and oily materials decreased from 80.6% to 37.2%, which solved the problem of fuzzy classification boundaries of powdery and oily materials due to the lack of representativeness of oily material model drugs. The classification of TCM materials was optimized, laying a foundation for optimizing the prediction model of the prescription of personalized water-paste pills.

Sanghuangporus sanghuang extract extended the lifespan and healthspan of Caenorhabditis elegans via DAF-16/SIR-2.1.

Sanghuangporus Sanghuang is a fungus species. As a traditional Chinese medicine, it is known for antitumor, antioxidant and anti-inflammatory properties. However, the antiaging effect of S. Sanghuang has not been deeply studied. In this study, the effects of S. Sanghuang extract (SSE) supernatants on the changes of nematode indicators were investigated. The results showed that different concentrations of SSE prolonged the lifespans of nematodes and substantially increased these by 26.41%. In addition, accumulations of lipofuscin were also visibly reduced. The treatment using SSE also played a role in increasing stress resistance, decreasing ROS accumulations and obesity, and enhancing the physique. RT-PCR analysis showed that the SSE treatment upregulated the transcription of daf-16, sir-2.1, daf-2, sod-3 and hsp-16.2, increased the expression of these genes in the insulin/IGF-1 signalling pathway and prolonged the lifespans of nematodes. This study reveals the new role of S. Sanghuang in promoting longevity and inhibiting stress and provides a theoretical basis for the application of S. Sanghuang in anti-ageing treatments.

Exercise-induced endothelial Mecp2 lactylation suppresses atherosclerosis via the Ereg/MAPK signalling pathway.

BACKGROUND AND AIMS: Lactylation, a recently identified post-translational modification (PTM), plays a central role in the regulation of multiple physiological and pathological processes. Exercise is known to provide protection against cardiovascular disease. However, whether exercise-generated lactate changes lactylation and is involved in the exercise-induced attenuation of atherosclerotic cardiovascular disease (ASCVD) remains unclear. The purpose of this study was to investigate the effects and mechanisms of exercise-induced lactylation on ASCVD. METHODS AND RESULTS: Using the high-fat diet-induced apolipoprotein-deficient mouse model of ASCVD, we found that exercise training promoted Mecp2 lysine lactylation (Mecp2k271la); it also decreased the expression of vascular cell adhesion molecule 1 (Vcam-1), intercellular adhesion molecule 1 (Icam-1), monocyte chemoattractant protein 1 (Mcp-1), interleukin (IL)-1ß, IL-6, and increased the level of endothelial nitric oxide synthase (Enos) in the aortic tissue of mice. To explore the underlying mechanisms, mouse aortic endothelial cells (MAECs) were subjected to RNA-sequencing and CHIP-qPCR, which confirmed that Mecp2k271la repressed the expression of epiregulin (Ereg) by binding to its chromatin, demonstrating Ereg as a key downstream molecule for Mecp2k271la. Furthermore, Ereg altered the mitogen-activated protein kinase (MAPK) signalling pathway through regulating the phosphorylation level of epidermal growth factor receptor, thereby affecting the expression of Vcam-1, Icam-1, Mcp-1, IL-1ß, IL-6, and Enos in ECs, which in turn promoted the regression of atherosclerosis. In addition, increasing the level of Mecp2k271la by exogenous lactate administration in vivo also inhibits the expression of Ereg and the MAPK activity in ECs, resulting in repressed atherosclerotic progression. CONCLUSIONS: In summary, this study provides a mechanistic link between exercise and lactylation modification, offering new insight into the anti-atherosclerotic effects of exercise-induced PTM.

Expertise increases planning depth in human gameplay.

A hallmark of human intelligence is the ability to plan multiple steps into the future1,2. Despite decades of research3-5, it is still debated whether skilled decision-makers plan more steps ahead than novices6-8. Traditionally, the study of expertise in planning has used board games such as chess, but the complexity of these games poses a barrier to quantitative estimates of planning depth. Conversely, common planning tasks in cognitive science often have a lower complexity9,10 and impose a ceiling for the depth to which any player can plan. Here we investigate expertise in a complex board game that offers ample opportunity for skilled players to plan deeply. We use model fitting methods to show that human behaviour can be captured using a computational cognitive model based on heuristic search. To validate this model, we predict human choices, response times and eye movements. We also perform a Turing test and a reconstruction experiment. Using the model, we find robust evidence for increased planning depth with expertise in both laboratory and large-scale mobile data. Experts memorize and reconstruct board features more accurately. Using complex tasks combined with precise behavioural modelling might expand our understanding of human planning and help to bridge the gap with progress in artificial intelligence.

Dual-branch hybrid network for lesion segmentation in gastric cancer images.

The effective segmentation of the lesion region in gastric cancer images can assist physicians in diagnosing and reducing the probability of misdiagnosis. The U-Net has been proven to provide segmentation results comparable to specialists in medical image segmentation because of its ability to extract high-level semantic information. However, it has limitations in obtaining global contextual information. On the other hand, the Transformer excels at modeling explicit long-range relations but cannot capture low-level detail information. Hence, this paper proposes a Dual-Branch Hybrid Network based on the fusion Transformer and U-Net to overcome both limitations. We propose the Deep Feature Aggregation Decoder (DFA) by aggregating only the in-depth features to obtain salient lesion features for both branches and reduce the complexity of the model. Besides, we design a Feature Fusion (FF) module utilizing the multi-modal fusion mechanisms to interact with independent features of various modalities and the linear Hadamard product to fuse the feature information extracted from both branches. Finally, the Transformer loss, the U-Net loss, and the fused loss are compared to the ground truth label for joint training. Experimental results show that our proposed method has an IOU of 81.3%, a Dice coefficient of 89.5%, and an Accuracy of 94.0%. These metrics demonstrate that our model outperforms the existing models in obtaining high-quality segmentation results, which has excellent potential for clinical analysis and diagnosis. The code and implementation details are available at Github, https://github.com/ZYY01/DBH-Net/ .

Upregulation of PTPRC and Interferon Response Pathways in HIV-1 Seroconverters Prior to Infection.

Human immunodeficiency virus 1 (HIV-1) exposed seronegative (HESN) individuals may have unique characteristics that alter susceptibility to HIV-1 infection. However, identifying truly exposed HESN is challenging. We utilized stored data and biospecimens from HIV-1 serodifferent couple cohorts, in which couples' HIV-1 exposures were quantified based on unprotected sex frequency and viral load of the partner with HIV-1. We compared peripheral blood gene expression between 15 HESN and 18 seroconverters prior to infection. We found PTPRC (encoding CD45 antigen) and interferon-response pathways had significantly higher expression among individuals who went on to become seropositive and thus may be a signature for increased acquisition risk.

High-quality restoration image encryption using DCT frequency-domain compression coding and chaos.

With the arrival of the age of big data, the amount and types of data in the process of information transmission have increased significantly, and the full-disk encryption mode used by traditional encryption algorithms has certain limitations of the times. In order to further improve the bandwidth efficiency of digital images in the transmission process and the information effectiveness of digital image transmission, this paper proposes an algorithm of high-quality restoration image encryption using DCT frequency-domain compression coding and chaos. Firstly, the image hash value is used for the generation of an encryption key with plaintext correlation, then lightweight chaos is generated based on the key to obtain a pseudo-random sequence. Secondly, the image is partitioned into subblock, and converted from time domain into frequency domain by employing Discrete Cosine Transform (DCT) on each block, then perform quantization operation based on frequency domain information to obtain DCT coefficient matrix. Thirdly, the direct current (DC) coefficients and alternating current (AC) coefficients are extracted in the DCT coefficient matrix and compressed by different encoding methods to obtain two sets of bitstream containing DC coefficient and AC coefficient information. Fourthly, permute the DC coefficient bit stream by the chaotic sequence, and reconstruct it with the AC coefficient bit stream to obtain the frequency domain ciphertext image. Finally, the chaotic sequence is used to diffuse ciphertext, and the processed hash value is hidden in the ciphertext to obtain the final ciphertext. The theoretical and experimental analysis showed that the key length reaches 341 bits, and the PSNR value of the restored image is close to 60, all of which satisfy the theoretical value. Therefore, the algorithm has the characteristics of high compression rate, high-quality image restoration large key space, strong plaintext sensitivity, strong key sensitivity and so on. Our method proposed in this paper is expected to provide a new idea for confidential and secure communication in the age of big data.

Hierarchically Porous Films Architectured by Self-Assembly of Prolamins at the Air-Liquid Interface.

Artificial recapitulation of hierarchically porous films gained great interest due to their versatile functionalities and applications. However, the development of novel eco-friendly and nontoxic biopolymer-based porous films is still limited by the time-consuming fabrication processes and toxic organic reagents involved. Here, we reported a novel approach to rapidly (within 5 s) fabricate biopolymer-based hierarchically porous films via inducing the laterally occurring interfacial self-assembly of prolamins at the air-liquid interface during an antisolvent dripping procedure. The as-prepared films exhibited a hierarchically porous microstructure (with sizes of about 500 nm to 5 µm) with location-graded and Janus features. The formation mechanism involved the solvent gradient controlled self-assembly of prolamin into an anisotropic defect structure in longitudinal and lateral directions. Accordingly, the macroscopic morphologies together with the porosity and pore size could be precisely tuned by solvents and operating parameters in a convenient way. Furthermore, alcohol-soluble but water-insoluble bioactive compounds could be incorporated simultaneously via a one-step loading procedure, which endowed films with large loading efficiency and sustained release features suitable for controlled release applications. The effect of the curcumin-loaded porous film on skin wound healing, as one of the potential applications of this novel material, was then investigated in vivo in a full-thickness wound model, wherein satisfying wound healing effects were achieved through multitarget and multipathway mechanisms. This pioneering work offers a novel strategy for the rapid architecture of biopolymer-based hierarchically porous film with versatile application potentials.

Discovery of 1,5-diaryl-1,2,4-triazole derivatives as myoferlin inhibitors and their antitumor effects in pancreatic cancer.

Aim: The first inhibitor targeting myoferlin (MYOF), WJ460, bears poor metabolic stability and water solubility. Therefore, this study aimed to improve the drug-like properties of WJ460. Materials & methods: The authors synthesized an array of 1,5-diaryl-1,2,4-triazole analogs and appraised the binding activities with MYOF and their antiproliferative and antimigratory activities against pancreatic cancer cells. Results: Molecular docking and surface plasmon resonance results showed that E4 was directly bound to the MYOF-C2D domain. E4 effectively inhibited the proliferation and migration of pancreatic cancer cells in vitro. An in silico study suggested that the water solubility of E4 was improved by about 22-times than that of WJ460. Conclusion: The findings suggested that the druglike ability of E4 was significantly improved.