High-Performance 2D Ambipolar MoTe2 Lateral Memristors by Mild Oxidation.

2D transition metal dichalcogenides (TMDCs) have been intensively explored in memristors for brain-inspired computing. Oxidation, which is usually unavoidable and harmful in 2D TMDCs, could also be used to enhance their memristive performances. However, it is still unclear how oxidation affects the resistive switching behaviors of 2D ambipolar TMDCs. In this work, a mild oxidation strategy is developed to greatly enhance the resistive switching ratio of ambipolar 2H-MoTe2 lateral memristors by more than 10 times. Such an enhancement results from the amplified doping due to O2 and H2O adsorption and the optimization of effective gate voltage distribution by mild oxidation. Moreover, the ambipolarity of 2H-MoTe2 also enables a change of resistive switching direction, which is uncommon in 2D memristors. Consequently, as an artificial synapse, the MoTe2 device exhibits a large dynamic range (≈200) and a good linearity (1.01) in long-term potentiation and depression, as well as a high-accuracy handwritten digit recognition (>96%). This work not only provides a feasible and effective way to enhance the memristive performance of 2D ambipolar materials, but also deepens the understanding of hidden mechanisms for RS behaviors in oxidized 2D materials.

Mapping Method of Human Arm Motion Based on Surface Electromyography Signals.

This paper investigates a method for precise mapping of human arm movements using sEMG signals. A multi-channel approach captures the sEMG signals, which, combined with the accurately calculated joint angles from an Inertial Measurement Unit, allows for action recognition and mapping through deep learning algorithms. Firstly, signal acquisition and processing were carried out, which involved acquiring data from various movements (hand gestures, single-degree-of-freedom joint movements, and continuous joint actions) and sensor placement. Then, interference signals were filtered out through filters, and the signals were preprocessed using normalization and moving averages to obtain sEMG signals with obvious features. Additionally, this paper constructs a hybrid network model, combining Convolutional Neural Networks and Artificial Neural Networks, and employs a multi-feature fusion algorithm to enhance the accuracy of gesture recognition. Furthermore, a nonlinear fitting between sEMG signals and joint angles was established based on a backpropagation neural network, incorporating momentum term and adaptive learning rate adjustments. Finally, based on the gesture recognition and joint angle prediction model, prosthetic arm control experiments were conducted, achieving highly accurate arm movement prediction and execution. This paper not only validates the potential application of sEMG signals in the precise control of robotic arms but also lays a solid foundation for the development of more intuitive and responsive prostheses and assistive devices.

Complete remission of advanced pancreatic cancer induced by claudin18.2-targeted CAR-T cell therapy: a case report.

Pancreatic cancer (PC) is one of the most malignant tumors in digestive system due to its highly invasive and metastatic properties. At present, conventional treatment strategies for PC show the limited clinical efficacy. Therefore, novel effective therapeutic strategies are urgently needed. Here, we report a case of complete remission of advanced PC induced by claudin18.2-targeted CAR-T cell therapy. The patient was a 72-year-old man who was diagnosed with pancreatic ductal adenocarcinoma 2 years ago, and he experienced tumor recurrence and multiple metastases after pancreaticoduodenectomy and multi-line chemotherapies, including liver, peritoneum, and cervical lymph node metastases. Then, the patient was referred to our department for further treatment of metastatic PC, and he was enrolled in a clinical trial of claudin18.2-targeted CAR-T cell therapy. After lymphodepleting chemotherapy, the patient received claudin18.2-targeted CAR-T cell infusion at a dose of 1.2 × 106 cells/kg on November 21, 2022. During CAR-T cell therapy, the patient experienced grade 2 cytokine release syndrome (CRS) and gastric mucosa injury, which were controlled by tocilizumab and conventional symptomatic and supportive treatment. The patient achieved a complete response (CR) 1 month after claudin18.2-targeted CAR-T cell therapy, and remained in clinical remission for 8 months. Unfortunately, the patient experienced claudin18.2-negative relapse in July, 2023. Despite antigen-negative relapse after claudin18.2-targeted CAR-T cell infusion, the patient achieved sustained remission for 8 months, which indicates that claudin18.2-targeted CAR-T cell therapy is an extremely effective therapeutic strategy for the treatment of advanced PC.

Synergistic efficacy of PI3Kδ inhibitor with anti-PD-1 mAbs in immune-humanized PDX model of endocrine resistance hormone receptor-positive advanced breast cancer.

Purpose: Endocrine resistance hormone receptor-positive (HR+) advanced breast cancer (ABC) is generally insensitive to immunecheckpoint inhibitors (ICIs). This study sought to determine whether PI3Kδ inhibitor could enhance the sensitivity of endocrine resistance HR + advanced BC to ICIs by reducing immune evasion. Methods: Patient-derived HR + ABC xenografts were implanted into immune-humanized NSG mice and subsequently treated with YY20394 (PI3Kδ inhibitor) and camrelizumab. The mice were monitored for tumor progression, biochemical blood indicators, and peripheral blood T-cell subsets. The xenografted tumors were collected at the end of the treatment cycle and subjected to HE staining, immunohistochemistry and protein phosphorylation analysis. Besides, the xenografted tumors were also used to isolate primary breast cancer cells (BCCs) and regulatory T-cells (Tregs), which were subsequently used to evaluate drug sensitivity in vitro. Results: The humanized PDX model showed a favorable initial treatment response to camrelizumab combined with YY20394 and manageable toxicity. YY20394 plus camrelizumab showed a strong inhibitory effect on HR + BC in vivo mediated by suppression of Treg activity and an increased proportion of CD8+ T cells. Mice bearing tumors treated with YY20394 and camrelizumab had less invasion, mitotic figures, and ki67 expression, while having higher IL-12 expression compared with other groups. Mechanistically, YY20394 only effectively inhibited the PI3K pathway and proliferation activity in Tregs but not in BCCs. Conclusion: Our study suggests PI3Kδ inhibitor could the enhance the efficacy of ICIs in HR + BC PDX models by combating immune suppression and provides a feasible approach that may overcome the resistance of ICIs in HR + BC patients.

Liquid Precursor-Guided Phase Engineering of Single-Crystal VO2 Beams.

The study of VO2 flourishes due to its rich competing phases induced by slight stoichiometry variations. However, the vague mechanism of stoichiometry manipulation makes the precise phase engineering of VO2 still challenging. Here, stoichiometry manipulation of single-crystal VO2 beams in liquid-assisted growth is systematically studied. Contrary to previous experience, oxygen-rich VO2 phases are abnormally synthesized under a reduced oxygen concentration, revealing the important function of liquid V2 O5 precursor: It submerges VO2 crystals and stabilizes their stoichiometric phase (M1) by isolating them from the reactive atmosphere, while the uncovered crystals are oxidized by the growth atmosphere. By varying the thickness of liquid V2 O5 precursor and thus the exposure time of VO2 to the atmosphere, various VO2 phases (M1, T, and M2) can be selectively stabilized. Furthermore, this liquid precursor-guided growth can be used to spatially manages multiphase structures in single VO2 beams, enriching their deformation modes for actuation applications.

Electrochemically Promoted Benzylation of [60]Fullerooxazolidinone.

Benzylation of the electrochemically generated dianion from N-p-tolyl-[60]fullerooxazolidinone with benzyl bromide provides three products with different addition patterns. The product distribution can be dramatically altered by varying the reaction conditions. Based on spectral characterizations, these products have been assigned as mono-benzylated 1,4-adduct and bis-benzylated 1,2,3,16- and 1,4,9,25-adducts, respectively. The assigned 1,2,3,16-adduct has been further established by X-ray diffraction analysis. It is believed that the 1,4-adduct is obtained by decarboxylative benzylation of the dianionic species, while bis-benzylated 1,2,3,16- and 1,4,9,25-adducts are achieved via a rearrangement process. In addition, the electrochemical properties of these products have been studied.

Review on Li Deposition in Working Batteries: From Nucleation to Early Growth.

Lithium (Li) metal is one of the most promising alternative anode materials of next-generation high-energy-density batteries demanded for advanced energy storage in the coming fourth industrial revolution. Nevertheless, disordered Li deposition easily causes short lifespan and safety concerns and thus severely hinders the practical applications of Li metal batteries. Tremendous efforts are devoted to understanding the mechanism for Li deposition, while the final deposition morphology tightly relies on the Li nucleation and early growth. Here, the recent progress in insightful and influential models proposed to understand the process of Li deposition from nucleation to early growth, including the heterogeneous model, surface diffusion model, crystallography model, space charge model, and Li-SEI model, are highlighted. Inspired by the abovementioned understanding on Li nucleation and early growth, diverse anode-design strategies, which contribute to better batteries with superior electrochemical performance and dendrite-free deposition behavior, are also summarized. This work broadens the horizon for practical Li metal batteries and also sheds light on more understanding of other important metal-based batteries involving the metal deposition process.

Insights into the Redox Chemistry of Organosulfides Towards Stable Molecule Design in Nonaqueous Energy Storage Systems.

Nonaqueous redox flow batteries (RFBs) have great potential to achieve high-energy storage systems. However, they have been limited by low solubility and poor stability of active materials. Here we demonstrate organosulfides as a new-type model material system to explore the rational design of redox-active molecules in nonaqueous systems. The tetraethylthiuram disulfide (TETD) molecule shows high solubility in various common organic solvents and achieves a high reversible capacity of ca. 50 Ah L-1 at a high concentration of 1 M. The resonance structures in the reduced product endow the molecule with high electrochemical stability in different organic electrolytes. The underlying mechanism in redox chemistry of organodisulfides involving the cleavage and reformation of disulfide bonds is revealed by material/structural characterizations. This study provides a new perspective of molecule designs for the development of redox-active materials for high-performance nonaqueous RFBs.

[Colorectal cancer preventive effect of combined administration of phenolic acids and supercritical extracts from Angelica sinensis].

This study aimed to investigate the colorectal cancer preventive effect of the combined administration of phenolic acids and supercritical extracts from Angelica sinensis. The AOM/DSS model in mice was adopted. Phenolic acids were administrated orally in the initial stage of the model at a dose of 1 g·kg⁻¹ BW, which was combined withtherectal administration with three doses of supercritical extracts (15, 30, 60 g·kg⁻¹ BW). PCNA, 8-oxoguaine, γ-H2AX, iNOS and COX-2 were tested by immunohistochemistry and Western blot assays. The results showed that the combined administration of phenolic acids and supercritical extracts from A. sinensis suppressed the tumor growth and cell proliferation, and DNA damages and inflammatory responses were reduced in a dose-dependent manner. These results indicate that the combined administration of phenolic acids and supercritical extracts from A. sinensis have a certain effect in preventing carcinogenesis.

Effect of Angelica sinensis Root Extract on Cancer Prevention in Different Stages of an AOM/DSS Mouse Model.

Angelica sinensis root (ASR) extract was obtained to investigate its effects on colorectal carcinogenesis in different stages of an Azoxymethane/Dextran sodium sulphate (AOM/DSS) model. In this study, we showed that ASR extract administration in the initial stage of the AOM/DSS model had cancer preventive effects with decreasing tumor incidence and a high-grade of intraepithelial neoplasia incidence. With respect to DNA damage, the amounts of 8-oxoguanine and γ-H2AX were suppressed in colon tissue. The balance of apoptosis and proliferation was approaching the normal state. In contrast, ASR extract administration in the promotion stage of the AOM/DSS model accelerated the progression of carcinogenesis. The maximum tumor size reached 49.85 ± 25.04 mm³. High-grade pathological changes were significantly increased. Decreased DNA damage and P53 level reflected the disrupted reactive oxygen species (ROS) concentration in colorectal tissue, which led to an imbalance of proliferative and apoptotic relationships. These findings suggested that the cancer-preventive effect of ASR extract may be stage-dependent in the process of carcinogenesis.

Effect of menthone and related compounds on skin permeation of drugs with different lipophilicity and molecular organization of stratum corneum lipids.

The objective of this article was to investigate the enhancing effect of menthone, menthol and pulegone on the transdermal absorption of drugs with different lipophilicity and probe their mechanisms of action at molecular level. Five model drugs, namely osthole, tetramethylpyrazine, ferulic acid, puerarin and geniposide, which were selected based on their lipophilicity denoted by logKo/w, were tested using in vitro permeation studies in which Franz diffusion cells and rat skin were employed. Infrared spectroscopy and molecular dynamic simulation were used to investigate the effect of these enhancers on the stratum corneum (SC) lipids, respectively. Three compounds could effectively promote the transdermal absorption of drugs with different lipophilicity, and the overall promoting capacities were in the following increasing order: pulegone < menthol < menthone. The penetration enhancement ratio was roughly in parabolic curve relationships with the drug lipophilicity after treatment with menthol or menthone, while the penetration enhancement effect of pulegone hardly changed with the alteration of the drug lipophilicity. The molecular mechanism studies suggested that menthone and menthol enhanced the skin permeability by disordering the ordered organization of SC lipids and extracted part of SC lipids, while pulegone appeared to promote drug transport across the skin only by extracting part of SC lipids.

Enhanced dissolution rate and oral bioavailability of Ginkgo biloba extract by preparing solid dispersion via hot-melt extrusion.

The aim of this study was to improve the dissolution rate and oral bioavailability of Ginkgo biloba extract (GBE) through the preparation of G. biloba extract solid dispersions (GBE-SD) via hot-melt extrusion (HME). First, we prepared the GBE-SD based on a Kollidon® VA64/Kolliphor® RH40 (85:15) spray dried powder. Then physicochemical properties were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR). The results indicated that GBE dispersed well in a carrier matrix. Subsequently, we studied the dissolution profile of total flavonoids (TFs) by HPLC-UV and total terpene lactones (TTLs) by HPLC-ELSD. The dissolution percentage of TFs and TTLs was improved within 120min. Finally, we studied the pharmacokinetic characteristics and bioavailability in rats by UPLC-MS/MS. The results showed that the Cmax and AUC0-t of bilobalide (BB), ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC), quercetin (QCT), kaempferol (KMF) and isorhamnetin (ISR) in rats were significantly increased after the oral administration of GBE-SD compared with results after the oral administration of GBE. These results suggest that the solid dispersion preparation by HME could serve as a promising formulation approach to enhancing the dissolution rate and oral bioavailability of GBE.

Simultaneous determination by UPLC-MS/MS of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets: application to a pharmacokinetic study.

A rapid, reliable, and sensitive method was developed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with an electrospray ionization (ESI) source for determination of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets (GBTs). The method simultaneously detects bilobalide (BB), ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC), quercetin (QCT), kaempferol (KMF), and isorhamnetin (ISR) for pharmacokinetic study. The analytes and internal standard (IS) were extracted from rat plasma by acetidin. An MS/MS detection was conducted using multiple reaction monitoring (MRM) and operating in the negative ionization mode. The calibration curve ranges were 5-500, 5-500, 2.5-250, 1-100, 1-100, 1-100, and 1-100 ng/ml for BB, GA, GB, GC, QCT, KMF, and ISR, respectively. The mean recovery of the analytes ranged from 68.11% to 84.42%. The intra- and inter-day precisions were in the range of 2.33%-9.86% and the accuracies were between 87.67% and 108.37%. The method was used successfully in a pharmacokinetic study of GBTs. The pharmacokinetic parameters of seven compounds were analyzed using a non-compartment model. Plasma concentrations of the seven compounds were determined up to 48 h after administration, and their pharmacokinetic parameters were in agreement with previous studies.

[Chemo-preventive effect of Angelica sinensis' supercritical extracts on AOM/DSS-induced mouse colorectal carcinoma associated with inflammation].

To study the chemo-preventive effect of the supercritical extracts from Angelica sinensis (SFE-AS) on induced colorectal carcinoma in mice by using the AOM/DSS-induced male mice colorectal carcinoma model, and discuss its possible action mechanism. Male Balb/c mice were subcutaneously injected with single dose of azoxymethane (AOM, 10 mg x kg(-1) body weight). One week later, they were given 2% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colorectal carcinoma. Each drug group was orally administered with supercritical extracts from Angelica sinensis at 15, 30, 60 mg x kg(-1) until the 17th week. The tumor incidence rate of the SFE-AS group, mice tumor-bearing quantity and tumor-bearing volume of the SFE-AS group were lower than that of the AOM/DSS model control group, which may be related with the significant reduction of PCNA, COX-2, iNOS in the AOM/DSS-induced mouse colorectal carcinoma model associated with inflammation by SFE-AS. According to the results of this study, SFE-AS showed an intervention effect in the incidence and development of AOM/DSS-induced mouse colorectal carcinoma associated with inflammation, and could be further used in chemo-preventive studies on human colorectal carcinoma.

[Preparation and optimization of zhitong micro-emulsion formula].

To prepare Zhitong micro-emulsion in this study, with the empirical formula of Zhitong preparation as the model medicine, the essential oil in the formula as the oil phase, and the water decoction as the water phase. The types of surfactant and co-surfactant were investigated. The changes in micro-emulsion conductivity and construction, the water percentage in the micro-emulsion system, the changing curve of conductivity and the fine pseudo-ternary phase diagram of micro-emulsion were drawn to determine the surfactant-co-surfactant mass ratio (K(m)). Subsequently, the D-mixture design was used to optimize Zhitong Micro-emulsion formula, with particle size and surface tension of micro-emulsion as the indexes. Finally, efforts were made to determine part of physical parameters of Zhitong micro-emulsion and preliminarily detect its stability. The results showed that the micro-emulsion was optimal with the EL-35-tween 20 ratio of 4:1 in surfactant, whereas the absolute ethyl alcohol was recommended as the co-surfactant. The ratio between surfactant and co-surfactant (K(m)) was 1.5. The finalized micro-emulsion formula contains 12% surfactant, 8% co-surfactant, 70% 1 g x mL(-1) water decoction and 8% oil. The results of the preliminary stability experiment showed a better stability of Zhitong micro-emulsion.

Cytotoxicity and enhancement activity of essential oil from Zanthoxylum bungeanum Maxim. as a natural transdermal penetration enhancer.

The aim of this present study is to investigate the effect of Zanthoxylum bungeanum oil (essential oil from Z. bungeanum Maxim.) on cytotoxicity and the transdermal permeation of 5-fluorouracil and indomethacin. The cytotoxicity of Z. bungeanum oil on dermal fibroblasts and epidermal keratinocytes was studied using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The rat skin was employed to determine the percutaneous penetration enhancement effect of Z. bungeanum oil on hydrophilic and lipophilic model drugs, i.e., 5-fluorouracil and indomethacin. The secondary structure changes of the rat stratum corneum (SC) were determined using attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and saturated solubilities and SC/vehicle partition coefficients of two model drugs with and without Z. bungeanum oil were also measured to understand its related mechanisms of action. It was found that the half maximal inhibitory concentration (IC50) values of Z. bungeanum oil were significantly lower in HaCaT and CCC-ESF-1 cell lines compared to the well-established and standard penetration enhancer Azone. The Z. bungeanum oil at various concentrations effectively facilitated the percutaneous penetration of two model drugs across the rat skin. In addition, the mechanisms of permeation enhancement by Z. bungeanum oil could be explained with saturated solubility, SC/vehicle partition coefficient, and secondary structure changes of SC.

[Studies on evaluation of sustained release tablets of extracts of Ginkgo biloba releasing rate in vitro by pharmacological indicatrix].

Using sustained release tablets of Ginkgo bibolia extract as model drug,discuss technical feasibility of using biotic index to evaluate sustained release tablets. Chosing two pharmacological indicatrix: antioxidant ability and inhibition of platelet aggregation, to investigate the influence factors on experimental result, optimize the method and experiment condition, and set up pharmacological indicatrix evaluation method. Using those methods to determinate biological effects of dissolved liquid. Drawing release curves and biological effects curves, discussing their correlation. A good correlation was observed, illustrating that pharmacological indicatrix could evaluate sustained release tablets.

[Effect of ethanol concentration in receiver fluid on in vitro transdermal test].

The present paper was designed to investigate the effect of varying concentrations of ethanol in receiver solution on the in vitro transdermal permeation of drug across the rat skin. 5-fluorouracil (5-FU) was used as the model drug on account of its good hydrophility, the excised rat skins were treated with different concentration ethanol prepared with normal saline for 12 h, then replaced by normal saline and added the saturated model drug into the donor compartment to determine the transdermal parameters of the drug. Meanwhile, scanning electron microscopy (SEM) was employed to monitor the effect of the different concentration ethanol on the stratum corneum of the rat skin. The ethanol below the concentration of 15% didn't significantly affect the barrier profile of the rat skin, while significant difference of in steady-state transdermal rate and lag times were observed when the concentration of ethanol was 20% or above. The SEM studies indicated that wrinkle of the intact rat skin gradually disappeared and a number of flakes were desquamated from the skin when the concentration of ethanol was above 20%. The results showed that the low concentration of the ethanol (below 15%) didn't obviously affect the excised skin, yet the barrier profile of rat skin would significantly disrupted with the concentration of ethanol above 20%.

[Effect of microemulsion technology on release of compounds in Zhitong cataplasm and content variation].

To study the varieties of adhesives in gels on the basis of previous studies, dosage of adhesives required for forming of gels by using the single factor design, as well as the drug loading capacity of gels with the adhesiveness and stickiness as the scoring indicators, in order to determine the forming method of analgesic micro-emulsion gel. Subsequently, the improved Franz diffusing cell method was adopted to study the release of water-soluble components and liposoluble components in analgesic gels, with imperatorin and ferulic acid as index components. The results showed that analgesic micro-emulsion gel could promote the release of imperatorin and ferulic acid. Finally, HPLC was used to detect that the loss amount of volatile components in analgesic micro-emulsion gel was 23.13% lower than that in the original analgesic gel. In the experiment, we finally prepared finished products of micro-emulsion gel, discovered that the micro-emulsion technology is helpful to improve the synchronous release of water-soluble components and liposoluble components in prescriptions and can reduce the loss of volatile components.