Bulbil initiation: a comprehensive review on resources, development, and utilisation, with emphasis on molecular mechanisms, advanced technologies, and future prospects.

Bulbil is an important asexual reproductive structure of bulbil plants. It mainly grows in leaf axils, leaf forks, tubers and the upper and near ground ends of flower stems of plants. They play a significant role in the reproduction of numerous herbaceous plant species by serving as agents of plant propagation, energy reserves, and survival mechanisms in adverse environmental conditions. Despite extensive research on bulbil-plants regarding their resources, development mechanisms, and utilisation, a comprehensive review of bulbil is lacking, hindering progress in exploiting bulbil resources. This paper provides a systematic overview of bulbil research, including bulbil-plant resources, identification of development stages and maturity of bulbils, cellular and molecular mechanisms of bulbil development, factors influencing bulbil development, gene research related to bulbil development, multi-bulbil phenomenon and its significance, medicinal value of bulbils, breeding value of bulbils, and the application of plant tissue culture technology in bulbil production. The application value of the Temporary Immersion Bioreactor System (TIBS) and Terahertz (THz) in bulbil breeding is also discussed, offering a comprehensive blueprint for further bulbil resource development. Additionally, additive, seven areas that require attention are proposed: (1) Utilization of modern network technologies, such as plant recognition apps or websites, to collect and identify bulbous plant resources efficiently and extensively; (2) Further research on cell and tissue structures that influence bulb cell development; (3) Investigation of the network regulatory relationship between genes, proteins, metabolites, and epigenetics in bulbil development; (4) Exploration of the potential utilization value of multiple sprouts, including medicinal, ecological, and horticultural applications; (5) Innovation and optimization of the plant tissue culture system for bulbils; (6) Comprehensive application research of TIBS for large-scale expansion of bulbil production; (7) To find out the common share genetics between bulbils and flowers.

Influencing factors of selenium transformation in a soil-rice system and prediction of selenium content in rice seeds: a case study in Ninghua County, Fujian Province.

Selenium (Se) is an essential element for human and animal health and has antioxidant, anticancer, and antiviral effects. However, more than 100 million people in China do not have enough Se in their diets, resulting in a state of low Se in the human body. Since the absorption of Se by crop seeds depends not only on the Se content in soil, there are many omissions and misjudgments in the division of Se-rich producing areas. Soil pH, total iron oxide content (TFe2O3), soil organic matter (SOM), and P and S contents were the main factors affecting Se migration and transformation in the soil-rice system. In this study, we compared the performance of the back propagation neural network (BP network) and multiple linear regression (MLR) using 177 pairs of soil-rice samples. Our results showed that the BP network had higher accuracy than MLR. The accuracy and precision of the prediction data met the requirements, and the prediction data were reliable. Based on the Se data of surface paddy fields, 26,900 ha of Se-rich rice planting area was planned using this model, accounting for 77% of the paddy field area. In the planned Se-rich area for rice, the proportion of soil Se content greater than 0.4 mg·kg-1 was only 5.29%. Our research is of great significance for the development of Se-rich lands.

Nanoparticles with Active Targeting Ability and Acid Responsiveness for an Enhanced Antitumor Effect of Docetaxel.

Docetaxel (DOC) is commonly used in cancer treatment, especially for breast cancer. However, there are severe side effects in clinical application. In order to deliver docetaxel more effectively, a novel, active targeting acid-responsive polymer called cRGD-PAE-PEG-DSPE was developed. The polymer structure incorporated poly(ethylene glycol) (PEG) as the hydrophilic segment, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) as the hydrophobic segment, and poly(ß-amino ester) (PAE) as the acid-responsive group, which was grafted onto the PEG. Furthermore, c(RGDyC) was grafted onto PAE to confer active targeting capability. Through self-assembly, docetaxel was encapsulated in RAED@DOC. Through in vitro experiments, it was confirmed that RAED@DOC had good serum stability and acid responsiveness, as well as enhanced uptake by MDA-MB-231 cells. Additionally, the antitumor efficiency in vivo and histopathological analysis showed that RAED@DOC exhibited higher antitumor activity and lower systemic toxicity in comparison to free docetaxel. These results suggested that RAED@DOC had considerable potential clinical use.

Evaluation of exogenous therapeutic protein activity under confinement and crowding effects.

Dysfunction of intracellular proteins is frequently associated with various diseases, such as cancer. The exogenous proteins in cells are usually assembled with specific configurations due to physiological confinement/crowding to exhibit novel features in the protein structure, folding or conformational stability, distinguished with their behaviors in buffer solutions. Here, we synthesized exogenous proteins under confined/crowded conditions, to explore protein activity within cells. The findings suggested that the confinement and crowding effects on protein activity are heterogeneous; they showed an inhibitory effect on HRP by decreasing Km from ∼9.5- and ∼21.7-fold and Vmax from ∼6.8- and ∼20.2-fold lower than that of dilute solutions. Interestingly, the effects on Cyt C seem to be more complicated, and crowding exerts a positive effect by increasing Km ∼ 3.6-fold and Vmax ∼ 1.5-fold higher than that of dilute solutions; however, confinement exhibits a negative effect by decreasing Km ∼2.0 and Vmax ∼8.3 times. Additionally, in contrast to traditional nanoparticle-based confinement models, we synthesized a biodegradable nanoparticle to mimic the confined space, and the biggest advantage of this novel model is that the particles can be degraded and thus it can provide more intuitive observations of the properties of the target proteins under confinement and after release. Furthermore, we also evaluated protein activity in different cellular environments, indicating that the exogenous protein activity was closely related to the crowdedness of cellular environments, and the inhibition of protein activity in MDA-MB-231 cancer cells was more obvious than in HEK293 normal cells. Finally, SAXS analysis revealed the correlation between the protein conformation and the different environments. Our work will provide a unique method for precisely assessing whether the target cellular environments are native matrix in which specific exogenous protein drugs are delivered to function or whether they display a therapeutic role, which is of great significance for screening and development of new drugs.

Knockdown of Yap attenuates TAA-induced hepatic fibrosis by interaction with hedgehog signals.

Liver fibrosis is an aberrant wound healing response to tissue injury characterized by excessive extracellular matrix deposition and loss of normal liver architecture. Hepatic stellate cells (HSCs) activation is regards to be the major process in liver fibrogenesis which is dynamic and reversible. Both Hippo signaling core factor Yap and Hedgehog (Hh) signaling promote HSCs transdifferentiation thereby regulating the repair process of liver injury. However, the molecular function of YAP and the regulation between Yap and Hh during fibrogenesis remain uncertain. In this study, the essential roles of Yap in liver fibrosis were investigated. Yap was detected to be increased in liver fibrotic tissue by the thioacetamide (TAA)-induced zebrafish embryonic and adult models. Inhibition of Yap by both embryonic morpholino interference and adult's inhibitor treatment was proved to alleviate TAA-induced liver lesions by and histology and gene expression examination. Transcriptomic analysis and gene expression detection showed that Yap and Hh signaling pathway have a cross talking upon TAA-induced liver fibrosis. In addition, TAA induction promoted the nuclear colocalization of YAP and Hh signaling factor GLI2α. This study demonstrates that Yap and Hh play synergistic protective roles in liver fibrotic response and provides new theoretical insight concerning the mechanisms of fibrosis progression.

Zn-MOF hydrogel: regulation of ROS-mediated inflammatory microenvironment for treatment of atopic dermatitis.

Atopic dermatitis (AD) is a chronic and recurrent inflammation disease associated with immune dysfunction. The high level of reactive oxygen species (ROS) causes high oxidative stress and further results in the deterioration of AD. At the same time, the ROS produced by bacterial infection can further aggravate AD. Here, the prepared PVA-based hydrogel (Gel) has a high ROS scavenging ability, and the antibacterial agent Zn-MOF(ZIF-8) loaded into the hydrogel shows a lasting and effective antibacterial activity. Thus, a Zn-MOF hydrogel (Gel@ZIF-8) is prepared to regulate ROS-mediated inflammatory microenvironment. In vitro experiments show that Gel@ZIF-8 has good antibacterial effect and cell biocompatibility. In the AD-induced mouse model, Gel@ZIF-8 can significantly enhance the therapeutic effect, such as reduce the thickness of epidermis, the number of mast cells and IgE antibodies. The results indicate that the ROS-scavenging hydrogel could treat the AD by regulating the inflammatory microenvironment, providing a promising treatment for managing AD.

Enhancing the Anti-tumor Potency of a Novel Siglec-15 Antibody by Engineering its Fc-mediated Effector Functions.

Siglec-15, an inhibitory immune checkpoint, is an emerging target in cancer immunotherapy. Blocking the function of Siglec-15 is an excellent strategy for cancer treatment and antibody blockade has been used to target Siglec-15. However, whether Fc-mediated effector functions contribute to the therapeutic effect of antibodies remains unclear. Herein, we generated a monoclonal antibody, 1-15D1, which had a high binding affinity with Siglec-15 and strongly activated T-cell immune response in vitro. Subsequently, the Fc-mediated effector functions of 1-15D1 were explored in a Siglec-15 humanized mouse model, and further improvement in antitumor efficacy was observed in the mouse IgG2a isotype group. Thus, we demonstrate that the antitumor effects of 1-15D1 were mediated via multiple factors. In addition to the T-cell immune response, 2 novel mechanisms were explored, including the internalization of the cell surface Siglec-15 and Fc-mediated effector functions. In conclusion, our studies not only provide a potential agent for the improvement of cancer immunotherapy but also suggest that a specific role of Fc-mediated immune regulation may improve the therapeutic potency of Siglec-15 monoclonal antibody.

Simulating and Predicting the Part Warping in Fused Deposition Modeling by Thermal-Structural Coupling Analysis.

As the most commonly used additive manufacturing technology, fused deposition modeling (FDM) still faces some technical issues caused by temperature change-induced unsteady thermal stress and warping. These issues can further lead to the deformation of printed parts and even terminate the printing process. In response to these issues, this article established a numerical model of temperature field and thermal stress field for FDM by finite element modeling and "birth-death element" technique to predict the deformation of the part. What makes sense in this process is that the logic of elements sort based on ANSYS Parametric Design Language (APDL) was proposed to sort the meshed elements, which was aimed to perform FDM simulation quickly on the model. In this work, the effects of the sheets shape and infill line directions (ILDs) on the distortion during FDM were simulated and verified. From the analysis of stress field and deformation nephogram, the simulation results indicated that ILD had greater effects on the distortion. Moreover, the sheet warping became most serious when the ILD was aligned with the diagonal of the sheet. The simulation results matched well with the experimental results. Thus, the proposed method in this work can be used to optimize the printing parameters for FDM process.

Ecological Risk Assessment of Geological Disasters Based on Probability-Loss Framework: A Case Study of Fujian, China.

Geological disaster could pose a great threat to human development and ecosystem health. An ecological risk assessment of geological disasters is critical for ecosystem management and prevention of risks. Herein, based on the "probability-loss" theory, a framework integrating the hazard, vulnerability, and potential damage for assessing the ecological risk of geological disasters was proposed and applied to Fujian Province. In the process, a random forest (RF) model was implemented for hazard assessment by integrating multiple factors, and landscape indices were adopted to analyze vulnerability. Meanwhile, ecosystem services and spatial population data were used to characterize the potential damage. Furthermore, the factors and mechanisms that impact the hazard and influence risk were analyzed. The results demonstrate that (1) the regions exhibiting high and very high levels of geological hazard cover an area of 10.72% and 4.59%, respectively, and are predominantly concentrated in the northeast and inland regions, often distributed along river valleys. Normalized difference vegetation index (NDVI), precipitation, elevation, and slope are the most important factors for the hazard. (2) The high ecological risk of the study area shows local clustering and global dispersion. Additionally, human activities have a significant influence on ecological risk. (3) The assessment results based on the RF model have high reliability with a better performance compared with the information quantity model, especially when identifying high-level hazard areas. Our study will improve research on the ecological risk posed by geological disasters and provide effective information for ecological planning and disaster mitigation.

pH/Redox Dual-Responsive Drug Delivery System with on-Demand RGD Exposure for Photochemotherapy of Tumors.

Purpose: Nanotechnology has been widely used in antitumor research. The complex physiological environment has brought significant challenges to the field of antitumor micelles. The ideal micelles must not only have an invisible surface to extend the circulation time but must also enhance the retention of drugs and cellular internalization at the tumor. Methods: A graded response micelle (RPPssD@IR780/DOC) was designed to self-assemble by cRGD-poly(ß-amino esters)-polyethylene glycol-ss-distearoyl phosphatidylethanolamine (cRGD-PBAE-PEG-ss-DSPE) loaded with docetaxel (DOC) and IR-780 iodide (IR780). The micelles were designed to allow the PEG shell to prolong the blood circulation time in the body and effectively accumulate in the tumor. Subsequently, the acidic microenvironment of the tumor could transform the PBAE to hydrophilic, thereby increasing the size of micelles and exposing cyclic Arg-Gly-Asp (cRGD) peptides to increase the retention and cellular internalization of micelles in the tumor. After tumor cells had captured micelles, the high expression of glutathione in the cells prompted the release of DOC and IR780. Subsequently, the IR780 was stimulated by an 808-nm laser to generate local heat and reactive oxygen species (ROS) to synergize with DOC to treat the tumor. Results: In vitro and in vivo experimental results suggested that RPPssD@IR780/DOC was a potential photochemical effective for the treatment of tumors with non-negligible antitumor activity and good biocompatibility. Conclusion: A dual-response pH/redox delivery system with on-demand RGD exposure was designed to achieve photochemotherapy of tumors with good biosafety and antitumor effects.

Calcium alginate/PNIPAAm hydrogel with body temperature response and great biocompatibility: Application as burn wound dressing.

Deep burns often do not heal easily, because the dermis of the skin is severely damaged, leading to severe inflammation and bacterial infection. Therefore, it is of great clinical significance to develop a dressing that promotes the healing process of deep burn wound. In this study, we used N-isopropyl acrylamide, sodium alginate and calcium chloride as the main materials, a series of calcium alginate/ poly (N-isopropyl acrylamide)(NIPAAm) hydrogel (CAPH) with different component ratios were synthesized. Its swelling properties, temperature response properties, rheological properties, biocompatibility properties, and in vitro drug release properties were investigated. Based on the above conditions, the CAPH(sodium alginate:NIPAAm = 2:15) with the best comprehensive performance was selected, which has a good biocompatibility. In addition, 0.02 % (w/v) mupirocin was loaded in CAPH. The temperature-responsive property of PNIPAAm in CAPH at 34 °C not only allowed the CAPH to rapidly release the drug under to prevent infection, but also to assist in wound contraction. Application of CAPH to localized wounds of deep second-degree burns in mice showed a faster healing rate and tissue regeneration. At the same time, collagen recovery was enhanced, collagen bundles were arranged in an orderly manner, and the scarring was not obvious after 16 days. Therefore, this research prepared a new safe and effective biomaterial.

Selection of Payloads for Antibody-Drug Conjugates Targeting Ubiquitously Expressed Tumor-Associated Antigens: a Case Study.

The main objective of this work was to demonstrate which kind of payload is the suitable choice for antibody-drug conjugates directed to widely expressed tumor-associated antigen. Trop-2 is overexpressed in various solid tumors, but it is also present on the epithelium of several normal tissues. A well-designed anti-Trop-2 ADC demands a good balance of efficacy and toxicity. In this research, MMAE, SN-38, and DXd were selected as candidates for payloads of the anti-Trop-2 mAb SY02. The antitumor activities and safety profiles of these ADCs were investigated to compare the therapeutic windows. Robust in vitro cytotoxicity was observed on human pancreatic cancer cell CFPAC-1 and breast cancer cell MDA-MB-468 with IC50 generally in the subnanomolar range. Consistent with in vitro assay, SY02-DXd and SY02-SN-38 demonstrated superior efficacy in CFPAC-1 xenograft models with TGI rates of 98.2% and 87.3%, respectively. However, SY02-MMAE could hardly inhibit the tumor growth. Subsequently, antitumor activities of these ADCs were further compared in MDA-MB-468 xenograft model. Complete tumor regression was observed in SY02-DXd and SY02-MMAE groups, indicating their potent antitumor activities. In an exploratory safety and pharmacokinetic study, SY02-DXd demonstrated the best safety profile with minimal adverse events in cynomolgus monkeys, while SY02-MMAE exhibited severe on-target skin toxicity which caused death. In conclusion, SY02-DXd demonstrated superior efficacy and safety with the widest therapeutic window. Based on the efficacy and safety results, moderate cytotoxic payloads would be ideal choices for ADCs targeting ubiquitously expressed antigens.

A Redox-Activatable and Targeted Photosensitizing Agent to Deliver Doxorubicin for Combining Chemotherapy and Photodynamic Therapy.

Currently, tumors have become a serious disease threatening human health and life in modern society. Photo-chemo combination therapy is considered to be an important method to improving the efficiency of tumor treatment, especially in the treatment of multi-drug-resistant tumors. However, the application of photo-chemo combination therapy has been limited by the poor water solubility of photosensitizers, low tumor targeting, and high side effects of chemotherapy drugs. In order to solve these problems, a smart nano drug delivery platform FA-PEG-ss-PLL(-g-Ce6) designed and synthesized by us. The smart nano drug carrier uses folic acid (FA) as the targeting group, polyethylene glycol (PEG) as the hydrophilic end, Ce6-grafted polylysine (PLL(-g-Ce6)) as the hydrophobic end, and Chlorin e6 (Ce6) as the photosensitizer of photodynamic therapy, and it connects PEG to PLL by a redox-responsive cleavable disulfide linker (-ss-). Finally, the combination of tumor chemotherapy and photodynamic therapy (PDT) is realized by loading with anticancer drug doxorubicin (DOX) to the intelligent carrier. In vitro experiments showed that the drug loading content (DLC%) of DOX@FA-PEG-ss-PLL(-g-Ce6) nanoparticles (DOX@FPLC NPs) was as high as 14.83%, and the nanoparticles had good serum stability, reduction sensitivity and hemocompatibility. From the cytotoxicity assays in vitro, we found that under 664 nm laser irradiation DOX@FPLC NPs showed stronger toxicity to MCF-7 cells than did DOX, Ce6 + laser, and DOX + Ce6 + laser. Moreover, the antitumor efficiency in vivo and histopathological analysis showed that DOX@FPLC NPs under 664 nm laser irradiation exhibited higher antitumor activity and lower systemic toxicity than single chemotherapy. These results suggested that the FA-PEG-ss-PLL(-g-Ce6) nano drug delivery platform has considerable potential for the combination of chemotherapy and PDT.

Drifts in N-Linked Glycosylation Result in ADCC Potency Variation of Perjeta® from August 2020 to October 2021 in China.

The proposed biosimilar candidate needs to demonstrate biosimilarity with reference products, and the quality target product profile and biosimilarity assessment criteria are prerequisite, which should be based on extensive characterization of the reference products. In this study, 13 lots of China-sourced pertuzumab (trademark: Perjeta®), with an expiration date from 2020 to 2021, were comprehensively characterized. Despite the consistency of purity, drifts in N-glycan profile were observed, which resulted in the variation of antibody-dependent cellular cytotoxicity (ADCC) activity. In detail, four parametric curves of ADCC activity of the reference product were unparalleled, and the maximum response value was highly related to the content of %afucose than half-maximal effective concentration (EC50). As ADCC is a potential critical quality attribute of Perjeta®, the glycosylation of Perjeta® and its biosimilars should be tightly monitored and controlled.

Zinc pyrithione (ZPT) -induced embryonic toxicogenomic responses reveal involvement of oxidative damage, apoptosis, endoplasmic reticulum (ER) stress and autophagy.

Zinc pyrithione (ZPT) is a frequently used organometallic biocide, carrying potentially adverse consequences to multiple species in the environment. Previously we have demonstrated its embryonic, organ developmental and liver metabolic toxicity of zebrafish. However, details of ZPT toxicity during embryogenesis are still limited. The present study was designed to evaluate the effects and possible mechanisms of ZPT-induced embryonic toxicogenomic responses by morphological investigations, transcriptome and gene quantitative analysis, as well as biochemical assays. The results revealed that treatment with ZPT caused embryogenesis toxicity, specifically in irregular cell division and rearrangement, delayed differentiations of eyes and notochords, the epiboly and germ ring formation and somite segmentation defects. In addition, ZPT exposure altered gene expression during early embryonic development, especially related with morphological abnormities and metabolic dysfunctions including reduction of oxidoreductase activity. Activities of antioxidants and caspases examinations showed inductions of oxidative stress and apoptosis by ZPT and quantitative analysis of marker genes further indicated that ZPT also triggered endoplasmic reticulum (ER) stress and autophagy. Thus, we deduce here that ZPT-induced embryonic toxicogenomic responses reveal involvement of oxidative damage, apoptosis, endoplasmic reticulum (ER) stress and autophagy.

A hydrogel based on nanocellulose/polydopamine/gelatin used for the treatment of MRSA infected wounds with broad-spectrum antibacterial and antioxidant properties and tissue suitability.

Most wound dressings encounter a series of problems when dealing with the bacterial infection of wounds, for example, the antibacterial and antioxidant capacities, comfort, and mechanical properties are not suitable to meet clinical requirements. Here, we synthesized ε-polylysine-grafted nanocellulose (NCF-EPL) and polydopamine (PDA) nanoparticles and embedded them in genipin-cross-linked gelatin to prepare a hydrogel (NCF-EPL/GTP/PDA). In this system, the embedded NCF-EPL and PDA interact with the gelatin matrix to form a hydrogel with excellent physical properties. The hydrogel has broad-spectrum antibacterial abilities and good antioxidant performance, and it can effectively promote cell proliferation. Full-thickness MRSA-infected skin wound healing experiments clearly show that the NCF-EPL/GTP/PDA hydrogel can significantly accelerate the healing of infected wounds via killing bacteria and reducing inflammation, and secondary damage caused by adhesion during dressing use is effectively avoided. In short, the hydrogel provides a new method for overcoming the shortcomings of traditional dressings, and this approach provides further solutions for the selection of clinical dressings for healing wounds.

Inclusion complex of lurasidone hydrochloride with Sulfobutylether-ß-cyclodextrin has enhanced oral bioavailability and no food effect.

OBJECTIVES: This study aimed to improve the solubility in water and bioavailability in vivo of lurasidone hydrochloride (LUR). METHODS: The saturated aqueous solution method was used to prepare an inclusion complex of LUR with sulfobutylether-ß-cyclodextrin, or SBE-ß-CD (LUR-SBE-ß-CD). A single-factor test was used for the preliminary screening of important preparing conditions including the ethanol concentration, the SBE-ß-CD concentration, temperature, and pH. Then central composite design response surface methodology (CCD) was adopted for the optimum craft. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and powder X-ray diffraction (PXRD) were used to confirm the formation of LUR-SBE-ß-CD. The in vitro release profiles of LUR-SBE-ß-CD were determined at different pHs and in simulated gastrointestinal fluid. RESULTS: The dissolution studies revealed that the dissolution of LUR in LUR-SBE-ß-CD was much improved in the four media and simulated gastrointestinal fluid. Similar profiles of LUR-SBE-ß-CD were obtained in pharmacokinetic studies whether beagle dogs took food or not. CONCLUSIONS: The bioavailability of LUR can be improved and the food effect can be eliminated by LUR-SBE-ß-CD.

NiS2 nanodots on N,S-doped graphene synthesized via interlayer confinement for enhanced lithium-/sodium-ion storage.

Rational design of high-capacity nanosized composites as anode nanomaterials is crucial to boosting electrochemical performances towards large-scale application for lithium- and sodium-ion batteries (LIBs and SIBs). The small sizes and homogeneous dimensional size distributions are achieved typically by either the surface confinement on the underlying supports, or the encapsulation confinement within the precursors (such as metal-organic frameworks). Herein, we report the ultrasmall NiS2 nanodots on reduced graphene oxide (NiS2/N,S-rGO) synthesized via interlayer confinement as anode nanomaterials for LIBs and SIBs. The composite is synthesized by pyrolyzing a host/guest precursor of sodium dodecyl sulfate ion/[NiEDTA]2- anions co-intercalated MgAl-layered double hydroxide LDH host, without additional sulfur source. The host/guest-derived interlayer nanoconfinement enables the composite to integrate the advantageous features: low-content active NiS2 nanodots (11.0 wt%) with a mean size of 3.8 ± 0.5 nm, high-content N,S-rGO (89.0 wt%), as well as a large specific surface area and mesopore size distribution. The composite used as anode nanomaterial exhibits reversible capacities of 801.2 mAh g-1 after 100 cycles at 100 mA g-1 for LIBs, and 207.7 mAh g-1 after 200 cycles at 0.1 A g-1 for SIBs, which are greatly higher than those of the pristine N,S-rGO without NiS2 nanodots. The enhancement is experimentally supported by the low charge transfer resistance, high capacitive-controlled contribution, and good structural stability. Our guest/host-based interlayer nanoconfinement can promise an effective synthesis strategy for designing various nanosized anodes for electrochemical energy storage.

Leonurine hydrochloride-a new drug for the treatment of menopausal syndrome: Synthesis, estrogen-like effects and pharmacokinetics.

This research aimed to investigate the estrogen-like effects of Leonurine hydrochloride (Leo). First, we developed a total synthesis of Leo from 3,4,5-trimethoxy-benzoic acid and the structure was confirmed through 1H NMR and mass spectrometry (MS). Then the estrogenic activity of Leo in vitro and in vivo was studied. The proliferation and proliferation inhibitory effects of Leo on MCF-7 cells and MDA-MB-231 cells indicate that Leo exerts estrogen-like effects through estrogen receptor α (ERα) and estrogen receptor ß((ERß) in vitro. Uterotrophic assay in juvenile mice showed that Leo has an estrogen-like effect in vivo, as it can promote the development of the uterus of juvenile mice, increase its uterine coefficient and the size of the uterine cavity, as well as the increased number of uterine glands and the thickened uterine wall. For further research, cyclophosphamide (CTX) was used to establish a mouse model of ovarian function decline. Through this model, we found that Leo can restore the estrous cycle of mice, increase the number of primordial and primary follicles in the ovaries of mice, and regulate the disordered hypothalamic-pituitary-ovarian (HPOA) axis of mice. Finally, the pharmacokinetics of Leo was studied and oral bioavailability of Leo was calculated to be 2.21%. Leo was synthesized and the estrogen-like effect in vitro and in vivo was confirmed as well as its pharmacokinetics.

Preparation and Characterization of Anti-Cancer Crystal Drugs Based on Erythrocyte Membrane Nanoplatform.

The simple and functional modification of the nanoparticle's surface is used to efficiently deliver chemotherapeutic drugs for anti-cancer treatment. Here, we construct a nanocrystalline drug delivery system with doxorubicin wrapped in red blood cell membranes for the treatment of mouse breast cancer models. Compared with traditional free drug treatments, the biodegradable natural red blood cell membrane is combined with pure crystalline drugs. The nanoparticles obtained by the preparation method have superior properties, such as good stability, significantly delaying the release of drugs and enhancing the inhibitory effect on tumor cells. This study shows that the design of RBC as an outsourced drug delivery system provides a promising foundation for the continued development, clinical trials, and nanomedicine research of anti-cancer drug nanocarriers in the future.