Two-pore domain potassium channels (K₂P) make up a subfamily of potassium channels discovered in the 1990s, and TREK-1 is the most widely studied subtype of K₂P. TREK-1 is widely expressed in the body and especially in the central nervous system, where its main role is to control cell excitability and maintain the membrane potential below the depolarization threshold. It thereby participates in regulating various physiological and pathological processes. TREK-1 is also a potential drug target in many diseases. It is known that many marketed drugs can affect the function of TREK-1, but currently there are no specific TREK-1 modulators or drugs. We review the structure, distribution and regulation of TREK-1 and focus on recent progress in understanding the pharmacology of TREK-1 and its role in neuroprotection, depression, anesthesia and epilepsy. The research status of TREK-1 modulators is discussed.

Hypertension is the most common cardiovascular disease. In recent years, reduced baroreceptor activity has been suggested as a main cause of hypertension. The cell body of the primary afferent nerve of the baroreceptor is located in the nodose ganglion (NG). The ion channels and receptors in the NG can affect baroreceptor sensitivity and neuronal excitability, thus regulating blood pressure. This review focuses on recent research progress on ion channels, receptors and other proteins in NG neurons that are involved in modulating the sensitivity of the baroreceptor reflex to regulate blood pressure.

Vascular endothelial cells play a major role in maintaining the oxygen and nutrient supply to all tissues in the body. Endothelial cells, together with vascular endothelial growth factor, are also the driving forces of tumor angiogenesis, a process describing the growth of blood vessels from the existing vasculature in tumor tissues. Reprogramming of endothelial cell metabolism satisfied the needs for biomass and energy in the process of tumor angiogenesis, which are known to involve the aspects of glucose metabolism, amino acid metabolism, and fatty acid metabolism. Recently, with the increasing interest to understand the metabolic regulation in cancer, the investigation into the metabolism of endothelial cells has made progress. We herein review the role of endothelial cell metabolism in angiogenesis, with a particular focus on the metabolic regulation of endothelial cells in tumor angiogenesis, which hopes to provide insights for the intervention of tumor angiogenesis in cancer therapy.

Uveal melanoma (UM) is one of most common ocular cancers and is extremely malignant; so far there is no effective treatment. Moreover, the survival period is only 2-7 months after metastasis. It has been proven that more than 83% of uveal melanomas harbor mutations in G protein subunit α q (GNAQ) or G protein subunit α 11 (GNA11), among which 95% are a Q209P/L single-site mutation. Q209P/L mutations lead to dysfunction of guanine triphosphatase (GTPase) in the G protein and result in constitutive activation of downstream pathways including mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), Ras homologue (Rho)/Rho-associated kinase (Rock)/Yes-associated protein (YAP) and others. Therefore, targeting GNAQ/GNA11 mutations are potential strategies for UM treatment. This review will focus on roles of G protein mutations in UM progression, and the potential therapeutic effects of GNAQ/GNA11 inhibitors, and will provide insights into basic and clinical research on UM treatment.

Psoriasis, bringing great trouble to patients' life, is a common chronic immune skin disease which is relapsed and difficult to cure. Further understanding of the pathogenesis of psoriasis will be benefit for potential drug targets and the development of therapeutic drugs. In recent years, "interleukin-23/T helper17 (IL-23/Th17) cell axis" has attracted more and more attention in the pathogenesis of psoriasis. Some drugs targeting the cell axis have also been successfully listed in the market to improve psoriasis and achieved good results. This review focuses on the "IL-23/Th17 cell axis" system to elaborate the role of a variety of immune cells involved in the pathogenesis of psoriasis, such as dendritic cells, macrophages, neutrophils and T cells, and summarizes multiple therapeutic antibodies targeting this cell axis in the treatment of psoriasis. In addition, this review also summarizes the current small molecule drugs for the treatment of psoriasis.

Galectin-3 is an endogenous β-galactoside-binding lectin widely distributed in the human body, and it plays an important role in various functions such as cell proliferation, differentiation, apoptosis, cell adhesion, immune response and signal transduction. Accumulating evidence has shown that galectin-3 is involved in the occurrence and development of respiratory diseases, including idiopathic pulmonary fibrosis, lung cancer, pulmonary hypertension and bronchial asthma. This review summarizes and analyzes the research progress on galectin-3 in the above respiratory diseases in order to clarify its role and mechanism, and to provide new ideas for clinical treatment.

The incidence and mortality of chronic obstructive pulmonary disease (COPD) and lung cancer are increasing year by year, which are causing massive social and financial burdens around the world. An increasing number of investigations indicate the possibility of COPD transforming into lung cancer. The pathogenesis of these two diseases have some common aspects, such as epithelial-mesenchymal transition, chronic inflammation, DNA damage, impaired immune system, oxidative stress and tumor angiogenesis, which are heavily complicated. This review summarizes the epidemiological connection between COPD and lung cancer, the molecular-level transformation mechanism as well as the therapeutic strategy. Exploring the transformation mechanism and related signaling pathway of COPD to lung cancer can contribute to block the risk factors for the transformation and provide guidance for the novel drug development and drug therapy.

Bile acids (BAs) are increasingly being appreciated as signaling molecules. Studies have shown that BAs regulate glucose and lipid metabolism mainly through the intracellular nuclear receptor farnesoid X receptor (FXR) and the transmembrane G protein-coupled receptor 5 (TGR5). FXR and TGR5 are highly expressed in the intestine. This article summarizes the synthesis, circulation, and regulation of BAs, as well as the effects of BAs on glycolipid metabolism through activation of liver FXR and inhibition or activation of intestinal FXR and TGR5. Furthermore, we illustrate the molecular mechanism of BAs on glycolipid metabolism by the relevant signaling pathways, including small heterodimer partner (SHP), fibroblast growth factor 15/19 (FGF15/19), ceramide and glucagon like peptide-1 (GLP-1). This review may serve as a reference for basic and clinical studies.

Autophagy is a widespread and unique degradation process in eukaryotic cells. When cells are under various stress conditions such as nutritional deficiencies, growth factor deficiencies or hypoxia, autophagy will be initiated to maintain the stability of the internal environment and ensure normal proliferation and differentiation. At present, research on autophagy-related targets is mostly focused on tumor cells. In contrast, research on fungal autophagy targets is still limited. Autophagy plays an important role in growth, development and morphological changes of fungal cells, suggesting that research on fungal autophagy as a drug target should be useful. This article reviews the signal regulation and detection strategies for autophagy in fungal cells, and provides a research basis for the screening of antifungal drugs targeting autophagy-related proteins.

Medicinally active molecules are those that have pharmacological effects. Research on protein targets of these molecules not only clarifies their mechanism of action, but also deepens our understanding of biological systems. Here we review recent advances in protein targets of drugs used in clinical practice or in preclinical research. They have various functions including anti-inflammatory, anti-malarial, anti-tumor and other biological activities. Activity-based protein profiling (ABPP) and cellular thermal shift assay (CETSA) are two useful methods to identify the protein targets of small molecules. ABPP depends on a derivative active molecule probe to pull down the protein targets to reveal the interaction mechanisms between the active molecules and targets. Drug target engagement also can be assessed by means of CETSA based on ligand-induced changes in protein thermal stability. In the CETSA approach, the active molecules do not need to be chemically modified. Combining the CETSA method with quantitative mass spectrometry is an effective approach to study the effect of compounds on the thermal profile of a cellular proteome and identify the protein targets.ABPP and CETSAcan be complementary and effectively clarify the protein targets. The study of protein targets will help reveal the mechanism of action of medicinal molecules, reveal toxic mechanisms and aid in the discovery of new medicinal targets to promote the process of drug development.

Reactive oxygen species (ROS) which were partial metabolites of oxygen are highly reactive. Different concentrations of ROS have different effects on tumor development. Tumor cells have a high level of reactive oxygen species. The antioxidant system of tumor is in highly activated state, and thus modulation of reactive oxygen species levels could be an effective strategy to target cancer cells. Treatment with small molecules that disrupt the redox balance can kill tumor cells first. This paper outlines the main ideas of developing anti-tumor drugs based on reactive oxygen species regulation, and summarizes the representative drugs and research progress according to the mechanism of action, in an effort to suggest potential reference and ideas for developing antitumor drugs based on reactive oxygen species regulation.

Snow lotus is a medicinal plant with a wide range of pharmacological activities. It has been used to treat rheumatoid arthritis, cough with cold, stomach ache, dysmenorrhea, and altitude sickness in traditional medicine. This review summarizes the bioactive components in six species of snow lotus including flavonoids, lignans, phenolic compounds, phenylpropanoids, and sesquiterpenes present in Saussurea involucrate (SI), Saussurea obvallata (SO), Saussurea laniceps (SL), Saussurea medusa (SM), Saussurea stella (SS) and Saussurea tridactyla (ST). We review the pharmacological and related molecular mechanisms by which these components exert antineoplastic, anti-inflammatory, and antioxidant effects and promote lipid catabolism, and provide a reference for the future study of the traditional Chinese medicinal chemistry and pharmacological activities of snow lotus.

Obesity is an important cause of a panel of metabolic diseases, such as hypertension, hyperlipidemia, arteriosclerosis, type 2 diabetes and various cancers. Discovery of anti-obesity agents has always been a hot spot in the field of new drug research and development. Pancreatic lipase (PL, also named triacylglycerol acyl hydrolase), a key enzyme responsible for the hydrolysis of 50%-70% dietary fats in the gastrointestinal system, which has been recognized as a crucial target for the prevention and treatment of obesity. PL inhibitors can reduce the decomposition and absorption of dietary fat in the digestive organs by decreasing the hydrolytic activity of this key enzyme, which can alleviate the symptoms of metabolic diseases such as obesity and hyperlipidemia. Although a potent PL inhibitor (orlistat) has been marketed, it may trigger gastrointestinal side effects after long-term use. Therefore, it is necessary to develop more new PL inhibitors with strong inhibition potency and safety. In recent years, a large number of studies have found that some Chinese herbal extracts and their constituents can regulate lipid metabolism and treat obesity via inhibiting PL. In this paper, the research progress in the field pancreatic lipase inhibitors, as well as the extracts of Chinese herbs and their constituents with pancreatic lipase inhibitory effects were summarized. Meanwhile, the PL inhibition activities and inhibitory mechanisms of herbal constitutes were also summarized systematically. In addition, the authors also highlight the challenges in this field and the future research directions. All information and knowledge presented in this review will be very helpful for the medicinal chemists to find more potent PL inhibitors from herbs or to develop next generation anti-obesity drugs, as well as helpful for the prevention and treatment of obesity and other related metabolic diseases using herba medicines or related products.

Traditional Chinese medicine (TCM) has made numerous contributions to the prosperity of China. However, the phytochemicals of TCM are complex, and there are significant differences in relative content. The material basis of TCM has restricted the modernization of TCM. Liquid chromatography-mass spectrometry (LCMS) combines the high separation performance of chromatography and the high sensitivity of mass spectrometry. It has been widely used in the analysis of natural medicines and can greatly promote the development of TCM. Many studies have focused on the comprehensive characterization of phytochemicals, building a strategy for the rapid, accurate and systematic analysis of the chemical components of TCM through the integration of different mass spectrometric techniques, and laying the foundation for quality control and rational utilization of TCM.

Natural products have been a major source of leading compounds in drug discovery. How to effectively screen active compounds from complex matrix remains an interesting topic. In this review, we comprehensively summarized advanced liquid chromatography based approaches in natural products screening, including pre-column, on-column and post-column screening methods. Their advantages, disadvantages and prospect are also discussed.

Metal-organic frameworks (MOFs) are porous crystalline polymers constructed from the coordination reaction between organic ligands and metal ions. Due to their advantages:adjustable periodic pore structure, large specific surface area and easy functional modification, etc., MOFs have been widely used in the fields of gas storage/separation, catalysis, sensing, biological imaging and drug delivery. In recent years, MOFs have shown great potential in disease diagnosis and treatment. This review summarizes the application of MOFs in the fields of bio-sensing, cell imaging, in vivo imaging, drug delivery, etc., discusses the problems and corresponding solutions in the application of MOFs for biomedicine. We hope this review can provide reference for the designing new methods for disease diagnosis and treatment.

The complexity of tumor microenvironment brings both challenges and opportunities for targeted drug delivery. On the one hand, using the special characteristic as stimuli, we can construct a variety of responsive drug delivery systems for tumor targeting. On the other hand, the abnormal vasculature and dense extracellular matrix in solid tumor become formidable barriers to the nanoparticles delivery, which greatly reduces the drug delivery efficiency. Lots of researches focus on regulating the tumor microenvironment to make it more conducive to drug delivery. In this review, we will highlight the recent advances both in tumor microenvironment responsive nano-drug delivery systems design and tumor microenvironment regulation to improve tumor targeted delivery efficiency, and discuss the existing problems and future development.

Cardiac glycoside is a class of steroidal glycosides with significant physiological activities to the heart. Several drugs had been approved for the treatment of heart failure and atrial fibrillation. In recent studies, the researchers have found that cardiac glycoside can selectively inhibit the proliferation of human tumor cells and has potent antitumor efficacy. Unfortunately, the poor solubility and severe adverse effects of cardiac glycoside hindered further clinical application in the field of anticancer. It is an effective strategy to solve the "drug-like" problem of cardiac glycoside by changing the pharmacokinetics and distribution in vivo and reducing the dosage and side effects by virtue of modern preparations technology and treatment scheme. In this review, a brief introduction of the developmental course and mechanism of cardiac glycosides in anticancer field was made, and recent research progress of cardiac glycosides preparations were summarized and discussed. Finally, the further research direction was prospected.

Exosomes are disk-shaped vesicles with a diameter of 40-100 nm, which are composed of natural lipid bilayers. Most cells can produce exosomes, which play an important role in physiological and pathological processes, affecting signal pathways, intercellular communication, tumor progression and molecular metastasis. Exosomes are characterized by low immunogenicity, good natural stability, long half-life, high delivery efficiency, and the ability to cross the blood-brain barrier, which can be used as a good carrier for drug delivery. This review focuses on the research progress of exosomes as drug delivery systems in the treatment of brain diseases, such as central nervous system degenerative diseases, brain tumors and cerebrovascular diseases and so on.

Diabetes is characterized by hyperglycemia, resulting from insulin deficiency or resistance, or both. Insulin plays an irreplaceable role in the treatment of diabetes. Subcutaneous injection is the main route of insulin administration, but usually leads to poor compliance and many side effects. Oral insulin is safer and more convenient, which has always been the Holy Grail for people to explore. After oral administration, insulin is absorbed into the hepatic portal vein and transported to the liver, which can activate the normal physiological functions and reduce the risk of hypoglycemia, insulin resistance, and improve patient compliance. However, the gastrointestinal tract has multiple absorption barriers such as chemical barrier, enzyme barrier, and permeation barrier. Due to the physical and chemical properties of insulin, it is difficult to achieve desired oral bioavailability. This article reviews the recent attempts and progress in the field of oral administration of insulin driven by innovative drug delivery technologies and biomaterials, including structural modification, enzyme inhibitors, absorption enhancers, various nanoparticles, liposomes, microspheres, and even microorganisms. Some clinical researches on oral insulin are also introduced.

To date, CRISPR/Cas systems represent the most widely used tool for genome editing; however, its application scope for gene therapy has been largely limited due to its limited efficiency in activating homologydirected repair for DNA and off-target effect. Base editing is a new CRISPR/Cas-based genome-editing strategy, which allows single nucleotide to be precisely corrected in a narrow window scope on the target DNA or RNA by taking advantage of different nucleobase deaminases. Base editors include cytosine base editors (CBEs) and adenine base editors (ABEs), which can induce the conversions from C·G to T·A and A·T to G·C, respectively. Base editors work independently of double-strand DNA breaks (DSBs) and DNA donor templates, and thus they are extensively adopted for a wide range of therapeutic applications for genetic diseases, largely owing to their high efficiency and great specificity. In this review, we summarize the development of base editors and their potentials as therapeutic drugs for treating genetic diseases, and future outlooks are also discussed.

Most of the active ingredients of herbs are secondary metabolites of plants. Cytochrome P450s (P450s) are hemoglobin-containing monooxygenases encoded by a super-gene family, which play important roles in the metabolic network of plants. This review focuses on the role of P450s on biosynthesis of secondary metabolites such as terpenoids, alkaloids, flavonoids and phenylpropanoids. This will provide references for biosynthesis and regulation of secondary metabolites in medicinal plants.

Puerarin, also known as daidzein 8-C-glucoside, is a major isoflavone glycoside from Pueraria lobata. Puerarin has been shown to possess a variety of pharmacological activities. It has been widely used for the treatment of cardiovascular and cerebrovascular diseases. However, the further applications are limited due to its low water solubility and poor bioavailability. Structural modification is thus regarded as an efficient approach to improve the solubility and bioavailability of puerarin. Unlike chemical modifications, enzyme-assisted modifications, namely biocatalysis, is a promising alternative for the regioselective synthesis of puerarin derivatives due to its high selectivity. Up to date, acylation, glycosylation and hydroxylation of puerarin had been achieved through enzyme-based biocatalysis. Diverse active puerarin derivatives with improved solubility and bioavailability have been thus developed. Based on modification groups, this paper focused on the progress in the preparation of puerarin derivatives by biocatalysis, in which the whole-cells or pure enzymes were used as the biocatalysts. This article was expected to provide new ideas for the synthesis and development of puerarin drugs.

To identify potential serum proteins that might serve as biomarkers for Alzheimer's disease (AD), we performed comparative proteomic profiling of sera from AD and healthy control subjects using label-free LC-MS/MS. Our study identified 387 proteins, 61 of which showed significant changes in the serum of AD patients compared to healthy controls. Gene ontology (GO) enrichment analysis showed that some GO terms related to the pathogenesis of AD were significantly enriched in differentially expressed proteins, including cholesterol and lipid metabolism, inflammation, coagulation and hemostasis processes, and immune responses. Therefore, based on the above results and the consistency of protein content changes in the 8 comparison groups, 18 proteins were selected as candidate biomarkers. Protein-protein interaction results suggest that these 18 proteins can directly or indirectly interact with APP. Therefore, changes in the levels or functions of these proteins may affect Aβ metabolism and participate in the occurrence of AD, and have the potential to become AD blood biomarkers.

This research investigated the mechanism by which bupivacaine inhibits glutamate-induced intracellular free Ca²⁺ increases in primary cultured hippocampal astrocytes. Immunofluorescence was used to demonstrate the expression of metabotropic glutamate receptor (mGluR5 receptor) on neurons and astrocytes. Calcium imaging was used to measure the alteration of intracellular free Ca²⁺ ([Ca²⁺]_i) in primary cultured rat hippocampal neurons and astrocytes. The animal experiments were approved by the Animal Experiments Ethical Committee of Hebei Medical University. The results showed that mGluR5 receptor was abundantly expressed in the primary cultured rat neurons and astrocytes. Bupivacaine (300 μmol·L^-1) significantly inhibited 1 mmol·L^-1 glutamate-induced[Ca²⁺]_i increase in astrocytes (P < 0.01). 2-Methyl-6-(2-phenylethynyl)-pyridine (MPEP) (10 μmol·L^-1) completely abolished the increase of[Ca²⁺]_i induced by 1 mmol·L^-1 glutamate in the astrocytes (P < 0.01), while the inhibitory effect on neurons was only 10%-20%. Bupivacaine (300 μmol·L^-1) completely inhibited the[Ca²⁺]_i increase induced by mGluR5 receptor agonists (RS)-3, 5-dihydroxyphenylglycine (DHPG) (50 μmol·L^-1) and (RS)-2-chloro-5-hydroxyphenylglycine sodium salt (CHPG) (1 mmol·L^-1) in astrocytes (P < 0.01). In addition, bupivacaine inhibited the CHPG-induced[Ca²⁺]_i increase in a dose-dependent manner in astrocytes with an IC₅₀ of 100 μmol·L^-1. The results from this study indicate that bupivacaine inhibits glutamate-induced[Ca²⁺]_i elevation by acting on the mGluR5 receptor in primary cultured hippocampal astrocytes.

This research investigated the effect of parthenolide on the proliferation and migration of human breast cancer cells and explored the molecular mechanism of that effect. Surface plasmon resonance and fluorescence resonance energy transfer melting were used to detect the binding and stabilizing ability of PTL and G-quadruplex. MTT assays were used to determine the effect of PTL on the proliferation of MCF-7 breast cancer cells. A wound healing assay was performed to detect the migration of MCF-7. The results indicate that PTL shows good binding and stabilizing activities with c-myc G-quadruplex with a K_D=13.1 μmol·L^-1. PTL inhibited the proliferation of MCF-7 cells with an IC₅₀ of 21.3 μmol·L^-1 (24 h), 14.5 μmol·L^-1 (48 h) and 9.1 μmol·L^-1 (72 h). PTL inhibited MCF-7 breast cancer cell proliferation and migration and down-regulated the transcription and expression level of c-myc by targeting G-quadruplex.

In this study, the model of Propionibacterium acnes/lipopolysaccharide (P. acnes/LPS)-induced acute liver injury in mice was employed to investigate the protective effects of Fuzheng Yanggan Fomula (FYF) on acute liver injury. The effects of FYF on the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and interleukin-1β (IL-1β) in the serum, and the levels of malondialdehyde (MDA), oxygen radical absorbance capacity (ORAC), and glutathione (GSH) were examined in the livers of mice treated with P. acnes/LPS; The protein expression levels of Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and IL-1β in liver tissues were detected by Western blot; Furthermore, hematoxylinendash-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemical assay were used to observe pathological changes, apoptosis index, and inflammation infiltration of the liver tissue sections. All animal welfare and experimental procedures were followed by the Animal Ethics Committee of Jinan University. We conclude that FYF could alleviate P. acnes/LPS induced pathological damage and inflammatory infiltration in the liver of mice. Meanwhile, FYF decreases the contents of ALT, AST, IL-1β, and MDA, increases the contents of ORAC and GSH, and downregulates the expression of caspase-1 and IL-1β proteins. Collectively, these findings suggested that FYF could alleviate P. acnes/LPS induced acute liver injury in mice by inhibiting the activation of NLRP3 inflammasome, which provides a theoretical basis and a new drug target for the prevention and treatment of liver injury.

This paper aimed to investigate the release efficiency of peptide at carbon terminal triggered by tetrazine bioorthogonal click-to-release reaction, and further explored the potential application of this reaction in functional modification and mild cleavage in solid-phase peptide synthesis. Thirteen peptide derivatives modified by trans-cyclooctene (TCO) were designed and synthesized, which were reacted with tetrazine to release the peptides. The results showed that the release rates of peptide were 90.0% to 97.7% in one hour. The strategy has good compatibility with the functional side-groups and the length of peptides, which expands the applications scope of tetrazine bioorthogonal click-to-release reaction. At the same time, a novel bifunctional trans-cyclooctene molecule was designed and synthesized. The active peptide GIRLRG was modified by fluorophore on the solid-phase resin, and released through tetrazine click-to-release reaction under mild condition, providing a new strategy for the solid-phase modification and release strategy of the peptide.

In recent years, the incidence and mortality of invasive fungal infections has increased. It is highly desirable to develop novel antifungal agents with new modes of action. Targeting virulence factors represents a new strategy for antifungal drug discovery. Secreted aspartic protease 2 (SAP2), a kind of virulence factor, is an emerging antifungal target. However, discovery of small-molecule SAP2 inhibitors remains a significant challenge. Based on the structure-activity relationship of our previously identified triazine small-molecule SAP2 inhibitor, we were able to identify two potent inhibitors, 8a and 8c, which showed excellent in vivo antifungal activity for the treatment of C. albicans infection. Moreover, compounds 8a and 8b effectively inhibited fungal biofilm. Taken together, triazine SAP2 inhibitors represent promising lead compounds for the discovery of novel antifungal agents.

The chemical constituents of gorgonian Junceella fragilis Ridley, collected from Ximao Island, the South China Sea, were investigated. A new briarane-type diterpenoid, named fragilide Y (1), together with five known compounds (2-6), namely fragilide D (2), cholesterol (3), ergosterol peroxide (4), 2'-deoxythymidine (5) and cis-thyminenol (6), were isolated from the acetone extract of J. fragilis. The structure of the new compound 1 was elucidated by extensive spectroscopic analysis, while the known compounds were identified by comparison with the reported data. In bioassay, none of these compounds displayed obvious anti-inflammatory and cytotoxic effects.

Prostate cancer is the most common malignant tumor of male reproductive system, which seriously threatens men's health. It has been shown that the existence of zinc ions can inhibit the growth of prostate cancer cells. In addition, photothermal treatment of cancer is attracting more and more attention due to its high accuracy and efficiency. In this study, zinc ions loaded black phosphorus nanosheets (BP-Zn) were prepared, and the photothermal therapy efficiency of the system on human prostate cancer cells (PC-3) was evaluated. The inhibition effect of zinc ions on PC-3 cells was studied. It was demonstrated that the toxicity of zinc ions on PC-3 cells was concentration- and time-dependent. Moreover, it can be seen from in vitro photothermal therapy that the treatment effect of black phosphorus assisted by zinc ions is superior to that of black phosphorus alone. This study further studied the in vivo therapeutic effect of BP-Zn. The results once again confirmed that the combinational photothermal treatment of zinc ions and BP had excellent anti-tumor effect. The animal procedures were approved by the Animal Ethics Committee of Tsinghua Shenzhen International Graduate School.

Inspired by the coordination effects between imidazole and metal ions in hemoglobin, biomimetic nanoparticles were constructed for photodynamic tumor therapy. The photosensitizer of protoporphyrin IX (PpIX) was modified with histidine, which could be self-assembled with Zn²⁺ to obtain the biomimetic nanoparticles (NPs). Under the conditions of high glutathione and low pH, the biomimetic nanoparticles could be degraded and released for enhanced photodynamic tumor therapy. The structures of NPs were characterized by dynamic light scattering (DLS), UV-visible spectrophotometer (UV-Vis), fluorescence microscope and transmission electron microscope (TEM). The reactive oxygen species (ROS) production ability of NPs was measured by singlet oxygen sensor green (SOSG) test kit. Mouse breast cancer cell lines (4T1 cells) were employed to investigate the subcellular organelle distribution and cytotoxicity of NPs. These results confirmed that NPs possessed a good dispersibility and stability with a uniform structure and particle size at 165 nm. Moreover, MTT assay and live/dead cell staining assay demonstrated that NPs could inhibit the proliferation of 4T1 cells and exhibit a good biocompatability. This research would promote the construction of intelligent biomedicine for tumor precision therapy.

To target neovasculature and tumor cells, a novel cationic liposome with verteporfin (BPD) active-loaded in lumen (CLL) was designed and its basic in vitro and in vivo behaviors were evaluated in this study. Calcium acetate gradient loading method was applied to encapsulate BPD actively and cationic lipid (2, 3-dioleoy-loxy-propyl)-trimethylammonium (DOTAP) was added by post-insertion for the positive charge of CLL. Results of characterization showed that the diameter and zeta-potential of CLL were around 100 nm and 28 mV, respectively. Compared with passive loading liposomes, CLL significantly enhanced the stability of BPD loading. What's more, the loaded BPD in lumen could switch off the fluorescence and photosensitization during blood circulation by homo-fluorescence resonance energy transfer (homo-FRET) effect, leading to the diminished phototoxicity to normal tissues. In vitro cellular uptake and cytotoxicity assay exhibited that positive charge dramatically enhanced the uptake of CLL both in vascular endothelial cells and tumor cells leading to superior therapeutic efficacy. In vivo study further showed that CLL reduced the clearance rate and increased tumor accumulation compared with passive loading group. Quantitative results of exvivo organ indicated that negligible CLL distributed in normal organs contributing to low phototoxicity. Animal experiments were conducted according to the Guidelines of the Experimental Animal Ethics Committee of Peking University Health Science Center and International Animal Experiments. In conclusion, we successfully designed a novel cationic targeting liposome that overcame the limitations of passive loading and significantly enhanced the efficacy of photodynamic therapy.

Shiraia bambusiccola is an important medicinal fungus in China. Hypocrellins with perylenequinone skeleton are main bioactive components of Shiraia bambusiccola, which are widely used in food, medicine, pesticide and other fields as natural photosensitizers. For example, "hypocrellin ointment" has already been used clinically. As a rare and vulnerable species, wild Shiraia bambusiccola resources are very limited. Due to the complex structure and chanllenge in chemical total synthesis of hypocrellins, it is urgent to find an effective strategy to rationally utilize its medicinal value while protecting the wild resources. In this study, a candidate gene cluster hpc was identified in Shiraia sp. cfcc 84681 based on careful bioinformatic analysis. A heterologous expression system for hpc gene cluster was successfully constructed and a mutant strain with high yield of hypocrellins was obtained, which mainly produced hypocrellin A and isohypocrellin A. The main ingredients in the mutant strain are consistent with that in the wild Shiraia bambusiccola. These results provide a new strategy to solve the shortage of wild Shiraia bambusiccola resources.

The near-infrared-Ⅱb (NIR-Ⅱb, 1 500-1 700 nm) window fluorescence with long emission wavelength has reduced light scattering and tissue auto-fluorescent background, achieving deep tissue imaging with high spatial resolution. Herein, we prepared an NIR-Ⅱb fluorescent quantum dots (QDs) composed of lead sulfide (PbS). The fluorescence spectrum of PbS QDs were adjusted by controlling the size of the PbS core. Cadmium sulfide (CdS) shell was synthesized by the cation exchange method to form the core/shelled lead sulfide/cadmium sulfide quantum dots (CSQDs). The surface of CSQDs was modified with polyethylene glycol (PEG) to increase their stability in aqueous solution. The resulting PEG-modified CSQDs (PEG-CSQDs) had the emission peak at ~1 550 nm with quantum yield of 7.2%. The animal procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of Fudan University School of Pharmacy. At 2 h postinjection, PEG-CSQDs clearly delineated the tumor region of mice bearing orthotopic CT26-Luc colon cancer model in the NIR-Ⅱb fluorescence imaging. The fluorescent intensity ratio of primary tumor and adjacent normal tissue was 42.3, and that of metastatic tumor and adjacent normal tissue was 22.3, which allowed to detect the primary tumor of 3.4 mm×2.5 mm in dimension and the metastatic tumor of 1.2 mm×0.9 mm in dimension, and accurately guided the excision of tumors. The PEG-CSQDs prepared in this study provided a new approach for the early diagnosis and guidance of surgical resection of colon cancer.