Nanozymes are a distinct category of nanomaterials that exhibit catalytic properties resembling those of enzymes such as peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Nanozymes derived from Chinese herbal medicines exhibit the catalytic functions of their enzyme mimics, while retaining the specific medicinal properties of the herb (termed "herbzymes"). These nanozymes can be categorized into three main groups based on their method of synthesis: herb carbon dot nanozymes, polyphenol-metal nanozymes, and herb extract nanozymes. The reported catalytic activities of herbzymes include POD, SOD, CAT, and GPx. This review presents an overview of the catalytic activities and potential applications of nanozymes, introduces the novel concept of herbzymes, provides a comprehensive review of their classification and synthesis, and discusses recent advances in their biomedical applications. Furthermore, we also discuss the significance of research into herbzymes, including the primary challenges faced and future development directions.
Nanostructures/chemistry* ; Humans ; Herbal Medicine/methods* ; Superoxide Dismutase/chemistry* ; Catalase/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Catalysis ; Glutathione Peroxidase/chemistry*

Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

OBJECTIVE: Benzylisoquinoline alkaloids (BIAs) have pharmacological functions and clinical use. BIAs are mainly distributed in plant species across the order Ranunculales and the genus Phellodendron from Sapindales. The BIA biosynthesis has been intensively investigated in Ranunculales species. However, the accumulation mechanism of BIAs in Phellodendron is largely unknown. The aim of this study is to unravel the biosynthetic pathways of BIAs in Phellodendron amurens. METHODS: The transcriptome and metabolome data from 18 different tissues of P. amurense were meticulously sequenced and subsequently subjected to a thorough analysis. Weighted gene co-expression network analysis (WGCNA), a powerful systems biology approach that facilitates the construction and subsequent analysis of co-expression networks, was utilized to identify candidate genes involved in BIAs biosynthesis. Following this, recombinant plasmids containing candidate genes were expressed in Escherichia coli, a widely used prokaryotic expression system. The purpose of this genetic engineering endeavor was to express the candidate genes within the bacteria, thereby enabling the assessment of the resultant enzyme activity. RESULTS: The synonymous substitutions per synonymous site for paralogs indicated that at least one whole genome duplication event has occurred. The potential BIA biosynthetic pathway of P. amurense was proposed, and two PR10/Bet v1 members, 14 CYP450s, and 33 methyltransferases were selected as related to BIA biosynthesis. One PR10/Bet v1 was identified as norcoclaurine synthase, which could catalyze dopamine and 4-hydroxyphenylacetaldehyde into (S)-norcoclaurine. CONCLUSION Our studies provide important insights into the biosynthesis and evolution of BIAs in non-Ranunculales species.

To investigate the effect of isthmin-1 (ISM1) on the invasion and metastasis of pancreatic cancer and its underlying mechanism, this study analyzed the expression of ISM1 in pancreatic cancer patients and normal pancreatic tissues using The Cancer Genome Atlas (TCGA) database. Western blot was employed to detect differences in ISM1 protein expression between pancreatic cancer cell lines (Aspc1, Bxpc3, PANC1, SW1990) and the pancreatic epithelial cell line (hPNE). Cell models with stable ISM1 overexpression and knockdown were constructed, and changes in cell migration and invasion capabilities were assessed via Transwell invasion assays and wound healing assays. Meanwhile, Western blot was used to detect the expression levels of key markers of epithelial-mesenchymal transition (EMT). Furthermore, TCGA and the Gene Expression Omnibus (GEO) database were utilized to analyze pathways regulated downstream of ISM1 and the mechanisms promoting pancreatic cancer invasion and metastasis. Immunoprecipitation combined with mass spectrometry (IP-MS) was used to screen for vimentin as an ISM1-binding protein, and the interaction between ISM1 and vimentin was verified by immunofluorescence and co-immunoprecipitation (Co-IP). Bxpc3 cells overexpressing ISM1 were treated with the protein synthesis inhibitor cycloheximide (CHX) to detect vimentin protein stability. The results indicate that ISM1 promotes the EMT process by inhibiting vimentin degradation, thereby enhancing the invasion and metastasis of pancreatic cancer. This study provides new experimental evidence for elucidating the mechanism of pancreatic cancer metastasis.

BACKGROUND:Increasing studies have shown that autophagy plays an important role in the treatment of osteoarthritis,and moderate autophagy can preserve the normal physiological function of osteoarticular chondrocytes.Traditional Chinese medicine(TCM)monomers can target and modulate autophagy to treat osteoarthritis,and their characteristics such as single components,clear efficacy,low price,and easy availability have obvious benefits in the treatment of osteoarthritis.OBJECTIVE:To review the effects of TCM monomers on the targeted regulation of autophagy in the treatment of osteoarthritis and the research progress,with a view to laying a foundation for the treatment of osteoarthritis and even other bone metabolic diseases.METHODS:Relevant literature published from January 2012 to October 2022 was retrieved in PubMed,Web of Science,CNKI,and WanFang using the keywords of"traditional Chinese medicine,Chinese herbal monomer,autophagy,osteoarthritis"in English and Chinese.Inclusion and exclusion criteria were developed,and 63 relevant articles were finally included by screening through reading the title,abstract,and full-text content.RESULTS AND CONCLUSION:TCM monomers can treat osteoarthritis by targeting autophagy to inhibit chondrocyte apoptosis,protect cartilage extracellular matrix,reduce inflammation and antagonize oxidative stress injury.Different TCM monomers can regulate autophagy in the same way,and the same TCM monomers can affect autophagy in different ways.The combination of multiple monomers and the multi-target and multi-pathway regulation of autophagy by TCM monomers remain to be explored.The regulation of autophagy by TCM monomers can provide new ideas and strategies for the prevention and treatment of osteoarthritis.Moderate regulation of autophagy by TCM monomers to keep the autophagic flux unimpeded may be the key to treating osteoarthritis.

BACKGROUND:More and more studies have shown that oxidative stress should play an important role in the treatment of osteoporosis.Oxidative stress should cause the accumulation of oxidation activity,which will damage bone-related cells.Finally,it causes the imbalance of bone resorption and bone formation,resulting in a decrease in bone volume and the destruction of the slight structure.Research in recent years has found that some natural products can regulate oxidative stress to treat osteoporosis.The characteristics of extensive sources and small side effects have obvious advantages in the treatment of osteoporosis,and the efficacy is objective. OBJECTIVE:To discuss the mechanism of natural product regulation of oxidation stress in treatment of osteoporosis,conduct a review based on the latest related research progress,provide reference and ideas for more natural products to treat osteoporosis in the future,and provide data support for the clinical application of natural compounds in the treatment of osteoporosis. METHODS:"oxidative stress,free radical,antioxidant,phytotherapy,plant extracts,medicinal plants,herbal medicine,osteoporosis,bone density,bone loss"were used as the keywords in PubMed,Web of Science,Embase,Cochrane,VIP,CBM,WanFang,and CNKI databases to search relevant articles published from January 2010 to February 2023.Inclusion and exclusion criteria were developed,and 64 relevant articles were selected by reading titles,abstracts,and full texts. RESULTS AND CONCLUSION:(1)Some natural products have antioxidant effects and can regulate osteogenic differentiation,osteoblast bone matrix mineralization,osteoclast-mediated bone resorption,proliferation,differentiation,activity,and apoptosis of bone-related cells by improving oxidative stress,thus affecting bone metabolism.(2)These natural products with antioxidant effects play a role in treating osteoporosis by improving bone remodeling balance.(3)The research on the combination of a variety of natural products to improve osteoporosis remains to be explored.(4)The use of natural products to regulate oxidative stress may become a powerful weapon for the clinical treatment of osteoporosis in the future.

Objective To evaluate the safety and effectiveness of endoscopic mucosal resection with circumferential incision(EMR-CI)and endoscopic submucosal dissection(ESD)for the rectal neuroendocrine neoplasm(RNEN).Methods Databases such as PubMed,the Cochrane Library,Embase,Web of Science,SinoMed,China National Knowledge Infrastructure(CNKI),Wanfang Data and Weipu database were searched by computer.The retrieval time limit was Nov.22,2022.The Chinese and English literatures on the efficacy of EMR-CI vs ESD in treatment of RNEN patients were collected.According to inclusion and exclusion criteria,the included literatures were screened,extracted data,and evaluated the methodological quality by Newcastle-Ottawa scale(NOS),Meta-analysis was performed using Rev Man 5.3 software.Results Seven clinical control studies were included,including 199 cases in the EMR-CI group and 443 cases in the ESD group.Results of Meta-analysis of validity outcome indicators,there was no significant difference in histological complete resection rate between the EMR-CI group and the ESD group(O(R) = 0.56,95%CI:0.30～1.02,P = 0.060);The endosopic complete resection rate of EMR-CI was similar to that of ESD with no significant difference(O(R) = 0.33,95%CI:0.09～1.17,P = 0.090);The size of lesions removed by EMR-CI was smaller than that of ESD with significant difference(WMD =-0.86,95%CI:-1.33～-0.40,P = 0.000);The time EMR-CI required to remove the lesion was significantly shorter than that of ESD(WMD =-12.48,95%CI:-16.42～-8.54,P = 0.000).The positive rate of horizontal resection margin of EMR-CI was similar to that of ESD,with no significant difference(O(R) = 1.74,95%CI:0.64～4.75,P = 0.280);The positive rate of vertical resection margin was significantly higher than that of ESD(O(R) = 2.41,95%CI:1.09～5.32,P = 0.030).Due to the low local recurrence rate and distant metastasis rate,Meta-analysis couldn't be compared.Safety outcome index showed that,there were no significant differences in the incidence of total complications,bleeding and perforation among groups.Conclusion In the treatment of RNEN,EMR-CI can achieve the endosopic complete resection,histological complete resection and positive rate of horizontal resection margin similar to ESD without increasing surgical complications and significantly saving surgical time.However,attention should be paid to the differences between EMR-CI and ESD in positive rate of vertical resection margin.

Integrating evidence from animal experiments is a critical component of biomedical research, providing essential prior information for in-depth investigations of disease mechanisms and new drug development. Animal models have played an irreplaceable role in simulating human diseases. However, the integration of evidence from animal experiments has faced numerous challenges, including insufficient emphasis, significant heterogeneity in study designs, high publication bias, and discrepancies with clinical research practices. This paper first identifies existing issues in the original research evidence from animal experiments, such as the selection and applicability of animal models, considerations in the design of experimental studies, and factors influencing the translation of animal experimental evidence. It then discusses various methods for integrating this evidence, including systematic review and meta-analysis, overview of systematic review/umbrella review, scoping review, and evidence mapping, while highlighting recent advancements in their application. Finally, the paper addresses the main challenges currently encountered in the integration of evidence from animal experiments and proposes targeted improvement strategies aimed at enhancing the efficiency of translating research outcomes into clinical practice and promoting the advancement of evidence-based medicine. By continuously optimizing original experimental research protocols and evidence integration practices, this work aims to establish a more efficient and scientific environment for the synthesis of evidence from animal experiments, ultimately contributing to clinical trials and human health.

Objective To evaluate the application value of artificial intelligence mixed reality(AI-MR)technology in the planning of ultrasound-guided percutaneous nephrolithotomy(PCNL)for special types of complex upper urinary stones.Methods The prospective single-center,single-arm clinical study involved 15 patients with complex upper urinary stones undergoing ultrasound-guided PCNL during Aug.2022 and May 2023,including 9 male and 6 female,3 cases of pelvic ectopic kidney stones,5 cases of horseshoe kidney stones,3 cases of renal stones combined with spinal deformity,and 4 cases of transplant kidney stones.Based on preoperative computed tomography urography(CTU)data,digital three-dimensional reconstruction was performed,and AI-MR was used to project surgery-related three-dimensional images in real space to obtain"perspective"information of the surgical area.This facilitated preoperative design and planning,including target calyx,number of channels,and auxiliary measures.The compliance of target calyx and number of channels,stone clearance rate,total operation time,time required to establish the percutaneous renal channel,decrease in hemoglobin level,surgical complications,and postoperative hospital stay were analyzed.Results All 15 patients underwent preoperative planning using AI-MR and successfully completed one-stage ultrasound-guided PCNL.Based on the preoperative planning,we utilized S-PCNL alone or combined with Needle-perc or antegrade/retrograde FURS/RIRS.Among all patients,4 underwent single-channel S-PCNL,3 multi-channel S-PCNL,and 8 S-PCNL combined with Needle-perc or FURS.The compliance of target calyx and number of channels was 86.7％,the one-stage stone clearance rate was 80.0％,the average time for establishing the channel was(2.3±0.3)minutes,the average total operation time was(61.5±12.2)minutes,the mean decrease in hemoglobin level was(9.6±1.2)g/L,and the average postoperative hospital stay was(4.6±0.5)days.There were no Clavien-Dindo grade ≥ Ⅱ complications,such as blood transfusion,organ injury,or urosepsis.Conclusion Before surgery,AI-MR can be used to quantitatively analyze imaging data for patients with special types of complex upper urinary stones,which can achieve three-dimensional fluoroscopy effects,formulate surgical plans,optimize puncture paths,effectively avoid the risk of damage to surrounding organs,reduce complications,shorten treatment cycle and improve the first-stage stone clearance rate.