Self-Delivery Nanobooster to Enhance Immunogenic Cell Death for Cancer Chemoimmunotherapy.

Inducing immunogenic cell death (ICD) is a promising strategy for cancer immunotherapy. Shikonin (SHK), a naphthoquinone compound from Lithospermum erythrorhizon, can stimulate antitumor immunity by inducing ICD. Nevertheless, the immunogenicity of tumor cells killed by SHK is weak. Endoplasmic reticulum (ER) stress is an important intracellular pathway of the ICD effect. Curcumin (CUR) can directly induce ER stress by disrupting Ca2+ homeostasis, which might enhance SHK-induced ICD effect. A self-delivery ICD effect nanobooster (CS-PEG NPs) was developed by the self-assembly of SHK (ICD inducer) and CUR (ICD enhancer) with the assistance of DSPE-PEG2K for cancer chemoimmunotherapy. CS-PEG NPs possessed effective CT26 tumor cell cellular uptake and tumor accumulation ability. Moreover, enhanced cytotoxicity against tumor cells and apoptosis promotion were achieved due to the synergistic effect of CUR and SHK. Notably, CS-PEG NPs induced obvious Ca2+ homeostasis disruption, ER stress, and ICD effect. Subsequently, the neoantigens produced by the robust ICD effect in vivo promoted dendritic cell maturation, which further recruited and activated cytotoxic T lymphocytes. Superior antitumor efficacy and systemic antitumor immunity were observed in the CT26-bearing BALB/c mouse model without side effects in major organs. This study offers a promising self-delivery nanobooster to induce strong ICD effect and antitumor immunity for cancer chemoimmunotherapy.

Platinum-ruthenium-iron embedded in nitrogen-doped ordered mesoporous carbon for adrenaline electrochemical sensing study.

A novel nitrogen-doped ordered mesoporous carbon (OMC) pore-embedded growth Pt-Ru-Fe nanoparticles (Pt1-Ru7.5-Fex@N-OMCs) composite was designed and synthesized for the first time. SBA-15 was used as a template, and dopamine was used as a carbon and nitrogen source and metal linking reagent. The oxidative self-polymerization reaction of dopamine was utilized to polymerize dopamine into two-dimensional ordered SBA-15 template pores. Iron porphyrin was introduced as an iron source at the same time as polymerization of dopamine, which was introduced inside and outside the pores using dopamine-metal linkage. Carbonization of polydopamine, nitrogen doping and iron nanoparticle formation were achieved by one-step calcination. Then the templates were etched to form Fex@N-OMCs, and finally the Pt1-Ru7.5-Fex@N-OMCs composites were stabilized by the successful introduction of platinum-ruthenium nanoparticles through the substitution reaction. The composite uniformly embeds the transition metal nanoparticles inside the OMC pores with high specific surface area, which limits the size of the metal nanoparticles inside the pores. At the same time, the metal nanoparticles are also loaded onto the surface of the OMCs, realizing the uniform loading of metal nanoparticles both inside and outside the pores. This enhances the active sites of the composite, promotes the mass transfer process inside and outside the pores, and greatly enhances the electrocatalytic performance of the catalyst. The material shows high electrocatalytic performance for adrenaline, which is characterized by a wide linear range, high sensitivity and low detection limit, and can realize the detection of actual samples.

Loss of Bcl-3 regulates macrophage polarization by promoting macrophage glycolysis.

M1/M2 macrophage polarization plays an important role in regulating the balance of the microenvironment within tissues. Moreover, macrophage polarization involves the reprogramming of metabolism, such as glucose and lipid metabolism. Transcriptional coactivator B-cell lymphoma-3 (Bcl-3) is an atypical member of the IκB family that controls inflammatory factor levels in macrophages by regulating nuclear factor kappa B pathway activation. However, the relationship between Bcl-3 and macrophage polarization and metabolism remains unclear. In this study, we show that the knockdown of Bcl-3 in macrophages can regulate glycolysis-related gene expression by promoting the activation of the nuclear factor kappa B pathway. Furthermore, the loss of Bcl-3 was able to promote the interferon gamma/lipopolysaccharide-induced M1 macrophage polarization by accelerating glycolysis. Taken together, these results suggest that Bcl-3 may be a candidate gene for regulating M1 polarization in macrophages.

Human ß-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506.

BACKGROUND: Colorectal cancer has a low 5-year survival rate and high mortality. Human ß-defensin-1 (hBD-1) may play an integral function in the innate immune system, contributing to the recognition and destruction of cancer cells. Long non-coding RNAs (lncRNAs) are involved in the process of cell differentiation and growth. AIM: To investigate the effect of hBD-1 on the mammalian target of rapamycin (mTOR) pathway and autophagy in human colon cancer SW620 cells. METHODS: CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration. Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation. Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway. Additionally, p-mTOR (Ser2448), Beclin1, and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis. RESULTS: hBD-1 inhibited the proliferative ability of SW620 cells, as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1. hBD-1 decreased the expression of p-mTOR (Ser2448) protein and increased the expression of Beclin1 and LC3II/I protein. Furthermore, bioinformatics analysis identified seven lncRNAs (2 upregulated and 5 downregulated) related to the mTOR pathway. The lncRNA TCONS_00014506 was ultimately selected. Following the inhibition of the lncRNA TCONS_00014506, exposure to hBD-1 inhibited p-mTOR (Ser2448) and promoted Beclin1 and LC3II/I protein expression. CONCLUSION: hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.

Comparison of the perioperative outcomes of robot-assisted laparoscopic transperitoneal versus retraperitoneal partial nephrectomy for posterior-lateral renal tumors: a systematic review and meta-analysis.

The study aims to assess the available literature and compare the perioperative outcomes of robotic-assisted partial nephrectomy (RAPN) for posterior-lateral renal tumors using transperitoneal (TP) and retroperitoneal (RP) approaches. Systematically searched the Embase, PubMed, and Cochrane Library databases for literature. Eligible studies were those that compared TP-RAPN and RP-RAPN for posterior-lateral renal tumors. The data from the included studies were analyzed and summarized using Review Manager 5.3, which involved comparing baseline patient and tumor characteristics, intraoperative and postoperative outcomes, and oncological outcomes. The analysis included five studies meeting the inclusion criteria, with a total of 1440 patients (814 undergoing RP-RAPN and 626 undergoing TP-RAPN). Both groups showed no significant differences in age, gender, BMI, R.E.N.A.L. score, and tumor size. Notably, compared to TP-RAPN, the RP-RAPN group demonstrated shorter operative time (OT) (MD: 17.25, P = 0.01), length of hospital stay (LOS) (MD: 0.37, P < 0.01), and lower estimated blood loss (EBL) (MD: 15.29, P < 0.01). However, no significant differences were found between the two groups in terms of warm ischemia time (WIT) (MD: -0.34, P = 0.69), overall complications (RR: 1.25, P = 0.09), major complications (the Clavien-Dindo classification ≥ 3) (RR: 0.97, P = 0.93), and positive surgical margin (PSM) (RR: 1.06, P = 0.87). The systematic review and meta-analysis suggests RP-RAPN may be more advantageous for posterior-lateral renal tumors in terms of OT, EBL, and LOS, but no significant differences were found in WIT, overall complications, major complications, and PSM. Both surgical approaches are safe, but a definitive advantage remains uncertain.

COVID-19 and chronic kidney disease: a bibliometric analysis.

Background: The COVID-19 pandemic has caused over 656 million confirmed cases and over 6.6 million deaths worldwide. Chronic kidney disease (CKD) is considered a high-risk factor for COVID-19; therefore, considerable research has been conducted in this field. Therefore, this study aims to conduct a bibliometric analysis of publications related to COVID-19 and CKD. Methods: Publications were retrieved from the Web of Science Core Collection database on 16 January 2023 and screened based on inclusion criteria. Then the authors used Microsoft Excel and CiteSpace to analyze the included publications from the following seven aspects: countries/regions, institutions, journals, authors, cited references, and keywords. Results: In total, 622 publications were included in the study. The USA has the most publications in this field, followed by China. The Icahn School of Medicine at Mount Sinai and Harvard Medical School had the highest number of publications in the field. Journal of Clinical Medicine had the largest number of publications, and Lancet was the most cited journal. Alberto Ortiz was the author with the largest number of publications, but there were no influential authors in this field. The highly cited references are mainly clinical studies on COVID-19. Research hotspots in this field include end-stage recent disease, cardiovascular disease, kidney metastasis, diabetes Mellitus, acute kidney injury, meta-analysis, and consistent plasma. Conclusions: The USA, China, and some European countries and their institutions are major contributors to these publications. End-stage renal disease, acute kidney injury, kidney transplantation and convalescent plasma are current hot topics in the field.

Enhanced denitrification performance in iron-carbon wetlands through biomass addition: Impact on nitrate and ammonia transformation.

This study investigated the influence of biomass addition on the denitrification performance of iron-carbon wetlands. During long-time operation, the effluent NO3--N concentration of CW-BFe was observed to be the lowest, registering at 0.418 ± 0.167 mg/L, outperforming that of CW-Fe, which recorded 1.467 ± 0.467 mg/L. However, the effluent NH4+-N for CW-BFe increased to 1.465 ± 0.121 mg/L, surpassing CW-Fe's 0.889 ± 0.224 mg/L. Within a typical cycle, when establishing first-order reaction kinetics based on NO3--N concentrations, the introduction of biomass was found to amplify the kinetic constants across various stages in the iron-carbon wetland, ranging between 2.4 and 5.4 times that of CW-Fe. A metagenomic analysis indicated that biomass augments the reduction of NO3--N and NO2--N nitrogen and significantly bolsters the dissimilation nitrate reduction to ammonia pathway. Conversely, it impedes the reduction of N2O, leading to a heightened proportion of 2.715 % in CW-BFe's nitrogen mass balance, a stark contrast to CW-Fe's 0.379 %.

S100a10 deficiency in neutrophils aggravates ulcerative colitis in mice.

BACKGROUND AND AIMS: S100a10 is a member of the S100 family of proteins, which plays a key role in the depression and tumor metastasis. However, the role of S100a10 is unclear in ulcerative colitis. METHODS: The effect of S100a10 was assessed using a murine ulcerative colitis model which was accompanied by parameters including body weight loss, disease activity index, histological score, colon weight and length. The quantity and role of immune cells was determined by flow cytometry and bone marrow chimeric mice. Neutrophils depletion, adoptive cell transfer and conditional knockout mice were used to ascertain which cells played the key role in ulcerative colitis. The function of neutrophils was evaluated by migration assay, phagocytosis assay, multiplex immunoassay and real-time PCR. RESULTS: In this study, our data showed that S100a10-/- mice were prone to ulcerative colitis induced by dextran sodium sulfate. Neutrophils number increased in colon of S100a10-/- mice after dextran sodium sulfate treatment significantly. Meanwhile, adoptive transfer of neutrophils from wild type mice partially decreased the susceptibility of S100a10-/- mice to dextran sodium sulfate. There was no difference in ulcerative colitis between the groups of S100a10-/- mice without neutrophils and wild type mice. Finally, we found that S100a10-/- neutrophils had stronger function in secretion and synthesis of inflammatory factor. CONCLUSIONS: In one word, these results suggest that S100a10 has a role in inhibiting the pathogenesis of ulcerative colitis through regulation of neutrophils function.

Identification and validation of obesity related genes signature based on microenvironment phenotypes in prostate adenocarcinoma.

BACKGROUND: The role of obesity related genes (ORGs) in the immune checkpoint inhibitors (ICIs) treatment of prostate adenocarcinoma (PRAD) has not yet been proved by research. METHODS: We comprehensively evaluated the ORGs patterns in PRAD based on tumor microenvironment (TME) phenotypes and immunotherapy efficacies. Then we constructed a ORGs risk score for prognosis and a ORGs signature for accurate prediction of TME phenotype and immunotherapy efficacy in order to evaluate individual patients. RESULTS: Two distinct ORGs patterns were generated. The two ORGs patterns were consistent with inflammatory and non-inflammatory TME phenotypes. ORGs patterns had an important role for predicting immunotherapy efficacies. Next, we constructed a ORGs risk score for predicting each patient's prognosis with high performance in TCGA-PRAD. The ORGs risk score could be well verified in the external cohorts including GSE70769 and GSE21034. Then, we developed a ORGs signature and found it was significantly positively correlated with tumor-infiltrating lymphocytes in TCGA-PRAD. We found that each patient in the high-risk ORGs signature group represented a non-inflamed TME phenotype on the single cell level. The patients with high ORGs signature had more sensitivity to immunotherapy. And those ORGs were verified. CONCLUSIONS: ORGs pattern depicts different TME phenotypes in PRAD. The ORGs risk score and ORGs signature have an important role for predicting prognosis and immunotherapy efficacies.

Circular RNA hsa_circ_0049657 as a Potential Biomarker in Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is a common lung disorder. In this study, we applied bioinformatics methods to analyze and investigate the role of the NFIX gene in NSCLC. Hsa_circ_0049657 is derived from the NFIX gene, this research aimed to verify the potential role of hsa_circ_0049657 in the development of NSCLC. The results suggested that NFIX was downregulated in most cancers. In addition, the NFIX expression in lung adenocarcinoma (LUAD) was associated with the clinicopathological stage. In LUAD, NFIX expression was associated with the degree of infiltration of most immune cells. The expression levels of hsa_circ_0049657 were significantly lower in cancerous tissues than in paracancerous tissues. Moreover, the results showed that hsa_circ_0049657 expression was downregulated in NSCLC cells. After overexpression of hsa_circ_0049657, the proliferation and migration ability of NSCLC cells were significantly inhibited and the level of apoptosis was increased. We could suppress the proliferation and invasion abilities and promote apoptosis of NSCLC cells by up-regulating hsa_circ_0049657, which might be a potential biomarker for NSCLC.

Limonoids from the roots of Melia azedarach and their anti-inflammatory activity.

Twelve undescribed limonoids, meliazedarines J-U (1-12), along with a known one, were isolated from the roots of Melia azedarach. Their structures were elucidated by extensive spectroscopic investigations, X-ray diffraction analyses, and ECD calculations. Compounds 1-8 were identified as ring intact limonoids, while compounds 9-12 were established as ring C-seco ones. The anti-inflammatory potential of compounds 1-4, 6, 8, 9, and 11-13 was evaluated on macrophages. Compounds 1, 3, 4, 6, and 9 significantly suppressed nitric oxide production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, among them compound 3 showed the best inhibitory effect with an IC50 value of 7.07 ± 0.48 µΜ. Furthermore, compound 3 effectively reduced interleukin-1ß secretion in LPS plus nigericin-induced THP-1 macrophages by inhibiting NLRP3 inflammasome activation. The results strongly suggested that limonoids from the roots of M. azedarach might be candidates for treating inflammation-related diseases.

Hot-Electron Dynamics Mediated Medical Diagnosis and Therapy.

Surface plasmon resonance excitation significantly enhances the absorption of light and increases the generation of "hot" electrons, i.e., conducting electrons that are raised from their steady states to excited states. These excited electrons rapidly decay and equilibrate via radiative and nonradiative damping over several hundred femtoseconds. During the hot-electron dynamics, from their generation to the ultimate nonradiative decay, the electromagnetic field enhancement, hot electron density increase, and local heating effect are sequentially induced. Over the past decade, these physical phenomena have attracted considerable attention in the biomedical field, e.g., the rapid and accurate identification of biomolecules, precise synthesis and release of drugs, and elimination of tumors. This review highlights the recent developments in the application of hot-electron dynamics in medical diagnosis and therapy, particularly fully integrated device techniques with good application prospects. In addition, we discuss the latest experimental and theoretical studies of underlying mechanisms. From a practical standpoint, the pioneering modeling analyses and quantitative measurements in the extreme near field are summarized to illustrate the quantification of hot-electron dynamics. Finally, the prospects and remaining challenges associated with biomedical engineering based on hot-electron dynamics are presented.

N6-methyladenosine-modified circIRF2, identified by YTHDF2, suppresses liver fibrosis via facilitating FOXO3 nuclear translocation.

Circular RNA (circRNA) has been implicated in liver fibrosis and modulated by multiple elusive molecular mechanisms, while the effects of N6-methyladenosine (m6A) modification on circRNA are still elusive. Herein, we identify circIRF2 from our circRNA sequencing data, which decreased in liver fibrogenesis stage and restored in resolution stage, indicating that dysregulated circIRF2 may be closely associated with liver fibrosis. Gain/loss-of-function analysis was performed to evaluate the effects of circIRF2 on liver fibrosis at both the fibrogenesis and resolution in vivo. Ectopic expression of circIRF2 attenuated liver fibrogenesis and HSCs activation at the fibrogenesis stage, whereas downregulation of circIRF2 impaired mouse liver injury repair and inflammation resolution. Mechanistically, YTHDF2 recognized m6A-modified circIRF2 and diminished circIRF2 stability, partly accounting for the decreased circIRF2 in liver fibrosis. Microarray was applied to investigate miRNAs regulated by circIRF2, our data elucidate cytoplasmic circIRF2 may directly harbor miR-29b-1-5p and competitively relieve its inhibitory effect on FOXO3, inducing FOXO3 nuclear translocation and accumulation. Clinically, circIRF2 downregulation was prevalent in liver fibrosis patients compared with healthy individuals. In summary, our findings offer a novel insight into m6A modification-mediated regulation of circRNA and suggest that circIRF2 may be an exploitable prognostic marker and/or therapeutic target for liver fibrosis.

Epithelial TIPE1 Protein Guards against Colitis by Inhibiting TNF-α-Mediated Inflammation.

Intestinal epithelial cells (IECs) at the internal/external interface orchestrate the mucosal immune response, and IEC dysfunction has been linked to multiple inflammatory diseases, including inflammatory bowel disease. In this study, we found that a member of the TNF-α-induced protein 8 (TNFAIP8 or TIPE) family called TIPE1 is indispensable for maintaining epithelial cell barrier integrity and homeostasis under inflammatory conditions. TIPE1-deficient mice, or chimeric mice that were deficient in TIPE1 in their nonhematopoietic cells, were more sensitive to dextran sulfate sodium-induced experimental colitis; however, TIPE1 deficiency had no impact on the development of inflammation-associated and sporadic colorectal cancers. Mechanistically, TIPE1 prevented experimental colitis through modulation of TNF-α-dependent inflammatory response in IECs. Importantly, genetic deletion of both TIPE1 and its related protein TNFAIP8 in mice led to the development of spontaneous chronic colitis, indicating that both of these two TIPE family members play crucial roles in maintaining intestinal homeostasis. Collectively, our findings highlight an important mechanism by which TIPE family proteins maintain intestinal homeostasis and prevent inflammatory disorders in the gut.

Binding Mechanism of CD47 with SIRPα Variants and Its Antibody: Elucidated by Molecular Dynamics Simulations.

The intricate complex system of the differentiation 47 (CD47) and the signal-regulatory protein alpha (SIRPα) cluster is a crucial target for cancer immunotherapy. Although the conformational state of the CD47-SIRPα complex has been revealed through crystallographic studies, further characterization is needed to fully understand the binding mechanism and to identify the hot spot residues involved. In this study, molecular dynamics (MD) simulations were carried out for the complexes of CD47 with two SIRPα variants (SIRPαv1, SIRPαv2) and the commercially available anti-CD47 monoclonal antibody (B6H12.2). The calculated binding free energy of CD47-B6H12.2 is lower than that of CD47-SIRPαv1 and CD47-SIRPαv2 in all the three simulations, indicating that CD47-B6H12.2 has a higher binding affinity than the other two complexes. Moreover, the dynamical cross-correlation matrix reveals that the CD47 protein shows more correlated motions when it binds to B6H12.2. Significant effects were observed in the energy and structural analyses of the residues (Glu35, Tyr37, Leu101, Thr102, Arg103) in the C strand and FG region of CD47 when it binds to the SIRPα variants. The critical residues (Leu30, Val33, Gln52, Lys53, Thr67, Arg69, Arg95, and Lys96) were identified in SIRPαv1 and SIRPαv2, which surround the distinctive groove regions formed by the B2C, C'D, DE, and FG loops. Moreover, the crucial groove structures of the SIRPα variants shape into obvious druggable sites. The C'D loops on the binding interfaces undergo notable dynamical changes throughout the simulation. For B6H12.2, the residues Tyr32LC, His92LC, Arg96LC, Tyr32HC, Thr52HC, Ser53HC, Ala101HC, and Gly102HC in its initial half of the light and heavy chains exhibit obvious energetic and structural impacts upon binding with CD47. The elucidation of the binding mechanism of SIRPαv1, SIRPαv2, and B6H12.2 with CD47 could provide novel perspectives for the development of inhibitors targeting CD47-SIRPα.

A Dual-Targeting Liposome Enhances Triple-Negative Breast Cancer Chemoimmunotherapy through Inducing Immunogenic Cell Death and Inhibiting STAT3 Activation.

Immunotherapy gains increasing focus in treating triple-negative breast cancer (TNBC), while its efficacy is greatly restricted owing to low tumor immunogenicity and immunosuppressive tumor microenvironment (ITM). Herein, a LyP-1 and chondroitin sulfate (CS) dual-modified liposome co-loaded with paclitaxel (PTX) and cryptotanshinone (CTS), namely CS/LyP-1-PC Lip, is engineered for TNBC chemoimmunotherapy via induction of immunogenic cell death (ICD) and inhibition of signal transducer and activator of transcript-3 (STAT3) activation. CS/LyP-1-PC Lip enhances cellular uptake through p32 and CD44 dual receptor-mediated endocytosis. Within the tumor, the CS layer is continuously detached by hyaluronidase to release drugs. Subsequently, CTS sensitizes the cytotoxicity of PTX to 4T1 tumor cells. PTX induces ICD of tumor cells and facilitates infiltration of cytotoxic T lymphocyte to provoke immune response. Meanwhile, the concomitant delivery of CTS inhibits STAT3 activation to decrease infiltration of regulatory T cell, M2-type tumor-associated macrophage, and myeloid-derived suppressor cell, thus reversing ITM. Markedly, the dual-targeting liposome shows superior anti-tumor efficacy in subcutaneous TNBC mice and significant lung metastasis suppression in tumor metastasis model. Overall, this work offers a feasible combination regimen and a promising nanoplatform for the development of TNBC chemoimmunotherapy.

The biogenesis, mechanism and function of the tRNA-derived small RNA (tsRNA): a review compared with microRNA.

Since the discovery of the first miRNA in 1993, numerous studies have focused on their biogenesis, their functions on regulating a diversity of cellular processes, and the molecular mechanisms underlying their regulatory activity. The critical roles they play during pathogenesis have also been explored. With the advancement on next-generation sequencing, new classes of small RNA with distinct functions have been discovered. Among them, tRNA derived fragment (tsRNAs) have become a center of studies due to their similarity to miRNA. In this review, we summarized the biogenesis of miRNA and tsRNAs, the molecular mechanisms of their functions, and their important roles during the development of diseases. The similarity and difference between miRNA and tsRNAs were also discussed.

The pharmacology and mechanisms of platycodin D, an active triterpenoid saponin from Platycodon grandiflorus.

Chinese doctors widely prescribed Platycodon grandiflorus A. DC. (PG) to treat lung carbuncles in ancient China. Modern clinical experiences have demonstrated that PG plays a crucial role in treating chronic pharyngitis, plum pneumonia, pneumoconiosis, acute and chronic laryngitis, and so forth. Additionally, PG is a food with a long history in China, Japan, and Korea. Furthermore, Platycodin D (PLD), an oleanane-type triterpenoid saponin, is one of the active substances in PG. PLD has been revealed to have anti-inflammatory, anti-viral, anti-oxidation, anti-obesity, anticoagulant, spermicidal, anti-tumor etc., activities. And the mechanism of the effects draws lots of attention, with various signaling pathways involved in these processes. Additionally, research on PLD's pharmacokinetics and extraction processes is under study. The bioavailability of PLD could be improved by being prescribed with Glycyrrhiza uralensis Fisch. or by creating a new dosage form. PLD has been recently considered to have the potential to be a solubilizer or an immunologic adjuvant. Meanwhile, PLD was discovered to have hemolytic activity correlated. PLD has broad application prospects and reveals practical pharmacological activities in pre-clinical research. The authors believe that these activities of PLD contribute to the efficacy of PG. What is apparent is that the clinical translation of PLD still has a long way to go. With the help of modern technology, the scope of clinical applications of PLD is probable to be expanded from traditional applications to new fields.

Micro-Leakage Image Recognition Method for Internal Detection in Small, Buried Gas Pipelines.

In order to resolve the problem that the sample of image for internal detection of DN100 buried gas pipeline microleakage is single and difficult to identify, a recognition method of microleakage image of the pipeline internal detection robot is proposed. First, nongenerative data augmentation is used to expand the microleakage images of gas pipelines. Secondly, a generative data augmentation network, Deep Convolutional Wasserstein Generative Adversarial Networks (DCWGANs), is designed to generate microleakage images with different features for detection in the pipeline of gas pipelines to achieve sample diversity of microleakage images of gas pipelines. Then, a bi-directional feature pyramid network (BiFPN) is introduced into You Only Look Once (YOLOv5) to retain more deep feature information by adding cross-scale connecting lines in the feature fusion structure; finally, a small target detection layer is constructed in YOLOv5 so that more shallow feature information can be retained to achieve small-scale leak point recognition. The experimental results show that the precision of this method for microleak identification is 95.04%, the recall rate is 94.86%, the mAP value is 96.31%, and the minimum size of identifiable leaks is 1 mm.

Promising Nanomedicines of Shikonin for Cancer Therapy.

Malignant tumor, the leading cause of death worldwide, poses a serious threat to human health. For decades, natural product has been proven to be an essential source for novel anticancer drug discovery. Shikonin (SHK), a natural molecule separated from the root of Lithospermum erythrorhizon, shows great potential in anticancer therapy. However, its further clinical application is significantly restricted by poor bioavailability, adverse effects, and non-selective toxicity. With the development of nanotechnology, nano drug delivery systems have emerged as promising strategies to improve bioavailability and enhance the therapeutic efficacy of drugs. To overcome the shortcoming of SHK, various nano drug delivery systems such as liposomes, polymeric micelles, nanoparticles, nanogels, and nanoemulsions, were developed to achieve efficient delivery for enhanced antitumor effects. Herein, this review summarizes the anticancer pharmacological activities and pharmacokinetics of SHK. Additionally, the latest progress of SHK nanomedicines in cancer therapy is outlined, focusing on long circulation, tumor targeting ability, tumor microenvironment responsive drug release, and nanosystem-mediated combination therapy. Finally, the challenges and prospects of SHK nanomedicines in the future clinical application are spotlighted.