Quality Evaluation of Lonicerae Flos Produced in Southwest China Based on HPLC Analysis and Antioxidant Activity.

Lonicera macranthoides, the main source of traditional Chinese medicine Lonicerae Flos, is extensively cultivated in Southwest China. However, the quality of L. macranthoides produced in this region significantly varies due to its wide distribution and various cultivation breeds. Herein, 50 Lonicerae Flos samples derived from different breeds of L. macranthoides cultivated in Southwest China were collected for quality evaluation. Six organic acids and three saponin compounds were quantitatively analyzed using HPLC. Furthermore, the antioxidant activity of a portion of samples was conducted with 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging experiments. According to the quantitative results, all samples met the quality standards outlined in the Chinese Pharmacopoeia. The samples from Guizhou, whether derived from unopened or open wild-type breeds, exhibited high quality, while the wild-type samples showed relatively significant fluctuation in quality. The samples from Chongqing and Hunan demonstrated similar quality, whereas those from Sichuan exhibited relatively lower quality. These samples demonstrated significant abilities in clearing ABTS and DPPH radicals. The relationship between HPLC chromatograms and antioxidant activity, as elucidated by multivariate analysis, indicated that chlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C are active components and can serve as Q-markers for quality evaluation.

Association between blood groups and myocardial injury after non-cardiac surgery: a retrospective cohort study.

Blood group is a potential genetic element in coronary artery disease. Nevertheless, the relationship between different ABO blood groups and myocardial injury after non-cardiac surgery (MINS) is poorly understood. This study verified whether ABO blood group is a potential MINS influencing factor. This retrospective cohort study included 1201 patients who underwent elective non-cardiac surgery and a mandatory troponin test on postoperative days 1 and 2 from 2019 to 2020 at a university-affiliated tertiary hospital. The primary outcome was associations between ABO blood groups and MINS, assessed using univariate and multivariate logistic-regression analyses. Path analysis was used to investigate direct and indirect effects between blood group and MINS. MINS incidence (102/1201, 8.5%) was higher in blood-type B patients than in non-B patients [blood-type B: 44/400 (11.0%) vs. non-B: 58/801 (7.2%); adjusted odds ratio = 1.57 (1.03-2.38); p = 0.036]. In the confounding factor model, preoperative hypertension and coronary artery disease medical history were associated with MINS risk [adjusted odds ratio: 2.00 (1.30-3.06), p = 0.002; 2.81 (1.71-4.61), p < 0.001, respectively]. Path analysis did not uncover any mediating role for hypertension, diabetes, or coronary artery disease between blood type and MINS. Therefore, blood-type B is associated with higher MINS risk; potential mediators of this association need to be investigated.

miR-206-3p Targets Brain-Derived Neurotrophic Factor and Affects Postoperative Cognitive Function in Aged Mice.

Postoperative cognitive dysfunction (POCD) occurs after surgery and severely impairs patients' quality of life. Finding POCD-associated variables can aid in its diagnosis and prognostication. POCD is associated with noncoding RNAs, such as microRNAs (miRNAs), involved in metabolic function, immune response alteration, and cognitive ability impairment; however, the underlying mechanisms remain unclear. The aim of this study was to investigate hub miRNAs (i.e., miRNAs that have an important regulatory role in diseases) regulating postoperative cognitive function and the associated mechanisms. Hub miRNAs were identified by bioinformatics, and their expression in mouse hippocampus tissues was determined using real-time quantitative polymerase chain reaction. Hub miRNAs were overexpressed or knocked down in cell and animal models to test their effects on neuroinflammation and postoperative cognitive function. Six differentially expressed hub miRNAs were identified. miR-206-3p was the only broadly conserved miRNA, and it was used in follow-up studies and animal experiments. Its inhibitors reduced the release of proinflammatory cytokines in BV-2 microglia by regulating its target gene, brain-derived neurotrophic factor (BDNF), and the downstream signaling pathways. miR-206-3p inhibition suppressed microglial activation in the hippocampi of mice and improved learning and cognitive decline. Therefore, miR-206-3p significantly affects POCD, implying its potential as a therapeutic target.

Investigation on muscle fiber types and meat quality and estimation of their heritability and correlation coefficients with each other in four pig populations.

The aim of this study was to investigate the muscle fiber types and meat quality in four populations and estimate the heritability and correlation coefficients of those traits in Shanxia long black pig (SX). In this study, a total of 318 pigs were recorded for 16 traits of the muscle fiber types and meat quality in four populations, including 256 individuals from the new breed SX. The population had a significant effect on all recorded traits, and the meat quality of the Lulai black pig was better than the remaining populations. The heritability (h2 ) of meat quality traits was from 0.06 (pH at 24 h) to 0.47 (shearing force), and the muscle fiber types belonged to the traits with low to medium heritability. The density of total fiber had the highest h2 (0.40), while the percentage of type IIA had the lowest h2 (0.04). Most traits are phenotypically correlated with each other, but only a small proportion of traits are genetically correlated with each other. None fiber type genetically correlated with meat quality significantly, because the genetic correlation coefficients had large standard errors. These results provided some insights into genetic improvements for the meat quality in pig breeds and also indicated that the parameters of muscle fiber characteristics can explain parts of the variation in meat quality.

Phenotypic correlations of carpal gland diverticular number with production traits and its genome-wide association analysis in multiple pig populations.

Pig carpal glands play crucial roles in territorial recognition, reproductive behavior, and information exchange; however, their effects on production traits and underlying genetic mechanisms remain unclear. In this study, 1028 pigs from six populations were counted for the carpal gland diverticular numbers (CGDNs) on the left (CGDNL) and right (CGDNR) legs, and their carcass and meat quality traits were assessed. The CGDNs were significantly different among the populations, and Licha Black pigs had a lower CGDN than the Bama Xiang breed. It was also significantly different between sexes, with males having more diverticula than females (p ≤ 0.0391). Moreover, the number was asymmetric, with CGDNR being significantly higher than CGDNL. Notably, CGDNs was significantly correlated with each other in phenotype and genetics and with 24-h pH, 24-h meat color score, 24-h marbling score, fat content, moisture content, sodium salt content, and saturated fatty acid content in phenotype. Furthermore, genome-wide association analyses identified seven SNPs in association with CGDNs at a 5% genome-wide significance level, all of which were located in a 1.78-Mb (35.347-37.129 Mb) region on chromosome 1. CNC10010837 and CNC10010840 were the top SNPs: both had an additive effect of 0.789 ± 0.120 on CGDNR with p = 8.31E-10. These findings provide important insights into the functions and underlying genetic mechanisms of swine carpal glands.

Parkin-mediated mitophagy is a potential treatment for oxaliplatin-induced peripheral neuropathy.

Oxaliplatin-induced peripheral nerve pain (OIPNP) is a common chemotherapy-related complication, but the mechanism is complex. Mitochondria are vital for cellular homeostasis and regulating oxidative stress. Parkin-mediated mitophagy is a cellular process that removes damaged mitochondria, exhibiting a protective effect in various diseases; however, its role in OIPNP remains unclear. In this study, we found that Parkin-mediated mitophagy was decreased, and reactive oxygen species (ROS) was upregulated in OIPNP rat dorsal root ganglion (DRG) in vivo and in PC12 cells stimulated with oxaliplatin (OXA) in vitro. Overexpression of Parkin indicated that OXA might cause mitochondrial and cell damage by inhibiting mitophagy. We also showed that salidroside (SAL) upregulated Parkin-mediated mitophagy to eliminate damaged mitochondria and promote PC12 cell survival. Knockdown of Parkin indicated that mitophagy is crucial for apoptosis and mitochondrial homeostasis in PC12 cells. In vivo study also demonstrated that SAL enhances Parkin-mediated mitophagy in the DRG and alleviates peripheral nerve injury and pain. These results suggest that Parkin-mediated mitophagy is involved in the pathogenesis of OIPNP and may be a potential therapeutic target for OIPNP.NEW & NOTEWORTHY This article discusses the effects and mechanisms of Parkin-mediated mitophagy in oxaliplatin-induced peripheral nerve pain (OIPNP) from both in vivo and in vitro. We believe that our study makes a significant contribution to the literature because OIPNP has always been the focus of clinical medicine, and mitochondrial quality regulation mechanisms especially Parkin-mediated mitophagy, have been deeply studied in recent years. We use a variety of molecular biological techniques and animal experiments to support our argument.

Combined analysis of inorganic elements and flavonoid metabolites reveals the relationship between flower quality and maturity of Sophora japonica L.

Flos Sophorae (FS), or the dried flower buds of Sophora japonica L., is widely used as a food and medicinal material in China. The quality of S. japonica flowers varies with the developmental stages (S1-S5) of the plant. However, the relationship between FS quality and maturity remains unclear. Inductively coupled plasma optical emission spectrometry (ICP-OES) and ultra-high performance liquid chromatography coupled with electrospray ionization-triple quadrupole-linear ion trap mass spectrometry (UPLC-ESI-Q TRAP-MS/MS) were used to analyze inorganic elements and flavonoid metabolites, respectively. A combined analysis of the inorganic elements and flavonoid metabolites in FS was conducted to determine the patterns of FS quality formation. Sixteen inorganic elements and 173 flavonoid metabolites that accumulated at different developmental stages were identified. Notably, 54 flavonoid metabolites associated with the amelioration of major human diseases were identified, and Ca, P, K, Fe, and Cu were postulated to influence flavonoid metabolism and synthesis. This study offers a novel perspective and foundation for the further exploration of the rules governing the quality of plant materials.

Association between MC1R gene and coat color segregation in Shanxia long black pig and Lulai black pig.

BACKGROUND: Coat color, as a distinct phenotypic characteristic of pigs, is often subject to preference and selection, such as in the breeding process of new breed. Shanxia long black pig was derived from an intercross between Berkshire boars and Licha black pig sows, and it was bred as a paternal strain with high-quality meat and black coat color. Although the coat color was black in the F1 generation of the intercross, it segregated in the subsequent generations. This study aims to decode the genetic basis of coat color segregation and develop a method to distinct black pigs from the spotted in Shanxia long black pig. RESULTS: Only a QTL was mapped at the proximal end of chromosome 6, and MC1R gene was picked out as functional candidate gene. A total of 11 polymorphic loci were identified in MC1R gene, and only the c.67_68insCC variant was co-segregating with coat color. This locus isn't recognized by any restriction endonuclease, so it can't be genotyped by PCR-RFLP. The c.370G > A polymorphic locus was also significantly associated with coat color, and has been in tightly linkage disequilibrium with the c.67_68insCC. Furthermore, it is recognized by BspHI. Therefore, a PCR-RFLP method was set up to genotype this locus. Besides the 175 sequenced individuals, another more 1,391 pigs were genotyped with PCR-RFLP, and all of pigs with GG (one band) were black. CONCLUSION: MC1R gene (c.67_68insCC) is the causative gene (mutation) for the coat color segregation, and the PCR-RFLP of c.370G > A could be used in the breeding program of Shanxia long black pig.

Characteristics and potential biomarkers of flavor compounds in four Chinese indigenous chicken breeds.

Chinese indigenous chickens have a long history of natural and artificial selection and are popular for their excellent meat quality and unique flavor. This study investigated six meat quality-related traits in Ningdu yellow, Baier yellow, Kangle, and Shengze 901 chickens. Two-dimensional gas chromatography-time-of-flight mass spectrometry was used to detect unique flavors in 24 breast muscle samples from the same phenotyped chickens. Overall, 685, 618, 502, and 487 volatile organic compounds were identified in Ningdu yellow, Baier yellow, Kangle, and Shengze 901 chickens, respectively. The flavor components were separated into eight categories, including hydrocarbons and aldehydes. Multivariate analyses of the identified flavor components revealed some outstanding features of these breeds. For example, the hydrocarbons (22.09%) and aldehydes (14.76%) were higher in Ningdu yellow chickens and the highest content of N, N-dimethyl-methylamine was in Ningdu yellow, Baier yellow, and Shengze 901 chickens, indicating the maximum attribution to the overall flavor (ROAV = 439.57, 289.21, and 422.80). Furthermore, we found that 27 flavor compounds differed significantly among the four Chinese breeds, including 20 (e.g., 1-octen-3-ol), two (e.g., 2-methyl-naphthalene), four (e.g., 2,6-lutidine), and one (benzophenone) flavor components were showed significant enrichment in Ningdu yellow, Baier yellow, Kangle, and Shengze 901 chickens, respectively. The flavor components enriched in each breed were key biomarkers distinguishing breeds and most were significantly correlated with meat quality trait phenotypes. These results provide novel insights into indigenous Chinese chicken meat flavors.

Analgesic effects of perioperative acupuncture methods: A narrative review.

Postoperative pain occurs immediately after surgery. The most common perioperative analgesic methods are nerve block, patient-controlled intravenous analgesia, and patient-controlled epidural analgesia. However, overuse of opioid analgesics can cause many adverse reactions including excessive sedation, respiratory inhibition, postoperative nausea, and vomiting. In recent years, many clinical trials have shown that perioperative acupuncture has unique advantages in patients. Perioperative acupuncture can relieve intraoperative pain, improve postoperative pain management, reduce postoperative nausea and vomiting, and shorten the length of hospital stay. This study aimed to confirm the analgesic effect of perioperative acupuncture by reviewing studies on the different methods of perioperative acupuncture and their analgesic effects. The cited literature was searched in English and Chinese from PubMed, China National Knowledge Infrastructure, and Wanfang data, using the following keywords: "perioperative pain," "acupuncture," "electroacupuncture," and "perioperative analgesia." Studies published from 2005 to 2023 were included. All retrieved papers were read in detail. Perioperative acupuncture has benefits in reducing postoperative pain and opioid need. Although analgesic drugs are still the primary means of postoperative pain control, acupuncture provides a safe analgesic supplement or alternative. This review aimed to assist practitioners in choosing appropriate perioperative acupuncture methods by summarizing the recent literature on the role of different acupuncture approaches for perioperative pain management.

Multi-Omics Analysis Reveals the Resistance Mechanism and the Pathogens Causing Root Rot of Coptis chinensis.

Coptis chinensis is a traditional Chinese medicinal herb used for more than 2,000 years. Root rot in C. chinensis can cause brown discoloration (necrosis) in the fibrous roots and rhizomes, leading to plants wilting and dying. However, little information exists about the resistance mechanism and the potential pathogens of the root rot of C. chinensis plants. As a result, in order to investigate the relationship between the underlying molecular processes and the pathogenesis of root rot, transcriptome and microbiome analyses were performed on healthy and diseased C. chinensis rhizomes. This study found that root rot can lead to the significant reduction of medicinal components of Coptis, including thaliotrine, columbamine, epiberberin, coptisine, palmatine chloride, and berberine, affecting its efficacy quality. In the present study, Diaporthe eres, Fusarium avenaceum, and Fusarium solani were identified as the main pathogens causing root rot in C. chinensis. At the same time, the genes in phenylpropanoid biosynthesis, plant hormone signal transduction, plant-pathogen interaction, and alkaloid synthesis pathways were involved in the regulation of root rot resistance and medicinal component synthesis. In addition, harmful pathogens (D. eres, F. avenaceum and F. solani) also induce the expression of related genes in C. chinensis root tissues to reduce active medicinal ingredients. These results provide insights into the root rot tolerance study and pave the way for process disease resistance breeding and quality production of C. chinensis. IMPORTANCE Root rot disease significantly reduces the medicinal quality of Coptis chinensis. In the present study, results found that the C. chinensis fibrous and taproot have different tactics in response to rot pathogen infection. Diaporthe eres, Fusarium avenaceum, and Fusarium solani were isolated and identified to cause different degrees of C. chinensis root rot. These results are helpful for researchers to further explore the mechanism of resistance to rhizoma Coptis root rot.

Sevoflurane-induced POCD-associated exosomes delivered miR-584-5p regulates the growth of human microglia HMC3 cells through targeting BDNF.

BACKGROUND: Inhalation of sevoflurane can cause neuronal apoptosis, and cognitive disorders, inducing to the occurrence and progression of post operative cognitive dysfunction (POCD). This study aimed to explore the roles of sevoflurane-induced POCD-associated exosomes on HMC3 cells and its related mechanisms. METHODS: Exosomes were isolated from the plasma of sevoflurane-induced POCD or non-POCD patients, and were then sent for small RNA sequencing. Real-time quantitative PCR (RT-qPCR) was used to verify the sequencing results, and miR-584-5p was chosen for subsequent study. HMC3 cells were respectively transfected with POCD-derived exosomes and miR-584-5p mimics, and cell viability and apoptosis were measured. Dual-luciferase reporter gene assay was applied to confirm the target of miR-584-5p. RESULTS: After sequencing, 301 differentially expressed miRNAs were identified, including 184 up-regulated miRNAs and 117 down-regulated miRNAs, and were significantly enriched in 3577 GO terms and 121 KEGG pathways. Due to the high level of miR-584-5p in sevoflurane-treated POCD-derived exosomes, HMC3 cells with miR-584-5p enrichment were successfully established. Compared with the control group, POCD-derived exosomes and miR-584-5p significantly inhibited viability and promoted apoptosis of HMC3 cells (P < 0.05). The IL-1ß and TNF-α levels were significantly increased after POCD-derived exosomes and miR-584-5p mimics treatment compared to the control group (P < 0.05). Besides, POCD-derived exosomes and miR-584-5p mimics significantly down-regulated the expression levels of BDNF and p-TrkB, and up-regulated Caspase 3 and IL-1ß. Finally, BDNF was confirmed to be the target of miR-584-5p. CONCLUSIONS: Sevoflurane-induced POCD-associated exosomes delivered miR-584-5p may regulate the growth of HMC3 cells via targeting BDNF.

First report of stem rot of Scrophularia ningpoensis caused by Fusarium commune in China.

Chinese figwort (Scrophularia ningpoensis Hemsl.) is an important annual herb and its dried root tubers are used as a traditional Chinese herbal medicine. In May 2021, a disease with stem rot symptoms on S. ningpoensis was observed at three randomly selected fields (~0.67 ha per field) in Nanchuan district (28.93°N, 107.27°E) of Chongqing, China. Disease incidence was estimated between 10% and 17% based on calculating the proportion of symptomatic plants. Initially, watery dark brown spots appeared on the epidermis of the stem. Then the spots expanded into spindle or strip shape, and the center of lesions were sunken, constricted and rotted finally (Figure 1A and Figure 1B). Leaves turned yellow and the plants wilted (Figure 1C). The infected parts of the stem broke easily and became brittle. The number of daughter buds used for reproduction was reduced by more than 24% and the production of root tubers decreased by more than 3%. Twelve stems with typical rot symptoms were sampled from the three fields for further investigation. Infested tissue fragments (4×4 mm) were surface sterilized with 75% ethanol for 30s and 2% sodium hypochlorite for 2 minutes in turn, finally, were rinsed 4 times with sterilized water. The disinfected tissue were air-dried and transferred onto potato dextrose agar (PDA) in the dark for 6 days at 25℃. The resulting fungal colonies were isolated by the single-spore isolation technique (Fang. 1998). Six different fungal colonies were isolated (X1-X6) and Koch's postulates were conducted to verify the pathogenicity of individual isolates. The stem surfaces of 8 months old plants were sterilized with 75% ethanol for 30 s, rinsed three times with sterilized water, and stabbed with a sterilized needle. Conidial from the fungal colonies grown on PDA plate were harvested by filtration through five layers of sterilized absorbent gauze. Conidial concentration was then adjusted to 106 conidia per mL. 10 µL of conidial suspension was sprayed on stems injured with a sterile syringe. For each isolate, 6 plants were inoculated. Stems inoculated with sterilized water were used as a blank control. All plants were all put in a growth chamber at 28℃ with 75 to 80% relative humidity under a 12 h photoperiod for 15 days. The pathogenicity test was repeated once. After 13 days, the stems inoculated with X3 showed the same rot symptoms as we observed in the fields (Figure 1D) whereas the control stems remained symptomless (Figure 1E). The fungus re-isolated from the plants showing 100% symptoms had a similar morphology than X3 as described below. At the same time, the stems inoculated with X1, X2, X4, X5 and X6 showed no sign of rot. After culturing on PDA for 9 days under 25℃ in dark, isolate X3 grew all over the dish with white or pale pink pigmentation in the center (Figure 1F). Macroconidia were produced on synthetic low nutrient agar (SNA) plates, which showed sickle or spindle, 3 septate, straight to slightly curved with a foot-shaped basal cell, ranging from 17.595~44.88 × 2.04~3.315 µm (n=30). Microconidia were oval, elliptical or reniform, 0 to 1 septate, 3.06~12.75 ×1.785~2.805 µm (n=30) in size (Figure 1G). Phialides of conidiophores were cylindrical, short and monophialides or polyphialides (Figure 1H). Chlamydospores were found terminal or cluster with round or oblong (Figure 1I). These morphological characteristics described as Fusarium commone (Skovgaard et al. 2003). For molecular identification, the ribosomal internal transcribed spacer (ITS), translation elongation factor 1-alpha (EF-1α), RNA polymerase II subunit 1 (RPB1), the largest subunit of RNA polymerase Ⅱ gene sequences (RPB2) and the mitochondrial small subunit rDNA (mtSSU) genes were amplified with primers V9G /ITS4 (Hoog et al. 1998; White et al. 1990), EF1-668F /EF1-1251R (Alves et al. 2008), Fa/G2R (O'Donnell et al. 2010), 5f2/7cr (Liu et al. 1999; O'Donnell et al. 2010) and NMS1/NMS2 (Li et al. 1994). The sequences of isolate X3 were deposited in GenBank (MZ571935 (ITS), MZ576201 (EF-1α), MZ882396 (RPB1), MZ882397 (RPB2) and MZ867716 (mtSSU)). All sequences were revealed more than 99.8% sequence identity with reported sequences of Fusarium commune (GenBank accession No: KY630717, JF740838, KU171680, KU171700 and MK439851). Based on the optimal nucleotide replacement model SYM of multi-gene series sequence matrix, the system development tree was constructed. Results showed the strain X3 and those of F. commune (Isolates numbers were NRRL 28387, MRC 2566, MRC 2564 and CZ3-5-6) were clustered into the same evolutionary branch with a post-mortem probability of 0.996 (Figure 2). According to the morphology, molecular identification and phylogenetic analysis based on the concatenated of EF-1α and RPB2 genes sequences, the isolated X3 was identified as F. commune. The ITS sequences of X1, X2, X4, X5 and X6 showed homology exceeding 97.1% to Fusarium tricinctum (MH931273), Plectosphaerella cucumerina (MH858371), Sordariomycetes sp. (JX179237), Whalleya microplace (EF026129) and Pestalotiopsis maculiformans (EU552147), respectively, suggested the five strains to be these species possibly. GeneBank accession number of X1, X2, X4, X5 and X6 was OM074010, OM074011, OM074013, OM074015 and OM074018, respectively. To our best knowledge, this is the first report of F. commune infecting S. ningpoensis in China. Stem rot caused by F. commune is a severe threat to Chinese figwort cultivation, and identification of this pathogen is important for effective disease management and control.

Metabolomic analysis reveals dynamic changes in secondary metabolites of Sophora japonica L. during flower maturation.

Sophora japonica L. is widely consumed in China because of its medicinal and nutritional value. Its quality is greatly affected by the accumulation of metabolites, which varies with the stage of flower development. However, changes in the characteristics of the secondary metabolites during flower maturity remain unclear. Ultra-high-performance liquid chromatography coupled with electrospray ionization-triple quadrupole-linear ion trap mass spectrometry (UPLC-ESI-QTRAP-MS/MS) revealed dynamic changes in the secondary metabolites of S. japonica during the five flower-maturity stages. We monitored 331 metabolites and screened 164. The differential metabolites showed seven trends during flower maturation, with flavonoids and phenolic acids having the most varied expressions. Flower buds (S2-S3) are rich in flavonoids and are thus suitable for use in high-quality medicine or industrial extraction. Our study provides an empirical basis for the informed harvesting of S. japonica based on its mode of utilization.

Extensive evaluation of prediction performance for 15 pork quality traits using large scale VIS/NIRS data.

Visible and near-infrared spectroscopy (VIS/NIRS) has been extensively used in the livestock and food industries to quantify meat quality. Here, we collected VIS/NIRS data of 1206 pigs longissimus muscle, measured the corresponding 15 meat quality traits, and used seven models to predict these meat quality traits. The prediction performances of 7 models varied among predicted traits, with the Rcv2 of most traits above 0.9 in the best model. We have also established a new method, spectral-wide association analysis (SWAS), to select the feature wavelengths of measured traits. Results showed that the prediction performance is proportionate to the number of identified significant association wavelengths. We used the selected wavelengths to perform prediction again, and the prediction accuracy was similar to results with full wavelength using the best model, indicating effectiveness of feature wavelengths selection methods.

Self-Assembly Catalase Nanocomplex Conveyed by Bacterial Vesicles for Oxygenated Photodynamic Therapy and Tumor Immunotherapy.

Background: Photodynamic therapy (PDT) is an effective therapeutic modality that has been extensively studied in treatment of various cancers. However, issues with inadequate oxygen (O2) concentration in tumor tissue and inadequate immune response generation have hindered its successful application in tumor therapy. Methods: Firstly, the self-assembly nanocomplex (CAT-Ce6), which is composed of hydrophilic catalase and hydrophobic photosensitizer Chlorin e6 (Ce6), was fabricated to support oxygenated PDT. Secondly, for supplying PDT with enhanced antitumoral immunity, CAT-Ce6 was coated with PD-L1 antibody modified-attenuated Salmonella outer membrane vesicles (OMV-aPDL1). Finally, the catalytic activity, tumor targeting, hypoxia ameliorating, immune effect initiating and anti-tumor capacities of the integral nanosystem CAT-Ce6@OMV-aPDL1 were evaluated systematically. Results: The self-assembly nanocomplex (CAT-Ce6) generated sufficient O2 and promoted the solubility of Ce6 simultaneously, which enhanced PDT significantly. OMV-aPDL1 inherited most of the immunogenic membrane-associated components from the parent bacteria, possessing immunomodulation ability for immunosuppressive tumor microenvironment reprogramming and reducing immune escape. The obtained nanosystem CAT-Ce6@OMV-aPDL1 durably relieved hypoxia, resulting in amplifying PDT-mediated cytotoxicity to generate a pool of tumor-associated antigens, stimulating anti-tumor immune responses and even inducing an immune memory effect, which inhibited tumor development efficiently. Conclusion: The resultant CAT-Ce6@OMV-aPDL1 displays excellent efficacy of PDT and immunotherapy to achieve antitumor effects, which provides a new avenue for combinatorial therapy against various cancers.

Enzyme-Loaded Catalytic Macrophage Vesicles with Cascade Amplification of Tumor-Targeting for Oxygenated Photodynamic Therapy.

BACKGROUND: Realizing that the potential of photodynamic therapy (PDT) is hindered by hypoxic microenvironment of tumor section, it is desirable to provide a cascade oxygenation strategy to enhance PDT. METHODS: The hydrophilic catalase protein was covalently linked to the hydrophobic photosensitizer Ce6 to form the nanocomplex Catalase-Ce6 with self-assembly. And the Catalase-Ce6 was loaded in the M1 macrophage vesicles (EVs) with GOX-modified to construct the nanosystem Catalase-Ce6@MEVs. The synergistic effects of PDT induced by Catalase-Ce6@MEVs were evaluated on the subcutaneous MFC tumor model. RESULTS: The construction of Catalase-Ce6 not only solved the insoluble problem of Ce6, but also induced a cascade effects for hydrolyzing glucose and increasing the hydrogen peroxide content, achieving the purpose of oxygenated PDT. Cascade tumor targeting was also realized through the binding between vascular cell adhesion molecule 1 (VCAM-1) of tumor tissue and α4 integrin of EVs and enhanced vascular permeability, triggering by PDT. Besides, in vivo experiments found that the Catalase-Ce6@MEVs presented M2 macrophage polarization effect. CONCLUSION: Catalase-Ce6@MEVs exhibit the cascade targeting ability after laser irradiation and prominent tumor treatment effect in vivo, which may provide new ideas and methods for targeted PDT in clinical practice.

FAT10 stimulates the development of osteosarcoma by regulating the JAK/STAT signaling pathway.

PURPOSE: To investigate the potential function of FAT10 in the development of osteosarcoma (OS) and its mechanism. METHODS: Relative level of FAT10 in OS specimens and cell lines was detected by qRT-PCR. The correlation between FAT10 level and clinical features of OS patients was assessed by χ2 test. After intervention of FAT10 in MG-63 and U2OS cells, changes of FAT10 level, cell viability, clonality and proliferative capacity were respectively detected by qRT-PCR, CCK-8, colony formation and EdU assay. Moreover, dynamic change of FAT10 in OS cells induced with pro-inflammatory factors was examined by qRT-PCR. Protein levels of FAT10, p-STAT1, p-STAT3 and p-STAT5 in OS cells induced with TNF-α were determined by Western blot. The JAK2 inhibitor AZ960 was used to further confirm the role of the JAK signaling in FAT10-regulated development of OS. RESULTS: FAT10 was upregulated in OS specimens and cell lines, which was correlated to tumor size, WHO grade and distant metastasis of OS patients. Knockdown of FAT10 inhibited viability, clonality and proliferative capacity of MG-63 and U2OS cells. FAT10 was time-dependently upregulated in OS cells stimulated with IFN-γ and TNF-α, which was dose-dependently downregulated by the treatment of AZ960. Protein levels of FAT10, p-STAT1, p-STAT3 and p-STAT5 in OS cells induced with AZ960 were remarkably downregulated. CONCLUSION: FAT10 is upregulated in OS samples, which stimulates the development of OS by activating the JAK/STAT signaling pathway.