Attenuative effects of collagen peptide from milkfish (Chanos chanos) scales on ovariectomy-induced osteoporosis.

Osteoporosis is characterized by low bone mass, bone microarchitecture disruption, and collagen loss, leading to increased fracture risk. In the current study, collagen peptides were extracted from milkfish scales (MS) to develop potential therapeutic candidates for osteoporosis. MS was used to synthesize a crude extract of fish scales (FS), collagen liquid (COL), and hydroxyapatite powder (HA). COL samples were further categorized according to the peptide size of total COL (0.1 mg/mL), COL < 1 kDa (0.1 mg/mL), COL: 1-10 kDa (0.1 mg/mL), and COL > 10 kDa (0.1 mg/mL) to determine it. Semi-quantitative reverse transcription polymerase chain reaction (sqRT-PCR) and immunofluorescence labeling were used to assess the expression levels of specific mRNA and proteins in vitro. For in vivo studies, mice ovariectomy (OVX)-induced postmenopausal osteoporosis were developed, while the sham surgery (Sham) group was treated as a control. Collagen peptides (CP) from MS inhibited osteoclast differentiation in RAW264.7 cells following an insult with nuclear factor kappa-B ligand (RANKL). CP also enhanced osteoblast proliferation in MG-63 cells, possibly through downregulating NFATc1 and TRAP mRNA expression and upregulating ALP and OPG mRNA levels. Furthermore, COL1 kDa also inhibited bone density loss in osteoporotic mice. Taken together, CP may reduce RANKL-induced osteoclast activity while promoting osteoblast synthesis, and therefore may act as a potential therapeutic agent for the prevention and control of osteoporosis.

Mucin-mediated mucosal retention via end-terminal modified Pluronic F127-based hydrogel to increase drug accumulation in the lungs.

Noninvasive lung drug delivery is critical for treating respiratory diseases. Pluronic-based copolymers have been used as multifunctional materials for medical and biological applications. However, the Pluronic F127-based hydrogel is rapidly degraded, adversely affecting the mechanical stability for prolonged drug release. Therefore, this study designed two thermosensitive copolymers by modifying the Pluronic F127 terminal groups with carboxyl (ADF127) or amine groups (EDF127) to improve the viscosity and storage modulus of drug formulations. ß-alanine and ethylenediamine were conjugated at the terminal of Pluronic F127 using a two-step acetylation process, and the final copolymers were characterized using 1H nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectra. According to the 1H NMR spectra, Pluronic F127 was functionalized to form ADF127 and EDF127 with 85 % and 71 % functionalization degrees, respectively. Rheological studies revealed that the ADF127 (15 wt%) and EDF127 (15 wt%) viscosities increased from 1480 Pa.s (Pluronic F127) to 1700 Pa.s and 1800 Pa.s, respectively. Furthermore, the elastic modulus of ADF127 and EDF127 increased, compared with that of native Pluronic F127 with the addition of 5 % mucin, particularly for ADF127, thereby signifying the stronger adhesive nature of ADF127 and EDF127 with mucin. Additionally, ADF127 and EDF127 exhibited a decreased gelation temperature, decreasing from 33 °C (Pluronic F127 at 15 wt%) to 24 °C. Notably, the in vitro ADF127 and EDF127 drug release was prolonged (95 %; 48 h) by the hydrogel encapsulation of the liposome-Bdph combined with mucin, and the intermolecular hydrogen bonding between the mucin and the hydrogel increased the retention time and stiffness of the hydrogels. Furthermore, ADF127 and EDF127 incubated with NIH-3T3 cells exhibited biocompatibility within 2 mg/mL, compared with Pluronic F127. The nasal administration method was used to examine the biodistribution of the modified hydrogel carrying liposomes or exosomes with fluorescence using the IVIS system. Drug accumulation in the lungs decreased in the following order: ADF127 > EDF127 > liposomes or exosomes alone. These results indicated that the carboxyl group-modified Pluronic F127 enabled well-distributed drug accumulation in the lungs, which is beneficial for intranasal administration routes in treating diseases such as lung fibrosis.

Efficiency of PGK1 proteins delivered to the brain via a liposomal system through intranasal route administration for the treatment of spinocerebellar ataxia type 3.

A patient-friendly and efficient treatment method for patients with spinocerebellar ataxia type 3 (SCA3) was provided through a nose-to-brain liposomal system. Initially, PGK1 was overexpressed in HEK 293-84Q-GFP diseased cells (HEK 293-84Q-GFP-PGK1 cells) to confirm its effect on the diseased protein polyQ. A decrease in polyQ expression was demonstrated in HEK 293-84Q-GFP-PGK1 cells compared to HEK 293-84Q-GFP parental cells. Subsequently, PGK1 was encapsulated in a liposomal system to evaluate its therapeutic efficiency in SCA3. The optimized liposomes exhibited a significantly enhanced positive charge, facilitating efficient intracellular protein delivery to the cells. The proteins were encapsulated within the liposomes using an optimized method involving a combination of heat shock and sonication. The liposomal system was further demonstrated to be deliverable to the brain via intranasal administration. PGK1/liposomes were intranasally delivered to SCA3 mice, which subsequently exhibited an amelioration of motor impairment, as assessed via the accelerated rotarod test. Additionally, fewer shrunken morphology Purkinje cells and a reduction in polyQ expression were observed in SCA3 mice that received PGK1/liposomes but not in the untreated, liposome-only, or PGK1-only groups. This study provides a non-invasive route for protein delivery and greater delivery efficiency via the liposomal system for treating neurodegenerative diseases.

Preconditioning of exosomes derived from human olfactory ensheathing cells improved motor coordination and balance in an SCA3/MJD mouse model: A new therapeutic approach.

Exosome therapy is a novel trend in regeneration medicine. However, identifying a suitable biomarker that can associate the therapeutic efficacy of exosomes with SCA3/MJD is essential. In this study, parental cells were preconditioned with butylidenephthalide (Bdph) for exosome preparation to evaluate the therapeutic effect of SCA3/MJD. The therapeutic agent hsa-miRNA-6780-5p was enriched up to 98-fold in exosomes derived from butylidenephthalide (Bdph)-preconditioned human olfactory ensheathing cells (hOECs) compared with that in naïve hOECs exosomes. The particle sizes of exosomes derived from naïve hOECs and those derived from hOECs preconditioned with Bdph were approximately 113.0 ± 3.5 nm and 128.9 ± 0.7 nm, respectively. A liposome system was used to demonstrate the role of hsa-miRNA-6780-5p, wherein hsa-miRNA-6780-5p was found to enhance autophagy and inhibit the expression of spinocerebellar ataxia type 3 (SCA3) disease proteins with the polyglutamine (polyQ) tract. Exosomes with enriched hsa-miRNA-6780-5p were further applied to HEK-293-84Q cells, leading to decreased expression of polyQ and increased autophagy. The results were reversed when 3MA, an autophagy inhibitor, was added to the cells treated with hsa-miRNA-6780-5p-enriched exosomes, indicating that the decreased polyQ expression was modulated via autophagy. SCA3 mice showed improved motor coordination behavior when they intracranially received exosomes enriched with hsa-miRNA-6780-5p. SCA3 mouse cerebellar tissues treated with hsa-miRNA-6780-5p-enriched exosomes showed decreased expression of polyQ and increased expression of LC3II/I, an autophagy marker. In conclusion, our findings can serve as a basis for developing an alternative therapeutic strategy for SCA3 disease treatment using miRNA-enriched exosomes derived from chemically preconditioned cells.

Application of Internet of Things to Agriculture-The LQ-FieldPheno Platform: A High-Throughput Platform for Obtaining Crop Phenotypes in Field.

The lack of efficient crop phenotypic measurement methods has become a bottleneck in the field of breeding and precision cultivation. However, high-throughput and accurate phenotypic measurement could accelerate the breeding and improve the existing cultivation management technology. In view of this, this paper introduces a high-throughput crop phenotype measurement platform named the LQ-FieldPheno, which was developed by China National Agricultural Information Engineering Technology Research Centre. The proposed platform represents a mobile phenotypic high-throughput automatic acquisition system based on a field track platform, which introduces the Internet of Things (IoT) into agricultural breeding. The proposed platform uses the crop phenotype multisensor central imaging unit as a core and integrates different types of equipment, including an automatic control system, upward field track, intelligent navigation vehicle, and environmental sensors. Furthermore, it combines an RGB camera, a 6-band multispectral camera, a thermal infrared camera, a 3-dimensional laser radar, and a deep camera. Special software is developed to control motions and sensors and to design run lines. Using wireless sensor networks and mobile communication wireless networks of IoT, the proposed system can obtain phenotypic information about plants in their growth period with a high-throughput, automatic, and high time sequence. Moreover, the LQ-FieldPheno has the characteristics of multiple data acquisition, vital timeliness, remarkable expansibility, high-cost performance, and flexible customization. The LQ-FieldPheno has been operated in the 2020 maize growing season, and the collected point cloud data are used to estimate the maize plant height. Compared with the traditional crop phenotypic measurement technology, the LQ-FieldPheno has the advantage of continuously and synchronously obtaining multisource phenotypic data at different growth stages and extracting different plant parameters. The proposed platform could contribute to the research of crop phenotype, remote sensing, agronomy, and related disciplines.

The efficacy of modified binding technique for renorrhaphy during robotic partial nephrectomy: surgical and functional outcomes from single-center experience.

BACKGROUND: To compare the traditional single-layer and double-layer suture renorrhaphy with modified "Binding" suture renorrhaphy (whole rim of the wound was closed by the all-layer flow suture starting from the parenchyma cut edges to hilum, followed by the final defect closure) in robotic partial nephrectomy (RPN) for treating localized renal cell carcinoma in our large institutional experience. METHODS: We retrospectively reviewed clinical data of 406 consecutive patients who underwent RPN from May 2018 and December 2020 in our center. The demographic and oncologic outcome variables were compared between different renal reconstruction groups and the effect of these suture techniques on renal function outcomes was also evaluated. RESULTS: For the single-layer group, median operative time and warm ischemic time were significantly less than that of the double-layer and "Binding" groups (p < 0.001), while the significantly lower eGFR drop (p = 0.014) was also detected within postoperative 3 months from baseline, but this difference lost its statistical significance from 3th month to the last follow-up. The changes in postoperative creatinine values were clinically insignificant among the three groups. In a sub-analysis over 258 patients with moderate/high nephrometry score, those patients who underwent "Binding" suture had an undifferentiated warm ischemic time, estimated blood loss, and length of hospitalization stay with a decreased risk of Grade III complications (postoperative hemorrhage requiring intervention) and improved renal function recovery during the whole follow-up. CONCLUSION: Single-layer suture renorrhaphy may be associated with better renal functional preservation and could prove to be reliable in patients with low-complexity tumor (RENAL score ≤ 6). Patients with moderate/high-complexity tumor (RENAL score ≥ 7) might represent a subgroup of patients having a functional benefit after "Binding" suture renorrhaphy even in the long-term period.

[Expression and significance analysis of GDF3 in testicular cancer based on TCGA and GTEx databases].

OBJECTIVE: To investigate the expression and significance of GDF3 in testicular cancer through bioinformatics analysis. METHODS: Using the TCGA and GTEx databases, differential expression analysis and pan-cancer analysis were performed to identify the target gene GDF3, and the clinical relevance of GDF3 in testicular cancer was analyzed using the UALCAN database. Based on the R packages "org.Hs.eg.db" and "clusterProfiler," gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore the potential functions of GDF3 in testicular cancer. The correlation of GDF3 with immune chemokines and immune inhibitors in testicular cancer was investigated using the TISIDB database. RESULTS: The GDF3 was significantly upregulated in testicular cancer (P<0.001) and closely associated with clinical staging (P<0.05) and tumor subtypes (P<0.001). The immune-related analysis revealed that GDF3 was strongly correlated with immune chemokines CCL26 (rho=0.599, P<0.001), CCL7 (rho=0.525, P<0.001), immune inhibitor ADORA2A (rho=0.723, P<0.001), and PVRL2 (rho=0.585, P<0.001). CONCLUSION: The GDF3 is closely related to the occurrence, development, and immune microenvironment of testicular cancer.

Anti-Inflammatory and Chondro-Protective Effects of Acidic Polysaccharide from Enteromorpha Prolifera in Experimental Models of Osteoarthritis In-Vitro and In-Vivo.

OBJECTIVE: Osteoarthritis (OA) progression has been shown to increase the expression of inflammatory cytokines in joints, leading to the destruction of cartilage matrix. Interleukin (IL)-1ß is a potent inflammatory cytokine associated with osteoarthritic synovial fluid. The protective effects of polysaccharides from Enteromorpha prolifera against acute hepatic injury was reported. DESIGN: In this study, we examined the effects of Enteromorpha polysaccharide extracts (EPEs) in the treatment of OA. The effects of the EPEs were assessed using an IL-1ß-stimulated SW1353 and SW982 cells. The expression levels of specific mRNA and proteins were evaluated using semi-quantitative reverse transcription polymerase chain reaction (sqRT-PCR) and western immunoblotting. An OA animal study involving C57BL/6J mice was also conducted to assess the effects on tactile sensitivity and anterior cruciate ligament transection (ACLT). RESULTS: Acidic polysaccharide extract (APE) was shown to significantly reduce cytokine and chemokine mRNA levels in IL-1ß-stimulated SW1353 and SW982 cells and attenuate the expression of proinflammatory cytokines and p38/AP-1 in SW1353 cells. APE was also shown to minimize the effect of osteolytic lesions in the knee joints of ACLT-induced osteoarthritic mice. CONCLUSIONS: APE is a potent inhibitor of joint degeneration associated with OA.

Predicting Hypnotic Use among Insomnia Patients with the Theory of Planned Behavior and Craving.

While long-term hypnotic use is very common in clinical practice, the associated factors have been understudied. This study aims to explore the cognitive factors that might influence the long-term use of hypnotics based on the theory of planned behavior (TPB), and examines the moderating effect of craving between cognitive intention and actual hypnotic-use behavior at follow-up. A total of 139 insomnia patients completed a self-constructed TPB questionnaire to measure their attitude, subjective norm, perceived behavioral control, and behavioral intention of hypnotic use, as well as the Hypnotic-Use Urge Scale (HUS) to measure their craving for hypnotics. They were then contacted through phone approximately three months later to assess their hypnotic use. Hierarchical regression showed that perceived behavioral control was the most significant determinant for behavioral intention of hypnotic use. Behavioral intention, in turn, can predict the frequency of hypnotic use after three months. However, this association was moderated by hypnotic craving. The association was lower among the participants with higher cravings for hypnotic use. The findings suggest that the patients' beliefs about their control over sleep and daily life situations, and their craving for hypnotics should be taken into consideration in the management of hypnotic use.

Hyperspectral Technique Combined With Deep Learning Algorithm for Prediction of Phenotyping Traits in Lettuce.

The currently available methods for evaluating most biochemical traits of plant phenotyping are destructive and have extremely low throughput. However, hyperspectral techniques can non-destructively obtain the spectral reflectance characteristics of plants, which can provide abundant biophysical and biochemical information. Therefore, plant spectra combined with machine learning algorithms can be used to predict plant phenotyping traits. However, the raw spectral reflectance characteristics contain noise and redundant information, thus can easily affect the robustness of the models developed via multivariate analysis methods. In this study, two end-to-end deep learning models were developed based on 2D convolutional neural networks (2DCNN) and fully connected neural networks (FCNN; Deep2D and DeepFC, respectively) to rapidly and non-destructively predict the phenotyping traits of lettuces from spectral reflectance. Three linear and two nonlinear multivariate analysis methods were used to develop models to weigh the performance of the deep learning models. The models based on multivariate analysis methods require a series of manual feature extractions, such as pretreatment and wavelength selection, while the proposed models can automatically extract the features in relation to phenotyping traits. A visible near-infrared hyperspectral camera was used to image lettuce plants growing in the field, and the spectra extracted from the images were used to train the network. The proposed models achieved good performance with a determination coefficient of prediction ( R p 2 ) of 0.9030 and 0.8490 using Deep2D for soluble solids content and DeepFC for pH, respectively. The performance of the deep learning models was compared with five multivariate analysis method. The quantitative analysis showed that the deep learning models had higher R p 2 than all the multivariate analysis methods, indicating better performance. Also, wavelength selection and different pretreatment methods had different effects on different multivariate analysis methods, and the selection of appropriate multivariate analysis methods and pretreatment methods increased more time and computational cost. Unlike multivariate analysis methods, the proposed deep learning models did not require any pretreatment or dimensionality reduction and thus are more suitable for application in high-throughput plant phenotyping platforms. These results indicate that the deep learning models can better predict phenotyping traits of plants using spectral reflectance.

Combination of ovalbumin-coated iron oxide nanoparticles and poly(amidoamine) dendrimer-cisplatin nanocomplex for enhanced anticancer efficacy.

Enhancement of drug efficacy is essential in cancer treatment. The immune stimulator ovalbumin (Ova)-coated citric acid (AC-)-stabilized iron oxide nanoparticles (AC-IO-Ova NPs) and enhanced permeability and retention (EPR)-based tumor targeted 4.5 generation poly(amidoamine) dendrimer(4.5GDP)-cisplatin (Cis-pt) nanocomplex (NC) (4.5GDP-Cis-pt NC) were used for enhanced anticancer efficiency. The formations of 4.5GDP-Cis-pt NC, AC-IO, and AC-IO-Ova NPs were examined via FTIR spectroscopy, X-ray diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy. The conjugation of Cis-pt with 4.5GDP was confirmed using carbon NMR spectroscopy. The tumor-specific 4.5GDP-Cis-pt NC provided 45%and 28% cumulative cisplatin release in 72 h at pH 6.5 and 7.4, respectively. A significant immune response with high TNF-α and IL-6 cytokine secretion was confirmed for the co-incubation of AC-IO-Ova with RAW 264.7 or HaCaT cells. AC-IO-Ova NPs were biocompatible with different cell lines, even at a high concentration (200 µg mL-1). However, AC-IO-Ova NPs mixed with 4.5GDP-Cis-pt NC (Cis-pt at 15 µg mL-1) significantly increased the cytotoxicity against the cancer cells in a dose-dependent manner with the increasing AC-IO-Ova NPs concentrations. The increased anticancer effects may be attributed to the generation of reactive oxygen species (ROS). Moreover, AC-IO-Ova NPs might assist the efficiency of anticancer cells, inducing an innate immune response via M1 macrophage polarization. We provide a novel synergistic chemoimmunotherapeutic strategy to enhance the anticancer efficacy of cisplatin via a chemotherapeutic agent 4.5GDP-Cis-pt NC and induce proinflammatory cytokines stimulating innate immunity through AC-IO-Ova NPs against tumors.

Matrix Metalloprotease-7 Mediates Nucleolar Assembly and Intra-nucleolar Cleaving p53 in Gefitinib-Resistant Cancer Stem Cells.

The enlarged distinct bulky-ball-like nucleolus matrix assembly is observed in most cancer stem cells (CSCs); however, the underlying mechanism is largely unknown. We show that matrix metalloproteinase-7 (MMP-7) shedding MUC-1 SEA domain releases MUC-1 C-ter, facilitating the nucleolus trafficking of p53 in gefitinib-resistant lung CSCs. The nucleolus colocalizations of p53, MUC-1 C-ter, MMP-7 and nucleolin were observed in the CD34+ CXADR+ CD44v3 + gefitinib-resistant EGFRL858R/T790M CSC colonies. MUC-1 C-ter induced a unique porous bulky-ball-shaped, cagelike nucleolus that functions as a nucleus molecular "garage" for potent tumor suppressor, p53. Nucleolus could also facilitate the novel sub-nucleus compartment for proteolytic processing p53 by MMP-7 to generate a 35 kDa fragment. Moreover, we show that salinomycin, an anti-CSC agent, disrupts nucleolus by inducing nucleoplasm translocation of p53 and sensitizing CSC to chemotherapy drugs. Thus, this study highlights the MMP-7-MUC-1-p53 axis in nucleolus as a potential therapeutic target for anti-CSCs to resolve the chemotherapy-resistance dilemma.

Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability in Brain.

Although butylidenephthalide (BP) is an efficient anticancer drug, its poor bioavailability renders it ineffective for treating drug-resistant brain tumors. However, this problem is overcome through the use of noninvasive delivery systems, including intranasal administration. Herein, the bioavailability, drug stability, and encapsulation efficiency (EE, up to 95%) of BP were improved by using cyclodextrin-encapsulated BP in liposomal formulations (CDD1). The physical properties and EE of the CDD1 system were investigated via dynamic light scattering, transmission electron microscopy, UV-Vis spectroscopy, and nuclear magnetic resonance spectroscopy. The cytotoxicity was examined via MTT assay, and the cellular uptake was observed using fluorescence microscopy. The CDD1 system persisted for over 8 h in tumor cells, which was a considerable improvement in the retention of the BP-containing cyclodextrin or the BP-containing liposomes, thereby indicating a higher BP content in CDD1. Nanoscale CDD1 formulations were administered intranasally to nude mice that had been intracranially implanted with temozolomide-resistant glioblastoma multiforme cells, resulting in increased median survival time. Liquid chromatography-mass spectrometry revealed that drug biodistribution via intranasal delivery increased the accumulation of BP 10-fold compared to oral delivery methods. Therefore, BP/cyclodextrin/liposomal formulations have potential clinical applications for treating drug-resistant brain tumors.

Non-Destructive Detection of Strawberry Quality Using Multi-Features of Hyperspectral Imaging and Multivariate Methods.

Soluble solid content (SSC), pH, and vitamin C (VC) are considered as key parameters for strawberry quality. Spectral, color, and textural features from hyperspectral reflectance imaging of 400-1000 nm was to develop the non-destructive detection approaches for SSC, pH, and VC of strawberries by integrating various multivariate methods as partial least-squares regression (PLSR), support vector regression, and locally weighted regression (LWR). SSC, pH, and VC of 120 strawberries were statistically analyzed to facilitate the partitioning of data sets, which helped optimize the model. PLSR, with spectral and color features, obtained the optimal prediction of SSC with determination coefficient of prediction (Rp2) of 0.9370 and the root mean square error of prediction (RMSEP) of 0.1145. Through spectral features, the best prediction for pH was obtained by LWR with Rp2 = 0.8493 and RMSEP = 0.0501. Combination of spectral and textural features with PLSR provided the best results of VC with Rp2 = 0.8769 and RMSEP = 0.0279. Competitive adaptive reweighted sampling and uninformative variable elimination (UVE) were used to select important variables from the above features. Based on the important variables, the accuracy of SSC, pH, and VC prediction both gain the promotion. Finally, the distribution maps of SSC, pH, and VC over time were generated, and the change trend of three quality parameters was observed. Thus, the proposed method can nondestructively and accurately determine SSC, pH, and VC of strawberries and is expected to design and construct the simple sensors for the above quality parameters of strawberries.

Identifying Therapeutic Targets for Spinocerebellar Ataxia Type 3/Machado-Joseph Disease through Integration of Pathological Biomarkers and Therapeutic Strategies.

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a progressive motor disease with no broadly effective treatment. However, most current therapies are based on symptoms rather than the underlying disease mechanisms. In this review, we describe potential therapeutic strategies based on known pathological biomarkers and related pathogenic processes. The three major conclusions from the current studies are summarized as follows: (i) for the drugs currently being tested in clinical trials; a weak connection was observed between drugs and SCA3/MJD biomarkers. The only two exceptions are the drugs suppressing glutamate-induced calcium influx and chemical chaperon. (ii) For most of the drugs that have been tested in animal studies, there is a direct association with pathological biomarkers. We further found that many drugs are associated with inducing autophagy, which is supported by the evidence of deficient autophagy biomarkers in SCA3/MJD, and that there may be more promising therapeutics. (iii) Some reported biomarkers lack relatively targeted drugs. Low glucose utilization, altered amino acid metabolism, and deficient insulin signaling are all implicated in SCA3/MJD, but there have been few studies on treatment strategies targeting these abnormalities. Therapeutic strategies targeting multiple pathological SCA3/MJD biomarkers may effectively block disease progression and preserve neurological function.

Exosomes in clinical trial and their production in compliance with good manufacturing practice.

Exosomes, 60-200-nm extracellular vesicles secreted from cells, have been used as an active pharmaceutical ingredient or drug carrier in disease treatment. Human- and plant-derived exosomes are registered in clinical trials, but more complete reports are available for human-derived exosomes. Because exosomes act as vesicles and carry cell secreting components, they have been used as drug or peptide vehicles to treat diseases. The dendritic cells (DCs) and mesenchymal stem cells (MSCs) are two popular cell sources for exosome preparation. Exosomes from DCs can initiate inflammation in patients, particularly in patients with cancer, as they contain the tumor antigen to induce specific inflammation response. A well-established cell bank of MSCs is available, and these cells can be used as an alternative source for exosome preparation. The major application of MSC-derived exosomes is in inflammation treatment. Exosomes in clinical trials need to comply with good manufacturing practice (GMP). Three important issues are prevalent in GMP for exosomes, i.e., upstream of cell cultivation process, downstream of the purification process, and exosome quality control. This paper concisely reviews exosome development, including exosome generation and clinical trial application.

SOX2 for Stem Cell Therapy and Medical Use: Pros or Cons?

Stem cell transplantation is a fast-developing technique, which includes stem cell isolation, purification, and storage, and it is in high demand in the industry. In addition, advanced applications of stem cell transplantation, including differentiation, gene delivery, and reprogramming, are presently being studied in clinical trials. In contrast to somatic cells, stem cells are self-renewing and have the ability to differentiate; however, the molecular mechanisms remain unclear. SOX2 (sex-determining region Y [SRY]-box 2) is one of the well-known reprogramming factors, and it has been recognized as an oncogene associated with cancer induction. The exclusion of SOX2 in reprogramming methodologies has been used as an alternative cancer treatment approach. However, the manner by which SOX2 induces oncogenic effects remains unclear, with most studies demonstrating its regulation of the cell cycle and no insight into the maintenance of cellular stemness. For controlling certain critical pathways, including Shh and Wnt pathways, SOX2 is considered irreplaceable and is required for the normal functioning of stem cells, particularly neural stem cells. In this report, we discussed the functions of SOX2 in both stem and cancer cells, as well as how this powerful regulator can be used to control cell fate.

Hyperspectral imaging for accurate determination of rice variety using a deep learning network with multi-feature fusion.

The phenomena of rice adulteration and shoddy rice arise continuously in high-quality rice and reduce the interests of producers, consumers and traders. Hyperspectral imaging (HSI) was conducted to determine rice variety using a deep learning network with multiple features, namely, spectroscopy, texture and morphology. HSI images of 10 representative high-quality rice varieties in China were measured. Spectroscopy and morphology were extracted from HSI images and binary images in region of interest, respectively. And texture was obtained from the monochromatic images of characteristic wavelengths which were highly correlated with rice varieties. A deep learning network, namely principal component analysis network (PCANet), was adopted with these features to develop classification models for determining rice variety, and machine learning methods as K-nearest neighbour and random forest were used to compare with PCANet. Meanwhile, multivariate scatter correction, standard normal variate, Savitzky-Golay smoothing and Savitzky-Golay's first-order were applied to eliminate spectral interference, and principal component analysis (PCA) was performed to obtain the main information of high-dimensional features. Multi-feature fusion improved recognition accuracy, and PCANet demonstrated considerable advantage in classification performance. The best result was achieved by PCANet with PCA-processed spectroscopic and texture features with correct classification rates of 98.66% and 98.57% for the training and prediction sets, respectively. In summary, the proposed method provides an accurate identification of rice variety and can be easily extended to the classification, attribution and grading of other agricultural products.

The Versatile Role of Matrix Metalloproteinase for the Diverse Results of Fibrosis Treatment.

Fibrosis is a type of chronic organ failure, resulting in the excessive secretion of extracellular matrix (ECM). ECM protects wound tissue from infection and additional injury, and is gradually degraded during wound healing. For some unknown reasons, myofibroblasts (the cells that secrete ECM) do not undergo apoptosis; this is associated with the continuous secretion of ECM and reduced ECM degradation even during de novo tissue formation. Thus, matrix metalloproteinases (MMPs) are considered to be a potential target of fibrosis treatment because they are the main groups of ECM-degrading enzymes. However, MMPs participate not only in ECM degradation but also in the development of various biological processes that show the potential to treat diseases such as stroke, cardiovascular diseases, and arthritis. Therefore, treatment involving the targeting of MMPs might impede typical functions. Here, we evaluated the links between these MMP functions and possible detrimental effects of fibrosis treatment, and also considered possible approaches for further applications.

Antibiotic resistance of clinical isolates of Clostridioides difficile in China and its association with geographical regions and patient age.

It is known that antibiotic usage is associated with the development of Clostridioides difficile infection (CDI), especially clindamycin, third-generation cephalosporins, and fuoroquinolones. Antibiotic resistance rates to many antibiotics varies a lot by study. We performed a study focused on antibiotic resistance in clinical isolates of C. difficile from more widespread geographic regions across China. Of 319 C. difficile isolates tested against 11 antibiotics, 313 (98.1%) were resistant to at least one antibiotic. The highest rate of resistance was to ciprofloxacin, clindamycin, and erythromycin across all age groups, similar to previous studies. However, all isolates were susceptible to metronidazole and vancomycin. Overall the resistance rate to tested antibiotics was lower than other reports in China except for chloramphenicol and meropenem. Genotype ST37/RT017 in clade 4 was resistant to more antibiotics than other types. Unexpectedly, RT078 isolates in this study were susceptible to almost all tested antibiotics. In addition, the proportion of multi-drug resistant (MDR) isolates observed (17%) in this study was much lower than several European studies (up to 55%) and a previous study in China (78%). Although isolates from patients aged between 65 and 85 were more resistant to antibiotics in comparison to other age groups, MDR isolates were still detected in children below 2-years of age. The highest percentage of MDR isolates was determined in South China, an area that is most developed economically. The clade 4, RT017 (ST37) has been associated with outbreaks in Europe and North America and is responsible for most C. difficile infections (CDIs) in Asia. In addition, RT017 is often clindamycin and fluoroquinolone resistant. This study provided a relatively comprehensive description of antibiotic resistance of C. difficile in China, and further elucidates the epidemiology and antibiotic resistance of clinical isolates of C. difficile in China at a national level.