Fangyukangsuan granules ameliorate hyperuricemia and modulate gut microbiota in rats.

Hyperuricaemia (HUA) is a metabolic disorder characterised by high blood uric acid (UA) levels; moreover, HUA severity is closely related to the gut microbiota. HUA is also a risk factor for renal damage, diabetes, hypertension, and dyslipidaemia; however, current treatments are associated with detrimental side effects. Alternatively, Fangyukangsuan granules are a natural product with UA-reducing properties. To examine their efficacy in HUA, the binding of small molecules in Fangyukangsuan granules to xanthine oxidase (XOD), a key factor in UA metabolism, was investigated via molecular simulation, and the effects of oral Fangyukangsuan granule administration on serum biochemical indices and intestinal microorganisms in HUA-model rats were examined. Overall, 24 small molecules in Fangyukangsuan granules could bind to XOD. Serum UA, creatinine, blood urea nitrogen, and XOD levels were decreased in rats treated with Fangyukangsuan granules compared to those in untreated HUA-model rats. Moreover, Fangyukangsuan granules restored the intestinal microbial structure in HUA-model rats. Functional analysis of the gut microbiota revealed decreased amino acid biosynthesis and increased fermentation of pyruvate into short-chain fatty acids in Fangyukangsuan granule-treated rats. Together, these findings demonstrate that Fangyukangsuan granules have anti-hyperuricaemic and regulatory effects on the gut microbiota and may be a therapeutic candidate for HUA.

CREB5 promotes the proliferation and self-renewal ability of glioma stem cells.

Glioblastoma multiforme (GBM) is the most fatal form of brain cancer in humans, with a dismal prognosis and a median overall survival rate of less than 15 months upon diagnosis. Glioma stem cells (GSCs), have recently been identified as key contributors in both tumor initiation and therapeutic resistance in GBM. Both public dataset analysis and direct differentiation experiments on GSCs have demonstrated that CREB5 is more highly expressed in undifferentiated GSCs than in differentiated GSCs. Additionally, gene silencing by short hairpin RNA (shRNA) of CREB5 has prevented the proliferation and self-renewal ability of GSCs in vitro and decreased their tumor forming ability in vivo. Meanwhile, RNA-sequencing, luciferase reporter assay, and ChIP assay have all demonstrated the closely association between CREB5 and OLIG2. These findings suggest that targeting CREB5 could be an effective approach to overcoming GSCs.

Integrated proteogenomic characterization of glioblastoma evolution.

The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological process that extends beyond genetic alterations alone. Here, we perform an integrative proteogenomic analysis of 123 longitudinal glioblastoma pairs and identify a highly proliferative cellular state at diagnosis and replacement by activation of neuronal transition and synaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analyses reveal that the molecular transition to neuronal state at recurrence is marked by post-translational activation of the wingless-related integration site (WNT)/ planar cell polarity (PCP) signaling pathway and BRAF protein kinase. Consistently, multi-omic analysis of patient-derived xenograft (PDX) models mirror similar patterns of evolutionary trajectory. Inhibition of B-raf proto-oncogene (BRAF) kinase impairs both neuronal transition and migration capability of recurrent tumor cells, phenotypic hallmarks of post-therapy progression. Combinatorial treatment of temozolomide (TMZ) with BRAF inhibitor, vemurafenib, significantly extends the survival of PDX models. This study provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance, highlighting promising therapeutic strategies for clinical intervention.

Soybean 40S Ribosomal Protein S8 (GmRPS8) Interacts with 6K1 Protein and Contributes to Soybean Susceptibility to Soybean Mosaic Virus.

Soybean mosaic virus (SMV), a member of Potyvirus, is the most destructive and widespread viral disease in soybean production. Our earlier studies identified a soybean 40S ribosomal protein S8 (GmRPS8) using the 6K1 protein of SMV as the bait to screen a soybean cDNA library. The present study aims to identify the interactions between GmRPS8 and SMV and characterize the role of GmRPS8 in SMV infection in soybean. Expression analysis showed higher SMV-induced GmRPS8 expression levels in a susceptible soybean cultivar when compared with a resistant cultivar, suggesting that GmRPS8 was involved in the response to SMV in soybean. Subcellular localization showed that GmRPS8 was localized in the nucleus. Moreover, the yeast two-hybrid (Y2H) experiments showed that GmRPS8 only interacted with 6K1 among the eleven proteins encoded by SMV. The interaction between GmRPS8 and 6K1 was further verified by a bimolecular fluorescence complementation (BiFC) assay, and the interaction was localized in the nucleus. Furthermore, knockdown of GmRPS8 by a virus-induced gene silencing (VIGS) system retarded the growth and development of soybeans and inhibited the accumulation of SMV in soybeans. Together, these results showed that GmRPS8 interacts with 6K1 and contributes to soybean susceptibility to SMV. Our findings provide new insights for understanding the role of GmRPS8 in the SMV infection cycle, which could help reveal potyviral replication mechanisms.

Present Status and Advances in Chimeric Antigen Receptor T Cell Therapy for Glioblastoma.

Adoptive chimeric antigen receptor (CAR) T cells designed to recognize specific tumor antigens have shown promising results in cancer therapy. While CAR T cell therapy has demonstrated notable clinical effectiveness for hematologic disease, efforts to develop therapies for solid tumors, including glioblastoma (GBM), have been hampered by heterogeneity, an immunosuppressive tumor microenvironment, and difficulty in trafficking. Several specific tumor antigens, such as IL13Rα2, EGFRvIII, and HER2, have been attempted in clinical trials; however, limited efficacy has been observed. In this review, we discuss the current status of CAR T therapy for GBM in clinical trials and highlight the potential target antigens for CAR T cells. Additionally, we summarize the mechanisms used to enhance their efficacy and explore the challenges and future prospects of CAR T cell therapy for GBM.

Cross-talk between PARN and EGFR-STAT3 Signaling Facilitates Self-Renewal and Proliferation of Glioblastoma Stem Cells.

Glioblastoma is the most common type of malignant primary brain tumor and displays highly aggressive and heterogeneous phenotypes. The transcription factor STAT3 has been reported to play a key role in glioblastoma malignancy. Thus, discovering targets and functional downstream networks regulated by STAT3 that govern glioblastoma pathogenesis may lead to improved treatment strategies. In this study, we identified that poly(A)-specific ribonuclease (PARN), a key modulator of RNA metabolism, activates EGFR-STAT3 signaling to support glioblastoma stem cells (GSC). Functional integrative analysis of STAT3 found PARN as the top-scoring transcriptional target involved in RNA processing in patients with glioblastoma, and PARN expression was strongly correlated with poor patient survival and elevated malignancy. PARN positively regulated self-renewal and proliferation of GSCs through its 3'-5' exoribonuclease activity. EGFR was identified as a clinically relevant target of PARN in GSCs. PARN positively modulated EGFR by negatively regulating the EGFR-targeting miRNA miR-7, and increased EGFR expression created a positive feedback loop to increase STAT3 activation. PARN depletion in GSCs reduced infiltration and prolonged survival in orthotopic brain tumor xenografts; similar results were observed using siRNA nanocapsule-mediated PARN targeting. Pharmacological targeting of STAT3 also confirmed PARN regulation by STAT3 signaling. In sum, these results suggest that a STAT3-PARN regulatory network plays a pivotal role in tumor progression and thus may represent a target for glioblastoma therapeutics. SIGNIFICANCE: A positive feedback loop comprising PARN and EGFR-STAT3 signaling supports self-renewal and proliferation of glioblastoma stem cells to drive tumor progression and can be targeted in glioblastoma therapeutics.

Dual-Role of Polyelectrolyte-Tethered Benzimidazolium Cation in Promoting CO2 /Pure Water Co-Electrolysis to Ethylene.

Electrochemical CO2 reduction reaction (CO2 RR), as a promising route to realize negative carbon emissions, is known to be strongly affected by electrolyte cations (i.e., cation effect). In contrast to the widely-studied alkali cations in liquid electrolytes, the effect of organic cations grafted on alkaline polyelectrolytes (APE) remains unexplored, although APE has already become an essential component of CO2 electrolyzers. Herein, by studying the organic cation effect on CO2 RR, we find that benzimidazolium cation (Beim+ ) significantly outperforms other commonly-used nitrogenous cations (R4 N+ ) in promoting C2+ (mainly C2 H4 ) production over copper electrode. Cyclic voltammetry and in situ spectroscopy studies reveal that the Beim+ can synergistically boost the CO2 to *CO conversion and reduce the proton supply at the electrocatalytic interface, thus facilitating the *CO dimerization toward C2+ formation. By utilizing the homemade APE ionomer, we further realize efficient C2 H4 production at an industrial-scale current density of 331 mA cm-2 from CO2 /pure water co-electrolysis, thanks to the dual-role of Beim+ in synergistic catalysis and ionic conduction. This study provides a new avenue to boost CO2 RR through the structural design of polyelectrolytes.

Soybean Mosaic Virus 6K1 Interactors Screening and GmPR4 and GmBI1 Function Characterization.

Host proteins are essential during virus infection, and viral factors must target numerous host factors to complete their infectious cycle. The mature 6K1 protein of potyviruses is required for viral replication in plants. However, the interaction between 6K1 and host factors is poorly understood. The present study aims to identify the host interacting proteins of 6K1. Here, the 6K1 of Soybean mosaic virus (SMV) was used as the bait to screen a soybean cDNA library to gain insights about the interaction between 6K1 and host proteins. One hundred and twenty-seven 6K1 interactors were preliminarily identified, and they were classified into six groups, including defense-related, transport-related, metabolism-related, DNA binding, unknown, and membrane-related proteins. Then, thirty-nine proteins were cloned and merged into a prey vector to verify the interaction with 6K1, and thirty-three of these proteins were confirmed to interact with 6K1 by yeast two-hybrid (Y2H) assay. Of the thirty-three proteins, soybean pathogenesis-related protein 4 (GmPR4) and Bax inhibitor 1 (GmBI1) were chosen for further study. Their interactions with 6K1 were also confirmed by bimolecular fluorescence complementation (BiFC) assay. Subcellular localization showed that GmPR4 was localized to the cytoplasm and endoplasmic reticulum (ER), and GmBI1 was located in the ER. Moreover, both GmPR4 and GmBI1 were induced by SMV infection, ethylene and ER stress. The transient overexpression of GmPR4 and GmBI1 reduced SMV accumulation in tobacco, suggesting their involvement in the resistance to SMV. These results would contribute to exploring the mode of action of 6K1 in viral replication and improve our knowledge of the role of PR4 and BI1 in SMV response.

IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis.

Diffuse infiltration is the main reason for therapeutic resistance and recurrence in glioblastoma (GBM). However, potential targeted therapies for GBM stem-like cell (GSC) which is responsible for GBM invasion are limited. Herein, we report Insulin-like Growth Factor-Binding Protein 5 (IGFBP5) is a ligand for Receptor tyrosine kinase like Orphan Receptor 1 (ROR1), as a promising target for GSC invasion. Using a GSC-derived brain tumor model, GSCs were characterized into invasive or non-invasive subtypes, and RNA sequencing analysis revealed that IGFBP5 was differentially expressed between these two subtypes. GSC invasion capacity was inhibited by IGFBP5 knockdown and enhanced by IGFBP5 overexpression both in vitro and in vivo, particularly in a patient-derived xenograft model. IGFBP5 binds to ROR1 and facilitates ROR1/HER2 heterodimer formation, followed by inducing CREB-mediated ETV5 and FBXW9 expression, thereby promoting GSC invasion and tumorigenesis. Importantly, using a tumor-specific targeting and penetrating nanocapsule-mediated delivery of CRISPR/Cas9-based IGFBP5 gene editing significantly suppressed GSC invasion and downstream gene expression, and prolonged the survival of orthotopic tumor-bearing mice. Collectively, our data reveal that IGFBP5-ROR1/HER2-CREB signaling axis as a potential GBM therapeutic target.

RSC3 K of soybean cv. Kefeng No.1 confers resistance to soybean mosaic virus by interacting with the viral protein P3.

Soybean mosaic virus (SMV) is one of the most devastating viral pathogens of soybean (Glycine max (L.) Merr). In total, 22 Chinese SMV strains (SC1-SC22) have been classified based on the responses of 10 soybean cultivars to these pathogens. However, although several SMV-resistance loci in soybean have been identified, no gene conferring SMV resistance in the resistant soybean cultivar (cv.) Kefeng No.1 has been cloned and verified. Here, using F2 -derived F3 (F2:3 ) and recombinant inbred line (RIL) populations from a cross between Kefeng No.1 and susceptible soybean cv. Nannong 1138-2, we localized the gene in Kefeng No.1 that mediated resistance to SMV-SC3 strain to a 90-kb interval on chromosome 2. To study the functions of candidate genes in this interval, we performed Bean pod mottle virus (BPMV)-induced gene silencing (VIGS). We identified a recombinant gene (which we named RSC3 K) harboring an internal deletion of a genomic DNA fragment partially flanking the LOC100526921 and LOC100812666 reference genes as the SMV-SC3 resistance gene. By shuffling genes between infectious SMV DNA clones based on the avirulent isolate SC3 and virulent isolate 1129, we determined that the viral protein P3 is the avirulence determinant mediating SMV-SC3 resistance on Kefeng No.1. P3 interacts with RNase proteins encoded by RSC3 K, LOC100526921, and LOC100812666. The recombinant RSC3 K conveys much higher anti-SMV activity than LOC100526921 and LOC100812666, although those two genes also encode proteins that inhibit SMV accumulation, as revealed by gene silencing in a susceptible cultivar and by overexpression in Nicotiana benthamiana. These findings demonstrate that RSC3 K mediates the resistance of Kefeng No.1 to SMV-SC3 and that SMV resistance of soybean is determined by the antiviral activity of RNase proteins.

The Characterization of the Tobacco-Derived Wild Tomato Mosaic Virus by Employing Its Infectious DNA Clone.

Viral diseases of cultivated crops are often caused by virus spillover from wild plants. Tobacco (N. tabacum) is an important economic crop grown globally. The viral pathogens of tobacco are traditional major subjects in virology studies and key considerations in tobacco breeding practices. A positive-strand RNA virus, wild tomato mosaic virus (WTMV), belonging to the genus potyvirus in the family potyviridae was recently found to infect tobacco in China. In this study, diseased tobacco leaf samples were collected in the Henan Province of China during 2020-2021. Several samples from different locations were identified as WTMV positive. An infectious DNA clone was constructed based on one of the WTMV isolates. By using this clone, we found that WTMV from tobacco could establish infections on natural reservoir hosts, demonstrating a possible route of WTMV spillover and overwintering in the tobacco field. Furthermore, the WTMV infection was found to be accompanied by other tobacco viruses in the field. The co-inoculation experiments indicate the superinfection exclusion (SIE) between WTMV and other potyvirus species that infect tobacco. Overall, our work reveals novel aspects of WTMV evolution and infection in tobacco and provides an important tool for further studies of WTMV.

Prospective approaches to enhancing CAR T cell therapy for glioblastoma.

Glioblastoma (GBM) is the most common malignant brain tumor. The poor clinical outcome and overall ineffectiveness of current standard treatments, including surgery, chemotherapy, and radiation, highlight the urgent need for alternative tumor-specific therapies for GBM. Chimeric antigen receptor (CAR) T cell therapy is a revolutionary therapeutic strategy for hematological malignancies, but the optimal potency of CAR T cell therapy for solid tumors, especially GBM, has not been achieved. Although CAR T cell therapeutic strategies for GBM have been assessed in clinical trials, the current antitumor activity of CAR T cells remains insufficient. In this review, we present our perspective on genetically modifying CAR constructs, overcoming T cell dysfunctions, and developing additional treatments that can improve CAR T cell effectiveness, such as functionality, persistence, and infiltration into tumor sites. Effectively improved CAR T cells may offer patients with GBM new treatment opportunities, and this review is intended to provide a comprehensive overview for researchers to develop potent CAR T cells using genetic engineering or combinatorial preparations.

Digs out and characterization of the resistance gene accountable to soybean mosaic virus in soybean (Glycine max (L.) Merrill).

KEY MESSAGE: A putative candidate gene conferring resistance to SMV strain SC1 was identified on chromosome 2, and the linked marker was validated in soybean cultivars Soybean mosaic, caused by the soybean mosaic virus, is the most common disease in soybean and a significant impediment to soybean production in the Huanghuai and Yangtze River regions of China. Kefeng No.1, a soybean cultivar, showed high resistance to soybean mosaic virus strain (SC1) collected from Huanghuai and Yangtze River regions. Genetic analysis based on the Mendelian genic population derived from the cross Kefeng No.1 × Nannong 1138-2 revealed that Kefeng No.1 possesses a single dominant gene. Furthermore, genetic fine-mapping using an F2 population containing 281 individuals delimited resistant gene to a genomic region of 186 kb flanked by SSR markers BS020610 and BS020620 on chromosome 2. Within this region, there were 14 genes based on the Williams 82 reference genome. According to sequence analysis, six of the 14 genes have amino acid differences, and one of these genes is the Rsv4 allele designated as Rsc1-DR. The functional analysis of candidate genes using the bean pod mottle virus (BPMV)-induced gene silencing (VIGS) system revealed that Rsc1-DR was accountable for Kefeng No.1's resistance to SMV-SC1. Based on the genome sequence of Rsc1-DR, an Insertion/Deletion (InDel) molecular marker, JT0212, was developed and genotyped using 100 soybean cultivars, and the coincidence rate was 89%. The study enriched our understanding of the SMV resistance mechanism. The marker developed in this study could be directly used by the soybean breeders to select the genotypes with favorable alleles for making crosses, and also it will facilitate marker-assisted selection of SMV resistance in soybean breeding.

The E3 Ligase GmPUB21 Negatively Regulates Drought and Salinity Stress Response in Soybean.

E3-ubiquitin ligases are known to confer abiotic stress responses in plants. In the present study, GmPUB21, a novel U-box E3-ubiquitin ligase-encoding gene, was isolated from soybean and functionally characterized. The expression of GmPUB21, which possesses E3-ubiquitin ligase activity, was found to be significantly up-regulated by drought, salinity, and ABA treatments. The fusion protein GmPUB21-GFP was localized in the cytoplasm, nucleus, and plasma membrane. Transgenic lines of the Nicotiana benthamiana over-expressing GmPUB21 showed more sensitive to osmotic, salinity stress and ABA in seed germination and inhibited mannitol/NaCl-mediated stomatal closure. Moreover, higher reactive oxygen species accumulation was observed in GmPUB21 overexpressing plants after drought and salinity treatment than in wild-type (WT) plants. Contrarily, silencing of GmPUB21 in soybean plants significantly enhanced the tolerance to drought and salinity stresses. Collectively, our results revealed that GmPUB21 negatively regulates the drought and salinity tolerance by increasing the stomatal density and aperture via the ABA signaling pathway. These findings improved our understanding of the role of GmPUB21 under drought and salinity stresses in soybean.

Electronic Modulation of Ru Nanosheet by d-d Orbital Coupling for Enhanced Hydrogen Oxidation Reaction in Alkaline Electrolytes.

The alkaline polymer electrolyte fuel cells (APEFCs) hold great promise for using nonnoble metal-based electrocatalysts toward the cathodic oxygen reduction reaction (ORR), but are hindered by the sluggish anodic hydrogen oxidation reaction (HOR) in alkaline electrolytes. Here, a strategy is reported to promote the alkaline HOR performance of Ru by incorporating 3d-transition metals (V, Fe, Co, and Ni), where the conduction band minimum (CBM) level of Ru can be rationally tailored through strong d-d orbital coupling. As expected, the obtained RuFe nanosheet exhibits outstanding HOR performance with the mass activity of 233.46 A gPGM -1 and 23-fold higher than the Ru catalyst, even threefold higher than the commercial Pt/C. APEFC employing this RuFe as anodic catalyst gives a peak power density of 1.2 W cm-2 , outperforming the documented Pt-free anodic catalyst-based APEFCs. Experimental results and density functional theory calculations suggest the enhanced OH-binding energy and reduced formation energy of water derived from the downshifted CBM level of Ru contribute to the enhanced HOR activity.

Brain Co-Delivery of Temozolomide and Cisplatin for Combinatorial Glioblastoma Chemotherapy.

Glioblastoma (GBM) is an intractable malignancy with high recurrence and mortality. Combinatorial therapy based on temozolomide (TMZ) and cisplatin (CDDP) shows promising potential for GBM therapy in clinical trials. However, significant challenges include limited blood-brain-barrier (BBB) penetration, poor targeting of GBM tissue/cells, and systemic side effects, which hinder its efficacy in GBM therapy. To surmount these challenges, new GBM-cell membrane camouflaged and pH-sensitive biomimetic nanoparticles (MNPs) inspired by the fact that cancer cells readily pass the BBB and localize with homologous cells, are developed. This study's results show that MNPs can efficiently co-load TMZ and CDDP, transport these across the BBB to specifically target GBM. Incorporation of pH-sensitive polymer then allows for controlled release of drug cargos at GBM sites for combination drug therapy. Mice bearing orthotopic U87MG or drug-resistant U251R GBM tumor and treated with MNPs@TMZ+CDDP show a potent anti-GBM effect, greatly extending the survival time relative to mice receiving single-drug loaded nanoparticles. No obvious side effects are apparent in histological analyses or blood routine studies. Considering these results, the study's new nanoparticle formulation overcomes multiple challenges currently limiting the efficacy of combined TMZ and CDDP GBM drug therapy and appears to be a promising strategy for future GBM combinatorial chemotherapy.

Preanodized Cu Surface for Selective CO2 Electroreduction to C1 or C2+ Products.

The electrochemical CO2 reduction over Cu catalysts has shown great potential in producing a wide range of valuable chemicals, but it is still plagued by a poor controllability on product distribution. Herein, we demonstrate an effective regulation of CO2 reduction paths through a preanodization treatment of Cu foil electrodes in different electrolytes. The Cu electrode exhibits a superior C1 and C2+ product selectivity after being preanodized in NaClO4 (Cu-NaClO4) and Na2HPO4 electrolyte (Cu-Na2HPO4), respectively. Combined with in situ electrochemical Raman, ATR-SEIRAS, and SEM characterizations, the preferential C1 path is due to the deposition of many Cu nanocrystals with dominant Cu(111) facets on the Cu-NaClO4 electrode. In contrast, the preferential C2+ path over the Cu-Na2HPO4 is attributed to formation of a unique Cu nanodendritic morphology, which strengthens the *CO intermediate adsorption and induces an environment of low local H2O/CO2 stoichiometric ratio, thus facilitating C-C coupling for C2+ production. Our findings may shed light on the rational control of the CO2 reduction path through engineering of the Cu surface structure.

The MAP3K1/c-JUN signaling axis regulates glioblastoma stem cell invasion and tumor progression.

Glioblastoma (GBM) stem cells (GSCs) are responsible for GBM initiation, progression, infiltration, standard therapy resistance, and recurrence. However, the mechanisms underlying GSC invasion remain incompletely understood. Using public single-cell RNA-Seq data, we identified MAP3K1 as a master regulator of infiltrative GSCs through c-JUN signaling regulation. MAP3K1 knockdown significantly decreased GSC invasion capacity, proliferation, and stemness in vitro. Moreover, in an orthotopic xenograft model, knockdown of MAP3K1 prominently suppressed GSC infiltration along the corpus callosum and tumor progression and prolonged mouse survival. Mechanistically, MAP3K1 regulates GSC invasion through phosphorylation of downstream c-JUN at serine 63 and 73, as confirmed using the CPTAC phosphoproteome dataset. Furthermore, the c-JUN inhibitor JNK-IN-8 significantly decreased GSC invasion, proliferation, and stemness. Taken together, our study demonstrates that MAP3K1 regulates GSC invasion and tumor progression via activation of c-JUN signaling and indicates that the MAP3K1/c-JUN signaling axis is a therapeutic target for infiltrative GBM.

Blood-brain barrier-penetrating single CRISPR-Cas9 nanocapsules for effective and safe glioblastoma gene therapy.

We designed a unique nanocapsule for efficient single CRISPR-Cas9 capsuling, noninvasive brain delivery and tumor cell targeting, demonstrating an effective and safe strategy for glioblastoma gene therapy. Our CRISPR-Cas9 nanocapsules can be simply fabricated by encapsulating the single Cas9/sgRNA complex within a glutathione-sensitive polymer shell incorporating a dual-action ligand that facilitates BBB penetration, tumor cell targeting, and Cas9/sgRNA selective release. Our encapsulating nanocapsules evidenced promising glioblastoma tissue targeting that led to high PLK1 gene editing efficiency in a brain tumor (up to 38.1%) with negligible (less than 0.5%) off-target gene editing in high-risk tissues. Treatment with nanocapsules extended median survival time (68 days versus 24 days in nonfunctional sgRNA-treated mice). Our new CRISPR-Cas9 delivery system thus addresses various delivery challenges to demonstrate safe and tumor-specific delivery of gene editing Cas9 ribonucleoprotein for improved glioblastoma treatment that may potentially be therapeutically useful in other brain diseases.

Research on Optimization of Process Parameters of Traditional Chinese Medicine Based on Data Mining Technology.

Data mining technology and methods are used to effectively optimize manufacturing process parameters due to the complexity and uniqueness of the process parameters. The data-mining-based optimization method for traditional Chinese medicine (TCM) process parameters is presented, along with a list of process parameters that have shown to be effective in actual production. The influencing factors of process parameters are analyzed and modeled using an attribute weight analysis and classification analysis algorithm. The optimization scheme of process parameters that meet the requirements is selected, and an example is given for verification, by selecting data records that fall within a certain error range and incorporating the rules of association knowledge discovery. The support vector classification algorithm has a higher accuracy, despite the algorithm's results being understandable. The support vector regression algorithm developed a reliable process optimization model.