Genome-wide analysis of the KNOX gene family in Moso bamboo: insights into their role in promoting the rapid shoot growth.

BACKGROUND: KNOTTED1-like homeobox (KNOX) genes, plant-specific homologous box transcription factors (TFs), play a central role in regulating plant growth, development, organ formation, and response to biotic and abiotic stresses. However, a comprehensive genome-wide identification of the KNOX genes in Moso bamboo (Phyllostachys edulis), the fastest growing plant, has not yet been conducted, and the specific biological functions of this family remain unknown. RESULTS: The expression profiles of 24 KNOX genes, divided into two subfamilies, were determined by integrating Moso bamboo genome and its transcriptional data. The KNOX gene promoters were found to contain several light and stress-related cis-acting elements. Synteny analysis revealed stronger similarity with rice KNOX genes than with Arabidopsis KNOX genes. Additionally, several conserved structural domains and motifs were identified in the KNOX proteins. The expansion of the KNOX gene family was primarily regulated by tandem duplications. Furthermore, the KNOX genes were responsive to naphthaleneacetic acid (NAA) and gibberellin (GA) hormones, exhibiting distinct temporal expression patterns in four different organs of Moso bamboo. Short Time-series Expression Miner (STEM) analysis and quantitative real-time PCR (qRT-PCR) assays demonstrated that PeKNOX genes may play a role in promoting rapid shoot growth. Additionally, Gene Ontology (GO) and Protein-Protein Interaction (PPI) network enrichment analyses revealed several functional annotations for PeKNOXs. By regulating downstream target genes, PeKNOXs are involved in the synthesis of AUX /IAA, ultimately affecting cell division and elongation. CONCLUSIONS: In the present study, we identified and characterized a total of 24 KNOX genes in Moso bamboo and investigated their physiological properties and conserved structural domains. To understand their functional roles, we conducted an analysis of gene expression profiles using STEM and RNA-seq data. This analysis successfully revealed regulatory networks of the KNOX genes, involving both upstream and downstream genes. Furthermore, the KNOX genes are involved in the AUX/IAA metabolic pathway, which accelerates shoot growth by influencing downstream target genes. These results provide a theoretical foundation for studying the molecular mechanisms underlying the rapid growth and establish the groundwork for future research into the functions and transcriptional regulatory networks of the KNOX gene family.

Trophic interactions in microbiomes influence plant host population size and ecosystem function.

Plant microbiomes that comprise diverse microorganisms, including prokaryotes, eukaryotes and viruses, are the key determinants of plant population dynamics and ecosystem function. Despite their importance, little is known about how species interactions (especially trophic interactions) between microbes from different domains modify the importance of microbiomes for plant hosts and ecosystems. Using the common duckweed Lemna minor, we experimentally examined the effects of predation (by bacterivorous protists) and parasitism (by bacteriophages) within microbiomes on plant population size and ecosystem phosphorus removal. Our results revealed that the addition of predators increased plant population size and phosphorus removal, whereas the addition of parasites showed the opposite pattern. The structural equation modelling further pointed out that predation and parasitism affected plant population size and ecosystem function via distinct mechanisms that were both mediated by microbiomes. Our results highlight the importance of understanding microbial trophic interactions for predicting the outcomes and ecosystem impacts of plant-microbiome symbiosis.

Efficacy and safety of CD19-specific CAR T cell-based therapy in B-cell acute lymphoblastic leukemia patients with CNSL.

Few studies have described chimeric antigen receptor (CAR) T-cell therapy for patients with B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system leukemia (CNSL) because of concerns regarding poor response and treatment-related neurotoxicity. Our study included 48 patients with relapsed/refractory B-ALL with CNSL to evaluate the efficacy and safety of CD19-specific CAR T cell-based therapy. The infusion resulted in an overall response rate of 87.5% (95% confidence interval [CI], 75.3-94.1) in bone marrow (BM) disease and remission rate of 85.4% (95% CI, 72.8-92.8) in CNSL. With a median follow-up of 11.5 months (range, 1.3-33.3), the median event-free survival was 8.7 months (95% CI, 3.7-18.8), and the median overall survival was 16.0 months (95% CI, 13.5-20.1). The cumulative incidences of relapse in BM and CNS diseases were 31.1% and 11.3%, respectively, at 12 months (P = .040). The treatment was generally well tolerated, with 9 patients (18.8%) experiencing grade ≥3 cytokine release syndrome. Grade 3 to 4 neurotoxic events, which developed in 11 patients (22.9%), were associated with a higher preinfusion disease burden in CNS and were effectively controlled under intensive management. Our results suggest that CD19-specific CAR T cell-based therapy can induce similar high response rates in both BM and CNS diseases. The duration of remission in CNSL was longer than that in BM disease. CD19 CAR T-cell therapy may provide a potential treatment option for previously excluded patients with CNSL, with manageable neurotoxicity. The clinical trials were registered at www.clinicaltrials.gov as #NCT02782351 and www.chictr.org.cn as #ChiCTR-OPN-16008526.

Design, synthesis, and biological evaluation of gambogenic acid derivatives: Unraveling their anti-cancer effects by inducing pyroptosis.

Gambogenic acid (GNA), a caged xanthone derived from Garcinia hanburyi, exhibits a wide range of anti-cancer properties. The caged skeleton of GNA serves as the fundamental pharmacophore responsible for its antitumor effects. However, limited exploration has focused on the structural modifications of GNA. This study endeavors to diversify the structure of GNA and enhance its anti-cancer efficacy. Sulfoximines, recognized as pivotal motifs in medicinal chemistry due to their outstanding properties, have featured in several anti-cancer drugs undergoing clinical trials. Accordingly, a series of 33 GNA derivatives combined with sulfoximines were synthesized and evaluated for their anti-cancer effects against MIAPaCa2, MDA-MB-231, and A549 cells in vitro. The activity screening led to the identification of compound 12k, which exhibited the most potent anti-cancer effect. Mechanistic studies revealed that 12k primarily induced pyroptosis in MIAPaCa2 and MDA-MB-231 cells by activating the caspase-3/gasdermin E (GSDME) pathway. These findings suggested that 12k is a promising drug candidate in cancer therapy and highlighted the potential of sulfoximines as a valuable functional group in drug discovery.

Medial-pivot total knee arthroplasty enhances tibiofemoral axial rotation stability in weight-bearing mid-range flexion compared to posterior-stabilised system.

PURPOSE: Total knee arthroplasty (TKA) stands as a primary intervention for severe knee ailments, yet concerns remain regarding postoperative patient satisfaction and flexion instability. This study aims to evaluate the in-vivo kinematics of medial-pivot (MP) and posterior-stabilised (PS) designs during step-up activity, in comparison to the kinematics of the nonoperated contralateral knee. METHODS: Sixteen patients with PS-TKA and 14 with MP-TKA were retrospectively examined. Clinical outcomes were assessed using patient-completed questionnaires. Motion during step-up was captured using a dual fluoroscopic system. Statistical analysis was applied to evaluate the in-vivo tibiofemoral six-degree-of-freedom kinematics and articular contact positions between the two groups. RESULTS: Despite being older, patients in the MP group reported higher postoperative subjective scores for weight-bearing functional activities. The axial rotation centres of MP-TKA located on the medial tibial plateau exhibited less variance compared to PS-TKA and contralateral knees. Compared to the contralateral knee (contralateral to medial-pivot [C-MP] or contralateral to posterior-stabilised [C-PS]), the MP group exhibited limited range of motion in terms of anteroposterior translation (MP: 3.6 ± 1.3 mm vs. C-MP: 7.4 ± 2.5 mm, p < 0.01) and axial rotation (MP: 6.6 ± 1.9° vs. C-MP: 10.3 ± 4.9°, p = 0.02), as well as in the PS group for anteroposterior translation (PS: 3.9 ± 1.7 mm vs. C-PS: 7.2 ± 3.7 mm, p < 0.01). CONCLUSION: The MP group with better postoperative ratings demonstrated a more stable MP axial rotation pattern during step-up activity compared to the PS group, underscoring the pivotal role of prosthetic design in optimising postoperative rehabilitation and functional recovery. LEVEL OF EVIDENCE: Level III.

Research progress in extraction, purification, structure of fruit and vegetable polysaccharides and their interaction with anthocyanins/starch.

Fruits and vegetables contain polysaccharides, polyphenols, antioxidant enzymes, and various vitamins, etc. Fruits and vegetables polysaccharides (FVPs), as an important functional factor in health food, have various biological activities such as lowering blood sugar, blood lipids, blood pressure, inhibiting tumors, and delaying aging, etc. In addition, FVPs exhibit good physicochemical properties including low toxicity, biodegradability, biocompatibility. Increasing research has confirmed that FVPs could enhance the stability and biological activities of anthocyanins, affecting their bioavailability to improve food quality. Simultaneously, the addition of FVPs in natural starch suspension could improve the physicochemical properties of natural starch such as viscosity, gelling property, water binding capacity, and lotion stability. Hence, FVPs are widely used in the modification of natural anthocyanins/starch. A systematic review of the latest research progress and future development prospects of FVPs is very necessary to better understand them. This paper systematically reviews the latest progress in the extraction, purification, structure, and analysis techniques of FVPs. Moreover, the review also introduces the potential mechanisms, evaluation methods, and applications of the interaction between polysaccharides and anthocyanins/starch. The findings can provide important references for the further in-depth development and utilization of FVPs.

Environment and Host Genetics Influence the Biogeography of Plant Microbiome Structure.

To understand how microbiota influence plant populations in nature, it is important to examine the biogeographic distribution of plant-associated microbiomes and the underlying mechanisms. However, we currently lack a fundamental understanding of the biogeography of plant microbiomes across populations and the environmental and host genetic factors that shape their distribution. Leveraging the broad distribution and extensive genetic variation in duckweeds (the Lemna species complex), we identified key factors that governed plant microbiome diversity and compositional variation geographically. In line with the microbial biogeography of free-living microbiomes, we observed higher bacterial richness in temperate regions relative to lower latitudes in duckweed microbiomes (with 10% higher in temperate populations). Our analyses revealed that higher temperature and sodium concentration in aquatic environments showed a negative impact on duckweed bacterial richness, whereas temperature, precipitation, pH, and concentrations of phosphorus and calcium, along with duckweed genetic variation, influenced the biogeographic variation of duckweed bacterial community composition. Analyses of plant microbiome assembly processes further revealed that niche-based selection played an important role (26%) in driving the biogeographic variation of duckweed bacterial communities, alongside the contributions of dispersal limitation (33%) and drift (39%). These findings add significantly to our understanding of host-associated microbial biogeography and provide important insights for predicting plant microbiome vulnerability and resilience under changing climates and intensifying anthropogenic activities.

Insight into Bioaccumulation of Decabromodiphenyl Ethane in Eisenia fetida Increased by Microplastics.

The rise of electronics inevitably induced the co-pollution of novel brominated flame retardants (NBFRs) and microplastics (MPs). However, studies on how they interact to influence their bioavailability are scarce. Here, we explored the influence mechanism of acrylonitrile butadiene styrene (ABS)-MPs on the bioaccumulation of decabromodiphenyl ethane (DBDPE) in soil-earthworm microcosms. The influence exhibited a temporal pattern characterized by short-term inhibition and long-term promotion. After 28 days of exposure, DBDPE bioaccumulation in a co-exposure (10 mg kg-1 DBDPE accompanied by 1000 mg kg-1 ABS-MPs) was 2.61 times higher than that in a separate exposure. The adsorption process in the soil, intestines, and mucus introduced DBDPE-carried MPs, which had a higher concentration of DBDPE than the surrounding soil and directly affected the bioavailability of DBDPE. MP-pre-exposure (100, 1000, and 10000 mg kg-1) reduced epidermal soundness, mucus secretion, and worm cast production. This eventually promoted the contact between earthworm and soil particles and enhanced the DBDPE of earthworm tissue by 6%-61% in the next DBDPE-postexposure period, confirming that MPs increased DBDPE bioaccumulation indirectly by impairing the earthworm health. This study indicates that MPs promoted DBDPE bioaccumulation via adsorption and self-toxicity, providing new insight into the combined risk of MPs and NBFRs.

Garcinol and its analogues: Synthesis, cytotoxic activity and mechanistic investigation.

Garcinol is a polyisoprenylated benzophenone isolated from Garcinia. It has been reported to have a variety of intriguing biological effects, including anticancer, anti-inflammatory, and antioxidant capabilities. The purpose of this research is to thoroughly evaluate garcinol and a series of its analogues in terms of synthesis, structural diversity, biosynthesis, and potential for preventing carcinoma cell proliferation. Garcinopicrobenzophenone and eugeniaphenone, which contain a unique cyclobutyl unit at C-5, were initially synthesized using the procedures utilized in the synthesis of garcinol. All the natural analogs of garcinol were produced at completion of the synthesis, and their structures and absolute configurations were clarified. Based on the synthesis, a possible biogenetic synthesis pathway towards cambogin, 13,14-didehydroxyisogarcinol via O-cyclization, and garcinopicrobenzophenone or eugeniaphenone via C-cyclization was proposed. The cytotoxicity of polyisoprenylated benzophenones produced in our group was tested, and the structure-activity relationship was summarized. The mechanism by which garcinol, cambogin, and 21' induce apoptosis was studied. Cambogin and 21' were shown to have a greater capacity to cause apoptosis in pancreatic cancer BXPC3 cells, and the suppression of BXPC3 cells by 21' might be attributed to the target of STAT3 signaling. Garcinol could cause pyroptosis and apoptosis in pancreatic cancer cells at the same time, which was the first time that garcinol was identified as a possible chemotherapeutic agent that could significantly promote pyroptosis in cancer cells.

Medial stability and lateral flexibility of the collateral ligaments during mid-range flexion in medial-pivot total knee arthroplasty patients demonstrates favorable postoperative outcomes.

PURPOSE: The objectives of the present study were to investigate the length change in different bundles of the superficial medial collateral ligament (sMCL) and lateral collateral ligament (LCL) during lunge, and to evaluate their association with Knee Society Score (KSS) following medial-pivot total knee arthroplasty (MP-TKA). METHODS: Patients with unilateral MP-TKA knees performed a bilateral single-leg lunge under dual fluoroscopy surveillance to determine the in-vivo six degrees-of-freedom knee kinematics. The contralateral non-operated knees were used as the control group. The attachment sites of the sMCL and LCL were marked to calculate the 3D wrapping length. The sMCL and LCL were divided into anterior, intermediate, and posterior portions (aMCL, iMCL, pMCL, aLCL, iLCL, pLCL). Correlations between lengths/elongation rate of ligament bundles from full extension to 100° flexion and the KSS were examined. RESULTS: The sMCL and LCL demonstrated relative stability in length at low flexion, but sMCL length decreased whereas LCL increased with further flexion on operated knees. The sMCL length increased at low flexion and remained stable with further flexion, while the LCL length decreased with flexion on the contralateral non-operated knees. The lengths of aMCL, iMCL, and pMCL showed moderate (0.5 < r < 0.7, p < 0.05) negative correlations with the KSS, and the lengths of aLCL, iLCL, and pLCL were positively correlated with the KSS at mid flexion on operated knees (p < 0.05). The elongation rates of aLCL, iLCL, and pLCL were negatively correlated with the KSS at high flexion on operated knees (p < 0.05). However, no significant correlations between the length of different bundles of sMCL or LCL with KSS were found on contralateral non-operated knees. CONCLUSIONS: The elongation pattern of sMCL/LCL on MP-TKA knees showed differences with contralateral non-operated knees. The sMCL is tense at low to middle flexion and relaxed at high flexion, while LCL is relaxed at low to middle flexion and tense at high flexion following MP-TKA. Medial stability and proper lateral flexibility during mid flexion were associated with favorable postoperative outcomes in MP-TKA patients. In contrast, lateral relaxation at deep flexion should be avoided when applying soft-tissue balancing in MP-TKA. LEVEL OF EVIDENCE: Level III.

Bioactive Substances and Biological Functions in Malus hupehensis: A Review.

Malus hupehensis (MH), as a natural resource, contains various active ingredients such as polyphenols, polysaccharides, proteins, amino acids, volatile substances, and other components. Increasingly, studies have indicated that MH showed a variety of biological activities, including antioxidant, hypoglycemic, hypolipidemic, anti-cancer, anti-inflammatory activities, and other activities. Hence, MH has attracted wide interest because of its high medical and nutritional value. It is necessary to review the active components and biological activities of MH. This paper systematically reviewed the chemical substances, biological activities, and potential problems of MH to further promote the related research of MH and provide an important reference for its application and development in medicine and food.

Impacts of global change on the phyllosphere microbiome.

Plants form complex interaction networks with diverse microbiomes in the environment, and the intricate interplay between plants and their associated microbiomes can greatly influence ecosystem processes and functions. The phyllosphere, the aerial part of the plant, provides a unique habitat for diverse microbes, and in return the phyllosphere microbiome greatly affects plant performance. As an open system, the phyllosphere is subjected to environmental perturbations, including global change, which will impact the crosstalk between plants and their microbiomes. In this review, we aim to provide a synthesis of current knowledge of the complex interactions between plants and the phyllosphere microbiome under global changes and to identify future priority areas of research on this topic.

Machine learning-based radiomics for histological classification of parotid tumors using morphological MRI: a comparative study.

OBJECTIVES: To evaluate the effectiveness of machine learning models based on morphological magnetic resonance imaging (MRI) radiomics in the classification of parotid tumors. METHODS: In total, 298 patients with parotid tumors were randomly assigned to a training and test set at a ratio of 7:3. Radiomics features were extracted from the morphological MRI images and screened using the Select K Best and LASSO algorithm. Three-step machine learning models with XGBoost, SVM, and DT algorithms were developed to classify the parotid neoplasms into four subtypes. The ROC curve was used to measure the performance in each step. Diagnostic confusion matrices of these models were calculated for the test cohort and compared with those of the radiologists. RESULTS: Six, twelve, and eight optimal features were selected in each step of the three-step process, respectively. XGBoost produced the highest area under the curve (AUC) for all three steps in the training cohort (0.857, 0.882, and 0.908, respectively), and for the first step in the test cohort (0.826), but produced slightly lower AUCs than SVM in the latter two steps in the test cohort (0.817 vs. 0.833, and 0.789 vs. 0.821, respectively). The total accuracies of XGBoost and SVM in the confusion matrices (70.8% and 59.6%) outperformed those of DT and the radiologist (46.1% and 49.2%). CONCLUSION: This study demonstrated that machine learning models based on morphological MRI radiomics might be an assistive tool for parotid tumor classification, especially for preliminary screening in absence of more advanced scanning sequences, such as DWI. KEY POINTS: • Machine learning algorithms combined with morphological MRI radiomics could be useful in the preliminary classification of parotid tumors. • XGBoost algorithm performed better than SVM and DT in subtype differentiation of parotid tumors, while DT seemed to have a poor validation performance. • Using morphological MRI only, the XGBoost and SVM algorithms outperformed radiologists in the four-type classification task for parotid tumors, thus making these models a useful assistant diagnostic tool in clinical practice.

Oxidative stress and detoxification mechanisms of earthworms (Eisenia fetida) after exposure to flupyradifurone in a soil-earthworm system.

Flupyradifurone (FLU) has great application potential in agricultural production as a new generation of neonicotinoid insecticide after imidacloprid. Nevertheless, the toxic effects of FLU on non-target soil organisms remain unclear, resulting in considerable environmental risks. We evaluated the acute and subchronic toxicities of FLU to earthworms. The results of acute toxicity show that the median lethal concentration (LC50) values (14 d) of FLU were 186.9773 mg kg-1 for adult earthworms and 157.6502 mg kg-1 for juveniles, respectively. The subchronic toxicity of FLU that focused on the activities of antioxidant and detoxication enzymes showed the superoxide dismutase (SOD), catalase (CAT), and glutathione-S transferase (GST) activities in earthworms increased while the peroxidase (POD) and acetylcholinesterase (AChE) activities decreased after exposure to FLU. Oxidative damage analyses revealed that the reactive oxygen species (ROS) level and malonaldehyde (MDA) content in earthworms were increased by FLU, resulting in DNA damage. Transcriptomics and RT-qPCR confirmed that FLU influenced the expression of genes related to antioxidant response and detoxification of earthworms. Ultimately detoxification metabolism, environmental information processing, cell processes, and immune system pathways are significantly enriched to respond jointly to FLU. Our study fills the gaps in the toxicity of FLU to earthworms, providing a basis for its risk assessment of soil ecosystems and non-target biological toxicity.

Experimental demonstration of the importance of keystone communities for maintaining metacommunity biodiversity and ecosystem functioning.

As local communities within a metacommunity may differ considerably in their contributions to biodiversity and ecosystem functioning, it has been suggested that conservation priority should be given to disproportionately important local communities (i.e., keystone communities). However, we know little about what characterizes a keystone community. Using laboratory protist microcosms as the model system, we examined how the environmental uniqueness and location of a local community affect its contributions to the metacommunities. We found that the removal of local communities with unique environmental conditions, which supported endemic species, reduced regional-scale diversity, qualifying them as regional-scale keystone communities. In addition, the local communities possessing unique environmental conditions had greater impacts on ecosystem functions, including biovolume production and particulate organic matter decomposition. We also found that keystone communities for biovolume production were not keystone for organic matter decomposition, and vice versa. Our study, therefore, demonstrates the important role of keystone communities in maintaining biodiversity and functioning of metacommunities.

CRISPR as a tool in tumor therapy: A short review.

Tumors remain a health concern worldwide, and gene therapy is a useful approach for treating tumors. The Clustered regulatory interspaced short palindromic repeat (CRISPR) system, an efficient and robust gene-editing system originating from bacteria, serves as an important tool in gene therapy. In this review, we briefly summarize the usage of CRISPR (including in gene knockout and gene knock-in applications) and the CRISPRa system in tumor therapy, including its delivery approaches and the general fields in which it has been applied. We summarize the application of the CRISPR system in tumor therapy in two aspects: its application in tumor cell modification and its application in drug engineering. This review also summarizes the advantages and challenges of using the CRISPR system in tumor therapy.

Cyanidin-3-glucoside prevents hydrogen peroxide (H2O2)-induced oxidative damage in HepG2 cells.

OBJECTIVE: The aim of this study is to evaluate the cytoprotection and potential molecular mechanisms of cyanidin-3-glucoside (C3G) on hydrogen peroxide (H2O2)-induced oxidative damage in HepG2 cells. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was carried out to examine the viability of HepG2 cells exposure to H2O2 or C3G. Meanwhile, the antioxidant properties of C3G were measured by determining the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and the malondialdehyde (MDA) levels. Flow cytometry was employed to determine HepG2 cells apoptosis, and HepG2 cells were stained with Hoechst 33342 to observe cell morphology. 2',7'-dichlorofluorescin diacetate (DCFH-DA) was used to evaluate the production of intracellular reactive oxygen species (ROS). Finally, the expression of apoptosis-related protein was monitored through western blot analysis. RESULTS: HepG2 cells induced with H2O2 presented a remarkable decrease in cell viability that was suppressed when HepG2 cells were interfered with C3G (2.5-10 µM). C3G interference memorably and dose-dependently inhibited H2O2-induced intracellular ROS and MDA overproduction, while C3G treatment markedly increased H2O2-induced the activities of intracellular SOD, GSH-Px and CAT. Eventually, the relative proteins expression levels of p53, cleaved caspase-9/3, cytochrome c, Fas-L, Fas, FADD and caspase-8 were substantially up-regulated in H2O2-triggered HepG2 cells, and Bax/Bcl-2 ratio and the relative protein expression levels of PARP were dramatically down-regulated. However, the expression levels of these relative proteins were reversed in C3G-interfered HepG2 cells. CONCLUSIONS: C3G could protect HepG2 cells from oxidative damage, and the effects that were mediated by the mitochondrial apoptotic pathways and the external pathways.

Ultrasound-Assisted Deep Eutectic Solvent Extraction of Anthocyanins from Blueberry Wine Residues: Optimization, Identification, and HepG2 Antitumor Activity.

Blueberry wine residues produced during the wine-brewing process contain abundant anthocyanins and other bioactive compounds. To extract anthocyanins from blueberry wine residues more efficiently, a novel procedure of ultrasound-assisted deep eutectic solvent extraction (UADESE) was proposed in this work. The extraction process was optimized by response surface methodology coupled with genetic algorithm. The optimum extraction parameters to achieve the highest yield of anthocyanins (9.32 ± 0.08 mg/g) from blueberry wine residues by UADESE were obtained at water content of 29%, ultrasonic power of 380 W, extraction temperature of 55 °C, and extraction time of 40 min. The AB-8 macroporous resin combined with Sephadex LH-20 techniques was used to purify the crude extract (CE) obtained under optimum extraction conditions and analyze the anthocyanins composition by HPLC-ESI-MS/MS. The cyanidin-3-rutinoside with purity of 92.81% was obtained. The HepG2 antitumor activity of CE was better than that of the purified anthocyanins component. Moreover, CE could increase the intracellular reactive oxygen species levels and the apoptosis, and arrest HepG2 cells in the S phases. These findings provided an effective and feasible method for anthocyanins extraction, and reduced the environmental burden of this waste.

SLC39A6/ZIP6 is essential for zinc homeostasis and T-cell development in zebrafish.

Zinc (Zn) is an essential trace element that modulate innate and acquired immune responses, and its deficiency triggers lymphopenia. However, the precise mechanisms underlying zinc-mediated lymphocyte maintenance have not been well clarified. Here, we have successfully generated a zip6-null mutant zebrafish line using TALENs. The Zip6-null mutant zebrafish developed normally during gastrulation. Loss of zip6 in zebrafish resulted in significant T lymphocyte reduction and a decrease in intracellular Zn levels. And the zip6 deficiency increases caspase-related cell apoptosis in both zebrafish cells and human T cells. Our results suggest that ZIP6 plays a critical part in T cell development, and enhance our understanding of Zn homeostasis and immune system maintenance.

2-D08 as a SUMOylation inhibitor induced ROS accumulation mediates apoptosis of acute myeloid leukemia cells possibly through the deSUMOylation of NOX2.

Acute myeloid leukemia (AML) is a heterogeneous clonal hematopoietic malignancy with poor survival and frequent relapse. Recently, a posttranslational modification of proteins with small ubiquitin-like modifiers (SUMO) has been notably implicated in a wide spectrum of diseases, especially cancers. Ubc9, as the sole E2-conjugating enzyme in SUMOylation cascade, particularly has been associated with adverse clinical outcomes. 2-D08, a small molecular agent, functions by blocking the transfer of SUMO from the Ubc9 thioester to SUMO substrates without any effects on other individual steps in this process. However, both the effects and mechanisms of 2-D08 on AML cells are still unknown. In this study, we found that 2-D08 significantly suppressed cell viability and colony formation ability. Additionally, it induced mitochondrial-mediated apoptosis with dramatic accumulation of the reactive oxygen species (ROS), which could be almost completely rescued by the ROS scavenger N-acetylcysteine (NAC). Furthermore, we confirmed that the fatal accumulation of ROS was due to its aberrant generation instead of defective scavenging. In summary, our results suggest that 2-D08, as a specific SUMOylation inhibitor, induces ROS accumulation-mediated intrinsic apoptosis of AML cells possibly through deSUMOylation of NOX2. Therefore, 2-D08 might be a promising therapeutic agent for the treatment of AML in the future.