Oxymatrine suppresses colorectal cancer progression by inhibiting NLRP3 inflammasome activation through mitophagy induction in vitro and in vivo.

Chinese herb Radix sophorae tonkinensis extract oxymatrine shows anticancer effects. This study evaluated the role of oxymatrine in colorectal cancer (CRC) and the underlying molecular events in vitro and in vivo. CRC cells were treated with different doses of oxymatrine to assess cell viability, reactive oxygen species production, gene expression, and gene alterations. Meanwhile, mouse xenograft and liver metastasis models were used to assess the effects of oxymatrine using histology examination, transmission electron microscopy, and Western blot, respectively. Our results showed that oxymatrine treatment triggered CRC cell mitophagy to inhibit CRC cell growth, migration, invasion, and metastasis in vitro and in vivo. At the gene level, oxymatrine inhibited LRPPRC to promote Parkin translocation into the mitochondria and reduce the mitophagy-activated NLRP3 inflammasome. Thus, oxymatrine had an anticancer activity through LRPPRC inhibition, mitophagy induction, and NLRP3 inflammasome suppression in the CRC cell xenograft and liver metastasis models. In conclusion, the study demonstrates the oxymatrine anti- CRC activity through its unique role in regulating CRC cell mitophagy and NLRP3 inflammasome levels in vitro and in vivo.

Functions of COP1/SPA E3 Ubiquitin Ligase Mediated by MpCRY in the Liverwort Marchantia polymorpha under Blue Light.

COP1/SPA1 complex in Arabidopsis inhibits photomorphogenesis through the ubiquitination of multiple photo-responsive transcription factors in darkness, but such inhibiting function of COP1/SPA1 complex would be suppressed by cryptochromes in blue light. Extensive studies have been conducted on these mechanisms in Arabidopsis whereas little attention has been focused on whether another branch of land plants bryophyte utilizes this blue-light regulatory pathway. To study this problem, we conducted a study in the liverwort Marchantia polymorpha and obtained a MpSPA knock-out mutant, in which Mpspa exhibits the phenotype of an increased percentage of individuals with asymmetrical thallus growth, similar to MpCRY knock-out mutant. We also verified interactions of MpSPA with MpCRY (in a blue light-independent way) and with MpCOP1. Concomitantly, both MpSPA and MpCOP1 could interact with MpHY5, and MpSPA can promote MpCOP1 to ubiquitinate MpHY5 but MpCRY does not regulate the ubiquitination of MpHY5 by MpCOP1/MpSPA complex. These data suggest that COP1/SPA ubiquitinating HY5 is conserved in Marchantia polymorpha, but dissimilar to CRY in Arabidopsis, MpCRY is not an inhibitor of this process under blue light.

The Arabidopsis HY2 Gene Acts as a Positive Regulator of NaCl Signaling during Seed Germination.

Phytochromobilin (PΦB) participates in the regulation of plant growth and development as an important synthetase of photoreceptor phytochromes (phy). In addition, Arabidopsis long hypocotyl 2 (HY2) appropriately works as a key PΦB synthetase. However, whether HY2 takes part in the plant stress response signal network remains unknown. Here, we described the function of HY2 in NaCl signaling. The hy2 mutant was NaCl-insensitive, whereas HY2-overexpressing lines showed NaCl-hypersensitive phenotypes during seed germination. The exogenous NaCl induced the transcription and the protein level of HY2, which positively mediated the expression of downstream stress-related genes of RD29A, RD29B, and DREB2A. Further quantitative proteomics showed the patterns of 7391 proteins under salt stress. HY2 was then found to specifically mediate 215 differentially regulated proteins (DRPs), which, according to GO enrichment analysis, were mainly involved in ion homeostasis, flavonoid biosynthetic and metabolic pathways, hormone response (SA, JA, ABA, ethylene), the reactive oxygen species (ROS) metabolic pathway, photosynthesis, and detoxification pathways to respond to salt stress. More importantly, ANNAT1-ANNAT2-ANNAT3-ANNAT4 and GSTU19-GSTF10-RPL5A-RPL5B-AT2G32060, two protein interaction networks specifically regulated by HY2, jointly participated in the salt stress response. These results direct the pathway of HY2 participating in salt stress, and provide new insights for the plant to resist salt stress.

Isoprenoid emissions from Schima superba and Cunninghamia lanceolata: Their responses to elevated temperature by two warming facilities.

Isoprenoids (including isoprene (ISO) and monoterpenes (MTs)) are the majority of biogenic volatile organic compounds (BVOCs) which are important carbon-containing secondary metabolites biosynthesized by organisms, especially plant in terrestrial ecosystem. Results of the warming effects on isoprenoid emissions vary within species and warming facilities, and thus conclusions remain controversial. In this study, two typical subtropical tree species seedlings of Schima superba and Cunninghamia lanceolata were cultivated under three conditions, namely no warming (CK) and two warming facilities (with infrared radiators (IR) and heating wires (HW)) in open top chamber (OTC), and the isoprenoid emissions were measured with preconcentor-GC-MS system after warming for one, two and four months. The results showed that the isoprenoid emissions from S. superba and C. lanceolata exhibited uniformity in response to two warming facilities. IR and HW both stimulated isoprenoid emissions in two plants after one month of treatment, with increased ratios of 16.3 % and 72.5 % for S. superba, and 2.47 and 5.96 times for C. lanceolata. However, the emissions were suppressed after four months, with more pronounced effect for HW. The variation in isoprenoid emissions was primarily associated with the levels of Pn, Tr, monoterpene synthase (MTPS) activity. C. lanceolata predominantly released MTs (mainly α-pinene, α-terpene, γ-terpene, and limonene), with 39.7 % to 99.6 % of the total isoprenoid but ISO was only a very minor constituent. For S. superba, MTs constituted 24.7 % to 96.1 % of total isoprenoid. It is noteworthy that HW generated a greater disturbance to physiology activity in plants. Our study provided more comprehensive and more convincing support for integrating temperature-elevation experiments of different ecosystems and assessing response and adaptation of forest carbon cycle to global warming.

Influence of Hole Transport Layers on Buried Interface in Wide-Bandgap Perovskite Phase Segregation.

Light-induced phase segregation, particularly when incorporating bromine to widen the bandgap, presents significant challenges to the stability and commercialization of perovskite solar cells. This study explores the influence of hole transport layers, specifically poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine (PTAA) and [4-(3,6-dimethyl-9H-carbazol-9-yl)butyl]phosphonic acid (Me-4PACz), on the dynamics of phase segregation. Through detailed characterization of the buried interface, we demonstrate that Me-4PACz enhances perovskite photostability, surpassing the performance of PTAA. Nanoscale analyses using in situ Kelvin probe force microscopy and quantitative nanomechanical mapping techniques elucidate defect distribution at the buried interface during phase segregation, highlighting the critical role of substrate wettability in perovskite growth and interface integrity. The integration of these characterization techniques provides a thorough understanding of the impact of the buried bottom interface on perovskite growth and phase segregation.

Arabidopsis cryptochrome 2 forms photobodies with TCP22 under blue light and regulates the circadian clock.

Cryptochromes are blue light receptors that regulate plant growth and development. They also act as the core components of the central clock oscillator in animals. Although plant cryptochromes have been reported to regulate the circadian clock in blue light, how they do so is unclear. Here we show that Arabidopsis cryptochrome 2 (CRY2) forms photobodies with the TCP22 transcription factor in response to blue light in plant cells. We provide evidence that PPK kinases influence the characteristics of these photobodies and that together these components, along with LWD transcriptional regulators, can positively regulate the expression of CCA1 encoding a central component of the circadian oscillator.

[Effect of electroacupuncture on expression of NF-κB and TNF-α in renal tissue of rats with acute cerebral infarction].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on motor function, serum Cystatin C (Cys C) content, and expressions of tumour necrosis factor-α (TNF-α) and nuclear factor-kappa B (NF-κB) in renal tissue of rats with acute cerebral infarction (ACI), so as to explore its underlying mechanisms in protecting renal tissue after ACI. METHODS: Seventy-two male SD rats were randomly divided into three groups: sham operation, model and EA groups which were further randomly allocated to 1 d, 3 d, 7 d and 14 d subgroups (n=6 per subgroup). The ACI model was established by occlusion of the middle cerebral artery (MCAO). Rats of the EA group received EA of "Neiguan" (PC6) and "Zusanli" (ST36) for 30 min, once daily for 1, 3, 7 and 14 days, respectively. The motor function and content of Cys C were determined on the 1st, 3rd, 7th and 14th day after ACI. The expressions of TNF-α and NF-κB were detected by immunohistochemistry. RESULTS: Compared with the sham operation group, the motor function scores and the content of Cys C increased significantly on the 1st, 3rd, 7th and 14th d (P<0.01), while the numbers of TNF-α and NF-κB positive cells of the model group increased significantly on the 3rd, 7th and 14th d (P<0.01). After EA treatment, the motor function scores and the content of Cys C on the 7th, and 14th d, and the numbers of TNF-α and NF-κB positive cells on the 3rd, 7th and 14th d obviously decreased (P<0.05). CONCLUSION: EA at PC6 and ST36 can improve motor function and alleviate renal injury in ACI rats, possibly by regulating the expression of TNF-α, NF-κB in renal tissue and Cys C in serum.

Roles of a Cryptochrome in Carbon Fixation and Sucrose Metabolism in the Liverwort Marchantia polymorpha.

In vascular plants, cryptochromes acting as blue-light photoreceptors have various functions to adapt plants to the fluctuating light conditions on land, while the roles of cryptochromes in bryophytes have been rarely reported. In this study, we investigated functions of a single-copy ortholog of cryptochrome (MpCRY) in the liverwort Marchantia polymorpha. Knock-out of MpCRY showed that a large number of the mutant plants exhibited asymmetric growth of thalli under blue light. Transcriptome analyses indicated that MpCRY is mainly involved in photosynthesis and sugar metabolism. Further physiological analysis showed that Mpcry mutant exhibited a reduction in CO2 uptake and sucrose metabolism. In addition, exogenous application of sucrose or glucose partially restored the symmetrical growth of the Mpcry mutant thalli. Together, these results suggest that MpCRY is involved in the symmetrical growth of thallus and the regulation of carbon fixation and sucrose metabolism in M. polymorpha.

MXene-Based Hydrogels Endow Polyetheretherketone with Effective Osteogenicity and Combined Treatment of Osteosarcoma and Bacterial Infection.

After an osteosarcoma resection, the risks of cancer recurrence, postoperative infection, and large bone loss still threaten patients' health. Conventional treatment relies on implanting orthopedic materials to fill bone defects after surgery, but it has no ability of destroying residual tumor cells and preventing bacterial invasion. To tackle this challenge, here, we develop a novel multifunctional implant (SP@MX/GelMA) that mainly consists of MXene nanosheets, gelatin methacrylate (GelMA) hydrogels, and bioinert sulfonated polyetheretherketone (SP) with the purpose of facilitating tumor cell death, combating pathogenic bacteria, and promoting osteogenicity. Because of the synergistic photothermal effects of MXene and polydopamine (pDA), osteosarcoma cells are effectively killed on the multifunctional coatings under 808 nm near-infrared (NIR) irradiation through thermal ablation. After loading tobramycin (TOB), the SP@MX-TOB/GelMA implants display robust antibacterial properties against Gram-negative/Gram-positive bacteria. More importantly, the multifunctional implants are demonstrated to have superior cytocompatibility and osteogenesis-promoting capability in terms of cell replication, spreading, alkaline phosphatase activity, calcium matrix mineralization, and in vivo osseointegration. Accordingly, such photothermally controlled multifunctional implants not only defeat osteosarcoma cells and bacteria but also intensify osteogenicity, which hold a greatly promising countermeasure for curing postoperative tissue lesion from an osteosarcoma excision.

Antimicrobial Resistance and Virulence Profiles of mcr-1-Positive Escherichia coli Isolated from Swine Farms in Heilongjiang Province of China.

ABSTRACT: The emergence and global distribution of the mcr-1 gene for colistin resistance have become a public concern because of threats to the role of colistin as the last line of defense against some bacteria. Because of the prevalence of mcr-1-positive Escherichia coli isolates in food animals, production of these animals has been regarded as one of the major sources of amplification and spread of mcr-1. In this study, 249 E. coli isolates were recovered from 300 fecal samples collected from swine farms in Heilongjiang Province, People's Republic of China. Susceptibility testing revealed that 186 (74.70%) of these isolates were colistin resistant, and 86 were positive for mcr-1. The mcr-1-positive isolates had extensive antimicrobial resistance profiles and additional resistance genes, including blaTEM, blaCTX-M, aac3-IV, tet(A), floR, sul1, sul2, sul3, and oqxAB. No mutations in genes pmrAB and mgrB were associated with colistin resistance. Phylogenetic group analysis revealed that the mcr-1-positive E. coli isolates belonged to groups A (52.33% of isolates), B1 (33.72%), B2 (5.81%), and D (8.14%). The prevalence of the virulence-associated genes iutA, iroN, fimH, vat, ompA, and traT was moderate. Seven mcr-1-positive isolates were identified as extraintestinal pathogenic. Among 20 mcr-1-positive E. coli isolates, multilocus sequence typing revealed that sequence type 10 was the most common (five isolates). The conjugation assays revealed that the majority of mcr-1 genes were transferable at frequencies of 7.05 × 10-7 to 7.57 × 10-4. The results of this study indicate the need for monitoring and minimizing the further dissemination of mcr-1 among E. coli isolates in food animals, particularly swine.

"Wet-state" mechanical properties of three-dimensional polyester porous scaffolds.

Porous poly(D,L-lactic-co-glycolic acid) (PLGA) scaffolds under a simulated physiological environment were investigated to estimate their "true" mechanical properties, with emphasis on the effect of "wet-state" on the compressive behaviors. The effect of the history of ethanol sterilization was also investigated. The studies were focused upon the "wet-state" mechanical properties of polyester porous scaffolds, because the potential implants must be used under a wet environment. The measurements of three-dimensional porous scaffolds composed of amorphous PLGA with five polymer formulations including poly(D,L-lactic acid) (PDLLA) demonstrated that the mechanical properties of PLGA scaffolds significantly decreased in phosphate buffer saline solution (PBS) at 37 degrees C and/or with an ethanol sterilization history, even though PLGA is a hydrophobic material. The decrease extent depends on the copolymer composition: when the porosity is about 90%, a PDLLA scaffold remained about 75-80% of initial mechanical properties in the dry state at 25 degrees C, whereas PLGA 85:15, 75:25, and 65:35 scaffolds remained only about 10% or less, and the PLGA 50:50 scaffolds examined were not sufficiently strong for mechanical tests. If scaffolds were prewetted with ethanol ahead of prewetting with PBS, the mechanical properties further decreased compared with those merely prewetted with PBS. These phenomena were elucidated experimentally from plasticization of PLGA with water or ethanol, and the consequent reduction of glass transition temperature. The results might be helpful for designing polyester porous scaffolds for tissue engineering or in situ tissue induction applications.

High oxygen-reduction activity and durability of nitrogen and sulfur dual doped porous carbon microspheres.

Nitrogen and sulfur co-doped monodisperse carbon microspheres (NS-CMSs) have been successfully synthesized as a new kind of outstanding metal-free ORR catalyst through a one-pot solvothermal reaction. The as-synthesized heteroatom-doped CMSs have been systematically characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) and by using Raman spectra and nitrogen adsorption and desorption isotherms. Compared with the commercially available 20 wt% Pt/C catalyst, the as-prepared NS-CMSs showed a much better tolerance toward methanol crossover and long-term operation stability for ORR in an alkaline medium.

Fabrication of three-dimensional porous scaffolds of complicated shape for tissue engineering. I. Compression molding based on flexible-rigid combined mold.

A novel method for the fabrication of complexly shaped three-dimensional porous scaffolds has been developed by combining modified compression molding and conventional particulate leaching. The resultant scaffolds of various shapes, including some shaped like auricles, were made of hydrophobic biodegradable and bioresorbable poly(D,L-lactic acid) (PDLLA) and poly(D,L-lactic-co-glycolic acid) (PLGA). A polymer-particulate mixture was first prepared by the conventional solvent casting method and then compressively molded in a specially designed flexible-rigid combined mold which facilitates shaping and mold release during the fabrication process. The molding was carried out at a moderate temperature, above the glass transition temperature and below the flow temperature of these amorphous polymers. A porous scaffold was then obtained after particulate leaching. The pores are highly interconnected and uniformly distributed both in the bulk and on the external surface of the scaffolds, and the porosity can exceed 90%. The mechanical properties of the resultant porous scaffolds are satisfactory as determined by measurements of compressive modulus and compressive stress at 10% strain. Good viability of cells seeded in the porous scaffolds was confirmed. This novel fabrication method is promising in tissue engineering because of its ability to produce precise and complexly (anatomically) shaped porous scaffolds.

Ultrahigh volumetric capacitance and cyclic stability of fluorine and nitrogen co-doped carbon microspheres.

Highly porous nanostructures with large surface areas are typically employed for electrical double-layer capacitors to improve gravimetric energy storage capacity; however, high surface area carbon-based electrodes result in poor volumetric capacitance because of the low packing density of porous materials. Here, we demonstrate ultrahigh volumetric capacitance of 521 F cm(-3) in aqueous electrolytes for non-porous carbon microsphere electrodes co-doped with fluorine and nitrogen synthesized by low-temperature solvothermal route, rivaling expensive RuO2 or MnO2 pseudo-capacitors. The new electrodes also exhibit excellent cyclic stability without capacitance loss after 10,000 cycles in both acidic and basic electrolytes at a high charge current of 5 A g(-1). This work provides a new approach for designing high-performance electrodes with exceptional volumetric capacitance with high mass loadings and charge rates for long-lived electrochemical energy storage systems.

In vivo chondrogenesis of adult bone-marrow-derived autologous mesenchymal stem cells.

The purpose of this study has been to investigate the possible effects of the normal joint cavity environment on chondrocytic differentiation of bone-marrow-derived mesenchymal stem cells (MSCs). Autologous bone marrow was aspirated from the iliac crest of male sheep. MSCs were purified, expanded, and labeled with the fluorescent dye PKH26. Labeled MSCs were then grown on a three-dimensional porous scaffold of poly (L-lactic-co-glycolic acid) in vitro and implanted into the joint cavity by a surgical procedure. At 4 or 8 weeks after implantation, the implants were removed for histochemical and immunohistochemical analysis. The cells labeled with red fluorescent PKH26 in the implants expressed type II collagen and synthesized sulfated proteoglycans. However, the osteoblast-specific marker, osteocalcin, was not detected by immunohistochemistry indicating that the implanted MSCs had not differentiated into osteoblasts by being directly exposed to the normal joint cavity. To investigate the possible factors involved in chondrocytic differentiation of MSCs further, we co-cultured sheep MSCs with the main components of the normal joint cavity, viz., synovial fluid or synovial cells, in vitro. After 1 or 2 weeks of co-culture, the MSCs in both co-culture systems expressed markers of chondrogenesis. These results suggest that synovial fluid and synovium from normal joint cavity are important for the chondrocytic differentiation of adult bone-marrow-derived MSCs.