A Hypochlorite-Activated Theranostic Prodrug for Selective Imaging of High Myeloperoxidase Expression Acute Myeloid Leukemia Cells and Drug Release.

Acute myeloid leukemia (AML) is a fatal hematologic disease. Diagnosis and proper treatment are important for prognosis. High myeloperoxidase (MPO) expression AML cells are characterized with high levels of hypochlorite (ClO-). In this study, we report a ClO--activated theranostic agent, FNC, for AML therapy. FNC responds to ClO- specifically in high MPO expression AML cells, resulting in bright fluorescence and chlorambucil release. FNC can be used to quickly distinguish high MPO expression AML cells from other cells, including low MPO expression leukemia and activated inflammatory cells. FNC exhibits selective toxicity to highly MPO expression AML cells and can efficiently inhibit tumor growth. Meanwhile, FNC can be used to indicate differentiation through the detection of ClO-.

Design optimization of Fucoidan-coating Cationic Liposomes for enhance Gemcitabine delivery.

Obstacles facing chemotherapeutic drugs for cancers led scientists to load Gemcitabine (GEM) into nanocarriers like liposomes, known for their nontoxicity profile and targeting capacity. The liposomal nanostructures containing GEM were coated with Fucoidan (FU) due to its anti-tumor properties by targeting cancer cells. Thus four different cationic liposomes formulations were prepared by thin-film hydration method in optimal conditions: DOTAP (formulation A); DPPC/DOTAP (4:1 molar ratio, formulation B), DPPC/DMPC/DOTAP (4:1:1 molar ratio, formulation C) and DPPC/DMPC/DOTAP/DSPE-mPEG2000 (4:1:1:0.1 molar ratio, formulation D). They were studied to identify lipid-compositions offering effective GEM-entrapment and successful coating of FU on the liposome surface. Additional qualitative characteristics, such as particle size, polydispersity index, zeta potential, stability and in vitro drug release were then evaluated. Formulation C gave the best GEM-entrapment efficiency (EE) but formed aggregates when coated with FU, giving non-homogenous large size particles then not suitable for effective delivery. It was the same situation with formulation A and B. Only the formulation D showed a good GEM-EE (> 80%) and affinity by successful coating FU from three different algae species. The PEGylated formulation D coated of FU, with regard to storage stability and drug release studies, revealed to be a promising approach on design of optimal drug delivery system.

Modulating the Microstructure and Surface Acidity of MnO2 by Doping-Induced Phase Transition for Simultaneous Removal of Toluene and NOx at Low Temperature.

It is a great challenge to remove VOCs and NOx simultaneously from flue gas in nonelectric industries. This study focuses on the construction of Fe-MnO2 catalysts that perform well in the simultaneous removal of toluene and NOx at low temperatures. Utilizing the Fe-induced phase transition of MnO2, Fe-MnO2-F&R catalysts with a composite morphology of nanoflowers and nanorods were successfully prepared that provided an abundant microporous structure to facilitate the diffusion of molecules of different sizes. Through in-depth investigation of the active sites and reaction mechanism, we discovered that Fe-induced phase transition could modulate the surface acidity of Fe-MnO2-F&R. The higher concentration of surface Mn4+ provided numerous Brønsted acid sites, which effectively promoted the activation of toluene to reactive intermediates, such as benzyl alcohol/benzoate/maleic acid. Simultaneously, Fe provided a large number of Lewis acid sites that anchor and activate NH3 species, thereby inhibiting NH3 nonselective oxidation. Furthermore, additional Brønsted acid sites were generated during the simultaneous reaction process, enhancing toluene activation. Consequently, the simultaneous removal of toluene and NOx was achieved through regulation of the physical structure and the concentration of acidic sites. The present work provides new insights into the rational design of bifunctional catalysts for the synergistic control of VOCs and NOx emissions.

Isobutyric acid promotes colorectal cancer metastasis through activating RACK1.

Colorectal cancer (CRC) metastasis plays a crucial role in disease progression, yet the regulatory mechanisms underlying metastasis remain incompletely understood. Isobutyric acid (IBA), a short-chain fatty acid found at high levels in serum of CRC patients, has been shown to be a critical metabolite influencing CRC proliferation. However, its role in tumor metastasis remains unknown. Here, utilizing liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis, we found that levels of IBA were significantly higher in patients with distant organ metastasis of CRC than in those without. Furthermore, IBA promoted CRC metastasis both in vitro and in vivo. Mass spectrometry, immunofluorescence, and cellular thermal shift assay revealed that IBA interacts with RACK1. Mechanistically, IBA binding to and activating RACK1 promotes regulation of downstream Akt and FAK signaling and CRC metastasis. Collectively, our study highlights the critical interplay between IBA and RACK1 and its impact on tumor metastasis. This study suggests that targeting the IBA-RACK1 signaling axis may be an effective therapeutic strategy for controlling CRC metastasis.

A Novel Microbial Consortia Catalysis Strategy for the Production of Hydroxytyrosol from Tyrosine.

Hydroxytyrosol, a valuable plant-derived phenolic compound, is increasingly produced from microbial fermentation. However, the promiscuity of the key enzyme HpaBC, the two-component flavin-dependent monooxygenase from Escherichia coli, often leads to low yields. To address this limitation, we developed a novel strategy utilizing microbial consortia catalysis for hydroxytyrosol production. We designed a biosynthetic pathway using tyrosine as the substrate and selected enzymes and overexpressing glutamate dehydrogenase GdhA to realize the cofactor cycling by coupling reactions catalyzed by the transaminase and the reductase. Additionally, the biosynthetic pathway was divided into two parts and performed by separate E. coli strains. Furthermore, we optimized the inoculation time, strain ratio, and pH to maximize the hydroxytyrosol yield. Glycerol and ascorbic acid were added to the co-culture, resulting in a 92% increase in hydroxytyrosol yield. Using this approach, the production of 9.2 mM hydroxytyrosol was achieved from 10 mM tyrosine. This study presents a practical approach for the microbial production of hydroxytyrosol that can be promoted to produce other value-added compounds.

Highly efficient metal-organic frameworks adsorbent for Pd(II) and Au(III) recovery from solutions: Experiment and mechanism.

With the boom of modern industry, the demand for precious metals palladium (Pd) and gold (Au) is increasing. However, the discharge of Pd(II) and Au(III) wastewater has caused environmental pollution and shortage of resources. Here, a new metal-organic frameworks adsorbent (MOF-AFH) was synthesized to efficiently separate Pd(II) and Au(III) from the water. The adsorption behavior of Pd(II) and Au(III) was explored at the same time. When gold and palladium are adsorbed separately, the adsorption capacity of gold and palladium is 389.02 mg/g and 191.27 mg/g, respectively. The equilibration time is 3 h. When gold and palladium coexist, the adsorption capacities of Au(III) and Pd(II) are 238.71 and 115.02 mg/g, respectively. The experimental results show that the adsorption of Pd(II) and Au(III) on MOF-AFH is a single-layer chemical adsorption, which is an endothermic process. MOF-AFH has excellent selectivity and after MOF-AFH is repeatedly used 4 times, the removal effect can still reach more than 90%. The adsorption mechanisms include reduction reaction and chelation with N and O-containing functional groups on the adsorbent. There is also electrostatic interaction for Au(III) adsorption. The adsorbent can be used to efficiently recover gold and palladium from wastewater.

Trojan Nanobacteria System for Photothermal Programmable Destruction of Deep Tumor Tissues.

A novel bacteria-based drug delivery system, termed "Trojan nanobacteria system", has been developed in which nanoagents are internalized into engineered bacteria through bacteria-specific maltodextrin (MD) transporters. Compared to the method of attaching nanoagents to bacterial surfaces, this Trojan system features higher payloads and better stability. In cancer therapy, Trojan nanobacteria can specifically discriminate the tumor region and then penetrate deep tumor tissues. Once in the tumor, the Trojan nanobacteria systems are able to destroy deep tumor tissues due to the combined effects of antitumor protein expression (e.g., tumor necrosis factor-α, TNF-α) and photothermal properties.

Advances in genome-wide association studies of complex traits in rice.

Genome-wide association studies (GWAS), genetic surveys of the whole genome to detect variants associated with a trait in natural populations, are a powerful approach for dissecting complex traits. This genetic mapping approach has been applied in rice over the last 10 years. During the last decade, GWAS was used to identify the loci underlying tens of rice traits, and several important genes were detected in GWAS and further confirmed in follow-up functional experiments. In this review, we present an overview of the whole process in a typical GWAS, including population design, genotyping, phenotyping and analysis methods. Recent advances in rice GWAS are also provided, including several examples of the functional characterization of candidate genes. The possible breakthroughs of rice GWAS in the next decade are discussed with regard to their application in breeding, the consideration of epistatic interactions and in-depth functional annotations of DNA elements and genetic variants throughout the rice genome.

Multifunctional Silicon-Carbon Nanohybrids Simultaneously Featuring Bright Fluorescence, High Antibacterial and Wound Healing Activity.

In this work, a class of multifunctional silicon-carbon nanohybrids (designated as SiCNs), which simultaneously possess aqueous dispersibility, bright fluorescence (photoluminescence quantum yield [PLQY]: ≈28%), as well as high antibacterial and wound healing activity, is presented. Taking advantage of these unique merits, cell distribution and pharmacological behavior of the SiCNs is first investigated through tracking their strong and stable fluorescence. The high bacteria inhibition ability (≈82.9% killing rate toward S. aureus) and hemostatic effects (shorten the bleeding time from ≈60 to ≈15 s) of the resultant SiCNs are then demonstrated. Moreover, the wound closure promotion activity (10% lead in wound contraction) is systematically demonstrated in vivo, which is especially suitable for wound healing applications. The results suggest the SiCNs as a new kind of high-performance multifunctional nanoagents suitable for various biological and biomedical utilizations.

Performance and microbial community of the completely autotrophic nitrogen removal over nitrite process with a submerged aerated biological filter.

Stable performance is a technical problem in the completely autotrophic nitrogen removal over nitrite (CANON) process with one single stage, which needs to be addressed. In the current work, a laboratory-scale submerged aerated biological filter (SABF) with a 3-L working volume was introduced into the CANON process to enhance its stable performance for 290 days under the following conditions: temperature of 30 ± 1 °C and dissolved oxygen (DO) level of 0.2-0.8 mg·L-1. The results showed that the average ammonium nitrogen removal efficiencies (ANRE) and total nitrogen removal efficiencies (TNRE) were 97.4% and 75.7%, respectively. A 16S rRNA gene high-throughput sequencing technology confirmed the phyla Proteobacteria and Planctomycetes as the ammonium oxidizing bacteria (AOB) and anaerobic ammonia-oxidizing bacteria (AnAOB) of this CANON process with SABF, respectively. The major contributor to nitrogen removal was the genus Candidatus Brocadia, in Brocadiae. The aim is to present an effective strategy as a reference for the design of full-scale plant for the CANON process.

Highly sensitive electrochemical DNA sensor based on the use of three-dimensional nitrogen-doped graphene.

This paper describes a voltammetric method for sensitive determination of specific sequences of DNA. The assay is based on three-dimensional nitrogen-doped graphene (3D-NG) which, due to its excellent electrical conductivity, provides a favorable microenvironment to retain the activity of immobilized probe single-stranded DNA and also facilitates electron transfer. The free-standing 3D-NG electrode was characterized by scanning electron microscopy, Raman and X-ray photoelectron spectroscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. Differential pulse voltammetry was applied to monitor DNA hybridization using Methylene Blue as an electrochemical indicator. Under optimal conditions, the peak currents (best measured at 0.28 V vs. Ag/AgCl) increase linearly with the logarithm of the concentrations of ssDNA in the 10 f. to 10 nM concentrations range, with a 3.5 f. detection limit (at a signal/noise ratio of 3). The biosensor exhibits good selectivity for ssDNA and can distinguish even single-base mismatches. The capability of the method was tested with spiked serum samples, and excellent reproducibility and stability is found. This indicates that the strategy is promising for use in clinical applications. Graphical abstract Three-dimensional nitrogen-doped graphene as an innovative and simple electrochemical DNA biosensor was fabricated and used in a biosensor that shows high sensitivity and good performance in the determination of target DNA in human serum samples.

A Novel Multi-Epitope Vaccine Based on Urate Transporter 1 Alleviates Streptozotocin-Induced Diabetes by Producing Anti-URAT1 Antibody and an Immunomodulatory Effect in C57BL/6J Mice.

Hyperuricemia (HUA) is related to diabetes. Uric acid-induced inflammation and oxidative stress are risk factors for diabetes and its complications. Human urate transporter 1 (URAT1) regulates the renal tubular reabsorption of uric acid. IA-2(5)-P2-1, a potent immunogenic carrier designed by our laboratory, can induce high-titer specific antibodies when it carries a B cell epitope, such as B cell epitopes of DPP4 (Dipeptidyl peptidase-4), xanthine oxidase. In this report, we describe a novel multi-epitope vaccine composing a peptide of URAT1, an anti-diabetic B epitope of insulinoma antigen-2(IA-2) and a Th2 epitope (P2:IPALDSLTPANED) of P277 peptide in human heat shock protein 60 (HSP60). Immunization with the multi-epitope vaccine in streptozotocin-induced diabetes C57BL/6J mice successfully induced specific anti-URAT1 antibody, which inhibited URAT1 action and uric acid reabsorption, and increased pancreatic insulin level with a lower insulitis incidence. Vaccination with U-IA-2(5)-P2-1 (UIP-1) significantly reduced blood glucose and uric acid level, increased Th2 cytokines interleukin (IL)-10 and IL-4, and regulated immune reactions through a balanced Th1/Th2 ratio. These results demonstrate that the URAT1-based multi-epitope peptide vaccine may be a suitable therapeutic approach for diabetes and its complications.

Reflective all-fiber magnetic field sensor based on microfiber and magnetic fluid.

A kind of reflective all-fiber magnetic field sensor based on a non-adiabatically tapered microfiber with magnetic fluid is proposed and experimentally demonstrated. The modal interference effect is caused by the abrupt tapers, which result in an approximately sinusoidal spectral response. The reflection spectra of the proposed sensor under different magnetic field strengths have been measured and theoretically analyzed. The maximum sensitivity of 174.4 pm/Oe is achieved at wavelength of around 1511 nm. Besides, an intensity tunability of -0.02 dB/Oe is also achieved. Comparing with the traditional sensors operating at transmission mode, the presented sensor in this work owns the advantages of smaller size and higher sensitivity and resolution due to the enhanced extinction ratio. The proposed structure is also promising for designing other tunable all-in-fiber photonic devices.

Magnetic field sensing based on magnetic-fluid-clad multimode-singlemode-multimode fiber structures.

Magnetic field sensing based on magnetic-fluid-clad multimode-singlemode- multimode fiber structures is proposed and experimentalized. The structures are fabricated out using fiber fusion splicing techniques. The sensing principle is based on the interference between the core mode and cladding modes. Two interference dips are observed in our spectral range. Experimental results indicate that the magnetic field sensing sensitivities of 215 pm/mT and 0.5742 dB/mT are obtained for interference dip around 1595 nm. For interference dip around 1565 nm, the sensitivities are 60.5 pm/mT and 0.4821 dB/mT. The response of temperature is also investigated. The temperature sensitivity for the dip around 1595 nm is obtained to be 9.93 pm/°C.

The regulating mechanism of salt tolerance of black walnut seedlings was revealed by the physiological and biochemical integration analysis.

Salt stress is an important abiotic stress that seriously affects plant growth. In order to research the salt tolerance of walnut rootstocks so as to provide scientific basis for screening salt-tolerant walnut rootstocks, two kinds of black walnut seedlings, Juglans microcarpa L. (JM) and Juglans nigra L. (JN), were treated under salt stress with different concentrations of NaCl (0, 50, 100, and 200 mM) and the growth situation of seedlings were observed. The physiological indexes of JM and JN seedlings were also measured in different days after treatment. Our study showed salt stress inhibited seedlings growth and limited biomass accumulation. Walnut mainly increased osmotic adjustment ability by accumulation Pro and SS. Furthermore, with the duration of treatment time increased, SOD and APX activities decreased, TPC and TFC contents increased. Walnut accumulated Na mostly in roots and transported more K and Ca to aboveground parts. The growth and physiological response performance differed between JM and JN, specifically, the differences occurred in the ability to absorb minerals, regulate osmotic stress, and scavenge ROS. Salt tolerance of JM and JN was assessed by principal component analysis (PCA) and resulted in JN > JM. In conclusion, our results indicated that JN has higher salt tolerance than JM, and JN might be used as a potential germplasm resource for the genetic breeding of walnuts.

Effect of Persistent Salt Stress on the Physiology and Anatomy of Hybrid Walnut (Juglans major × Juglans regia) Seedlings.

Soil salinization has become one of the major problems that threaten the ecological environment. The aim of this study is to explore the mechanism of salt tolerance of hybrid walnuts (Juglans major × Juglans regia) under long-term salt stress through the dynamic changes of growth, physiological and biochemical characteristics, and anatomical structure. Our findings indicate that (1) salt stress inhibited seedling height and ground diameter increase, and (2) with increasing salt concentration, relative water content (RWC) decreased, and proline (Pro) and soluble sugar (SS) content increased. The Pro content reached a maximum of 549.64 µg/g on the 42nd day. The increase in superoxide dismutase (SOD) activity (46.80-117.16%), ascorbate peroxidase (APX) activity, total flavonoid content (TFC), and total phenol content (TPC) under salt stress reduced the accumulation of malondialdehyde (MDA). (3) Increasing salt concentration led to increases and subsequent decreases in the thickness of palisade tissues, spongy tissues, leaves, and leaf vascular bundle diameter. Upper and lower skin thickness, root periderm thickness, root diameter, root cortex thickness, and root vascular bundle diameter showed different patterns of change at varying stress concentrations and durations. Overall, the study concluded that salt stress enhanced the antireactive oxygen system, increased levels of osmotic regulators, and low salt concentrations promoted leaf and root anatomy, but that under long-term exposure to high salt levels, leaf anatomy was severely damaged. For the first time, this study combined the anatomical structure of the vegetative organ of hybrid walnut with physiology and biochemistry, which is of great significance for addressing the challenge of walnut salt stress and expanding the planting area.

A selective mitochondria-targeted fluorescent probe for imaging cysteine in drug-induced liver injury.

Cysteine (Cys) is involved in many physiological processes. It's challenging to detect Cys selectively as it has similar chemical structure with other biothiols such as homocysteine (Hcy) and glutathione (GSH). In this work, a novel fluorescence probe toward mitochondrial cysteine, HPXI-6C, has been developed by employing carbonate as a new recognizing unit and hemicyanine as a chromophore. HPXI-6C exhibits a high selectivity to Cys over hydrogen sulfide, homocysteine and glutathione. The limit of detection toward Cys was determined to be 42 nM. HPXI-6C can localize in mitochondria and produce strong fluorescence peaked at 725 nm in response to Cys in tumor cells. The uptake and generation pathways of Cys in acetaminophen hepatotoxicity cells was revealed by using HPXI-6C. HPXI-6C has been successfully applied in imaging of Cys in drug-induced liver injury in vivo. The research demonstrated that HPXI-6C is powerful in monitoring Cys and is conducive to the early diagnosis of drug-induced liver injury diseases.

Differential Strategies of Two Arbuscular Mycorrhizal Fungi Varieties in the Protection of Lycium ruthenicum under Saline-Alkaline Stress.

To delve into the growth and physiological adaptations exhibited by the economically vital black wolfberry (Lycium ruthenicum) upon inoculation with arbuscular mycorrhizal fungi (AMF) under varying levels of saline-alkaline stress A series of pot experiments were conducted in a gradient saline-alkaline environment (0, 200, 400 mM NaCl: NaHCO3 = 1:1). One-year-old cuttings of black wolfberry, inoculated with two AMF species-Funneliformis mosseae (Fm) and Rhizophagus intraradices (Ri)-served as the experimental material, enabling a comprehensive analysis of seedling biomass, chlorophyll content, antioxidant enzyme activities, and other crucial physiological parameters. This study demonstrated that both Fm and Ri could form a symbiotic relationship with the root of Lycium ruthenicum. Notably, Fm inoculation significantly bolstered the growth of the underground parts, while exhibiting a remarkable capacity to scavenge reactive oxygen species (ROS), thereby effectively mitigating membrane oxidative damage induced by stress. Additionally, Fm promoted the accumulation of abscisic acid (ABA) in both leaves and roots, facilitating the exclusion of excess sodium ions from cells. Ri Inoculation primarily contributed to an enhancement in the chlorophyll b (Chlb) content, vital for sustaining photosynthesis processes. Furthermore, Ri's ability to enhance phosphorus (P) absorption under stressful conditions ensured a steady influx of essential nutrients. These findings point to different strategies employed for Fm and Ri inoculation. To holistically assess the saline-alkaline tolerance of each treatment group, a membership function analysis was employed, ultimately ranking the salt tolerance as Fm > Ri > non-mycorrhizal (NM) control. This finding holds paramount importance for the screening of highly resilient Lycium ruthenicum strains and offers invaluable theoretical underpinnings and technical guidance for the remediation of saline-alkaline soils, fostering sustainable agricultural practices in challenging environments.

A Common Neuronal Ensemble in the Lateral Habenula Regulates Ciprofol Anesthesia in Mice.

General anesthetics were first used over 170 years ago; however, the mechanisms of how general anesthetics induce loss of consciousness (LOC) remain unclear. Ciprofol, a novel intravenous anesthetic, has been developed by incorporating cyclopropyl into the chemical structure of propofol. This modification offers the benefits of rapid onset and minimal injection pain. Recent studies have revealed that the glutamatergic neurons of the lateral habenula (LHb) play a crucial role in modulating the LOC induced by propofol and sevoflurane. Nevertheless, the specific involvement of LHb in the anesthetic effects of ciprofol remains uncertain. Here, using targeted recombination in active populations (TRAP) combined with electroencephalogram/electromyography recordings and the righting reflex behavioral test, our study revealed that intravenous infusion of ciprofol for 1 h could lead to the induction of c-Fos expression in the LHb in mice. The combination of TRAP and gene ablation, aimed at selectively ablating ciprofol-activated neurons in the LHb, has been shown to facilitate the emergence of ciprofol anesthesia and decrease the proportion of delta waves during the emergence phase. Chemogenetic inhibition of these neurons produced a comparable effect, whereas chemogenetic activation resulted in the opposite outcome. Chemogenetic activation of ciprofol-activated neurons in the LHb delays the emergence of anesthesia and induces a deep hypnotic state during the emergence phase. Taken together, our findings suggest that LHb ciprofol-activated neurons modulate the state of consciousness and could potentially be targeted to manipulate consciousness during ciprofol anesthesia.

Biosynthesis and Biotechnological Synthesis of Hydroxytyrosol.

Hydroxytyrosol (HT), a plant-derived phenolic compound, is recognized for its potent antioxidant capabilities alongside a spectrum of pharmacological benefits, including anti-inflammatory, anti-cancer, anti-bacterial, and anti-viral properties. These attributes have propelled HT into the spotlight as a premier nutraceutical and food additive, heralding a new era in health and wellness applications. Traditional methods for HT production, encompassing physico-chemical techniques and plant extraction, are increasingly being supplanted by biotechnological approaches. These modern methodologies offer several advantages, notably environmental sustainability, safety, and cost-effectiveness, which align with current demands for green and efficient production processes. This review delves into the biosynthetic pathways of HT, highlighting the enzymatic steps involved and the pivotal role of genetic and metabolic engineering in enhancing HT yield. It also surveys the latest progress in the biotechnological synthesis of HT, examining innovative strategies that leverage both genetically modified and non-modified organisms. Furthermore, this review explores the burgeoning potential of HT as a nutraceutical, underscoring its diverse applications and the implications for human health. Through a detailed examination of both the biosynthesis and biotechnological advances in HT production, this review contributes valuable insights to the field, charting a course towards the sustainable and scalable production of this multifaceted compound.