MicroRNA-148a-3p suppresses the glycolysis and Cell proliferation by targeting transmembrane protein 54 in liver cancer.

Liver cancer is the fourth most lethal cancer, but the treatment options for liver cancer are usually limited. Metabolic reprogramming is a hallmark of malignancy, ensuring activated cell glycolysis and increased macromolecular precursors required for the proliferation and migration of exuberant cancer cells. MicroRNAs (miRNAs) have been reported to participate in cancer metabolic shifts mainly by directly silencing the expression of specific genes. Here, we identified miR-148a-3p as a negative regulator for glycometabolism and cell proliferation in liver cancer. miR-148a-3p directly targets the 3'UTR of transmembrane protein 54 (TMEM54), leading to the significant inhibition of lactate production, glucose consumption, intracellular ATP level and extracellular acidification rate (ECAR), as well as the repression of the proliferation and colony formation ability of liver cancer cells. miR-148a-3p expression is often down-regulated in liver cancer tissues. In addition, there was a negative correlation between the expression levels of miR-148a-3p and TMEM54 in liver cancer tissues. Moreover, the low miR-148a-3p expression levels or high TMEM54 expression levels were associated with poorer prognosis in hepatocellular carcinoma (HCC) patients. Together, these findings support that the miR-148a-3p/TMEM54 regulatory pathway regulates the glycometabolism and cell proliferation in liver cancer, which is a possible target for the diagnosis and treatment of liver cancer.

The impact of public leadership on collaborative administration and public health delivery.

BACKGROUND: This research depicts the linkage of public leadership on public health delivery (PHD) and collaborative administration. The research is also focused to examine the effect of public leadership on public health delivery through the intervening variable of collaborative administration by using both social information processing theory and collaboration theory. METHODS: This research is based on quantitative method. Data was collected from 464 public hospital administration in the context of Pakistan. This study evaluated data using SPSS, AMOS, and PROCESS Macro. RESULTS: Public leadership has a positive profound effect on public health delivery and collaborative administration, and that collaborative administration significantly promotes public health delivery. The outcomes also exposed that public leadership has substantial influence on public health delivery through intervening collaborative administration. CONCLUSIONS: Whilst public leadership demonstrated positive outcomes on public health delivery and collaborative administration, there is a need for more rigor studies on collaborative governance leadership, collaborative ethics and collaborative norms in the public health service.

Serum and urine metabolomics based on UPLC-QTOF/MS reveal the effect and potential mechanism of "schisandra-evodia" herb pair in the treatment of Alzheimer's disease.

The "schisandra-evodia" herb pair (S-E) is a herbal preparation to treat Alzheimer's disease (AD). This study aims to investigate the therapeutic efficacy and potential mechanism of S-E in AD rats, utilizing pharmacodynamic assessments and serum- and urine-based metabolomic analyses. Pharmacodynamic assessments included Morris water maze test, hematoxylin-eosin staining and immunohistochemistry experiments. The results of the study showed that the AD model was successful; the S-E significantly enhanced long-term memory and spatial learning in AD rats. Meanwhile, S-E notably ameliorated Aß25-35-induced cognitive impairment, improved hippocampal neuron morphology, decreased Aß deposition in the hippocampus and mitigated inflammatory damage. We then analyzed serum and urine samples using UPLC-MS/MS to identify potential biomarkers and metabolic pathways. Metabolomic analysis revealed alterations in 40 serum metabolites and 38 urine metabolites following S-E treatment, predominantly affecting pathways related to taurine and hypotaurine metabolism, linoleic acid metabolism, α-linolenic acid metabolism, glycerophospholipid metabolism and arachidonic acid metabolism. This study elucidates the biochemical mechanism underlying AD and the metabolic pathway influenced by S-E, laying the groundwork for future clinical applications.

A Novel Ultrafiltrate Extract of Propolis Exerts Anti-inflammatory Activity through Metabolic Rewiring.

Thousands of years ago, humans started to use propolis because of its medicinal properties, and modern science has successfully identified several bioactive molecules within this resinous bee product. However, a natural propolis extract which has been removed the adhesive glue and preserved propolis bioactive compounds is urgently needed to maximise the therapeutic opportunities. In this study, a novel ultrafiltrate fraction from Brazilian green propolis, termed P30K, was demonstrated with anti-inflammatory properties, both in vitro and in vivo. Total flavonoids and total phenolic acids content in P30K were 244.6 mg/g and 275.8 mg/g respectively, while the IC50 value of inhibition of cyclooxygenase-2 (COX-2) was 8.30 µg/mL. The anti-inflammatory activity of P30K was furtherly corroborated in experimental models of lipopolysaccharides (LPS)-induced acute liver and lung injury. Mechanistically, integrated GC-MS and LC-MS based serum metabolomics analysis revealed that P30K modulated citrate cycle (TCA), pyruvate, glyoxylate and dicarboxylate metabolism pathways to inhibit secretion of pro-inflammatory cytokines. Results of network pharmacology and molecular docking suggested that P30K targeted catechol-O-methyltransferases (COMT), 11ß-hydroxysteroid dehydrogenases (HSD11B1), and monoamine oxidases (MAOA and MAOB) to promote cellular metabolomic rewiring. Collectively, our work reveals P30K as an efficient therapeutic agent against inflammatory conditions and its efficacy is related to metabolic rewiring.

Spontaneous Reduction of Transition Metal Ions by One Electron in Water Microdroplets and the Atmospheric Implications.

Freshman chemistry teaches that Fe3+ and Cu2+ ions are stable in water solutions, but their reduced forms, Fe2+ and Cu+, cannot exist in water as the major oxidation state due to the fast oxidation by O2 and/or disproportionation. Contrary to these well-known facts, significant fractions of dissolved Fe and Cu species exist in their reduced oxidation states in atmospheric water such as deliquesced aerosols, clouds, and fog droplets. Current knowledge attributes these phenomena to the stabilization of the lower oxidation states by the complexation of ligands and the various photochemical or thermal pathways that can reduce the higher oxidation states. In this study, by spraying the water solutions of transition metal ions into microdroplets, we show the results of the spontaneous reduction of ligated Fe(III) and Cu(II) species into Fe(II) and Cu(I) species, presenting a previously unknown source of reduced transition metal ions in atmospheric water. It is the spontaneously generated electrons in water microdroplets that are responsible for the reduction. Control experiments in the atmosphere and in a glove box filled with precisely controlled gaseous contents reveal that O2, CO2, and NO2 are the major competitors for the electrons, forming O2-, HCO2-, and NO2-, respectively. Taking these findings together, we opine that microdroplet chemistry might play significant but previously underestimated roles in atmospheric redox chemistry.

Spontaneous Reduction by One Electron on Water Microdroplets Facilitates Direct Carboxylation with CO2.

Recent advances in microdroplet chemistry have shown that chemical reactions in water microdroplets can be accelerated by several orders of magnitude compared to the same reactions in bulk water. Among the large plethora of unique properties of microdroplets, an especially intriguing one is the strong reducing power that can be sometimes as high as alkali metals as a result of the spontaneously generated electrons. In this study, we design a catalyst-free strategy that takes advantage of the reducing ability of water microdroplets to reduce a certain molecule, and the reduced form of that molecule can convert CO2 into value-added products. By spraying the water solution of C6F5I into microdroplets, an exotic and fragile radical anion, C6F5I•-, is observed, where the excess electron counter-intuitively locates on the σ* antibonding orbital of the C-I bond as evidenced by anion photoelectron spectroscopy. This electron weakens the C-I bond and causes the formation of C6F5-, and the latter attacks the carbon atom on CO2, forming the pentafluorobenzoate product, C6F5CO2-. This study provides a good example of strategically making use of the spontaneous properties of water microdroplets, and we anticipate that microdroplet chemistry will be a green avenue rich in new opportunities in CO2 utilization.

High Electric Fields on Water Microdroplets Catalyze Spontaneous and Fast Reactions in Halogen-Bond Complexes.

The use of external electric fields as green and efficient catalysts in synthetic chemistry has recently received significant attention for their ability to deliver remarkable control of reaction selectivity and acceleration of reaction rates. Technically, methods of generating high electric fields in the range of 1-10 V/nm are limited, as in-vacuo techniques have obvious scalability issues. The spontaneous high fields at various interfaces promise to solve this problem. In this study, we take advantage of the spontaneous high electric field at the air-water interface of sprayed water microdroplets in the reactions of several halogen bond systems: Nu:--X-X, where Nu: is pyridine or quinuclidine and X is bromine or iodine. The field facilitates ultrafast electron transfer from Nu:, yielding a Nu-X covalent bond and causing the X-X bond to cleave. This reaction occurs in microseconds in microdroplets but takes days to weeks in bulk solution. Density functional theory calculations predict that the reaction becomes barrier-free in the presence of oriented external electric fields, supporting the notion that the electric fields in the water droplets are responsible for the catalysis. We anticipate that microdroplet chemistry will be an avenue rich in opportunities in the reactions facilitated by high electric fields and provides an alternative way to tackle the scalability problem.

Harnessing the High Interfacial Electric Fields on Water Microdroplets to Accelerate Menshutkin Reactions.

Even though it is still an emerging field, the application of a high external electric field (EEF) as a green and efficient catalyst in synthetic chemistry has recently received significant attention for the ability to deliver remarkable control of reaction selectivity and acceleration of reaction rates. Here, we extend the application of the EEF to Menshutkin reactions by taking advantage of the spontaneous high electric field at the air-water interfaces of sprayed water microdroplets. Experimentally, a series of Menshutkin reactions were accelerated by 7 orders of magnitude. Theoretically, both density functional theory calculations and ab initio molecular dynamics simulations predict that the reaction barrier decreases significantly in the presence of oriented external electric fields, thereby supporting the notion that the electric fields in the water droplets are responsible for the catalysis. In addition, the ordered solvent and reactant molecules oriented by the electric field alleviate the steric effect of solvents and increase the successful collision rates, thus facilitating faster nucleophilic attack. The success of Menshutkin reactions in this study showcases the great potential of microdroplet chemistry for green synthesis.

Neutrophil extracellular traps promote keratinocyte inflammation via AIM2 inflammasome and AIM2-XIAP in psoriasis.

The infiltration of neutrophils in the epidermis and the release of neutrophil extracellular traps (NETs) are important events in the pathogenesis of psoriasis, but the regulatory roles and internal mechanism of NETs in psoriasis are largely unknown. Here, we demonstrate that NETs can activate the absent-in-melanoma-2 (AIM2) inflammasome in keratinocytes through the p38-MAPK signalling pathway, and targeting NETs with CI-amidine in vivo reduces AIM2 expression and ameliorates imiquimod-induced psoriasis-like phenotype in mice. Notably, NETs-activated AIM2 in keratinocytes not only promotes IL-1ß production through the classical inflammasome pathway but also promotes IFN-γ production via X-linked inhibitor of apoptosis protein (XIAP), thereby mediating the immune responses of keratinocytes. In conclusion, our study demonstrates that the NETs-AIM2 axis exerts multiple pro-inflammatory effects on keratinocytes and may serve as a potential target for psoriasis therapy.

Investigation of the mechanical and transport properties of InGeX3 (X = S, Se and Te) monolayers using density functional theory and machine learning.

Recently, novel 2D InGeTe3 has been successfully synthesized and attracted attention due to its excellent properties. In this study, we investigated the mechanical properties and transport behavior of InGeX3 (X = S, Se and Te) monolayers using density functional theory (DFT) and machine learning (ML). The key physical parameters related to mechanical properties, including Poisson's ratio, elastic modulus, tensile strength and critical strain, were revealed. Using a ML method to train DFT data, we developed a neuroevolution-potential (NEP) to successfully predict the mechanical properties and lattice thermal conductivity. The fracture behavior predicted using NEP-based MD simulations in a large supercell containing 20 000 atoms could be verified using DFT. Due to the effects of size, these predicted physical parameters have a slight difference between DFT and ML methods. At 300 K, these monolayers exhibited a low thermal conductivity with the values of 13.27 ± 0.24 W m-1 K-1 for InGeS3, 7.68 ± 0.30 W m-1 K-1 for InGeSe3, and 3.88 ± 0.09 W m-1 K-1 for InGeTe3, respectively. The Boltzmann transport equation (BTE) including all electron-phonon interactions was used to accurately predict the electron mobility. Compared with InGeS3 and InGeSe3, the InGeTe3 monolayer showed flexible mechanical behavior, low thermal conductivity and high mobility.

Spontaneous and Simultaneous Oxidation and Reduction of o-Quinones in Water Microdroplets.

Microdroplet chemistry has been an emerging new field for its large plethora of unique properties, among which an especially intriguing one is the strong oxidizing and reducing powers. The hydroxide ion in water microdroplets is considered to split into a hydroxyl radical and an electron at the air-water interface, and the former is responsible for the oxidizing capability while the latter is responsible for the reducing power, making a unity of opposites. However, to date there are only two examples showing that oxidation and reduction occur simultaneously to the same substrates, which might be a result of the redox properties of the substrate per se. In this study, we carefully chose a group of ο-quinone compounds as the substrates in water microdroplets and discovered that they can be both oxidized by the hydroxyl radical and reduced by the electron. These results keep pushing the limit of the unique redox properties of microdroplet chemistry.

[Research advances in role of angiogenesis in diabetic ulcer and traditional Chinese medicine intervention].

Diabetic ulcer(DU) is one of the common complications of diabetes often occurring in the peripheral blood vessels of lower limbs or feet with a certain degree of damage. It has high morbidity and mortality, a long treatment cycle, and high cost. DU is often clinically manifested as skin ulcers or infections in the lower limbs or feet. In severe cases, it can ulcerate to the surface of tendons, bones or joint capsules, and even bone marrow. Without timely and correct treatment, most of the patients will have ulceration and blackening of the extremities. These patients will not be able to preserve the affected limbs through conservative treatment, and amputation must be performed. The etiology and pathogenesis of DU patients with the above condition are complex, which involves blood circulation interruption of DU wound, poor nutrition supply, and failure in discharge of metabolic waste. Relevant studies have also confirmed that promoting DU wound angiogenesis and restoring blood supply can effectively delay the occurrence and development of wound ulcers and provide nutritional support for wound healing, which is of great significance in the treatment of DU. There are many factors related to angiogenesis, including pro-angiogenic factors and anti-angiogenic factors. The dynamic balance between them plays a key role in angiogenesis. Meanwhile, previous studies have also confirmed that traditional Chinese medicine can enhance pro-angiogenic factors and down-regulate anti-angiogenic factors to promote angiogenesis. In addition, many experts and scholars have proposed that traditional Chinese medicine regulation of DU wound angiogenesis in the treatment of DU has broad prospects. Therefore, by consulting a large number of studies available, this paper expounded on the role of angiogenesis in DU wound and summarized the research advance in traditional Chinese medicine intervention in promoting the expression of angiogenic factors [vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), and angiopoietin(Ang)] which played a major role in promoting wound angiogenesis in the treatment of DU to provide ideas for further research and new methods for clinical treatment of DU.

[Research progress in role of autophagy in diabetic wound healing and traditional Chinese medicine intervention].

Diabetic ulcer(DU) is a chronic and refractory ulcer which often occurs in the foot or lower limbs. It is a diabetic complication with high morbidity and mortality. The pathogenesis of DU is complex, and the therapies(such as debridement, flap transplantation, and application of antibiotics) are also complex and have long cycles. DU patients suffer from great economic and psychological pressure while enduring pain. Therefore, it is particularly important to promote rapid wound healing, reduce disability and mortality, protect limb function, and improve the quality of life of DU patients. By reviewing the relevant literatures, we have found that autophagy can remove DU wound pathogens, reduce wound inflammation, and accelerate ulcer wound healing and tissue repair. The main autophagy-related factors microtubule-binding light chain protein 3(LC3), autophagy-specific gene Beclin-1, and ubiquitin-binding protein p62 mediate autophagy. The traditional Chinese medicine(TCM) treatment of DU mitigates clinical symptoms, accelerates ulcer wound healing, reduces ulcer recurrence, and delays further deterioration of DU. Furthermore, under the guidance of syndrome differentiation and treatment and the overall concept, TCM treatment harmonizes yin and yang, ameliorates TCM syndrome, and treats underlying diseases, thereby curing DU from the root. Therefore, this article reviews the role of autophagy and major related factors LC3, Beclin-1, and p62 in the healing of DU wounds and the intervention of TCM, aiming to provide reference for the clinical treatment of DU wounds and subsequent in-depth studies.

High Electric Field on Water Microdroplets Catalyzes Spontaneous and Ultrafast Oxidative C-H/N-H Cross-Coupling.

Oxidative C-H/N-H cross-coupling has emerged as an atom-economical method for the construction of C-N bonds. Conventional oxidative C-H/N-H coupling requires at least one of the following: high temperatures, strong oxidizers, transition metal catalysts, organic solvents, light, and electrochemical cells. In this study, by merely spraying the water solutions of the substrates into microdroplets at room temperature, we show a series of oxidative C-H/N-H coupling products that are strikingly produced in a spontaneous and ultrafast manner. The reactions are accelerated by six orders of magnitude compared to the same reactions in the bulk. It has been previously proposed by fluorescence microscopy and theory that the spontaneously generated electric field at the microdroplets peripheries can be in the ∼109 V/m range. Based on mass spectrometric analysis of key radical intermediates, we opine that the ultrahigh electric field catalytically oxidizes the substrates by removing an electron, which further promotes C/N coupling. Taken together, we anticipate that microdroplet chemistry will be an avenue rich in green opportunities of constructing C-heteroatom bonds.

Spontaneous Reduction-Induced Degradation of Viologen Compounds in Water Microdroplets and Its Inhibition by Host-Guest Complexation.

Water serves as an inert environment for the dispersion and application of many kinds of herbicides. Viologen compounds, a type of widely used but highly toxic herbicide, are stable in bulk water, whose half-life can be up to 23 weeks in natural water, imposing a severe health risk to mammals. In this study, we present the striking results of the spontaneous and ultrafast reduction-induced degradation of three viologen compounds in water microdroplets and provide the concentration, time, temperature dependence, mechanism, and scale-up of the reactions. We postulate that the electrons existing at the air-water interface of the microdroplets due to the unique redox potential therein initiate the reduction, from which further degradation occurs. The host-guest complexation between cucurbit[7]uril and viologens only slightly changes the redox potential of viologens in the bulk but completely inhibits the reactions in microdroplets, adding to the uniqueness of the redox potentials at the air-water interfaces of microdroplets. Taken together, microdroplets might have been functioning as naturally occurring ubiquitous tiny electrochemical cells for a plethora of unique redox reactions that were thought to be impossible in the bulk water.

Fast Sulfate Formation Initiated by the Spin-Forbidden Excitation of SO2 at the Air-Water Interface.

The multiphase oxidation of SO2 to sulfate in aerosol particles is a key process in atmospheric chemistry. However, there is a large gap between the observed and simulated sulfate concentrations during severe haze events. To fill in the gaps in understanding SO2 oxidation chemistry, a combination of experiments and theoretical calculations provided evidence for the direct, spin-forbidden excitation of SO2 to its triplet states using UVA photons at an air-water interface, followed by reactions with water and O2 that facilitate the rapid formation of sulfate. The estimated reaction energy for the whole process, 3SO2 + H2O + 1/2O2 → HSO4- + H+ (298 K, 1 M), was ΔGr = -107.8 kcal·mol-1. Moreover, calculations revealed that this was a multistep reaction involving submerged, small energy barriers (∼10 kcal·mol-1). These results indicate that photochemical oxidation of SO2 at the air-water interface with solar actinic light may be an important unaccounted source of sulfate aerosols under polluted haze conditions.

An 241Am Plasma Desorption Ionization (AmDI) Source Scavenged from Smoke Detectors for Ambient Mass Spectrometry Sampling.

The development of efficient, low-cost, easy-to-use ambient ionization methods has been a major goal of modern mass spectrometry. In this Letter, we present a gas-free, voltage-free, economic, and safe desorption ionization method using the plasma generated by a radioactive element, americium-241, scavenged from smoke detectors that equip almost every household. No other energy sources, such as laser, discharge, fast-moving carrier gas, solvent droplet, ultrasound, or heat are needed. We name this new method as americium-241 desorption ionization (AmDI). AmDI is tested for the detection of more than 20 volatile and nonvolatile chemicals under different sampling conditions, and the detection limit can be in the range of tens of picograms for some analytes. Mechanistically, we provide evidence that the α particles emitted from radioactive decay ionize ambient air, and the resulting plasma further energizes and ionizes the surface analytes for mass spectrometry detection. We anticipate wide applications of AmDI in mass spectrometric sampling in the near future because of the plethora of merits.

Fecal metabolomic analysis of rabbits infected with Eimeria intestinalis and Eimeria magna based on LC-MS/MS technique.

Rabbit coccidiosis is a common parasitic disease leading to economic losses in the rabbit industry. The intestinal flora plays a key role in pathogenesis of coccidiosis, and fecal metabolome mediates host-microbiome interactions as a functional readout of the gut microbiome. In this study, the E. intestinalis-infected and E. magna-infected rabbit models were established to investigate metabolic alterations and metabolic pathways based on LC-MS/MS technique for the first time. Multivariate OPLS-DA analysis was performed to explore differential metabolites. In total, 288 metabolites were detected from infected and uninfected rabbits. The level of 33 metabolites increased and 4 decreased in rabbits infected with E. intestinalis. Eight pathways were significantly perturbed during E. intestinalis infection including biosynthesis of unsaturated fatty acids, fatty acid biosynthesis, etc. After rabbits infected with E. magna, 13 metabolites were altered and 7 metabolic pathways were dysregulated. These metabolites and metabolic pathways were mainly involved in tuberculosis, parathyroid hormone synthesis, etc. Besides, 25 metabolites differed in abundance between E. intestinalis infection group and E. magna infection group, the major perturbed metabolic pathways were lipid metabolism and endocrine system, respectively. In general, it is confirmed that E. intestinalis and E. magna infection destroyed the intestinal flora, which caused corresponding changes in metabolites, and provide novel insights into the molecular mechanisms of rabbit-parasite interactions.

Neutrophil extracellular traps contribute to immune dysregulation in bullous pemphigoid via inducing B-cell differentiation and antibody production.

Bullous pemphigoid (BP), an autoimmune skin disease, is characterized by autoantibodies against hemidesmosomal proteins in the skin and mucous membranes. Neutrophils infiltrate BP skin lesions, however, their role in immune dysregulation remains unclear. We investigated whether BP involves aberrant neutrophil extracellular traps (NETs) formation in skin lesions and circulation; and examined the triggers and deleterious immuno-inflammatory consequences. In the present study, we found that circulating NET-related biomarker levels increased in serum and blister fluid of BP patients and significantly correlated with disease severity. Additionally, circulating neutrophils from BP patients displayed enhanced spontaneous NETs formation than healthy controls. In vitro, BP180-NC16A immune complexes-induced NETosis in neutrophils from BP patients, which was abrogated by Fcγ receptor and/or NADPH pathway blockade. Furthermore, the elevated levels of NETs from BP patients boosted autoantibody production by inducing B-cell differentiation into plasma cells, mediated by MAPK P38 cascade activation. Together, our findings provide strong evidence that NETs are involved in a pathogenic loop, causing excessive differentiation of B cells and promotion of autoantibody production. Hence, targeting aberrant neutrophil responses will provide novel potential targets for the treatment of BP.

Oxidative [2 + 1 + 1 + 1] Annulation of Aldehydes and Methylene Nitriles: Synthesis of Diastereoselective Polysubstituted Cyclopentenes.

Herein, we report a green cascade approach to prepare a variety of diastereoselective polysubstituted cyclopentene derivatives through metal-free oxidative [2 + 1 + 1 + 1] annulation of aldehydes and methylene nitriles. Mechanistic studies demonstrated that the reaction underwent a four-step cascade reaction including air oxidation and Michael addition to obtain the final product. This reaction features readily available starting materials, transition metal-free, eco-friendly operations, gram-scale syntheses, and wide functional group tolerance. The methodology may be useful for the construction of polysubstituted cyano-cyclopentene heterocycles with potential biological activity.