AgNPs loaded adenine-modified chitosan composite POSS-PEG hybrid hydrogel with enhanced antibacterial and cell proliferation properties for promotion of infected wound healing.

Wound healing is a dynamic and complex process, it's urgent to develop new wound dressings with excellent performance to promote wound healing at the different stages. Here, a novel composite hydrogel dressing composed by silver nanoparticles (AgNPs) impregnated adenine-modified chitosan (CS-A) and octafunctionalized polyhedral oligomeric silsesquioxane (POSS) of benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO) solution was presented to solve the problem of wound infection. Modification of chitosan with adenine, not only can improve the water solubility of chitosan, but also introduce bioactive substances to promote cell proliferation. CS-A and POSS-PEG-CHO were cross-linked by Schiff-base reaction to form the injectable self-healing hydrogel. On this basis, AgNPs were added into the hydrogel, which endows the hydrogel with better antibacterial activity. Moreover, this kind of hydrogel exhibits excellent cell proliferation properties. Studies demonstrated that the hydrogel can significantly accelerate the closure of infected wounds. The histological analysis and immunofluorescence staining demonstrated that the wounds treated with the composite hydrogel exhibited fewer inflammatory cells, more collagen deposition and angiogenesis, faster regeneration of epithelial tissue. Above all, adenine-modified chitosan composite hydrogel with AgNPs loaded was considered as a dressing material with great application potential for promoting the healing of infected wounds.

Studies on adsorption properties of magnetic composite prepared by one-pot method for Cd(II), Pb(II), Hg(II), and As(III): Mechanism and practical application in food.

A one-pot synthesis afforded a magnetic, crosslinked polymer adsorbent (m-P6) with a variety of functional groups to realize simultaneous adsorption of Cd2+, Pb2+, Hg2+, and As3+. The material was characterized by TEM-EDS, XRD, FT-IR, VSM, and XPS. Kinetic and isothermal analyses suggested mainly chemisorption processes of heavy metal ions that form multiple layers on heterogeneous surfaces. Theoretical adsorption capacities calculated by a pseudo-2nd-order kinetic model and the Sips isothermal model were 282.88 mg/g for Cd2+, 326.18 mg/g for Pb2+, 117.85 mg/g for Hg2+, and 320.29 mg/g for As3+. m-P6 not only can efficiently adsorb divalent heavy metals (Cd2+, Pb2+, Hg2+), but also demonstrate a process of adsorption-driven catalytic oxidation by single-electron transfer (SET) from As3+ to As5+. In application, in addition to adsorption in water, m-P6 is capable of minimizing matrix interference, and extracting trace heavy metals in a complex environment (cereal) through easy operations for improving the detection accuracy, as well as it is potential for application in detection of trace heavy metals in foodstuffs. m-P6 can be readily regenerated and efficiently recycled for 5 cycles using eluent E12 and dilute acid.

Polo-like kinase 4 promotes tumorigenesis and glucose metabolism in glioma by activating AKT1 signaling.

Glioblastoma (GBM) is an extremely aggressive tumor associated with a poor prognosis that impacts the central nervous system. Increasing evidence suggests an inherent association between glucose metabolism dysregulation and the aggression of GBM. Polo-like kinase 4 (PLK4), a highly conserved serine/threonine protein kinase, was found to relate to glioma progression and unfavorable prognosis. As revealed by the integration of proteomics and phosphoproteomics, PLK4 was found to be involved in governing metabolic processes and the PI3K/AKT/mTOR pathway. For the first time, this study supports evidence demonstrating that PLK4 activated PI3K/AKT/mTOR signaling through direct binding to AKT1 and subsequent phosphorylating AKT1 at S124, T308, and S473 to promote tumorigenesis and glucose metabolism in glioma. In addition, PLK4-mediated phosphorylation of AKT1 S124 significantly augmented the phosphorylation of AKT1 S473. Therefore, PLK4 exerted an influence on glucose metabolism by stimulating PI3K/AKT/mTOR signaling. Additionally, the expression of PLK4 protein exhibited a positive correlation with AKT1 phosphorylation in glioma patient tissues. These findings highlight the pivotal role of PLK4-mediated phosphorylation of AKT1 in glioma tumorigenesis and dysregulation of glucose metabolism.

Biomimetic hybrid nanovesicles improve infected diabetic wound via enhanced targeted delivery.

Infected diabetic wounds have been raising the global medical burden because of its high occurrence and resulting risk of amputation. Impaired endothelium has been well-documented as one of the most critical reasons for unhealed wounds. Recently, endothelial cell-derived nanovesicles (NVs) were reported to facilitate angiogenesis, whereas their efficacy is limited in infected diabetic wounds because of the complex niche. In this study, extrusion-derived endothelial NVs were manufactured and then hybridized with rhamnolipid liposomes to obtain biomimetic hybrid nanovesicles (HNVs). The HNVs were biocompatible and achieved endothelium-targeted delivery through membrane CXCR4-mediated homologous homing. More importantly, the HNVs exhibited better penetration and antibacterial activity compared with NVs, which further promote the intrinsic endothelium targeting in infected diabetic wounds. Therefore, the present research has established a novel bioactive delivery system-HNV with enhanced targeting, penetration, and antibacterial activity-which might be an encouraging strategy for infected diabetic wound treatment.

Undescribed indole lactones from Alstonia scholaris protecting hepatic cell damage.

Six previously undescribed rigidly monoterpenoid indole alkaloids, alstolactines F-K (1-6), were isolated from Alstonia scholaris. Among them, a pair of cage-like epimers, 1 and 2, featuring a rare 6/5/6/6/7 ring system, represent the first example of C5→C20-olide, while compound 3 possesses unique degraded C18 and C19. The structures of the isolates were established by multiple spectroscopic analyses, quantum computational chemistry methods, and X-ray diffraction. Furthermore, the expression levels of proteins including NLRP3, TLR4, P-p65, NF-ĸB, Notch-2, IL-18, P-p38, and p38 in LPS-induced human normal hepatocyte (LO2) cells could be significantly downregulated by compounds 1-6, which showed potent anti-inflammatory bioactivity.

Long non­coding RNAs in gallbladder cancer: From mechanisms to therapeutic opportunities (Review).

Due to the lack of specific symptoms, characteristic diagnostic markers and effective comprehensive treatment, gallbladder cancer (GBC) is currently considered one of the most malignant abdominal tumors. With the rapid development of biological technologies, long non­coding RNAs (lncRNAs), once regarded as transcriptional junk, have been demonstrated to participate in almost the whole process of the central dogma of molecular biology. The central dogma deals with the transfer of sequential information at the level of individual residues. LncRNAs have an effect on multiple cancer types. However, evidence of dysregulated lncRNA functions in GBC is limited. In the present review, the regulatory mechanisms of lncRNA function on gene expression were examined, including epigenetic modification, transcriptional regulation and post­translational modulation. These mechanisms are strongly associated with tumor development and metastasis. Next, it was summarized how lncRNAs affect GBC diverse malignant phenotypes through various mechanisms. Moreover, predictions of lncRNA interactions with other functional molecules in malignancies were made using several valuable databases, including crosstalk between lncRNA and DNA, mRNA, microRNA, and protein. Additionally, several potential therapeutic methods targeting pathological lncRNAs in tumors were identified. Finally, perspectives about lncRNA research and applications in GBC were presented in the current study, including viewpoints of coding potential of lncRNAs and feasible usage of micropeptides encoded by lncRNAs; roles of lncRNAs in tumor cell metabolic reprogramming and tumor microenvironment; and function of lncRNAs as possible biomarkers and therapeutic targets for improving GBC diagnosis, treatment and prognosis.

Flow-driven translocation of comb-like copolymer micelles through a nanochannel.

Using hybrid lattice-Boltzmann molecular dynamics simulations, we investigate the flow-driven translocation of comb-like copolymer micelles through a nanochannel, in particular, making a detailed comparison with micelles formed by the corresponding diblock copolymers. Our results demonstrate that the critical flow flux of micelles formed by the comb-like copolymers is higher than that of micelles formed by the corresponding diblock copolymers, which is more pronounced with increasing side chain lengths or grafting densities, as evidenced by the free energy computed by self-consistent field theory. Our work indicates that the impact of chain topology on the stability of micelles, especially with the same size, can be well characterized using the critical flow fluxes, which provides a theoretical basis for designing self-assembling micelles for various applications.

Bimetallic UiO-66-NH2(Zr-Hf) synergistic photocatalytic and piezoelectric effects for the degradation of rhodamine B.

A series of bimetallic UiO-66-NH2(Zr-Hf) metal-organic frameworks (MOFs) were prepared by a green hydrothermal method and tested for their photocatalytic and piezo-catalytic properties. Among them, UN(0.75Zr) (metal node: 0.75Zr : 0.25Hf) shows the most superior piezo-photocatalytic activity. The degradation rate for 40 mg L-1 rhodamine B (Rh B) could reach 96.78% within 30 min, which was ∼4.66 and ∼3.30 times higher than that of photocatalysis and piezo-catalysis, respectively. Moreover, the main reactive oxidizing substances (ROS), including vacancies (h+) and hydroxyl radicals (˙OH), were identified by free radical scavenging experiments. In addition, the intermediates generated during Rh B degradation were analyzed by HPLC-MS, while a reasonable degradation pathway was presented. Our work utilizes a green and environmentally friendly method to prepare bimetallic MOFs, providing a novel solution for the rapid degradation of highly concentrated dye wastewater.

Targeted quantitative analysis of monoterpenoid indole alkaloids in Alstonia scholaris by ultra-high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry.

Monoterpene indole alkaloids exhibit structural diversity in herbal resources and have been developed as promising drugs owing to their significant biological activities. Confidential identification and quantification of monoterpene indole alkaloids is the key to quality control of target plants in industrial production but has rarely been reported. In this study, quantitative performance of three data acquisition modes of ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry including full scan, auto-MS2 and target-MS2 , was evaluated and compared for specificity, sensitivity, linearity, precision, accuracy, and matrix effect using five monoterpene indole alkaloids (scholaricine, 19-epi-scholaricine, vallesamine, picrinine, and picralinal). Method validations indicated that target-MS2 mode showed predominant performance for simultaneous annotation and quantification of analytes, and was then applied to determine monoterpene indole alkaloids in Alstonia scholaris (leaves, barks) after extraction procedures optimization using Box-Behnken design of response surface methodology. The variations of A. scholaris monoterpene indole alkaloids in different plant parts, harvest periods, and post-handling processes, were subsequently investigated. The results indicated that target-MS2 mode could improve the quantitative capability of ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry for structure-complex monoterpene indole alkaloids in herbal matrices. Alstonia scholaris, monoterpene indole alkaloids, quadrupole time of flight mass spectrometry, qualitative and quantitative analysis, ultra-high-performance liquid chromatography.

Phytochemical Analysis and Anti-Ascaris suum Activity of Different Zanthoxylum Species In Vitro and In Vivo.

Zanthoxylum plants (ZPs), including multiple Chinese prickly ash species, are dual-purpose functional foods favored by the general population around the world in foods, cosmetics, and traditional medicines and have antipruritic, insecticidal, and fungicidal bioactivities. For the first time, the anti-roundworm bioactivity of ZPs and the active ingredients were compared and investigated. Through nontarget metabolomics following targeted quantitative analysis, qinbunamides, sanshools, sanshooel, asarinin, and sesamin were found to be the main different components of Zanthoxylum species. Coincidentally, the 12 chemical components were also the dominant anti-roundworm ingredients of ZP extracts. The extracts of three species of Chinese prickly ash (1 mg/mL) decreased the hatchability of roundworm eggs significantly, and the ChuanJiao seed killed roundworms (insecticidal rate 100%) and alleviated the symptoms of pneumonia in mice. Furthermore, retention time-accurate mass-tandem mass spectrometry-ion ratio (RT-AM-MS/MS-IR) were modeled by assaying 108 authentic compounds of ZP extracts, and 20 metabolites were confidently identified in biological samples from ZP extract-treated mice by analyzing the m/z values and the empirical substructures. This study provides a good reference for the proper application of ZPs.

Steroidal alkaloids from the roots of Veratrum stenophyllum.

Three new steroidal alkaloids, veratrasines A - C (1-3), along with ten known analogues (4-13) were isolated from the roots of Veratrum stenophyllum. Their structures were elucidated by NMR and HRESIMS data and comparison with the reported data in the literatures. A plausible biosynthetic pathway for 1 and 2 were proposed. Compounds 1, 3, and 8 showed moderate cytotoxic activity against MHCC97H and H1299 cell lines.

Steroidal alkaloid with unprecedented triheterocyclic architecture.

Veratrazine A (1), a steroidal alkaloid with a unique 6/5/5 triheterocyclic scaffold as the side chain, was isolated from Veratrum stenophyllum, and its structure was established via spectroscopic analyses and X-ray diffraction. A plausible biosynthetic pathway for 1 is proposed. Bioassy exhibits moderate anti-inflammatory activities in vitro and in vivo.

LncRNA HOXA11-AS promotes glioma malignant phenotypes and reduces its sensitivity to ROS via Tpl2-MEK1/2-ERK1/2 pathway.

Our previous studies showed that dysregulation of the long noncoding RNA (lncRNA) HOXA11-AS plays an important role in the development of glioma. However, the molecular mechanism of HOXA11-AS in glioma remains largely unknown. In this study, we explore the molecular mechanisms underlying abnormal expression and biological function of HOXA11-AS for identifying novel therapeutic targets in glioma. The expression of HOXA11-AS, and the relationship between HOXA11-AS and the prognosis of glioma patients were analyzed using databases and glioma samples. Transcriptomics, proteomics, RIP, ChIRP, luciferase, and ChIP assays were used to explore its upstream and downstream targets in glioma. The role of HOXA11-AS in regulating the sensitivity of glioma cells to reactive oxygen species (ROS) was also investigated in vitro and in vivo. We found that HOXA11-AS was significantly upregulated in glioma, and was correlated with the poor prognosis of glioma patients. Ectopic expression of HOXA11-AS promoted the proliferation, migration, and invasion of glioma cells in vitro and in vivo. Mechanistically, HOXA11-AS acted as a molecular sponge for let-7b-5p in the cytoplasm, antagonizing its ability to repress the expression of CTHRC1, which activates the ß-catenin/c-Myc pathway. In addition, c-Myc was involved in HOXA11-AS dysregulation via binding to its promoter region to form a self-activating loop. HOXA11-AS, functioned as a scaffold in the nucleus, also recruited transcription factor c-Jun to the Tpl2 promoter, which activates the Tpl2-MEK1/2-ERK1/2 pathway to promote ROS resistance in glioma. Importantly, HOXA11-AS knockdown could sensitize glioma cells to ROS. Above, oncogenic HOXA11-AS upregulates CTHRC1 expression as a ceRNA by adsorbing let-7b-5p, which activates c-Myc to regulate itself transcription. HOXA11-AS knockdown promotes ROS sensitivity in glioma cells by regulating the Tpl2-MEK1/2-ERK1/2 axis, demonstrating that HOXA11-AS may be translated to increase ROS sensitivity therapeutically.

Novel insight into the functions of N6­methyladenosine modified lncRNAs in cancers (Review).

Emerging evidence has suggested that N6­methyladenosine (m6A) modification, a typical RNA methylation modification, controls the fate of modified transcripts and is involved in the pathogenesis of various human diseases, such as metabolic disorders, nephropathology, osteoarthritis and malignant tumours. Long noncoding RNAs (lncRNAs), transcripts of >200 nt in length, have also been indicated to be involved in various diseases by participating in processes such as epigenetic modifications, transcriptional alternations and posttranslational regulation. Recent studies revealed that lncRNAs were widely modified by m6A, which has a critical role in various cellular processes that are associated with numerous disorders, particularly human cancers. The present review first examined functions of m6A modification of lncRNAs, including changing the lncRNA structure, mediating transcriptional regulation, affecting mRNA precursor splicing, and regulating lncRNA stability and translation. Furthermore, the regulatory mechanisms of m6A­modified lncRNAs in cancers were summarized and the up­to­date detection methods and prediction tools for identifying m6A sites on lncRNAs were presented. In addition, viewpoints on potential future directions in the field were discussed, including more accurate detection methods, roles of lncRNAs­encoded micropeptides in cancers, the relationship between m6A­modified lncRNAs and the tumour microenvironment, and m6A­modified lncRNAs as potential biomarkers and therapeutic targets in human cancer.

Use of folic acid supplementation to halt and even reverse the progression of gastric precancerous conditions: a meta-analysis.

BACKGROUND: Current data indicate that supplements such as folic acid and vitamin B may be beneficial in halting and even reversing atrophic gastritis, intestinal metaplasia and intraepithelial neoplasia, generally referred to as gastric precancerous conditions(GPC). However, there is no Meta-analysis article to evaluate the prevention and treatment of folic acid in the gastric precancerous conditions. We therefore conducted a meta-analysis to confirm the efficacy of folic acid in treating GPC. METHODS: Using a systematic review method, consider randomized controlled trials (RCT), including clinical trial reports, unpublished clinical trial data, and conference papers. The search time was been set from the database's establishment to June 2, 2021. The language was not limited, using PubMed, SinoMed, Lancet, Web of Science, CNKI, Cochrane, Ovid, Science Direct, Embase, and EBSCO databases. Data were extracted using a pre-designed extraction tool and analysis was undertaken using RevMan5.2.Besides,we use Origin software to construct the Time-dose interval analysis. RESULTS: Of the 225 records identified, 13 studies involving 1252 patients (including 11 clinical controlled trials, 1 conference paper report and 1 unpublished research report) met the inclusion conditions. Folic acid dose maintained at 20-30 mg / d for 3-6 months may be beneficial to pathological changes of GPC. Moreover, in the 3 month treatment of 5 trials, the effect was more obvious when the folic acid dose was maintained at 30 mg / d. In the 7 trials, the symptom ineffective rate of GPC treated with folic acid was 32% (RR:0.32, 95% confidence interval CI:0.21-0.48), which was combined using a fixed analysis model; The effect of folic acid on gastric mucosal atrophy in 5 trials (RR: 1.61, 95%CI 1.07-2.41). The changes of folic acid on intestinal metaplasia in the 2 experiments (RR: 1.77, 95% CI: 1.32-2.37).The 2 results are combined using a fixed analytical model. However, the subgroup analysis of 9 trials revealed no significant effectiveness of symptom. CONCLUSIONS: Our research showed that folic acid supplementation brings benefits in preventing and even reversing the progression of GPC in the stomach, and provided evidence for its potential clinical use in management of GPC. REGISTRATION: The logn number of our Meta-anlysis on PROSPERO is CRD420223062.

Corrigendum: Pan-Cancer Analysis Shows That ALKBH5 Is a Potential Prognostic and Immunotherapeutic Biomarker for Multiple Cancer Types Including Gliomas.

[This corrects the article DOI: 10.3389/fimmu.2022.849592.].

A two-dimensional superlattice membrane enables high-performance desalination and enhanced Li ion selectivity.

Here, we report a two-dimension (2D) superlattice-like membrane composed of periodic MoS2 and GO nanosheets, which delivers enhanced salt rejection capability, high water flux, and Li ion selectivity. It opens a new perspective in assembling 2D membranes and can be utilized as a green and low-cost approach for desalination.

The Protective Effect of Sweet Potato Root Tuber on Chemotherapy-Induced Thrombocytopenia.

SCOPE: Sweet potato (Ipomoea batatas L.) is one of the leading crops worldwide, containing high nutritional components such as fiber and polyphenols. Root tuber of Simon 1 (SIMON), a cultivar of sweet potato, is a folk food in China with a hemostasis function but lacking experimental data support. METHODS AND RESULTS: Now the protective effect of SIMON on chemotherapy-induced thrombocytopenia (CIT), a serious complication of cancer treatment, is investigated for the first time by a CIT mouse model induced by intraperitoneal injection of carboplatin. As a result, SIMON raises the number of peripheral platelets, white blood cells, and bone marrow nucleated cells in CIT mice significantly. Besides, carboplatin-induced atrophy of the thymus, spleen, and disordered metabolism of the inflammatory immune system and glycerophospholipids are also reversed by SIMON. Phytochemical analysis of SIMON indicates 16 compounds including eight phenolic derivatives, which might be associated with its anti-CIT bioactivity. CONCLUSION: Sweet potato (SIMON) may be an efficient function food in the prevention of bleeding disorders.

Tuberindine A, a Truffle Alkaloid with an Unprecedented Skeleton Exhibiting Anti-hyperuricemic Bioactivity.

Tuberindines A and B (1 and 2), truffle alkaloids with intriguing structures, were isolated from Tuber indicum and detected in other truffle species. They appear to arise biosynthetically from amino acid and isosaccharinic units. Compound 1 upregulated the expression of organic anion transporters OAT1 and ABCG2 and significantly exhibited antihyperuricemic bioactivity in vitro and in vivo, which might support the value of truffles as a dietary supplement.