Precise coordination of high-loading Fe single atoms with sulfur boosts selective generation of nonradicals.

Nonradicals are effective in selectively degrading electron-rich organic contaminants, which unfortunately suffer from unsatisfactory yield and uncontrollable composition due to the competitive generation of radicals. Herein, we precisely construct a local microenvironment of the carbon nitride-supported high-loading (~9 wt.%) Fe single-atom catalyst (Fe SAC) with sulfur via a facile supermolecular self-assembly strategy. Short-distance S coordination boosts the peroxymonosulfate (PMS) activation and selectively generates high-valent iron-oxo species (FeIV=O) along with singlet oxygen (1O2), significantly increasing the 1O2 yield, PMS utilization, and p-chlorophenol reactivity by 6.0, 3.0, and 8.4 times, respectively. The composition of nonradicals is controllable by simply changing the S content. In contrast, long-distance S coordination generates both radicals and nonradicals, and could not promote reactivity. Experimental and theoretical analyses suggest that the short-distance S upshifts the d-band center of the Fe atom, i.e., being close to the Fermi level, which changes the binding mode between the Fe atom and O site of PMS to selectively generate 1O2 and FeIV=O with a high yield. The short-distance S-coordinated Fe SAC exhibits excellent application potential in various water matrices. These findings can guide the rational design of robust SACs toward a selective and controllable generation of nonradicals with high yield and PMS utilization.

Genome-wide identification and expression-pattern analysis of sulfate transporter (SULTR) gene family in cotton under multiple abiotic stresses and fiber development.

Sulfate transporter (SULTR) proteins are in charge of the transport and absorption on sulfate substances, and have been reported to play vital roles in the biological processes of plant growth and stress response. However, there were few reports of genome-wide identification and expression-pattern analysis of SULTRs in Hibiscus mutabilis. Gossypium genus is a ideal model for studying the allopolyploidy, therefore two diploid species (G. raimondii and G. arboreum) and two tetraploid species (G. hirsutum and G. barbadense) were chosen in this study to perform bioinformatic analyses, identifying 18, 18, 35, and 35 SULTR members, respectively. All the 106 cotton SULTR genes were utilized to construct the phylogenetic tree together with 11 Arabidopsis thaliana, 13 Oryza sativa, and 8 Zea mays ones, which was divided into Group1-Group4. The clustering analyses of gene structures and 10 conserved motifs among the cotton SULTR genes showed the consistent evolutionary relationship with the phylogenetic tree, and the results of gene-duplication identification among the four representative Gossypium species indicated that genome-wide or segment duplication might make main contributions to the expansion of SULTR gene family in cotton. Having conducted the cis-regulatory element analysis in promoter region, we noticed that the existing salicylic acid (SA), jasmonic acid (JA), and abscisic acid (ABA) elements could have influences with expression levels of cotton SULTR genes. The expression patterns of GhSULTR genes were also investigated on the 7 different tissues or organs and the developing ovules and fibers, most of which were highly expressed in root, stem, sepal, receptacel, ovule at 10 DPA, and fiber at 20 and 25 DPA. In addition, more active regulatory were observed in GhSULTR genes responding to multiple abiotic stresses, and 12 highly expressed genes showed the similar expression patterns in the quantitative Real-time PCR experiments under cold, heat, salt, and drought treatments. These findings broaden our insight into the evolutionary relationships and expression patterns of the SULTR gene family in cotton, and provide the valuable information for further screening the vital candidate genes on trait improvement.

Insights into the Roles of Natural Killer Cells in Osteoarthritis.

Osteoarthritis (OA) is now widely acknowledged as a low-grade inflammatory condition, in which the intrinsic immune system plays a significant role in its pathogenesis. While the involvement of macrophages and T cells in the development of OA has been extensively reviewed, recent research has provided mounting evidence supporting the crucial contribution of NK cells in both the initiation and advancement of OA. Accumulated evidence has emerged in recent years indicating that NK cells play a critical role in OA development and progression. This review will outline the ongoing understanding of the utility of NK cells in the etiology of OA, focusing on how NK cells interact with chondrocytes, synoviocytes, osteoclasts, and other immune cells to influence the course of OA disease.

The size-dependent in vivo toxicity of amorphous silica nanoparticles: A systematic review.

The extensive application of amorphous silica nanoparticles (aSiNPs) in recent years has resulted in unavoidable human exposure in daily life, thus raising widespread concerns regarding the safety of aSiNPs on human health. The particle size is one of the important characteristics of nanomaterials that could influence their toxicity. For the reason that particles with smaller sizes possess larger surface area, which may lead to higher surface activity and biological reactivity. However, due to the complexity of experimental conditions and biological systems, the relationship between the particle size and the toxic effect of aSiNPs remains unclear. Therefore, this systematic review aims to investigate how particle size influences the toxic effect of aSiNPs in vivo and to analyze the relevant experimental factors affecting the size-dependent toxicity of aSiNPs in vivo. We found that 83.8% of 35 papers included in the present review came to the conclusion that smaller-sized aSiNPs exhibited stronger toxicity, though a few papers (6 papers) put forward different opinions. The reasons for smaller aSiNPs manifested greater toxicity were summarized. In addition, certain important experimental factors could influence the size-dependent effects and in vivo toxicity of aSiNPs, such as the synthesis method of aSiNPs, disperse medium of aSiNPs, administration route of aSiNPs, species or strain of experimental animals, sex of experimental animals, aggregation/agglomeration and protein corona of aSiNPs.

Small-Molecule Modulation of Protein Lipidation: From Chemical Probes to Therapeutics.

Protein lipidation is a widespread modification that regulates protein subcellular localization, structure and function. Dysregulation of protein lipidation has been implicated in various human diseases, including neurological disorders, infectious diseases and cancers. Thus lipid-modifying enzymes and their substrate proteins are emerging as attractive drug targets. The development of small-molecule modulators of protein lipidation has remarkably impacted our understanding of lipid-modification biology and potential therapeutics. In this review, we summarize recent progress in small-molecule targeting of protein lipidation and highlight therapeutic opportunities.

Opening KATP channels induces inflammatory tolerance and prevents chronic pain.

Current treatments for chronic pain are unsatisfactory, therefore, new therapeutics are urgently needed. Our previous study indicated that KATP channel openers have analgesic effects, but the underlying mechanism has not been elucidated. We speculated that KATP channel openers might increase suppressor of cytokine signaling (SOCS)-3 expression to induce inflammatory tolerance and attenuate chronic pain. Postoperative pain was induced by plantar incision to establish a chronic pain model. Growth arrest-specific 6 (Gas6)-/- and Axl-/- mice were used for signaling studies. The microglia cell line BV-2 was cultured for the in vitro experiments. The KATP channel opener significantly attenuated incision-induced mechanical allodynia in mice associated with the upregulated expression of SOCS3. Opening KATP channels induced the expression of SOCS3 in the Gas6/Axl signaling pathway in microglia, inhibited incision-induced mechanical allodynia by activating the Gas6/Axl-SOCS3 signaling pathway, and induced inflammatory tolerance to relieve neuroinflammation and postoperative pain. We demonstrated that opening of the KATP channel opening activated Gas6/Axl/SOCS3 signaling to induce inflammatory tolerance and relieve chronic pain. We explored a new target for anti-inflammatory and analgesic effects by regulating the innate immune system and provided a theoretical basis for clinical preemptive analgesia.

The effect of precipitation timing on phylogenetic and functional community structure in a semi-arid steppe.

Changes in the amount and timing of precipitation may affect plant species coexistence. However, little is known about how these changes in precipitation structure plant communities. Here, we conducted a 6-year field precipitation manipulation experiment in the semi-arid steppe of Inner Mongolia, China, to assess the importance of species extinction and colonization in community assembly by incorporating information on phylogenetic and functional relatedness. Our results demonstrated that the decline in plant species richness under decreasing precipitation in the late and entire growing season could be attributed to a decrease in species colonization and an increase in species loss, respectively. The increase in species richness under increasing precipitation in the late growing season was mainly caused by increases in colonizing species. The loss of species that were more closely related to other residents under decreasing precipitation in the late growing season did not alter patterns of phylogenetic overdispersion, and the colonization of species that were more distantly related to residents under increasing precipitation in the late growing season shifted functional relatedness from clustering to randomness. Increasing precipitation may weaken the strength of environmental filtering induced by water stress in this semi-arid steppe and thus increase the probability of successful colonization of functionally dissimilar species relative to residents. Our study suggests that incorporating information on the functional and phylogenetic relatedness of locally lost resident species and the colonization of new species into analyses of community assembly processes can provide new insights into the general responses of plant communities to global change.

Genetic characterisation of sarcomatoid carcinomas reveals multiple novel actionable mutations and identifies KRAS mutation as a biomarker of poor prognosis.

BACKGROUND: Sarcomatoid component occurs in various epithelial malignancies and is associated with an aggressive disease course and poor clinical outcome. As it is largely rare, the molecular events underlying sarcomatoid carcinomas (SCs) remain poorly characterised. Here, we performed targeted next-generation sequencing (NGS) on patients with surgically resected SCs comprising distinct tissues of origin. METHODS: A total of 71 patients with pathological diagnosis of sarcomatoid carcinomas and underwent surgery were retrospectively enrolled in this study. Overall survival (OS) was defined as the time from surgery to death from any cause. Patients alive or lost to follow-up were censored. Genomic DNA from formalin-fixed paraffin-embedded samples was extracted for NGS and tumour mutation burden (TMB) analysis. RESULTS: In general, SCs occurred more commonly in males, except those of the gallbladder. SCs of the lung and the larynx were associated with a higher proportion of smokers (p=0.0015). Alterations in TP53, RB1, TERT and KRAS were highly frequent, with KRAS mutations being a biomarker of poor prognosis (median OS=8 vs 16 months, p=0.03). Multiple alterations in potentially actionable genes, including ROS1 and NTRK1 fusions and ERBB2 amplification, were detected in the extra-pulmonary cohort. A relatively high proportion (30%) of patients with extra-pulmonary SC had high TMB, with a median of 5.39 mutations per Mb. Lastly, copy number variations were common in SCs, and were non-overlapping between the primary and metastatic tumours. CONCLUSION: Taken together, our results suggest that comprehensive genetic testing may be necessary to inform treatment options and identify prognostic biomarkers.

Integrated Secondary Metabolomic and Antioxidant Ability Analysis Reveals the Accumulation Patterns of Metabolites in Momordica charantia L. of Different Cultivars.

Bitter gourd (Momordica charantia L.) contains rich bioactive ingredients and secondary metabolites; hence, it has been used as medicine and food product. This study systematically quantified the nutrient contents, the total content of phenolic acids (TPC), flavonoids (TFC), and triterpenoids (TTC) in seven different cultivars of bitter gourd. This study also estimated the organic acid content and antioxidative capacity of different cultivars of bitter gourd. Although the TPC, TFC, TTC, organic acid content, and antioxidative activity differed significantly among different cultivars of bitter gourd, significant correlations were also observed in the obtained data. In the metabolomics analysis, 370 secondary metabolites were identified in seven cultivars of bitter gourd; flavonoids and phenolic acids were significantly more. Differentially accumulated metabolites identified in this study were mainly associated with secondary metabolic pathways, including pathways of flavonoid, flavonol, isoflavonoid, flavone, folate, and phenylpropanoid biosyntheses. A number of metabolites (n = 27) were significantly correlated (positive or negative) with antioxidative capacity (r ≥ 0.7 and p < 0.05). The outcomes suggest that bitter gourd contains a plethora of bioactive compounds; hence, bitter gourd may potentially be applied in developing novel molecules of medicinal importance.

Artificial Light for Improving Tomato Recovery Following Grafting: Transcriptome and Physiological Analyses.

Grafting is widely used to enhance the phenotypic traits of tomatoes, alleviate biotic and abiotic stresses, and control soil-borne diseases of the scion in greenhouse production. There are many factors that affect the healing and acclimatization stages of seedlings after grafting. However, the role of light has rarely been studied. In this study, we compared the effects of artificial light and traditional shading (under shaded plastic-covered tunnels) on the recovery of grafted tomato seedlings. The results show that the grafted tomato seedlings recovered using artificial light had a higher healthy index, leaf chlorophyll content, shoot dry weight, and net photosynthetic rate (Pn) and water use efficiency (WUE) compared with grafted seedling recovered using the traditional shading method. Transcriptome analysis showed that the differentially expressed genes (DEGs) of grafted seedlings restored using artificial light were mainly enriched in the pathways corresponding to plant hormone signal transduction. In addition, we measured the endogenous hormone content of grafted tomato seedlings. The results show that the contents of salicylic acid (SA) and kinetin (Kin) were significantly increased, and the contents of indoleacetic acid (IAA) and jasmonic acid (JA) were decreased in artificial-light-restored grafted tomato seedlings compared with those under shading treatments. Therefore, we suggest that artificial light affects the morphogenesis and photosynthetic efficiency of grafted tomato seedlings, and it can improve the performance of tomato seedlings during grafting recovery by regulating endogenous hormone levels.

Relationship between the Change in E/T Ratio and the Cooking Performance of Eucalyptus and Acacia Woods during Kraft Pulping Process.

Lignin structure is an important factor affecting the cooking part of the pulping process. In this study, the effect of lignin side chain spatial configuration on cooking performance was analyzed, and the structural characteristics of eucalyptus and acacia during cooking were compared and studied by combining ozonation, GC-MS, NBO, and 2D NMR (1H-13C HSQC). In addition, the changes in the lignin content of four different raw materials during the cooking process were studied via ball milling and UV spectrum analysis. The results showed that the content of lignin in the raw material decreased continuously during the cooking process. Only in the late cooking stage, when the lignin removal reached its limit, did the lignin content tend to be stable due to the polycondensation reaction of lignin. At the same time, the E/T ratio and S/G ratio of the reaction residual lignin also followed a similar rule. At the beginning of cooking, the values of E/T and S/G decreased rapidly and then gradually rose when they reached a low point. The different initial E/T and S/G values of different raw materials lead to the disunity of cooking efficiency and the different transformation rules of different raw materials in the cooking process. Therefore, the pulping efficiency of different raw materials can be improved using different technological means.

Mechanism analysis of the immobilization of heavy metal ions with the water-soluble polymer: The influence of resin structure and the further adsorption of chelate.

Polymer materials have become one of the potential materials for remediation of heavy metal (HM) contamination in water and soil. However, the specific advantages of polymers are rarely studied. Water-soluble thiourea formaldehyde resin (WTF) is one of the effective polymer amendments. Through leaching experiments, WTF can stabilize 93.0% of Cd2+ and 99.7% of Cu2+. The results of HM morphology analysis show that after adding WTF, most of the HMs have been transformed into a relatively stable state. For example, in the process of remediation of 6 mg/kg Cd contaminated soil, the proportion of acid-soluble Cd decreased from 56.5% to 12.8%, and the residual state increased from 13.5% to 45.4%. Compared with the resin-free structure, the three-dimensional structure of the resin plays an important role, but the efficiency of precipitation with HMs is doubled. According to the simulation of the adsorption process by Materials Studio, the characterization of the scanning electron microscope-energy dispersive instrument and the results of the adsorption experiment, in the solution, the precipitate formed by WTF and Cd2+ has multilayer adsorption of HMs, and can further adsorb HM by -OH. Soil enzyme activity experiments proved that the risk of secondary pollution by adding WTF is rare, and even WTF can achieve the effect of slow-release nitrogen fertilizer. In the WTF remediation process, the biological toxicity reduction of HMs is result from, on the one hand, the complexation of functional group of WTF; on the other hand, the resin structure of WTF; in addition, multi-layer adsorption and adsorption of end groups in the precipitation formed by WTF and HM. This work provides a theoretical basis for the potential capabilities of water-soluble resins and is beneficial to the design and development of subsequent amendments.

[Clinical features of children and their family members with family clusters of SARS-CoV-2 Omicron variant infection in Shanghai, China: an analysis of 380 cases]. / 上海380例家庭聚集性感染Omicronå˜å¼‚æ ªçš„å„¿ç«¥åŠå ¶å®¶å±žä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical features and prognosis of children and their family members with family clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection under the admission mode of parent-child ward. METHODS: A retrospective analysis was performed on the medical data of 190 children and 190 family members with SARS-CoV-2 Omicron variant infection who were admitted to Shanghai Sixth People's Hospital, the designated hospital for coronavirus disease 2019 (COVID-19), April 8 to May 10, 2022. RESULTS: Both the child and adult groups were mainly mild COVID-19, and the proportion of mild cases in the child group was higher than that in the adult group (P<0.05). Respiratory symptoms were the main clinical manifestations in both groups. Compared with the adult group, the child group had higher incidence rates of fever, abdominal pain, diarrhea, and wheezing (P<0.05) and lower incidence rates of nasal obstruction, runny nose, cough, dry throat, throat itching, and throat pain (P<0.05). Compared with the child group, the adult group had higher rates of use of Chinese patent drugs, traditional Chinese medicine decoction, recombinant interferon spray, cough-relieving and phlegm-eliminating drugs, and nirmatrelvir/ritonavir tablets (P<0.05). Compared with the adult group, the child group had a lower vaccination rate of SARS-CoV-2 vaccine (30.5% vs 71.1%, P<0.001) and a shorter duration of positive SARS-CoV-2 nucleic acid (P<0.05). The patients with mild COVID-19 had a shorter duration of positive SARS-CoV-2 nucleic acid than those with common COVID-19 in both groups (P<0.05). The patients with underlying diseases had a longer duration of positive SARS-CoV-2 nucleic acid than those without such diseases in both groups (P<0.05). CONCLUSIONS: Both children and adults with family clusters of SARS-CoV-2 Omicron variant infection manifest mainly mild COVID-19. Despite lower vaccination rate of SARS-CoV-2 vaccine in children, they have rapid disease recovery, with a shorter duration of positive SARS-CoV-2 nucleic acid than adults, under the admission mode of parent-child ward.

Correlation of serum uromodulin levels with renal fibrosis and renal function progression in patients with CKD.

To explore the relationship of serum uromodulin levels with renal function progression and renal fibrosis in chronic kidney disease (CKD) patients. Totally 168 CKD patients treated in Department of Nephrology of the present hospital between June 2017 and June 2019 were recruited. These patients were allocated to the deterioration and control groups according to the estimated glomerular filtration rate (eGFR). Multi-factor Logistic regression analysis was utilized for the correlation factors influencing renal function progression and the correlation between serum uromodulin and renal fibrosis was also compared. Number of patients receiving ARB or ACEI drugs intervention was lower in the deterioration group than that in the control group (P<0.05). 24-hour urine protein quantification and HA were higher, while eGFR and uromodulin were lower in the deterioration group compared with the control group (both P<0.05). eGFR (OR=0.373) and uromodulin (OR=0.717) were the protective factors for renal function progression. The risk of renal fibrosis was higher in the deterioration group compared with the control group (P<0.05). Uromodulin was significantly higher in the fibrosis group compared with the normal group (P<0.05). Serum uromodulin is an independent risk factor for renal function progression, and is remarkably correlated with renal fibrosis, which deserves clinical promotion.

The autophagy-related gene Atg101 in Drosophila regulates both neuron and midgut homeostasis.

Atg101 is an autophagy-related gene identified in worms, flies, mice, and mammals, which encodes a protein that functions in autophagosome formation by associating with the ULK1-Atg13-Fip200 complex. In the last few years, the critical role of Atg101 in autophagy has been well-established through biochemical studies and the determination of its protein structure. However, Atg101's physiological role, both during development and in adulthood, remains less understood. Here, we describe the generation and characterization of an Atg101 loss-of-function mutant in Drosophila and report on the roles of Atg101 in maintaining tissue homeostasis in both adult brains and midguts. We observed that homozygous or hemizygous Atg101 mutants were semi-lethal, with only some of them surviving into adulthood. Both developmental and starvation-induced autophagy processes were defective in the Atg101 mutant animals, and Atg101 mutant adult flies had a significantly shorter lifespan and displayed a mobility defect. Moreover, we observed the accumulation of ubiquitin-positive aggregates in Atg101 mutant brains, indicating a neuronal defect. Interestingly, Atg101 mutant adult midguts were shorter and thicker and exhibited abnormal morphology with enlarged enterocytes. Detailed analysis also revealed that the differentiation from intestinal stem cells to enterocytes was impaired in these midguts. Cell type-specific rescue experiments disclosed that Atg101 had a function in enterocytes and limited their growth. In summary, the results of our study indicate that Drosophila Atg101 is essential for tissue homeostasis in both adult brains and midguts. We propose that Atg101 may have a role in age-related processes.

Small Foreign Object Debris Detection for Millimeter-Wave Radar Based on Power Spectrum Features.

Foreign object debris (FOD) detection can be considered a kind of classification that distinguishes the measured signal as either containing FOD targets or only corresponding to ground clutter. In this paper, we propose a support vector domain description (SVDD) classifier with the particle swarm optimization (PSO) algorithm for FOD detection. The echo features of FOD and ground clutter received by the millimeter-wave radar are first extracted in the power spectrum domain as input eigenvectors of the classifier, followed with the parameters optimized by the PSO algorithm, and lastly, a PSO-SVDD classifier is established. However, since only ground clutter samples are utilized to train the SVDD classifier, overfitting inevitably occurs. Thus, a small number of samples with FOD are added in the training stage to further construct a PSO-NSVDD (NSVDD: SVDD with negative examples) classifier to achieve better classification performance. Experimental results based on measured data showed that the proposed methods could not only achieve a good detection performance but also significantly reduce the false alarm rate.

Histone Deacetylase Inhibitor SAHA Improves High Salinity Tolerance Associated with Hyperacetylation-Enhancing Expression of Ion Homeostasis-Related Genes in Cotton.

Histone acetylation plays an important role in regulation of chromatin structure and gene expression in terms of responding to abiotic stresses. Histone acetylation is modulated by histone deacetylases (HDACs) and histone acetyltransferases. Recently, the effectiveness of HDAC inhibitors (HDACis) for conferring plant salt tolerance has been reported. However, the role of HDACis in cotton has not been elucidated. In the present study, we assessed the effects of the HDACi suberoylanilide hydroxamic acid (SAHA) during high salinity stress in cotton. We demonstrated that 10 µM SAHA pretreatment could rescue of cotton from 250 mM NaCl stress, accompanied with reduced Na+ accumulation and a strong expression of the ion homeostasis-related genes. Western blotting and immunostaining results revealed that SAHA pretreatment could induce global hyperacetylation of histone H3 at lysine 9 (H3K9) and histone H4 at lysine 5 (H4K5) under 250 mM NaCl stress, indicating that SAHA could act as the HDACi in cotton. Chromatin immunoprecipitation and chromatin accessibility coupled with real time quantitative PCR analyses showed that the upregulation of the ion homeostasis-related genes was associated with the elevated acetylation levels of H3K9 and H4K5 and increased chromatin accessibility on the promoter regions of these genes. Our results could provide a theoretical basis for analyzing the mechanism of HDACi application on salt tolerance in plants.

An MIMO Radar System Based on the Sparse-Array and Its Frequency Migration Calibration Method.

In this paper, a Multiple Input Multiple Output (MIMO) radar system based on a sparse-array is proposed. In order to reduce the side-lobe level, a genetic algorithm (GA) is used to optimize the array arrangement. To reduce the complexity of the system, time-division multiplexing (TDM) technology is adopted. Since the signals are received in different periods, a frequency migration will emerge if the target is in motion, which will lead to the lower direction-of-arrival (DOA) performance of the system. To solve this problem, a stretching transformation method in the fast-frequency slow-time domain is proposed, in order to eliminate frequency migration. Only minor adjustments need to be implemented for the signal processing, and the root-mean-square error (RMSE) of the DOA estimation will be reduced by about 90%, compared with the one of an uncalibrated system. For example, a uniform linear array (ULA) MIMO system with 2 transmitters and 20 receivers can be replaced by the proposed system with 2 transmitters and 12 receivers, achieving the same DOA performance. The calibration formulations are given, and the simulation results of the automotive radar system are also provided, which validate the theory.

Epigallocatechin-3-Gallate Suppresses Human Herpesvirus 8 Replication and Induces ROS Leading to Apoptosis and Autophagy in Primary Effusion Lymphoma Cells.

Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, has been shown to induce cell death in cancer cells. Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by human herpesvirus 8 (HHV8). In this study, we examined the role of EGCG on PEL cells in cell death and HHV8 replication. We performed trypan blue exclusion assay to assess the cell viability of PEL cells, flow cytometry analysis to examine the cell cycle distribution and reactive oxygen species (ROS) generation, caspase-3 activity to assay apoptosis, acridine orange staining to determine autophagy, and immunoblotting to detect the protein levels involved in apoptosis and autophagy as well as mitogen activated protein kinases (MAPKs) activation upon EGCG treatment. The expression of the HHV8 lytic gene was determined by luciferase reporter assay and reverse transcription-PCR, and viral progeny production was determined by PCR. Results revealed that EGCG induced cell death and ROS generation in PEL cells in a dose-dependent manner. N-acetylcysteine (NAC) inhibited the EGCG-induced ROS and rescued the cell from EGCG-induced cell death. Even though EGCG induced ROS generation in PEL cells, it reduced the production of progeny virus from PEL cells without causing HHV8 reactivation. These results suggest that EGCG may represent a novel strategy for the treatment of HHV8 infection and HHV8-associated lymphomas.

Resveratrol suppresses glial activation and alleviates trigeminal neuralgia via activation of AMPK.

BACKGROUND: Glial activation and neuroinflammation in the spinal trigeminal nucleus (STN) play a pivotal role in the genesis and maintenance of trigeminal neuralgia (TN). Resveratrol, a natural compound from grape and red wine, has a potential anti-inflammatory effect. We hypothesized that resveratrol could significantly suppress neuroinflammation in the STN mediated by glial activation and further relieve TN. In this study, we evaluated whether resveratrol could alleviate trigeminal allodynia and explore the mechanism underlying the antinociceptive effect of resveratrol. METHODS: Animals were orally injected with resveratrol after chronic constriction injury (CCI) of the infraorbital nerve. Mechanical thresholds of the affected whisker pad were measured to assess nociceptive behaviors. The STN was harvested to quantify the changing levels of p-NR1, p-PKC, TNF-α, and IL1-ß by western blotting and detect the expression of calcitonin gene-related peptide (CGRP) and c-Fos by immunofluorescence. Glial activation was observed by immunofluorescence and western blotting. Mitogen-activated protein kinase (MAPK) phosphorylation in vivo and in vitro was examined by western blotting. RESULTS: We found that resveratrol significantly attenuated trigeminal allodynia dose-dependently and decreased the increased expression of CGRP and c-Fos in the STN. Additionally, resveratrol showed an inhibitory effect on CCI-evoked astrocyte and microglia activation and reduced production of pro-inflammatory cytokines in the STN. Furthermore, the antinociceptive effect of resveratrol was partially mediated by reduced phosphorylation of MAP kinases via adenosine monophosphate-activated protein kinase (AMPK) activation. CONCLUSIONS: AMPK activation in the STN glia via resveratrol has utility in the treatment of CCI-induced neuroinflammation and further implicates AMPK as a novel target for the attenuation of trigeminal neuralgia.