Sp1 Inhibits PGC-1α via HDAC2-Catalyzed Histone Deacetylation in Chronic Constriction Injury-Induced Neuropathic Pain

Background: Our previous study has illuminated that PGC-1α downregulation promoted chronification of pain after burn injury. RNA-seq analysis predicted association between Sp1 and chronic constriction injury (CCI)-provoked neuropathic pain. Further ChIP-Atlas data investigation suggested the binding to Sp1 to PGC-1α. Thereby, we performed this study to illustrate the functional relevance of the Sp1/PGC-1α axis in neuropathic pain. Methods: Neuropathic pain was induced by CCI in vivo in rats, followed by assessment of neuropathic pain-like behaviors. The expression of Sp1 and correlated genes was determined in CCI rat spinal cord tissues. Furthermore, microglia were exposed to lipopolysaccharide (LPS) to mimic inflammation and then cocultured with neurons. Knockdown and ectopic expression methods were used in vivo and in vitro to define the role the Sp1/HDAC2/PGC-1α axis. Results: Sp1 expression was upregulated in spinal cord tissues of CCI rats. Silencing Sp1 ameliorated CCI-induced neuropathic pain, as reflected by elevated paw withdrawal threshold and paw withdrawal latency, as well as alleviated microglia activation, neuronal dysfunction, inflammatory responses, mitochondrial dysfunction, and oxidative stress in spinal cord tissues. Sp1 knockdown also reversed LPS-induced microglial inflammation and neuronal dysfunction. Sp1 promoted histone deacetylation in the PGC-1α promoter and inhibited PGC-1α expression via recruiting HDAC2. PGC-1α overexpression diminished CCI-induced neuropathic pain and LPS-induced inflammation and mitochondrial dysfunction, based on which Sp1 aggravated microglial inflammation and neuronal dysfunction in neuropathic pain. Conclusion: This study elucidated the promoting effects of Sp1 on CCI-induced neuropathic pain via the HDAC2/PGC-1α axis

New asymmetrical bispyrrolidinoindoline diketopiperazines from the marine fungus <i>Aspergillus</i> sp. DX4H

<p>Known diketopiperazine WIN 64821 and its asymmetric stereoisomers (<b>1</b>–<b>3</b>) had been isolated from the culture broth of a marine gut fungus <i>Aspergillus</i> sp. DX4H. The planar and stereochemistry for new compounds were determined by a suite of techniques including mass, NMR and CD spectra together with Marfey’s method. Their inhibitory activity against PC3 cell line had been tested.</p

Datasheet1_Risk factors for death associated with severe influenza in children and the impact of the COVID-19 pandemic on clinical characteristics.pdf

BackgroundTo summarize the clinical features of severe influenza in children and the high-risk factors for influenza-related deaths and to raise awareness among pediatricians.MethodsA retrospective study of clinical manifestations, laboratory tests, and diagnosis and treatment of 243 children with severe influenza admitted to Shenzhen Children's Hospital from January 2009 to December 2022 was conducted. Univariate logistic regression analysis and Boruta analysis were also performed to identify potentially critical clinical characteristics associated with death, and clinically significant were used in further multivariate logistic regression analysis. Subject receiver operating characteristic (ROC) curves were applied to assess the efficacy of death-related independent risk factors to predict death from severe influenza.ResultsThere were 169 male and 74 female patients with severe influenza, with a median age of 3 years and 2 months and 77.4% of patients under six. There were 46 cases (18.9%) in the death group. The most common pathogen was Influenza A virus (IAV) (81.5%). The most common complication in the death group was influenza-associated acute necrotizing encephalopathy (ANE [52.2%]). Severe influenza in children decreased significantly during the COVID-19 pandemic, with a median age of 5 years, a high predominance of neurological symptoms such as ANE (P = 0.001), and the most common pathogen being H3N2 (P ConclusionNeurological disorders such as ANE are more significant in children with severe influenza after the COVID-19 pandemic. Influenza virus infection can cause serious multisystem complications such as ARDS and ANE, and D-dimer has predictive value for early diagnosis and determination of the prognosis of children with severe influenza.</p

Extracellular Polymeric Substances Induced Porous Polyaniline for Enhanced Cr(VI) Removal from Wastewater

Extracellular polymeric substances (EPS) of bacteria were used as templates for synthesizing unique polyaniline nanocomposites, i.e., porous EPS-modified polyaniline (EPS@PANI). The proteins were responsible for forming porous structure, while polysaccharides for the fiber morphology of EPS@PANI. The specific surface area (53.2 m²/g) of these unique EPS@PANI with an optimal EPS loading of 2 wt % was ∼2 times larger than that of pristine PANI. The PANI in EPS@PANI stayed as the emeraldine form and acted as the electron donor for reduction of Cr­(VI) to Cr­(III). Herein, 1.0 mg/L Cr­(VI) was completely reduced to Cr­(III) by 600 mg/L of EPS@PANI within 10 min, which was much faster than the pristine PANI (1 h). A maximum Cr­(VI) removal capacity of 913.2 mg/g was achieved by these unique EPS@PANI nanocomposites and was ∼4.7 times higher than the pristine PANI (193.8 mg/g). Moreover, the isoelectric point (pI) was decreased from pH 7.5 for pure PANI to ∼4.5 for these porous EPS@PANI nanocomposites due to the low pI of polysaccharides remained in the composites. This lowered pI facilitated further Cr­(III) removal on the surface of EPS@PANI from the wastewater

Table_1_Comparison of Robotic-Assisted vs. Conventional Laparoscopy for Para-aortic Lymphadenectomy in Gynecological Malignancies: A Systematic Review and Meta-Analysis.DOCX

BackgroundRobotic-assisted surgery is one of the novel minimally invasive surgical techniques for the treatment of gynecological malignancies. The aim of this systematic review and meta-analysis was to compare the outcomes of robot-assisted vs. conventional laparoscopy for para-aortic lymphadenectomy (PAL) in patients with gynecological malignancies.MethodsAn electronic search in PubMed, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases was performed for articles, published up to 01st November 2021. Outcomes including operating time (OT), total blood loss (TBL), length of stay (LOS), and complication rate (CR) in robot-assisted vs. conventional laparoscopy were investigated.ResultsA total of nine studies (7 non-RCTs and 2 RCTs) involving 914 participants were included. Of them, 332 patients underwent robotic laparoscopy (robotic group) and 582-conventional laparoscopy (conventional laparoscopy group). A significant decrease in TBL (MD = −149.1; 95% CI: −218.4 to −79.91) [ml] was observed in the robotic group as compared to the conventional laparoscopy group. However, no significant difference was noted for OT, CR, and LOS in the overall findings. Further subgroup analysis showed that the robotic group had a lower OT in mixed histological populations and studies reporting on the extraperitoneal approach. The lower chance of TBL was observed in mixed histological populations and studies involving extraperitoneal approach, Caucasian population, and non-RCTs design.ConclusionsRobotic laparoscopy has a significant advantage over the conventional laparoscopy approach for PAL in gynecological malignancies. Further prospective observational studies embedded with a large sample size are needed to validate our findings.</p

Ultrasonic Pretreated Sludge Derived Stable Magnetic Active Carbon for Cr(VI) Removal from Wastewater

A stable magnetic carbon was synthesized using activated sludge as the carbon precursor. The ultrasonic pretreatment was used to destroy the cells in the activated sludge and to release the soluble carbon source, which was responsible for the improved stability of the synthesized magnetic carbon. 800 W was demonstrated as the optimized ultrasonication power for the pretreatment of activated sludge. Then, the carbonization parameters, such as pyrolysis temperature, heating rate, and dwell time were optimized as 800 °C, 10 °C/min, and 60 min, respectively. To be more specific, this activated sludge derived magnetic carbon can reduce almost all the hexavalent chromium (Cr­(VI)) (2.0 mg/L) in 10 min and has a maximum capacity as high as 203 mg/g. The iron release rate of the synthesized activated sludge derived magnetic carbon was decreased, which improved the electron utilization of zerovalent iron (ZVI). This composite was demonstrated to have a good stability and recyclability as well. Finally, the Cr­(VI) removal mechanisms were clarified under the acidic and the natural conditions

DataSheet_1_Calcium nutrition nanoagent rescues tomatoes from mosaic virus disease by accelerating calcium transport and activating antiviral immunity.docx

As an essential structural, metabolic and signaling element, calcium shows low remobilization from old to young tissues in plants, restricting the nutrient-use efficiency and control efficacy against mosaic virus disease. Nanotechnology has been applied to prevent/minimize nutrient losses and improve the accessibility of poorly-available nutrients. Herein, the current study applied a star polycation (SPc) to prepare a calcium nutrition nanoagent. The SPc could assemble with calcium glycinate through hydrogen bond and Van der Waals force, forming stable spherical particles with nanoscale size (17.72 nm). Transcriptomic results revealed that the calcium glycinate/SPc complex could activate the expression of many transport-related genes and disease resistance genes in tomatoes, suggesting the enhanced transport and antiviral immunity of SPc-loaded calcium glycinate. Reasonably, the calcium transport was accelerated by 3.17 times into tomato leaves with the help of SPc, and the protective effect of calcium glycinate was remarkably improved to 77.40% and 67.31% toward tomato mosaic virus with the help of SPc after the third and fifth applications. Furthermore, SPc-loaded calcium glycinate could be applied to increase the leaf photosynthetic rate and control the unusual fast growth of tomatoes. The current study is the first success to apply nano-delivery system for enhanced calcium transport and antiviral immunity, which is beneficial for increasing nutrient-use efficiency and shows good prospects for field application.</p

Additional file 1 of Impacts of longitudinal water curtain cooling system on transcriptome-related immunity in ducks

Supplementary Material

Co-delivery of Doxorubicin and Interferon‑γ by Thermosensitive Nanoparticles for Cancer Immunochemotherapy

A dual-sensitive nanoparticle delivery system was constructed by incorporating an acid sensitive hydrazone linker into thermosensitive nanoparticles (TSNs) for co-encapsulating doxorubicin (DOX) and interferon γ (IFNγ) and to realize the co-delivery of chemotherapy and immunotherapy agents against melanoma. DOX, a chemotherapeutic drug, was conjugated to TSNs by a pH-sensitive chemical bond, and IFNγ, a potent immune-modulator, was absorbed into TSNs through the thermosensitivity and electrostatics of nanoparticles. Consequently, the dual sensitive drug-loaded TSN delivery systems were successfully built and showed an obvious core–shell structure, good encapsulation efficiency of drugs, sustained and sensitive drug release, prolonged circulation time, as well as excellent synergistic antitumor efficiency against B16F10 tumor bearing mice. Moreover, the combinational antitumor immune responses of hydrazone bearing DOX/IFNγ-TSN (hyd) were strengthened by activating Th1-type CD4⁺ T cells, cytotoxic T lymphocytes, and natural killer cells, downregulating the expression levels of immunosuppressive cytokines, such as IL10 and TGFβ, and upregulating the secretion of IL2 and TNFα. Taken together, the multifunctional TSNs system provides a promising strategy for multiple drugs co-delivery with distinct properties

Licorice root extract and magnesium isoglycyrrhizinate protect against triptolide-induced hepatotoxicity <i>via</i> up-regulation of the Nrf2 pathway

<p>Triptolide, the predominant biologically active component of the Chinese herb <i>Tripterygium wilfordii</i> Hook f., possesses numerous pharmacological activities, including anti-inflammatory, anti-fertility, anti-neoplastic, and immunosuppressive effects. However, toxicity and severe adverse effects, particularly hepatotoxicity, limit the clinical application of triptolide. Licorice root extract contains various bioactive compounds and is potent hepatoprotective. Magnesium isoglycyrrhizinate, a magnesium salt of the 18α-glycyrrhizic acid stereoisomer of glycyrrhizic acid, is used clinically in China to treat chronic viral hepatitis and acute drug-induced liver injury. The aim of this study was to investigate the role of the factor erythroid 2-related factor 2 pathway in the protective effects of LE and MIG against triptolide-induced hepatotoxicity. Hepatotoxicity models were established in L-02 cells and rats using triptolide, and the protective effects of LE and MIG were investigated <i>in vitro</i> and <i>in vivo</i>, respectively. LE and MIG significantly protected against triptolide-induced cytotoxicity. Additionally, triptolide decreased the mRNA and protein levels of Nrf2 and down-regulated Nrf2 target genes, including <i>UGT1A</i>, <i>BSEP</i>, and <i>MRP2</i>, while pretreatment with LE and MIG reversed these effects. Finally, Nrf2-involved antioxidant responses were activated in the presence of LE and MIG.</p