Construction of multileveled and oriented micro/nano channels in Mg doped hydroxyapitite bioceramics and their effect on mimicking mechanical property of cortical bone and biological performance of cancellous bone.

Drawing on the structure and components of natural bone, this study developed Mg-doped hydroxyapatite (Mg-HA) bioceramics, characterized by multileveled and oriented micro/nano channels. These channels play a critical role in ensuring both mechanical and biological properties, making bioceramics suitable for various bone defects, particularly those bearing loads. Bioceramics feature uniformly distributed nanogrooves along the microchannels. The compressive strength or fracture toughness of the Mg-HA bioceramics with micro/nano channels formed by single carbon nanotube/carbon fiber (CNT/CF) (Mg-HA(05-CNT/CF)) are comparable to those of cortical bone, attributed to a combination of strengthened compact walls and microchannels, along with a toughening mechanism involving crack pinning and deflection at nanogroove intersections. The introduction of uniform nanogrooves also enhanced the porosity by 35.4 %, while maintaining high permeability owing to the capillary action in the oriented channels. This leads to superior degradation properties, protein adsorption, and in vivo osteogenesis compared with bioceramics with only microchannels. Mg-HA(05-CNT/CF) exhibited not only high strength and toughness comparable to cortical bone, but also permeability similar to cancellous bone, enhanced cell activity, and excellent osteogenic properties. This study presents a novel approach to address the global challenge of applying HA-based bioceramics to load-bearing bone defects, potentially revolutionizing their application in tissue engineering.

Functional properties, structural characteristics, and anti-complementary activities of two degraded polysaccharides from strawberry fruits.

Two low-molecular-weight polysaccharides (DPSP50 and DPSP70) were obtained using hydrogen peroxide-vitamin C (H2O2-Vc) treatment at 50 °C and 70 °C, respectively. Both DPSP50 and DPSP70 comprised the same six monosaccharides in different ratios, and their molecular weights (Mws) were 640 kDa and 346 kDa, respectively. Functional properties analyses demonstrated that DPSP50 and DPSP70 each had an excellent water holding capacity, oil absorption capacity, and emulsion properties, as well as shear-thinning characteristics and viscoelastic properties. Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopic assays confirmed the existence of α-, ß-pyranose rings and the same six sugar residues in DPSP50 and DPSP70. The results of Congo red test, scanning electron microscopy (SEM), and X-ray diffraction (XRD) demonstrated that DPSP50 and DPSP70 did not contain triple-helix conformations, but were amorphous aggregates with flake-like shape and rough surface. Additionally, both DPSP50 and DPSP70 showed strong anti-complementary activities through the classical pathway and the alternative pathway. The results support the potential utility of these degraded polysaccharides from strawberry fruits in functional foods and medicines.

Engineering APOBEC3A deaminase for highly accurate and efficient base editing.

Cytosine base editors (CBEs) are effective tools for introducing C-to-T base conversions, but their clinical applications are limited by off-target and bystander effects. Through structure-guided engineering of human APOBEC3A (A3A) deaminase, we developed highly accurate A3A-CBE (haA3A-CBE) variants that efficiently generate C-to-T conversion with a narrow editing window and near-background level of DNA and RNA off-target activity, irrespective of methylation status and sequence context. The engineered deaminase domains are compatible with PAM-relaxed SpCas9-NG variant, enabling accurate correction of pathogenic mutations in homopolymeric cytosine sites through flexible positioning of the single-guide RNAs. Dual adeno-associated virus delivery of one haA3A-CBE variant to a mouse model of tyrosinemia induced up to 58.1% editing in liver tissues with minimal bystander editing, which was further reduced through single dose of lipid nanoparticle-based messenger RNA delivery of haA3A-CBEs. These results highlight the tremendous promise of haA3A-CBEs for precise genome editing to treat human diseases.

Influence of Zr aggregation on Li-ion conductivity of amorphous solid-state electrolyte Li-La-Zr-O.

In our study, we investigated the influence of the local structure of amorphous Li-La-Zr-O (a-LLZO) on Li-ion conductivity using ab initio molecular dynamics (AIMD). A-LLZO has shown promising properties in inhibiting the growth of lithium dendrites, making it a potential candidate for solid electrolytes in all-solid-state lithium batteries. The low Li-ion conductivity of a-LLZO is currently limiting its practical applications. Our findings revealed that the homogeneous distribution of Zr-O polyhedra within the pristine structure of a-LLZO contributes to enhanced Li-ion conductivity. By reducing the interconnections among Zr-O polyhedra, the AIMD-simulated a-LLZO sample achieved a Li-ion conductivity of 5.78 × 10-4 S/cm at room temperature, which is slightly lower than that of cubic LLZO (c-LLZO) with a Li-ion conductivity of 1.63 × 10-3 S/cm. Furthermore, we discovered that Li-ion conductivity can be influenced by adjusting the elemental ratios within a-LLZO. This suggests that fine-tuning the composition of a-LLZO can potentially further enhance its Li-ion conductivity and optimize its performance as a solid electrolyte in lithium batteries.

Quality grade evaluation of Nvjin Pills based on traditional Chinese medicine reference drug and network pharmacology of target-focused compounds.

To improve the effectiveness of marketed drugs related to active ingredients, it is necessary to designate a more unified quality evaluation standard. Taking Nvjin Pills as an example, this study reported the development of a novel principle of analysis in traditional Chinese medicine. The core of the experiment is to prepare three batches of traditional Chinese medicine reference drugs by high-quality Chinese materia medica. The active ingredients identified in the herbal formula including glycyrrhizic acid, cinnamaldehyde, paeonol, baicalin, hesperidin, paeoniflorin, and ferulic acid were analyzed in traditional Chinese medicine reference drugs by the high-performance liquid chromatography method combined with wavelength switching. The simple prediction results of network pharmacological analysis verified the feasibility and reliability of the established quantitative analysis method for seven target-focused compounds in Nvjin Pills, which were recommended as candidate indicators for quality evaluation ultimately. Using the seven target-focused compounds as the scientific ruler, quality grade specifications of Nvjin Pills were proposed by comprehensive analysis. Accordingly, 16, 47, and 13 batches of samples were primarily graded as first grade, second grade, and unqualified grade, respectively. This study will provide a chemical basis for quality control of Nvjin Pills, which is necessary for the production process of pharmaceutical development.

In vivo base editing rescues primary hyperoxaluria type 1 in rats.

Primary hyperoxaluria type 1 (PH1) is a childhood-onset autosomal recessive disease, characterized by nephrocalcinosis, multiple recurrent urinary calcium oxalate stones, and a high risk of progressive kidney damage. PH1 is caused by inherent genetic defects of the alanine glyoxylate aminotransferase (AGXT) gene. The in vivo repair of disease-causing genes was exceedingly inefficient before the invention of base editors which can efficiently introduce precisely targeted base alterations without double-strand DNA breaks. Adenine base editor (ABE) can precisely convert A·T to G·C with the assistance of specific guide RNA. Here, we demonstrated that systemic delivery of dual adeno-associated virus encoding a split-ABE8e could artificially repair 13% of the pathogenic allele in AgxtQ84X rats, a model of PH1, alleviating the disease phenotype. Specifically, ABE treatment partially restored the expression of alanine-glyoxylate-aminotransferase (AGT), reduced endogenous oxalate synthesis and alleviated calcium oxalate crystal deposition. Western blot and immunohistochemistry confirmed that ABE8e treatment restored AGT protein expression in hepatocytes. Moreover, the precise editing efficiency in the liver remained stable six months after treatment. Thus, our findings provided a prospect of in vivo base editing as a personalized and precise medicine for PH1 by directly correcting the mutant Agxt gene.

Improved catalytic performance in gas-phase dimethyl ether carbonylation over facile NH4F etched ferrierite.

Gas-phase dimethyl ether (DME) carbonylation to methyl acetate (MA) initiates a promising route for producing ethanol from syngas. Ferrierite (FER, ZSM-35) has received considerable attention as it displays excellent stability in the carbonylation reaction and its modification strategy is to improve its catalytic activity on the premise of maintaining its stability as much as possible. However, conventional post-treatment methods such as dealumination and desilication usually selectively remove framework Al or Si atoms, ultimately altering the intrinsic composition, crystallinity, and acidity of zeolites inevitably. In this study, we successfully prepared a series of hierarchical ZSM-35 materials through post-treatment with NH4F etching, which dissolved framework Al and Si at similar rates and preferentially attacked the defective sites. Interestingly, the produced pore systems effectively penetrated the [100] plane, offering elevated access to both the 8-membered ring (8-MR) and 10-membered ring (10-MR) channels. The physicochemical and acid properties of the pristine and NH4F etched ZSM-35 samples were comprehensively characterized using various techniques, including XRD, XRF, FESEM, HRTEM, Nitrogen adsorption-desorption, NH3-TPD, Py-IR, 27Al MAS NMR, and 29Si MAS NMR. Under moderate treatment conditions, the intrinsic microporous structure, acid properties, and crystallinity of zeolite were retained, leading to superior catalytic activity and stability with respect to the pristine sample. Nonetheless, severe NH4F etching disrupted the crystalline framework and created additional defective sites, bringing about faster deposition of coke precursors on the interior Brønsted acid sites (BAS) and decreased catalytic performance. This technique provides a novel and efficient method to slightly enhance the micropore and mesopore volume of industrially pertinent zeolites through a straightforward post-treatment, thus elevating the catalytic performance of these zeolites.

Multiplex gene editing reduces oxalate production in primary hyperoxaluria type 1.

Targeting key enzymes that generate oxalate precursors or substrates is an alternative strategy to eliminate primary hyperoxaluria type I (PH1), the most common and life-threatening type of primary hyperoxaluria. The compact Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) from the Prevotella and Francisella 1 (Cpf1) protein simplifies multiplex gene editing and allows for all-in-one adeno-associated virus (AAV) delivery. We hypothesized that the multiplex capabilities of the Cpf1 system could help minimize oxalate formation in PH1 by simultaneously targeting the hepatic hydroxyacid oxidase 1 ( Hao1) and lactate dehydrogenase A ( Ldha) genes. Study cohorts included treated PH1 rats ( Agxt Q84X rats injected with AAV-AsCpf1 at 7 days of age), phosphate-buffered saline (PBS)-injected PH1 rats, untreated PH1 rats, and age-matched wild-type (WT) rats. The most efficient and specific CRISPR RNA (crRNA) pairs targeting the rat Hao1 and Ldha genes were initially screened ex vivo. In vivo experiments demonstrated efficient genome editing of the Hao1 and Ldha genes, primarily resulting in small deletions. This resulted in decreased transcription and translational expression of Hao1 and Ldha. Treatment significantly reduced urine oxalate levels, reduced kidney damage, and alleviated nephrocalcinosis in rats with PH1. No liver toxicity, ex-liver genome editing, or obvious off-target effects were detected. We demonstrated the AAV-AsCpf1 system can target multiple genes and rescue the pathogenic phenotype in PH1, serving as a proof-of-concept for the development of multiplex genome editing-based gene therapy.

Effect of SARS-CoV-2 infection on seizure, anxiety, and depression in 107 patients with epilepsy.

OBJECTIVE: To study the effects of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) on epileptic seizures, anxiety, and depression in patients with epilepsy. METHODS: Based on the inclusion and exclusion criteria, an ambispective cohort study was hereby conducted on patients with epilepsy infected with SARS-CoV-2 who visited the outpatient and ward of the Department of Neurology of Xinyang Central Hospital from December 2022 (when the domestic epidemic prevention and control policy was lifted) to February 2023. A face-to-face questionnaire survey involving factors including basic information, vaccination with inactivated COVID-19 vaccines, number of seizures within 2 months before and after SARS-CoV-2 infection, and scores of anxiety and depression was carried out. RESULTS: A total of 107 patients with epilepsy satisfying the inclusion and exclusion criteria completed the follow-up after 2 months. It was found that enrolled patients maintained the original dose of antiepileptic drugs, but the frequency of seizures after COVID-19 infection could not be controlled. After infection with SARS-CoV-2, the frequency of seizures in patients with epilepsy in 2 months increased compared with that before infection (P < 0.05). Meanwhile, compared with the vaccinated group, the high-frequency seizure rate of epilepsy in the unvaccinated group was higher. (P < 0.05), and the anxiety and depression scores of patients with epilepsy were worse than those before they were infected (P < 0.05). CONCLUSION: Being infected with SARS-CoV-2 can increase the number of seizures and aggravate the degree of anxiety and depression in patients with epilepsy. The inactivated vaccine is protective, and the inactivated SARS-CoV-2 vaccine can reduce the rate of high-frequency seizures.

Black Phosphorus Nanosheets Assist Nanoerythrosomes for Efficient mRNA Vaccine Delivery and Immune Activation.

Messenger RNA (mRNA)-based vaccines have enormous potential in infectious disease prevention and tumor neoantigen application. However, developing an advanced delivery system for efficient mRNA delivery and intracellular release for protein translation remains a challenge. Herein, a biocompatible biomimetic system is designed using red blood cell-derived nanoerythrosomes (NER) and black phosphorus nanosheets (BP) for mRNA delivery. BP is covalently modified with polyethyleneimine (PEI), serving as a core to efficiently condense mRNA via electrostatic interactions. To facilitate the spleen targeting of the mRNA-loaded BP (BPmRNA ), NER is co-extruded with BPmRNA to construct a stable "core-shell" nanovaccine (NER@BPmRNA ). The mRNA nanovaccine exhibits efficient protein expression and immune activation via BP-mediated adjuvant effect and enhanced lysosomal escape. In vivo evaluation demonstrates that the system delivery of mRNA encoding coronavirus receptor-binding domain (RBD) significantly increases the antibody titer and pseudovirus neutralization effect compared with that of NER without BP assistance. Furthermore, the mRNA extracted from mouse melanoma tissues is utilized to simulate tumor neoantigen delivered by NER@BPmRNA . In the vaccinated mice, BP-assisted NER for the delivery of melanoma mRNA can induce more antibodies that specifically recognize tumor antigens. Thus, BP-assisted NER can serve as a safe and effective delivery vehicle in mRNA-based therapy.

Mitochondria-Targeting Pyroptosis Amplifier of Lonidamine-Modified Black Phosphorus Nanosheets for Glioblastoma Treatments.

Pyroptosis is accompanied by immunogenic mediators' release and serves as an innovative strategy to reprogram tumor microenvironments. However, damaged mitochondria, the origin of pyroptosis, are frequently eliminated by mitophagy, which will severely impair pyroptosis-elicited immune activation. Herein, black phosphorus nanosheets (BP) are employed as a pyroptosis inducer delivery and mitophagy flux blocking system since the degradation of BP could impair lysosomal function by altering the pH within lysosomes. The pyroptosis inducer of lonidamine (LND) was precoupled with the mitochondrial target moiety of triphenylphosphonium to facilitate the occurrence of pyroptosis. The mitochondria-targeting LND-modified BP (BPTLD) were further encapsulated into the macrophage membrane to endow the BPTLD with blood-brain barrier penetration and tumor-targeting capability. The antitumor activities of membrane-encapsulated BPTLD (M@BPTLD) were investigated using a murine orthotopic glioblastoma model. The results demonstrated that the engineered nanosystem of M@BPTLD could target the mitochondria, and induce as well as reinforce pyroptosis via mitophagy flux blocking, thereby boosting the release of immune-activated factors to promote the maturation of dendritic cells. Furthermore, upon near-infrared (NIR) irradiation, M@BPTLD induced stronger mitochondrial oxidative stress, which further advanced robust immunogenic pyroptosis in glioblastoma cells. Thus, this study utilized the autophagy flux inhibition and phototherapy performance of BP to amplify LND-mediated pyroptosis, which might greatly contribute to the development of pyroptosis nanomodulators.

Identification of natural killer cell associated subtyping and gene signature to predict prognosis and drug sensitivity of lung adenocarcinoma.

Introduction: This research explored the immune characteristics of natural killer (NK) cells in lung adenocarcinoma (LUAD) and their predictive role on patient survival and immunotherapy response. Material and methods: Molecular subtyping of LUAD samples was performed by evaluating NK cell-associated pathways and genes in The Cancer Genome Atlas (TCGA) dataset using consistent clustering. 12 programmed cell death (PCD) patterns were acquired from previous study. Riskscore prognostic models were constructed using Least absolute shrinkage and selection operator (Lasso) and Cox regression. The model stability was validated in Gene Expression Omnibus database (GEO). Results: We classified LUAD into three different molecular subgroups based on NK cell-related genes, with the worst prognosis in C1 patients and the optimal in C3. Homologous Recombination Defects, purity and ploidy, TMB, LOH, Aneuploidy Score, were the most high-expressed in C1 and the least expressed in C3. ImmuneScore was the highest in C3 type, suggesting greater immune infiltration in C3 subtype. C1 subtypes had higher TIDE scores, indicating that C1 subtypes may benefit less from immunotherapy. Generally, C3 subtype presented highest PCD patterns scores. With four genes, ANLN, FAM83A, RHOV and PARP15, we constructed a LUAD risk prediction model with significant differences in immune cell composition, cell cycle related pathways between the two risk groups. Samples in C1 and high group were more sensitive to chemotherapy drug. The score of PCD were differences in high- and low-groups. Finally, we combined Riskscore and clinical features to improve the performance of the prediction model, and the calibration curve and decision curve verified that the great robustness of the model. Conclusion: We identified three stable molecular subtypes of LUAD and constructed a prognostic model based on NK cell-related genes, maybe have a greater potential for application in predicting immunotherapy response and patient prognosis.

A novel signature combing cuproptosis- and ferroptosis-related genes in sepsis-induced cardiomyopathy.

Objective: Cardiac dysfunction caused by sepsis, usually termed sepsis-induced cardiomyopathy (SIC), is one of the most serious complications of sepsis, and ferroptosis can play a key role in this disease. In this study, we identified key cuproptosis- and ferroptosis-related genes involved in SIC and further explored drug candidates for the treatment of SIC. Methods: The GSE79962 gene expression profile of SIC patients was downloaded from the Gene Expression Omnibus database (GEO). The data was used to identify differentially expressed genes (DEGs) and to perform weighted correlation network analysis (WGCNA). Furthermore, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted. Then, gene set enrichment analysis (GSEA) was applied to further analyze pathway regulation, with an adjusted p-value <0.05 and a false discovery rate (FDR) <0.25. Ferroptosis-related genes were obtained from the FerrDb V2 database, and cuproptosis-related genes were obtained from the literature. We constructed a novel signature (CRF) by combing cuproptosis-related genes with ferroptosis-related genes using the STRING website. The SIC hub genes were obtained by overlapping DEGs, WGCNA-based hub genes and CRF genes, and receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of hub genes. A transcription factor-microRNA-hub gene network was also constructed based on the miRnet database. Finally, potential therapeutic compounds for SIC were predicted based on the Drug Gene Interaction Database. Results: We identified 173 DEGs in SIC patients. Four hub modules and 411 hub genes were identified by WGCNA. A total of 144 genes were found in the CRF. Then, POR, SLC7A5 and STAT3 were identified as intersecting hub genes and their diagnostic values were confirmed with ROC curves. Drug screening identified 15 candidates for SIC treatment. Conclusion: We revealed that the cuproptosis- and ferroptosis-related genes, POR, SLC7A5 and STAT3, were significantly correlated with SIC and we also predicted therapeutic drugs for these targets. The findings from this study will make contributions to the development of treatments for SIC.

Clinical Features and Blood Indicators for Severity and Prognosis in COVID-19 Patients.

BACKGROUND: This study aimed to analyze the clinical manifestations and blood indicators to deepen the understanding of Coronavirus disease 2019 (COVID-19). METHODS: COVID-19 patients admitted to C10 West Ward, Tongji Hospital in Wuhan City ("West Ward") between January 31 and March 28, 2020, were retrospectively analyzed. RESULTS: A total of 61 COVID-19 patients were hospitalized, wherein the non-critical Group had 30 cases, while the critical group had 31 (including 14 survivors and 17 deaths). Age, the proportion of fever cases, white blood cell (WBC), basophils, red blood cell (RBC), hemoglobin, lactate dehydrogenase (LDH), C-reactive protein (CRP), high-sensitivity troponin, pro-BNP (brain natriuretic peptide), prothrombin time (PT), and D-dimer were higher in the critical group while lymphocytes, eosinophils, albumin were lower compared with those of the non-critical group (all p < 0.05). WBC (p = 0.008), basophils (p = 0.034), and LDH (p = 0.005) of the death subgroup climbed remarkably in comparison with those of the survival subgroup. CONCLUSIONS: Advanced age, high fever, increases in indicators such as WBC, basophils, CRP, LDH, high-sensitivity troponin, pro-BNP, and D-dimer, and decreases in indicators, including lymphocytes, eosinophils, and albumin, might forebode a critical condition.

Intradermal miR-16-5p targets Akt3 and reduces RTX-induced postherpetic neuralgia-mimic pain in mice.

The molecular mechanisms of refractory pain in postherpetic neuralgia (PHN) patients are not fully understood. PHN may be related to skin abnormality after herpes zoster induced skin lesions. We previously reported 317 differentially expressed microRNAs (miRNAs) in PHN skin compared with the contralateral normal mirror skin. In this study, 19 differential miRNAs were selected and the expression was validated in other 12 PHN patients. The expression levels of miR-16-5p, miR-20a-5p, miR-505-5p, miR-3664-3p, miR-4714-3p and let-7a-5p are lower in PHN skin, which is the same as those in microarray experiment. To evaluate the effects of cutaneous miRNA on PHN, the expression of candidate miRNAs is further observed in resiniferatoxin (RTX) induced PHN-mimic mice model. In the plantar skin of RTX mice, miR-16-5p and let-7a-5p are downregulated, with the same expression trend of PHN patients. In addition, intraplantar injection of agomir-16-5p reduced mechanical hyperalgesia, and improved thermal hypoalgesia in RTX mice. Furthermore, agomir-16-5p down-regulated the expression levels of Akt3, which is the target gene of agomir-16-5p. These results suggest that intraplantar miR-16-5p may alleviate RTX induced PHN-mimic pain by inhibiting the expression of Akt3 in the skin.

Honokiol attenuates mitochondrial fission and cell apoptosis by activating Sirt3 in intracerebral hemorrhage.

BACKGROUND: Sirtuin-3 (Sirt3) has been documented to protect against mitochondrial dysfunction and apoptosis. Honokiol (HKL) is a Sirt3 pharmacological activator with reported neuroprotective effects in multiple neurological disorders. The present study aimed to explore the neuroprotective effects of HKL and the role of Sirt3 following intracerebral hemorrhage (ICH). METHODS: An in vivo ICH model in rats was established by injecting autologous blood into the right basal ganglia. PC12 cells were stimulated with hemin. For the in vivo investigation, the modified Neurological Severity Scores and the Morris water maze test were performed to assess neurological deficits. Hematoxylin-Eosin and Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining were employed to evaluate the histopathology and apoptosis. Immunohistochemical staining was used to investigate the expression of Sirt3. Adenosine triphosphate (ATP) levels were quantified to assess mitochondrial dysfunction. Cell counting kit-8, lactate dehydrogenase assay, and flow cytometry were used to analyze cell vitality and apoptosis in vitro. Immunofluorescence staining was performed to observe mitochondrial morphology and dynamin-related protein 1 (Drp1) localization to mitochondria. Western blot was applied to quantify the expression of Sirt3, Bax, Bcl-2, cleaved-caspase-3, Drp1, phosphorylation of Drp1 at serine-616, and phosphorylation of Drp1 at serine-637 in vivo and in vitro. RESULTS: HKL treatment alleviated neurological deficits, attenuated the histopathological damage and cell apoptosis, and restored the decreased ATP levels in ICH rats. HKL improved cell survival rate, reduced cell apoptosis, and inhibited mitochondrial fission in PC12 cells. Moreover, both in vivo and in vitro models showed increased phosphorylation of Drp1 at Ser616, and reduced phosphorylation of Drp1 at Ser637. Meanwhile, immunofluorescence co-localization analysis revealed that hemin increased the overlap of Drp1 and mitochondria in PC12 cells. The phosphorylation and mitochondrial translocation of Drp1 were effectively reversed by HKL treatment. Importantly, the selective Sirt3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine suppressed these effects. CONCLUSION: Our findings demonstrated that HKL ameliorated ICH-induced apoptosis and mitochondrial fission by Sirt3, suggesting that HKL has immense prospects for the treatment of ICH.

Effects of Maturity and Processing on the Volatile Components, Phytochemical Profiles and Antioxidant Activity of Lotus (Nelumbo nucifera) Leaf.

In this study, fresh lotus leaves at two maturity stages were processed to tea products by different methods (white-tea process, green-tea process and black-tea process). The volatile compounds, phytochemical profiles and antioxidant activities of lotus-leaf tea were investigated. A total of 81 volatile components were identified with HS-GC-IMS. The mature lotus-leaf tea showed more volatile compounds than the tender lotus-leaf tea. The lotus leaf treated with the white-tea process had more aroma components than other processing methods. In addition, six types of phenolic compounds, including luteolin, catechin, quercetin, orientin, hyperoside and rutin were identified in the lotus-leaf tea. The mature leaves treated with the green-tea process had the highest levels of TPC (49.97 mg gallic acid/g tea) and TFC (73.43 mg rutin/g tea). The aqueous extract of lotus-leaf tea showed positive scavenging capacities of DPPH and ABTS radicals, and ferric ion reducing power, whereas tender lotus leaf treated with the green-tea process exhibited the strongest antioxidant activity. What is more, the antioxidant activities had a significant positive correlation with the levels of TPC and TFC in lotus-leaf tea. Our results provide a theoretical basis for the manufacture of lotus-leaf-tea products with desirable flavor and health benefits.

Resveratrol Ameliorates LPS-induced Acute Lung Injury Mouse Model via Induction of Tristetraprolin.

AIM: In this study, we aimed to investigate whether resveratrol has anti-inflammatory effects on LPS-induced ALI via TTP enhancement. BACKGROUND: Acute lung injury (ALI) is a syndrome of diffuse infammatory lung injury with increased pulmonary edema and the rapid onset of hypoxemic respiratory failure. Resveratrol is a stilbenoid, a form of natural phenol, and a phytoalexin produced by a variety of plants in reaction to injury or when they are attacked by pathogens like bacteria or fungi. Resveratrol exhibits a potent antiinflammatory effect in LPS-induced ALI, while the underlying mechanisms remain elusive. OBJECTIVE: Tristetraprolin (TTP) is a RNA binding protein that is an important endogenous inhibitor of inflammation. The objective of the present study is to investigate whether resveratrol has anti- inflammatory effects on LPS-induced ALI via TTP enhancement. METHODS: Forty male C57BL/6 mice were randomly assigned to four groups and intratracheally instilled with 5 mg/kg lipopolysaccharide (LPS) to induce ALI. RESULTS: LPS-induced lung pathological damage, lung edema, and neutrophil infiltration were reduced by resveratrol pretreatment. Furthermore, resveratrol inhibited the LPS-induced rise in TNF- α, IL-1ß and IL-6 levels in BAL fluids. In the LPS-challenged mouse's lung tissue, resveratrol clearly boosted sirtuin1 (SIRT1) and TTP protein expression, while also increasing TTP expression while reducing proinflammatory cytokines. EX527, on the other hand, reversed resveratrol's effects. CONCLUSION: According to our findings, resveratrol attenuated pulmonary inflammation and lung injury in mice with LPS­induced ALI， at least partly correlated with promoting the activation of SIRT1/TTP signaling pathway, highlighting these pathways as potential targets for intervention in LPS -induced lung injury.

Oxidative stress and DNA damage in earthworms induced by methyl tertiary-butyl ether in natural soils.

Adverse effects of methyl tertiary-butyl ether (MTBE) have been noticed at different trophic levels by international researchers. However, there was unclear evidence about its effects on oxidative stress and DNA damage in earthworms. In this study, earthworms were cultivated in various doses of MTBE (0.0 mg/kg, 10.0 mg/kg, 30.0 mg/kg, and 60.0 mg/kg) contaminated agricultural soil for 7 days, 14 days, 21 days, and 28 days, respectively. The result showed that the reactive oxygen species (ROS) content of earthworms significantly increased in MTBE treatment groups compared to the control group. In MTBE treatment groups, the activities of superoxide dismutase, catalase, peroxidase, and glutathione S-transferase were significantly activated at the exposure of 7 days, which increased by 36.3-78.9%, 51.8-97.3%, 36.5-61.9%, and 12.0-54.8%, respectively. Then, the activities of these defense enzymes showed various changes following the changes in exposure times and MTBE concentrations. Especially in the 60.0 mg kg-1 group, both antioxidant enzymes and GST were still significantly activated at the exposure of 14 days and then significantly inhibited at the exposure of 28 days. The analysis of olive tail moment showed significant DNA damage in the 10.0 mg kg-1 group at the exposure of 28 days, and this damage in 30.0 mg/kg and 60.0 mg/kg groups was found at the exposure of 7 days. This result was consistent with the malondialdehyde accumulation in earthworms. Additionally, the analysis of IBRv2 showed the effects of MTBE treatments on earthworms in dose- and time-dependent manners. This study helps better to understand the effects of MTBE on soil invertebrate animals and provide theoretical support for soil protection in governing MTBE application.

Facile construction of dibenzodioxo[3.3.1]nonanes bearing spirocyclohexadienones via domino [4 + 2] cycloaddition/C(sp3)-H oxidative dehydrogenation coupling reactions.

A novel palladium catalyzed homodimerization of ortho-hydroxyphenyl substituted p-QMs has been developed via [4 + 2] cycloaddition/oxidative dehydrogenation coupling domino reactions. An interesting palladium catalyzed intramolecular benzyl C-H oxidation dehydrogenation to form a transannular C(sp3)-O bond was found. This protocol provided an efficient method to construct various dibenzodioxo[3.3.1]nonanes bearing spirocyclohexadienones.