Selective removal of thiosulfate from coke oven gas desulfurization wastewater by catalytic wet air oxidation with manganese-based oxide from spent ternary lithium-ion batteries.

Selective and efficient removal of thiosulfates (S2O32-) to recover high-purity and value-added thiocyanate products by fractional crystallization process is a promising route for the resource treatment of coke oven gas desulfurization wastewater. Herein, catalytic wet air oxidation (CWAO), with manganese-based oxide synthesized from spent ternary lithium-ion batteries (MnOx-LIBs), was proposed to selectively remove S2O32- from desulfurization wastewater. 98.0 % of S2O32- is selectively removed by the MnOx-LIBs CWAO system, which was 4.1 times that of the MnOx CWAO system. The synergistic effect among multiple metals from spent LIBs induces the enlarged specific surface area, increased reactive sites and formation of oxygen vacancy, promoting the adsorption and activation of O2, thereby realizing high-efficiency removal of S2O32-. The satisfactory selective removal efficiency can be maintained in the proposed system under complex environmental conditions. Notably, the proposed system is cost-effective and applicable to actual wastewater, in which 81.2 % of S2O32- is selectively removed from coke oven gas desulfurization wastewater. More importantly, compared with the typical processes, the proposed process is simpler and more environmentally-friendly. This work provides an alternative route to selectively remove S2O32- from coke oven gas desulfurization wastewater, expecting to drive the development of resource utilization of coke oven gas desulfurization wastewater.

Celastrol Elicits Antitumor Effects through Inducing Immunogenic Cell Death and Downregulating PD-L1 in ccRCC.

BACKGROUND: Targeting immunogenic cell death (ICD) is considered a promising therapeutic strategy for cancer. However, the commonly identified ICD inducers promote the expression of programmed cell death ligand 1 (PD-L1) in tumor cells, thus aiding them to evade the recognition and killing by the immune system. Therefore, the finding of novel ICD inducers to avoid enhanced PD-L1 expression is of vital significance for cancer therapy. Celastrol (CeT), a triterpene isolated from Tripterygium wilfordii Hook. F induces various forms of cell death to exert anti-cancer effects, which may make celastrol an attractive candidate as an inducer of ICD. METHODS: In the present study, bioinformatics analysis was combined with experimental validation to explore the underlying mechanism by which CeT induces ICD and regulates PD-L1 expression in clear cell renal cell carcinoma (ccRCC). RESULTS: The results showed that EGFR, IKBKB, PRKCQ and MAPK1 were the crucial targets for CeT-induced ICD, and only MAPK1 was an independent prognostic factor for the overall survival (OS) of ccRCC patients. In addition, CeT triggered autophagy and up-regulated the expressions of HMGB1 and CRT to induce ICD in 786-O cells in vitro. Importantly, CeT can down-regulate PD-L1 expression through activating autophagy. At the molecular level, CeT suppressed PD-L1 via the inhibition of MAPK1 expression. Immunologically, the core target of celastrol, MAPK1, was tightly correlated with CD8+ T cells and CD4+ T cells in ccRCC. CONCLUSION: These findings indicate that CeT not only induces ICD but also suppresses PD-L1 by down-regulating MAPK1 expression, which will provide an attractive strategy for ccRCC immunotherapy.

Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Reclaiming Agriceuticals from Sweetpotato (Ipomoea batatas [L.] Lam.) By-Products.

Sweetpotato (SP, Ipomoea batatas [L.] Lam.) is a globally significant food crop known for its high nutritional and functional values. Although the contents and compositions of bioactive constituents vary among SP varieties, sweetpotato by-products (SPBs), including aerial parts, storage root peels, and wastes generated from starch processing, are considered as excellent sources of polyphenols (e.g., chlorogenic acid, caffeoylquinic acid, and dicaffeoylquinic acid), lutein, functional carbohydrates (e.g., pectin, polysaccharides, and resin glycosides) or proteins (e.g., polyphenol oxidase, ß-amylase, and sporamins). This review summarises the health benefits of these ingredients specifically derived from SPBs in vitro and/or in vivo, such as anti-obesity, anti-cancer, antioxidant, cardioprotective, and anti-diabetic, evidencing their potential to regenerate value-added bio-products in the fields of food and nutraceutical. Accordingly, conventional and novel technologies have been developed and sometimes combined for the pretreatment and extraction processes aimed at optimising the recovery efficiency of bioactive ingredients from SPBs while ensuring sustainability. However, so far, advanced extraction technologies have not been extensively applied for recovering bioactive compounds from SPBs except for SP leaves. Furthermore, the incorporation of reclaimed bioactive ingredients from SPBs into foods or other healthcare products remains limited. This review also briefly discusses current challenges faced by the SPB recycling industry while suggesting that more efforts should be made to facilitate the transition from scientific advances to commercialisation for reutilising and valorising SPBs.

A single-centre, real-world study of BTK inhibitors for the initial treatment of MYD88mut /CD79Bmut diffuse large B-cell lymphoma.

BACKGROUND: MCD (MYD88L265P /CD79Bmut ) diffuse large B-cell lymphoma has a poor prognosis. There is no published clinical research conclusion regarding zanubrutinib or orelabrutinib for the initial treatment of MCD DLBCL. AIMS: This study aimed to analyse the efficacy and safety of Bruton's tyrosine kinase inhibitor (BTKi) (zanubrutinib or orelabrutinib) therapy for newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut . MATERIALS AND METHODS: Twenty-three newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut from June 2020 to June 2022 received BTKi combined with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or rituximab + lenalidomide (R2 ). A control group of 17 patients with MYD88mut and/or CD79Bmut DLBCL who received the standard R-CHOP therapy was also assessed. We retrospectively analysed clinical characteristics, safety, overall response rate (ORR), complete response (CR) rate and progression-free survival (PFS) of the two groups. RESULTS: The main clinical features were a high International Prognostic Index (IPI) score (≥3, 22/40, 55%) and a high rate of extranodal involvement (27/40,67.5%). Among the 23 DLBCL patients, 18 received BTKi + R-CHOP, and five elderly DLBCL patients were treated with BTKi + R2 . Compared with those in the control group (ORR 70.6%, CRR 52.9%, 1-year PFS rate 41.2%), improved ORR, CRR and PFS results were observed in the BTKi + R-CHOP group (100%, 94.4% and 88.9%, p = 0.019, 0.007, and 0.0001). In subgroup analyses based on genetic subtypes, cell origin, dual expression or IPI score, patients in the BTKi + R-CHOP group had better PFS than patients in the control group. In the BTKi + R-CHOP group, no significant difference was found in ORR, CRR and PFS based on subtype analysis, while BTKi-type subgroups exhibited statistically significant differences in 1-year PFS (p = 0.028). There were no significant differences in grade 3-4 haematological toxicity (p = 1) and grade 3-4 non-haematological toxicity (p = 0.49) between the BTKi + R-CHOP and R-CHOP treatment groups. In the BTKi + R2 group, the ORR was 100%, the CRR was 80%, and the 1-year PFS rate was 80%. The incidences of grade 3-4 haematologic toxicity and non-haematological toxicity were both 40%. No bleeding or cardiovascular events of grade 3 or higher occurred in any patients. DISCUSSION: The efficacy of BTKi combined with R-CHOP was similar to previous reports, which was significantly better than R-CHOP alone. It is necessary to fully consider that 14 patients in the BTKi + R-CHOP group received a BTKi as maintenance therapy when evaluating efficacy. Meanwhile, the addition of a BTKi may improve the prognosis of non-GCB, DEL or high-IPI-score DLBCL patients with MYD88mut and/or CD79Bmut . In our study, five elderly DLBCL patients with MYD88mut and/or CD79Bmut were achieved better ORR, CRR, PFS than the historical data of R-miniCHOP treatment and Ibrutinib + R2 treatment. However, the efficacy and benefit of BTKis for this type of DLBCL need to be further analysed using a larger sample size. CONCLUSION: This study suggests that newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut may benefit from BTKis according to real-world clinical data.

Mobile-based ecological momentary assessment and intervention: bibliometric analysis.

Objective: The aim of this article was to review existing documents in the field of mobile-based EMA and EMI, provide an overview of current hot topics, and predict future development trends. Methods: We conducted a bibliometric study on mobile-based EMA and EMI publications that were collected from the Web of Science Core Collection database. Biblioshiny and CiteSpace were utilized to analyze scientific productions, leading sources, authors, affiliations, documents, research hot topics, keywords, and trend topics. Results: A total of 2222 documents related to EMA and EMI published between 1992 and 2023 were retrieved. In recent years, scholarly publications have generally increased in mobile-based EMA and EMI research, particularly in the last decade. JMIR mHealth and uHealth (n=86), as well as JMIR (n=73), showed the highest number of publications. The United States (n=1038), Germany (n=218) and Netherlands (n=175) were leading countries. Regarding keyword co-occurrence and trend topics analysis, mental health, health behaviors, and feasibility were hot topics in mobile-based EMA and EMI research. Future research trends included using EMA for tailoring EMI, just-in-time adaptive interventions (JITAI), and digital phenotyping. Conclusion: This bibliometric study on mobile-based EMA and EMI is a valuable resource for understanding the field's evolution and future trends. Our analysis indicates that EMA and EMI have great potential in health behaviors and mental health, but implementation should consider feasibility and reactivity issues carefully. Emerging trends include EMA-tailored EMI, JITAI, and digital phenotyping. In the future, strengthening multidisciplinary cooperation will be necessary to promote the continued development of the field.

Lifestyle intervention in children with obesity and nonalcoholic fatty liver disease (NAFLD): study protocol for a randomized controlled trial in Ningbo city (the SCIENT study).

BACKGROUND: The increasing prevalence of childhood obesity has become an urgent public health problem, evidence showed that intervention for childhood obesity bring enormous health benefits. However, an effective individualized intervention strategy remains to be developed, and the accompanying remission of related complications, such as nonalcoholic fatty liver disease (NAFLD), needs to be assessed. This study aimed to develop an m-Health-assisted lifestyle intervention program targeting overweight/obese children and assess its effectiveness on indicators of adiposity and NAFLD. METHODS: This is a cluster-randomized controlled trial that conducted in children with overweight/obesity in Ningbo city, Zhejiang Province, China. Students in Grade 3 (8-10 years old) were recruited from six primary schools, with three be randomized to intervention group and three to usual practice group. The intervention program will last for one academic year and consists of health education, dietary guidance, and physical activity reinforcement. This program is characterized by encouraging four stakeholders, including School, Clinic, famIly, and studENT (SCIENT), to participate in controlling childhood obesity, assisted by m-Health technology. Assessments will be conducted at baseline and 3 months, 9 months, 24 months, and 36 months after baseline. The primary outcome will be the differences between the two groups in students' body mass index and fatty liver index at the end of the intervention (9 months after baseline). During the implementation process, quality control methods will be adopted. DISCUSSION: The program will test the effectiveness of the m-Health-assisted lifestyle intervention on children with obesity and NAFLD. The results of this study will provide evidence for establishing effective lifestyle intervention strategy aimed at childhood obesity and NAFLD and may help develop guidelines for the treatment of obesity and NAFLD in Chinese children. TRIAL REGISTRATION: Clinicaltrials.gov NCT05482191. Registered on July 2022.

Treatment of Refractory p53 Mutation Large B-cell Lymphoma with Daratumumab and Venetoclax Followed by CAR-T Cell Therapy: Case Report and Animal Study.

BACKGROUND: The tumor burden before chimeric antigen receptor T (CAR-T) cell therapy was one of the critical factors affecting the prognosis of lymphoma. It was a challenge to effectively reduce the tumor burden of relapsed/refractory large B-cell lymphoma with p53 mutation. OBJECTIVE: Here, we have presented a case of relapsed/refractory large B-cell lymphoma with p53 mutation being controlled by the treatment with daratumumab and venetoclax, followed by CAR-T cell therapy. CASE PRESENTATION: The patient was a 56-year-old female who was diagnosed with relapsed/ refractory diffuse large B cell lymphoma (DLBCL) transformed from follicular lymphoma. The patient was treated with daratumumab, venetoclax, and GEMOX (gemcitabine and oxaliplatin) under the guidance of high-throughput drug sensitivity analysis. We used a CD38 positive lymphoma cell line with p53 mutation to construct tumor models for validating the anti- lymphoma effect of the combination therapy of daratumumab and venetoclax. RESULTS: The patient achieved a complete metabolic response after treatment with daratumumab, venetoclax, and GEMOX. Then, she further achieved a complete molecular response after she subsequently received CAR-T cell therapy, and she has been living without a lymphoma recurrence. The results from the animal study showed that the combination of daratumumab and venetoclax could significantly enhance the antitumor effect on CD38-positive lymphoma with p53 mutation. CONCLUSION: The results from our successful case and animal experiments provide new avenues for the treatment of relapsed/refractory large B-cell lymphoma with p53 mutation. Further clinical trials are reuqired to treat CD38-positive lymphoma with the combination of daratumumab and venetoclax.

Formation and toxicity contribution of chlorinated and dechlorinated halobenzoquinones from dichlorophenols after ozonation.

Halobenzoquinones (HBQs) are a class of disinfection byproducts with high cytotoxicity and potential carcinogenicity, which have been widely detected in chlorination of drinking water and swimming pool water. However, to date, the formation of HBQs upon ozonation and the HBQ precursors have been overlooked. This study investigated the formation of chlorinated and dechlorinated HBQs from six dichlorophenol (DCP) isomers. The monomeric and dimeric HBQs were identified in all the ozonation effluents, exhibiting 1-100 times higher toxicity levels than their precursors. The sum of detected HBQs intensity had a satisfactory linear relation with the maximum toxic unit (R2 = 0.9657), indicating the primary toxicity contribution to the increased overall toxicity of effluents. Based on density functional theory calculations, when ozone attacks the para carbon to the hydroxyl group of 2,3-DCP, the probability of producing chlorinated HBQs is 80.41 %, indicating that the para carbon attack mainly resulted in the formation of monomeric HBQs. 2,3-dichlorophenoxy radicals were successfully detected in ozonated 2,3-DCP effluent through electron paramagnetic resonance and further validated using theoretical calculation, revealing the formation pathway of dimeric HBQs. The results indicate that chlorinated phenols, regardless of the positions of chlorine substitution, can potentially serve as precursors for both chlorinated and dechlorinated HBQs formation during ozonation.

Somatic GATA4 mutation contributes to tetralogy of Fallot.

Tetralogy of Fallot (TOF) is the most prevalent cyanotic congenital heart pathology and causes infant morbidity and mortality worldwide. GATA-binding protein 4 (GATA4) serves as a pivotal transcriptional factor for embryonic cardiogenesis and germline GATA4 mutations are causally linked to TOF. However, the effects of somatic GATA4 mutations on the pathogenesis of TOF remain to be ascertained. In the present study, sequencing assay of GATA4 was performed utilizing genomic DNA derived from resected heart tissue specimens as well as matched peripheral blood specimens of 62 patients with non-familial TOF who underwent surgical treatment for TOF. Sequencing of GATA4 was also performed using the heart tissue specimens as well as matched peripheral venous blood samples of 68 sporadic cases who underwent heart valve displacement because of rheumatic heart disorder and the peripheral venous whole blood samples of 216 healthy subjects. The function of the mutant was explored by dual-luciferase activity analysis. Consequently, a new GATA4 mutation, NM_002052.5:c.708T>G;p.(Tyr236*), was found in the heart tissue of one patient with TOF. No mutation was detected in the heart tissue of the 68 cases suffering from rheumatic heart disorder or in the venous blood samples of all 346 individuals. GATA4 mutant failed to transactivate its target gene, myosin heavy chain 6. Additionally, this mutation nullified the synergistic transactivation between GATA4 and T-box transcription factor 5 or NK2 homeobox 5, two genes causative for TOF. Somatic GATA4 mutation predisposes TOF, highlighting the significant contribution of somatic variations to the molecular pathogenesis underpinning TOF.

Three-Dimensional Scaffolds for Intestinal Cell Culture: Fabrication, Utilization, and Prospects.

The intestine is a visceral organ that integrates absorption, metabolism, and immunity, which is vulnerable to external stimulus. Researchers in the fields such as food science, immunology, and pharmacology have committed to developing appropriate in vitro intestinal cell models to study the intestinal absorption and metabolism mechanisms of various nutrients and drugs, or pathogenesis of intestinal diseases. In the past three decades, the intestinal cell models have undergone a significant transformation from conventional two-dimensional cultures to three-dimensional (3D) systems, and the achievements of 3D cell culture have been greatly contributed by the fabrication of different scaffolds. In this review, we first introduce the developing trend of existing intestinal models. Then, four types of scaffolds, including Transwell, hydrogel, tubular scaffolds, and intestine-on-a-chip, are discussed for their 3D structure, composition, advantages, and limitations in the establishment of intestinal cell models. Excitingly, some of the in vitro intestinal cell models based on these scaffolds could successfully mimic the 3D structure, microenvironment, mechanical peristalsis, fluid system, signaling gradients, or other important aspects of the original human intestine. Furthermore, we discuss the potential applications of the intestinal cell models in drug screening, disease modeling, and even regenerative repair of intestinal tissues. This review presents an overview of state-of-the-art scaffold-based cell models within the context of intestines, and highlights their major advances and applications contributing to a better knowledge of intestinal diseases. Impact statement The intestine tract is crucial in the absorption and metabolism of nutrients and drugs, as well as immune responses against external pathogens or antigens in a complex microenvironment. The appropriate experimental cell model in vitro is needed for in-depth studies of intestines, due to the limitation of animal models in dynamic control and real-time assessment of key intestinal physiological and pathological processes, as well as the "R" principles in laboratory animal experiments. Three-dimensional (3D) scaffold-based cell cultivation has become a developing tendency because of the superior cell proliferation and differentiation and more physiologically relevant environment supported by the customized 3D scaffolds. In this review, we summarize four types of up-to-date 3D cell culture scaffolds fabricated by various materials and techniques for a better recapitulation of some essential physiological and functional characteristics of original intestines compared to conventional cell models. These emerging 3D intestinal models have shown promising results in not only evaluating the pharmacokinetic characteristics, security, and effectiveness of drugs, but also studying the pathological mechanisms of intestinal diseases at cellular and molecular levels. Importantly, the weakness of the representative 3D models for intestines is also discussed.

Cation-Intercalated Clay-Based Two-Dimensional Membranes for Effective Desalination and Molecule Sieving.

Montmorillonite (MMT) is known as an ion-exchangeable material, and cations between MMT nanosheets are easily exchanged by other cations. In this work, Ca2+, Fe3+, and Al3+ intercalated two-dimensional MMT membranes were developed by ion exchange of pristine MMT membranes (Na+-MMT), and their ion and dye removal abilities were investigated. The d-spacings of hydrated Fe3+ intercalated MMT membrane (Fe3+-MMT) and Al3+ intercalated MMT membrane (Al3+-MMT) were decreased compared with hydrated Na+-MMT membrane due to the stronger electrostatic attraction between Fe3+/Al3+ and negatively charged MMT nanosheets. Ion and dye sieving performances were improved significantly after the intercalation of Ca2+, Fe3+, and Al3+ into MMT membranes. Al3+-MMT membrane with a thickness of 1.17 µm could exclude 94% of Na+, and its ion sieving performance remained stable during a 120-h ion sieving experiment. Moreover, the rejection rate for rhodamine B (RB) reached 94% using an Al3+-MMT membrane with a thickness of 500 nm, and a water permeance of 73 L m-2 h-1 bar-1 was achieved. The excellent ion and dye sieving performances make it promising in the application of desalination and nanofiltration.

Insights into the population pharmacokinetics and pharmacodynamics of quetiapine: a systematic review.

INTRODUCTION: Quetiapine exhibits notable pharmacokinetic and pharmacodynamic (PK/PD) variability, the origins of which are poorly understood. This systematic review summarizes published population PK/PD studies and identifies significant covariates accounting for this variability to inform precision dosing. METHODS: We systematically searched the PubMed, Web of Science, and Embase databases and compared study characteristics, model parameters, and covariate effects. Visual predictive distributions were used to compare different models. Forest plots and Monte Carlo simulations were used to assess the influence of covariates. RESULTS: Six population PK and three population PK/PD studies were included. The median apparent clearance in adults was 87.7 L/h. Strong and moderate cytochrome P450 3A4 inducers increased the apparent clearance approximately fourfold, while strong cytochrome P450 3A4 inhibitors reduced it by 93%. The half-maximum effect concentrations were 82.8 ng/mL for the Brief Psychiatric Rating Scale and 583 ng/mL for dopamine D2 receptor occupancy. Both treatment duration and quetiapine exposure were associated with weight gain. CONCLUSIONS: Concurrent administration of potent or moderate CYP3A4 inducers and inhibitors need to be avoided in quetiapine-treated patients. When co-medication is required, it is recommended to adjust the dosage based on therapeutic drug monitoring. Additional research is warranted to delineate the dose-exposure-response relationships of quetiapine and active metabolite norquetiapine in pediatrics, geriatrics, hepatically-impaired patients, and women using contraceptives or are pregnant or menopausal. PROSPERO REGISTRATION: CRD42023446654.

EBV-Encoded MicroRNA-BART17-3p Targets DDX3X and Promotes EBV Infection in EBV-Associated T/Natural Killer-Cell Lymphoproliferative Diseases.

Background: Epstein-Barr virus (EBV) persistently infects T/natural killer (NK) cells causing an array of refractory EBV-associated T/NK-cell lymphoproliferative disorders. EBV-encoded microRNAs are important regulators for EBV latent infection and tumorigenesis. However, the roles of most EBV microRNAs in EBV-infected T/NK cells remain poorly understood. Methods: On the basis of a search of the doRiNA database and the BiBiServ2-RNAhybrid website, we predicted that EBV-miR-BART17-3p targeted DDX3X, and we verified the hypothesis by dual-luciferase reporter assay and cell function experiments. In addition, we collected 50 EBV-positive T-, B-, and NK-cell samples from the peripheral blood of EBV-positive cases to examine the role of EBV-miR-BART17-3p in the disease. Results: We found that EBV-miR-BART17-3p directly targeted DDX3X and downregulated DDX3X expression. By analyzing EBV-positive cell samples from cell lines and patients, we found that EBV-miR-BART17-3p was highly expressed only in EBV-positive NK cells and that the overexpression was significantly related to high EBV loads in EBV-infected NK cells. Furthermore, we found that EBV-miR-BART17-3p downregulated the RIG-I-like receptor antiviral pathway and promoted the expression of EBV-encoded proteins in EBV-infected NK cells by targeting DDX3X. Conclusions: Our study showed that EBV-miR-BART17-3p was abundantly expressed in EBV-infected NK cells and inhibited the important antivirus immune responses of hosts by targeting DDX3X of the RIG-I-like receptor pathway. These findings could help us gain insights into the pathogenic mechanisms underlying EBV-associated T/NK-cell lymphoproliferative disorders and find the potential therapeutic target.

In situ observation of a stepwise [2 + 2] photocycloaddition process using fluorescence spectroscopy.

Using highly sensitive and selective in situ techniques to investigate the dynamics of intermediates formation is key to better understand reaction mechanisms. However, investigating the early stages of solid-state reactions/transformations is still challenging. Here we introduce in situ fluorescence spectroscopy to observe the evolution of intermediates during a two-step [2 + 2] photocycloaddition process in a coordination polymer platform. The structural changes and kinetics of each step under ultraviolet light irradiation versus time are accompanied by the gradual increase-decrease of intensity and blue-shift of the fluorescence spectra from the crystals. Monitoring the fluorescence behavior using a laser scanning confocal microscope can directly visualize the inhomogeneity of the photocycloaddition reaction in a single crystal. Theoretical calculations allow us to rationalize the fluorescence behavior of these compounds. We provide a convenient strategy for visualizing the solid-state photocycloaddition dynamics using fluorescence spectroscopy and open an avenue for kinetic studies of a variety of fast reactions.

Effects of maize and soybean intercropping on soil phosphorus bioavailability and microbial community structure in rhizosphere.

To investigate the effect of maize/soybean intercropping on rhizosphere soil microbial communities and phosphorus (P) bioavailability, we examined the changes of soil bioavailable P fractions and microbial community characteristics in the monoculture and intercropping systems based on high-throughput sequencing. The results showed that maize/soybean intercropping increased the contents of rhizosphere soil organic matter (SOM), available phosphorus (AP), microbial biomass phosphorus (MBP), and aboveground biomass. The increase of AP was mainly related to the increasing enzyme extracted phosphorus (Enzyme-P) and hydrochloric acid extracted phosphorus (HCl-P) contents. The dominant bacterial phyla under each treatment were Proteobacteria, Actinobacteria, Acidobacteria and Chloroflexi, while the dominant bacterial genera were Nocardioides, Solirubacter, Sphingomonas and Arthrobacter, with Proteobacteria and Sphingomonas having the highest relative abundance. The relative abundance of Proteobacteria and Sphingomonas in intercropping maize rhizosphere soil was significantly higher than that in monoculture, and that of Proteobacteria in intercropping soybean rhizosphere soil was significantly higher than monoculture. Soil properties and P fractions were closely related to the rhizosphere soil microbial composition. In all, maize/soybean intercropping could affect the rhizosphere soil P bioavailability by altering the structure of rhizosphere microbial communities.

TIGIT reverses IFN-α-promoted Th1-like Tregs via in-sequence effects dependent on STAT4.

OBJECTIVES: The induction direction of interferon (IFN)-α in T-cell phenotype and function varies depending on the activation state of the cell and the time of stimulation. To assess the effects of elevated IFN-α on regulatory T cells (Tregs) in systemic lupus erythematosus (SLE) patients, we investigated the differentiation of Th1-like Tregs under in-sequence and out-of-sequence conditions and the reversal effect of activating TIGIT on immune suppression. METHODS: Phenotypes and activation levels of Tregs from SLE patients and healthy controls were analyzed using flow cytometry. In vitro culture conditions based on the sequence of TCR activation and IFN-α stimulation simulated in-sequence or out-of-sequence effects. CD4+T cells and Tregs were cultured under the above conditions with or without TIGIT agonist. Expression of related characteristic markers and phosphorylation levels of AKT, mTOR, and STATs were detected using flow cytometry and ELISA. RESULTS: The frequency of Th1-like Tregs and activation levels of Tregs increased, but TIGIT expression in Tregs decreased in SLE patients. IFN-α promoted the conversation of Tregs to Th1-like Tregs while reducing immunosuppressive function under in-sequence conditions. The STAT4 pathway, but not the STAT1 pathway, was crucial for the IFN-α-mediated in-sequence effects. Reactivation of TIGIT reversed Th1 polarization of Tregs by suppressing AKT/mTOR and STAT4 signaling. CONCLUSIONS: Our findings suggest that IFN-α mediated in-sequence effects on Tregs may be responsible for the expansion of Th1-like Tregs in SLE. TIGIT can restore immune suppression damage in Tregs and represents a potential therapeutic target for SLE.

[Structural characterization of PCP-â from Poria as vaccine adjuvant and its hydrolytic oligosaccharide].

Poria is an important medical herb in clinic. The authors isolated a polysaccharide(PCP-Ⅰ) from Poria in previous studies, which is composed of galactose, mannose, fucose and glucose. PCP-Ⅰ exhibited significant adjuvant effects on H1N1 influenza vaccine, hepatitis B surface antigen and anthrax protective antigen, and its adjuvant activity was stronger than aluminium adjuvant. However, little is known about the chemical structure of PCP-Ⅰ at present. In this study, weak acid hydrolysis was used to obtain the backbone oligosaccharide of PCP-Ⅰ. Then periodate oxidation, Smith degradation, methylation analysis, Fourier transform infrared spectroscopy(FT-IR), nuclear magnetic resonance(NMR) and gas chromatography-mass spectrometry(GC-MS) were performed to investigate the chemical structural features of PCP-Ⅰ and its hydrolytic oligosaccharide(PCP-Ⅰ-hy-1). These results suggested that the backbone of PCP-Ⅰ was composed of galactose with α anomeric carbon and ß anomeric carbon. The linking residues of galactan are(1→),(l→6) and(1→2,6).

[Serum metabolomics study of Psoraleae Fructus in improving learning and memory ability of APP/PS1 mice].

This study aimed to investigate the mechanism of Psoraleae Fructus in improving the learning and memory ability of APP/PS1 mice by serum metabolomics, screen the differential metabolites of Psoraleae Fructus on APP/PS1 mice, and reveal its influence on the metabolic pathway of APP/PS1 mice. Thirty 3-month-old APP/PS1 mice were randomly divided into a model group and a Psoraleae Fructus extract group, and another 15 C57BL/6 mice of the same age were assigned to the blank group. The learning and memory ability of mice was evaluated by the Morris water maze and novel object recognition tests, and metabolomics was used to analyze the metabolites in mouse serum. The results of the Morris water maze test showed that Psoraleae Fructus shortened the escape latency of APP/PS1 mice(P<0.01), and increased the number of platform crossing and residence time in the target quadrant(P<0.01). The results of the novel object recognition test showed that Psoraleae Fructus could improve the novel object recognition index of APP/PS1 mice(P<0.01). Eighteen differential metabolites in serum were screened out by metabolomics, among which the levels of arachidonic acid, tryptophan, and glycerophospholipid decreased after drug administration, while the levels of glutamyltyrosine increased after drug administration. The metabolic pathways involved included arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, linoleic acid metabolism, α-linolenic acid metabolism, and glycerolipid metabolism. Therefore, Psoraleae Fructus can improve the learning and memory ability of APP/PS1 mice, and its mechanism may be related to the effects in promoting energy metabolism, reducing oxidative damage, protecting central nervous system, reducing neuroinflammation, and reducing Aß deposition. This study is expected to provide references for Psoraleae Fructus in the treatment of Alzheimer's disease(AD) and further explain the mechanism of Psoraleae Fructus in the treatment of AD.