HSP90ß prevents aging-related cataract formation through regulation of the charged multivesicular body protein (CHMP4B) and p53.

Cataract is a leading ocular disease causing global blindness. The mechanism of cataractogenesis has not been well defined. Here, we demonstrate that the heat shock protein 90ß (HSP90ß) plays a fundamental role in suppressing cataractogenesis. HSP90ß is the most dominant HSP in normal lens, and its constitutive high level of expression is largely derived from regulation by Sp1 family transcription factors. More importantly, HSP90ß is significantly down-regulated in human cataract patients and in aging mouse lenses, whereas HSP90ß silencing in zebrafish causes cataractogenesis, which can only be rescued by itself but not other HSP90 genes. Mechanistically, HSP90ß can directly interact with CHMP4B, a newly-found client protein involved in control of cytokinesis. HSP90ß silencing causes upregulation of CHMP4B and another client protein, the tumor suppressor p53. CHMP4B upregulation or overexpression induces excessive division of lens epithelial cells without proper differentiation. As a result, these cells were triggered to undergo apoptosis due to activation of the p53/Bak-Bim pathway, leading to cataractogenesis and microphthalmia. Silence of both HSP90ß and CHMP4B restored normal phenotype of zebrafish eye. Together, our results reveal that HSP90ß is a critical inhibitor of cataractogenesis through negative regulation of CHMP4B and the p53-Bak/Bim pathway.

Plasma exosomes and contained MiRNAs affect the reproductive phenotype in polycystic ovary syndrome.

Anovulation is the main feature of infertile women with polycystic ovary syndrome (PCOS), and there is very limited understanding of the role of plasma exosomes and miRNAs in it. To identify the effect of PCOS patients' plasma exosomes and exosomal miRNAs, we isolated plasma exosomes of PCOS patients and normal women and injected into 8-week-old ICR female mice via tail vein. The changes in estrus cycle, serum hormone levels, and ovarian morphology were observed. KGN cells were cultured and transfected with mimics and inhibitors of differentially expressed exosomal miRNAs (miR-18a-3p, miR-20b-5p, miR-106a-5p, miR-126-3p, and miR-146a-5p) and then tested for steroid hormone synthesis, proliferation, and apoptosis. The results showed that female ICR mice injected with plasma exosomes from PCOS patients presented ovarian oligo-cyclicity. Hormone synthesis and proliferation of granulosa cells were affected by differentially expressed PCOS plasma-derived exosomal miRNAs, of which miR-126-3p having the most evident effect. MiR-126-3p affected the proliferation of granulosa cells by inhibiting PDGFRß and its downstream PI3K-AKT pathway. Our results demonstrated plasma exosomes and contained miRNAs in PCOS patients affect the estrus cycle of mice, hormone secretion, and proliferation of granulosa cells. This study provides a novel understanding about the function of plasma exosomes and exosomal miRNAs in PCOS.

Let-7c-3p suppresses lens epithelial-mesenchymal transition by inhibiting cadherin-11 expression in fibrotic cataract.

Fibrotic cataract, including anterior subcapsular cataract (ASC) and posterior capsule opacification, always lead to visual impairment. Epithelial-mesenchymal transition (EMT) is a well-known event that causes phenotypic alterations in lens epithelial cells (LECs) during lens fibrosis. Accumulating studies have demonstrated that microRNAs are important regulators of EMT and fibrosis. However, the evidence explaining how microRNAs modulate the behavior and alter the cellular phenotypes of the lens epithelium in fibrotic cataract is insufficient. In this study, we found that hsa-let-7c-3p is downregulated in LECs in human ASC in vivo as well as in TGFß2-induced EMT in vitro, indicating that hsa-let-7c-3p may participate in modulating the profibrotic processes in the lens. We then demonstrated that overexpression of hsa-let-7c-3p markedly suppressed human LEC proliferation and migration and attenuated TGFß2-induced EMT and injury-induced ASC in a mouse model. In addition, hsa-let-7c-3p mediated lens fibrosis by directly targeting the CDH11 gene, which encodes cadherin-11 protein, an important mediator in the EMT signaling pathway. It decreased cadherin-11 protein expression at the posttranscriptional level but not at the transcriptional level by binding to a specific site in the 3-untranslated region (3'-UTR) of CDH11 mRNA. Moreover, blockade of cadherin-11 expression with a specific short hairpin RNA reversed TGFß2-induced EMT in LECs in vitro. Collectively, these data demonstrated that hsa-let-7c-3p plays a clear role in attenuating ASC development and may be a novel candidate therapeutic for halting fibrosis and maintaining vision.

IVF exposure induced intergenerational effects on metabolic phenotype in mice.

RESEARCH QUESTION: What is the potential transmission of metabolic phenotype from IVF offspring to the subsequent generation? DESIGN: An IVF mouse model was established. The F1 generation mice were produced though IVF or natural mating and the F2 generation was obtained through the mating of F1 generation males with normal females. Their metabolic phenotype, including systemic and hepatic glucolipid metabolism, was examined. RESULTS: It was found that IVF F1 males exhibited metabolic changes. Compared with the control group, the IVF F1 generation showed increased body weight, elevated fasting glucose and insulin, and increased serum triglyceride concentrations. IVF F1 mice also showed an increased expression of hepatic lipogenesis and autophagy genes. Moreover, IVF F1 males transmitted some metabolic changes to their own male progeny (IVF F2) in the absence of a dietary challenge. IVF F2 mice had increased peri-epididymal and subcutaneous fat and decreased insulin sensitivity. Under the 'second hit' of a high-fat diet, IVF F2 mice further showed increased hepatic lipid deposition with unaltered autophagy levels. CONCLUSION: This research demonstrates the impact of IVF on hepatic glucose-lipid metabolism in two successive generations of offspring, highlighting the need for additional investigation. Enhanced understanding of the mechanisms underlying the transmission of multigenerational effects induced by IVF could potentially lead to the advancement of therapeutic interventions for individuals experiencing infertility.

Targeted Protein Degradation Mediated by Genetically Engineered Lysosome-Targeting Exosomes.

Protein-degrading chimeras are superior drug modalities compared to traditional protein inhibitors because of their effective therapeutic performance. So far, various targeted protein degradation strategies, including proteolysis-targeting chimeras and lysosome-targeting chimeras, have emerged as essential technologies for tackling diseases caused by abnormal protein expression. Here, we report the development and application of lysosome-targeting exosomes (LYTEXs) for the selective degradation of membrane protein targets. LYTEXs are genetically engineered exosomes expressing multivalent single-chain fragment variables, simultaneously recognizing cell-surface lysosome-targeting and to-be-degraded protein. We show that by targeting the lysosome-directing asialoglycoprotein receptor, bispecific LYTEXs can induce lysosomal degradation of membrane-associated therapeutic targets. This strategy provides a generalizable, easy-to-prepare platform for modulating surface protein expression, with the advantage of therapeutic delivery.

LncRNA NEAT1/miR-211/IL-10 Axis Regulates Inflammation of Peripheral Blood Mononuclear Cells in Acute Myocardial Infarction.

This study aimed to explore the expression of long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in patients with acute myocardial infarction (AMI) and its inflammatory regulation mechanism through miR-211/interleukin 10 (IL-10) axis.A total of 75 participants were enrolled in this study: 25 healthy people in the control group, 25 patients with stable angina pectoris (SAP) in the SAP group, and 25 patients with AMI in the AMI group. Real-time qPCR was used to detect mRNA expression levels of NEAT1, miR-211, and IL-10. The interaction between miR-211, NEAT1, and IL-10 was confirmed by dual-luciferase reporter assay, and protein expression was detected using western blot.High expression of NEAT1 in peripheral blood mononuclear cells (PBMCs) of patients with AMI was negatively related to serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), IL-6, and IL-1ß and was positively correlated with left ventricular ejection fraction (LVEF). In THP-1 cells, miR-211 was confirmed to target and inhibit IL-10 expression. NEAT1 knockdown and miR-211-mimic markedly decreased IL-10 protein levels, whereas anti-miR-211 markedly increased IL-10 protein levels. Importantly, miR-211 level was negatively related to NEAT1 and IL-10 levels, whereas IL-10 level was positively related to the level of NEAT1 expression in PBMCs of patients with AMI.LncRNA NEAT1 was highly expressed in PBMCs of patients with AMI, and NEAT1 suppressed inflammation via miR-211/IL-10 axis in PBMCs of patients with AMI.

Comparative Analysis of Structural and Functional Properties of Dietary Fiber from Four Grape Varieties.

Muscadine grapes are characterized by their large and abundant seeds and hard and thick skins that contain significant amounts of dietary fiber (DF). The current study investigated the chemical constituents, molecular architecture, and physicochemical attributes of DF derived from Muscadine grapes (Granny Val and Alachua) and compared them with those derived from Shine Muscat and Kyoho. Using a combined enzymatic method, the total dietary fiber (TDF) was extracted and divided into two parts: soluble dietary fiber (SDF) and insoluble dietary fiber (IDF). TDF (mainly IDF, with a small fraction of SDF) was dominated by cellulose, followed by pectin and hemicellulose. In addition, Granny Val and Alachua had a significantly higher abundance of TDF and IDF compared with Shine Muscat and Kyoho. Moreover, Shine Muscat had significantly the highest abundance of SDF among the four grape varieties. Of note, IDF from Granny Val and Alachua exhibited a complex and dense texture on its surface, and notably outperformed Shine Muscat and Kyoho in terms of cholesterol, fatty acid, heavy metal adsorption, and antioxidant activity. Collectively, Muscadine grapes, i.e., Granny Val and Alachua in the current study, possessed elevated DF levels (predominantly IDF), and their enhanced bioactivity underscored their potential as a potential food ingredient for further use.

Efficient Quantum Private Comparison Based on GHZ States.

Quantum private comparison (QPC) is a fundamental cryptographic protocol that allows two parties to compare the equality of their private inputs without revealing any information about those inputs to each other. In recent years, QPC protocols utilizing various quantum resources have been proposed. However, these QPC protocols have lower utilization of quantum resources and qubit efficiency. To address this issue, we propose an efficient QPC protocol based on GHZ states, which leverages the unique properties of GHZ states and rotation operations to achieve secure and efficient private comparison. The secret information is encoded in the rotation angles of rotation operations performed on the received quantum sequence transmitted along the circular mode. This results in the multiplexing of quantum resources and enhances the utilization of quantum resources. Our protocol does not require quantum key distribution (QKD) for sharing a secret key to ensure the security of the inputs, resulting in no consumption of quantum resources for key sharing. One GHZ state can be compared to three bits of classical information in each comparison, leading to qubit efficiency reaching 100%. Compared with the existing QPC protocol, our protocol does not require quantum resources for sharing a secret key. It also demonstrates enhanced performance in qubit efficiency and the utilization of quantum resources.

New Quantum Private Comparison Using Four-Particle Cluster State.

Quantum private comparison (QPC) enables two users to securely conduct private comparisons in a network characterized by mutual distrust while guaranteeing the confidentiality of their private inputs. Most previous QPC protocols were primarily used to determine the equality of private information between two users, which constrained their scalability. In this paper, we propose a QPC protocol that leverages the entanglement correlation between particles in a four-particle cluster state. This protocol can compare the information of two groups of users within one protocol execution, with each group consisting of two users. A semi-honest third party (TP), who will not deviate from the protocol execution or conspire with any participant, is involved in assisting users to achieve private comparisons. Users encode their inputs into specific angles of rotational operations performed on the received quantum sequence, which is then sent back to TP. Security analysis shows that both external attacks and insider threats are ineffective at stealing private data. Finally, we compare our protocol with some previously proposed QPC protocols.

Selective Proteolysis of Activated Transcriptional Factor by NIR-Responsive Palindromic DNA Thalidomide Conjugate Inhibits the Canonical Smad Pathway.

Dysfunctional transcription factors that activate abnormal expressions of specific proteins are often associated with the progression of various diseases. Despite being attractive drug targets, the lack of druggable sites has dramatically hindered their drug development. The emergence of proteolysis targeting chimeras (PROTACs) has revitalized the drug development of many conventional hard-to-drug protein targets. Here, the use of a palindromic double-strand DNA thalidomide conjugate (PASTE) to selectively bind and induce proteolysis of targeted activated transcription factor (PROTAF) is reported. The selective proteolysis of the dimerized phosphorylated receptor-regulated Smad2/3 and inhibition of the canonical Smad pathway validates PASTE-mediated PROTAF. Further aptamer-guided active delivery of PASTE and near-infrared light-triggered PROTAF are demonstrated. Great potential in using PASTE for the selective degradation of the activated transcription factor is seen, providing a powerful tool for studying signaling pathways and developing precision medicines.

Deep-learning-based 3D super-resolution MRI radiomics model: superior predictive performance in preoperative T-staging of rectal cancer.

OBJECTIVES: To investigate the feasibility and efficacy of a deep-learning (DL)-based three-dimensional (3D) super-resolution (SR) MRI radiomics model for preoperative T-staging prediction in rectal cancer (RC). METHODS: Seven hundred six eligible RC patients (T1/2 = 287, T3/4 = 419) were retrospectively enrolled in this study and chronologically allocated into a training cohort (n = 565) and a validation cohort (n = 141). We conducted a deep-transfer-learning network on high-resolution (HR) T2-weighted imaging (T2WI) to enhance the z-resolution of the images and acquired the preoperative SRT2WI. The radiomics models named modelHRT2 and modelSRT2 were respectively constructed with high-dimensional quantitative features extracted from manually segmented volume of interests of HRT2WI and SRT2WI through the Least Absolute Shrinkage and Selection Operator method. The performances of the models were evaluated by ROC, calibration, and decision curves. RESULTS: ModelSRT2 outperformed modelHRT2 (AUC 0.869, sensitivity 71.1%, specificity 93.1%, and accuracy 83.3% vs. AUC 0.810, sensitivity 89.5%, specificity 70.1%, and accuracy 77.3%) in distinguishing T1/2 and T3/4 RC with significant difference (p < 0.05). Both radiomics models achieved higher AUCs than the expert radiologists (0.685, 95% confidence interval 0.595-0.775, p < 0.05). The calibration curves confirmed high goodness of fit, and the decision curve analysis revealed the clinical value. CONCLUSIONS: ModelSRT2 yielded superior predictive performance in preoperative RC T-staging by comparison with modelHRT2 and expert radiologists' visual assessments. KEY POINTS: • For the first time, DL-based 3D SR images were applied in radiomics analysis for clinical utility. • Compared with the visual assessment of expert radiologists and the conventional radiomics model based on HRT2WI, the SR radiomics model showed a more favorable capability in helping clinicians assess the invasion depth of RC preoperatively. • This is the largest radiomics study for T-staging prediction in RC.

The machine learning methods to analyze the using strategy of antiplatelet drugs in ischaemic stroke patients with gastrointestinal haemorrhage.

BACKGROUND: For ischaemic stroke patients with gastrointestinal haemorrhage, stopping antiplatelet drugs or reducing the dose of antiplatelet drugs was a conventional clinical therapy method. But not a study to prove which way was better. And the machinery learning methods could help to obtain which way more suit for some patients. METHODS: Data from consecutive ischaemic stroke patients with gastrointestinal haemorrhage were prospectively collected. The outcome was a recurrent stroke rate, haemorrhage events, mortality and favourable functional outcome (FFO). We analysed the data using conventional logistic regression methods and a supervised machine learning model. We used unsupervised machine learning to group and analyse data characters. RESULTS: The patients of stopping antiplatelet drugs had a lower rate of bleeding events (p = 0.125), mortality (p = 0.008), rate of recurrence of stroke (p = 0.161) and distribution of severe patients (mRS 3-6) (p = 0.056). For Logistic regression, stopping antiplatelet drugs (OR = 2.826, p = 0.030) was related to lower mortality. The stopping antiplatelet drugs in the supervised machine learning model related to mortality (AUC = 0.95) and FFO (AUC = 0.82). For group by unsupervised machine learning, the patients of better prognosis had more male (p < 0.001), younger (p < 0.001), had lower NIHSS score (p < 0.001); and had a higher value of serum lipid level (p < 0.001). CONCLUSIONS: For ischemic stroke patients with gastrointestinal haemorrhage, stopping antiplatelet drugs had a better prognosis. Patients who were younger, male, with lesser NIHSS scores at admission, with the fewest history of a medical, higher value of diastolic blood pressure, platelet, blood lipid and lower INR could have a better prognosis.

Biphenyl Au(III) Complexes with Phosphine Ancillary Ligands: Synthesis, Optical Properties, and Electroluminescence in Light-Emitting Electrochemical Cells.

A series of ten cationic complexes of the general formula [(C^C)Au(P^P)]X, where C^C = 4,4'-di-tert-butyl-1,1'-biphenyl, P^P is a diphosphine ligand, and X is a noncoordinating counteranion, have been synthesized and fully characterized by means of chemical and X-ray structural methods. All the complexes display a remarkable switch-on of the emission properties when going from a fluid solution to a solid state. In the latter, long-lived emission with lifetime τ = 1.8-83.0 µs and maximum in the green-yellow region is achieved with moderate to high photoluminescence quantum yield (PLQY). This emission is ascribed to an excited state with a mainly triplet ligand-centered (3LC) nature. This effect strongly indicates that rigidification of the environment helps to suppress nonradiative decay, which is mainly attributed to the large molecular distortion in the excited state, as supported by density functional theory (DFT) and time-dependent DFT (TD-DFT) computation. In addition, quenching intermolecular interactions of the emitter are avoided thanks to the steric hindrance of the substituents. Emissive properties are therefore restored efficiently. The influence of both diphosphine and anion has been investigated and rationalized as well. Using two complexes as examples and owing to their enhanced optical properties in the solid state, the first proof-of-concept of the use of gold(III) complexes as electroactive materials for the fabrication of light-emitting electrochemical cell (LEC) devices is herein demonstrated. The LECs achieve peak external quantum efficiency, current efficiency, and power efficiency up to ca. 1%, 2.6 cd A-1, and 1.1 lm W-1 for complex 1PF6 and 0.9%, 2.5 cd A-1, and 0.7 lm W-1 for complex 3, showing the potential use of these novel emitters as electroactive compounds in LEC devices.

Development of a tumor microenvironment-related prognostic signature in glioma to predict immune landscape and potential therapeutic drugs.

The involvement of the tumor microenvironment (TME) in the biology of gliomas has expanded, while it is yet uncertain its potential of supporting diagnosis and therapy choices. According to immunological characteristics and overall survival, cohorts of glioma patients from public databases were separated into two TME-relevant clusters in this analysis. Based on differentially expressed genes between TME clusters and correlative regression analysis, a 21-gene molecular classifier of TME-related prognostic signature (TPS) was constructed. Afterward, the prognostic efficacy and effectiveness of TPS were assessed in the training and validation groups. The outcome demonstrated that TPS might be utilized alone or in conjunction with other clinical criteria to act as a superior prognostic predictor for glioma. Also, high-risk glioma patients classified by TPS were considered to associate with enhanced immune infiltration, greater tumor mutation, and worse general prognosis. Finally, possible treatment medicines specialized for different risk subgroups of TPS were evaluated in drug databases.

Comparisons of potential values of D-dimer and the neutrophil- to-lymphocyte ratio in patients with suspected acute aortic syndrome.

OBJECTIVES: This study aimed to investigate and compare the discriminative performance and clinical utility of D-dimer and the neutrophil-to-lymphocyte ratio (NLR) in the early differential diagnosis of acute aortic syndrome (AAS). METHODS: The consecutive patients presenting to Tianjin Chest Hospital for suspected AAS were retrospectively investigated between June 2018 and December 2021. The baseline values of D-dimer and NLR were analyzed and compared in the study population. The discriminative ability of D-dimer and NLR was illustrated and compared using the area under the receiver operating characteristic (ROC) curve (AUC), net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Clinical utility was evaluated by means of decision curve analysis (DCA). RESULTS: In the study period, a total of 697 participants suspected of having AAS were enrolled and 323 had a final diagnosis of AAS. The baseline level of NLR as well as D-dimer was higher in patients with AAS. The use of NLR showed excellent overall diagnostic performance for AAS with a comparable AUC to that of D-dimer (0.845 vs. 0.822, P > 0.05). The reclassification analyses further confirmed that NLR had better discriminative properties for AAS with a significant NRI of 66.1% and IDI of 12.4% (P < 0.001). Moreover, NLR provided higher net benefit than D-dimer as shown by DCA. Similar results were observed in subgroup analyses according to the different classes of AAS. CONCLUSIONS: NLR outperformed D-dimer with improved discriminative performance and superior clinical utility in identifying AAS. As a more readily available biomarker, NLR may be a reliable alternative to D-dimer for the screening of suspected AAS in clinical practice.

Associations of parental feeding practices with children's eating behaviors and food preferences: a Chinese cross-sectional study.

BACKGROUND: Childhood inadequate eating behaviors contribute to the epidemic of obesity. Previous research suggests that parental feeding practices are partially associated with development of eating behaviors among children, but the results are inconsistent. The present study was to investigate whether parental feeding practices were associated with eating behaviors and food preferences among Chinese children. METHODS: A cross-sectional study was conducted to collect data from 242 children (ages 7-12) in six-primary schools in Shanghai, China. A series of questionnaires including parental feeding practices and children's eating behaviors have been validated, and were completed by one of parent who has responded for child's daily diet and living. In addition, researchers instructed children to complete the questionnaire of food preference. After adjustment for children's age, sex and BMI status, as well as parental education and family income, the linear regression analysis was used to evaluate relationships of parental feeding practices with children's eating behaviors and food preferences. RESULTS: Parents with boys had higher level of control overeating practice than those with girls. Mothers who responded to child's daily diet and living and completed feeding practices questionnaire used a greater level of emotional feeding practices than fathers. Boys had higher levels of food responsiveness, emotional overeating, enjoyment of food and desire to drink than girls. Boys had different preferences for meat, processed meat products, fast foods, dairy foods, eggs, and snacks and starchy staples & beans from girls. In addition, scores of instrumental feeding practice and preference for meat significantly differed among children with different weight status. Furthermore, parental emotional feeding practice was positively associated with children's emotional undereating (ß 0.54, 95% CI 0.16 to 0.92). There were also positive associations of parental encouragement to eat with children's preference for the processed meat (ß 0.43, 95% CI 0.08 to 0.77). Moreover, instrumental feeding practice was negatively associated with children's fish liking (ß -0.47, 95% CI -0.94 to -0.01). CONCLUSION: The current findings support associations of emotional feeding practice with some children's emotional undereating, as well as parental encouragement to eat and instrumental feeding practice related to preference for processed meat and fish, respectively. Further studies should continue to ascertain these associations using longitudinal designs, and to evaluate efficacy of parental feeding practices impacting developments of healthy eating behaviors and preferences for healthy foods among children by interventional studies.

An AIE-Active NIR Fluorescent Probe with Good Water Solubility for the Detection of Aß1-42 Aggregates in Alzheimer's Disease.

Alzheimer's disease (AD), an amyloid-related disease, seriously endangers the health of elderly individuals. According to current research, its main pathogenic factor is the amyloid protein, which is a kind of fibrillar aggregate formed by noncovalent self-assembly of proteins. Based on the characteristics of aggregation-induced emission (AIE), a bislactosyl-decorated tetraphenylethylene (TPE) molecule TMNL (TPE + malononitrile + lactose), bearing two malononitrile substituents, was designed and synthesized in this work. The amphiphilic TMNL could self-assemble into fluorescent organic nanoparticles (FONs) with near-infrared (NIR) fluorescence emission in physiological PBS (phosphate buffered saline), achieving excellent fluorescent enhancement (47-fold) upon its combination with Aß1-42 fibrils. TMNL was successfully applied to image Aß1-42 plaques in the brain tissue of AD transgenic mice, and due to the AIE properties of TMNL, no additional rinsing process was necessary. It is believed that the probe reported in this work should be useful for the sensitive detection and accurate localization mapping of Aß1-42 aggregates related to Alzheimer's disease.

Preparation of Biomass Biochar with Components of Similar Proportions and Its Methylene Blue Adsorption.

Rapeseed straw, bagasse, and walnut peel have a large amount of resource reserves, but there are few technologies for high value-added utilization. In the research of biochar, walnut green husk is rarely used as raw material. In addition, the three main components of biomass (lignin, cellulose, and hemicellulose) are present in similar proportions, and the differences between the physical and chemical properties of biochar prepared with similar amounts of biomass raw materials are not clear. Using three kinds of biomass of the same quality as raw materials, biochar was prepared via pyrolysis at 400 °C, and activated carbon was prepared via CO2 activation at 800 °C. The results showed that the pore numbers of the three kinds of biochar increased after activation, resulting in the increase of the specific surface area. The resulting numbers were 352.99 m2/g for sugarcane bagasse biochar (SBB)-CO2, 215.04 m2/g for rapeseed straw biochar (RSB)-CO2, and 15.53 m2/g for walnut green husk biochar (WGB)-CO2. Ash increased the amount of carbon formation, but a large amount of ash caused biochar to form a perforated structure and decreased the specific surface area (e.g., WGB), which affected adsorption ability. When the three main components were present in similar proportions, a high content of cellulose and lignin was beneficial to the preparation of biochar. The adsorption value of MB by biochar decreased with the increase of biomass ash content. After activation, the maximum adsorption value of MB for bagasse biochar was 178.17 mg/g, rapeseed straw biochar was 119.25 mg/g, and walnut peel biochar was 85.92 mg/g when the concentration of methene blue solution was 300 mg/L and the biochar input was 0.1 g/100 mL at room temperature. The adsorption of MB by biochar in solution occurs simultaneously with physical adsorption and chemical adsorption, with chemical adsorption being dominant. The optimal MB adsorption by SBB-CO2 was dominated by multimolecular-layer adsorption. This experiment provides a theoretical basis for the preparation of biochar and research on its applications in the future.

Asymmetric Total Synthesis of Hasubanan Alkaloids: Periglaucines A-C, N,O-Dimethyloxostephine and Oxostephabenine.

We report herein the asymmetric total synthesis of periglaucines A-C, N,O-dimethyloxostephine and oxostephabenine. The key strategies used include: 1) a RhI -catalyzed regio- and diastereoselective Hayashi-Miyaura reaction to connect two necessary fragments; 2) an intramolecular photoenolization/Diels-Alder (PEDA) reaction to construct the highly functionalized tricyclic core skeleton bearing a quaternary center; 3) a bio-inspired intramolecular Michael addition and transannular acetalization to generate the aza[4.4.3]propellane and the tetrahydrofuran ring.

Peritoneal GATA6+ macrophage drives hepatic immunopathogenesis and maintains the Treg cell niche in the liver.

The source of macrophages that contribute to human liver disease remains poorly understood. The purpose of this study is to investigate the functional mechanism of peritoneal macrophages in the development of hepatic immunopathology. By performing the natural infection with the blood fluke Schistosoma japonicum (S. japonicum) and the chemically carbon tetrachloride (CCl4 )-induced liver injured mouse model, we identified the peritoneal cavity as an essential source of hepatic macrophages. Here, we show that a large number of F4/80+ macrophages was accumulated in the peritoneal cavity during liver injury. An unknown source population of macrophages, which highly expressed GATA6 that is specific to peritoneal macrophages, was found to exist in the injured livers. Peritoneal macrophage deletion by injection with clodronate-containing liposomes led to an attenuated hepatic pathology and the inflammatory microenvironment, while adoptive transfer of macrophages into the abdominal cavity, by contrast, results in restoring liver pathology. Importantly, there are set genes of monocyte chemoattractant protein (MCP)-1, -2, and -3 that are highly related to recruit GATA6+ macrophages during S. japonicum infection, while administration of bindarit, a selective inhibitor of MCPs synthesis, dramatically decreased the hepatic expression of GATA6+ macrophages and thus attenuated hepatic pathology. Furthermore, in vivo study showed that peritoneal macrophages promote hepatic immunopathology is dependent on the accumulation of regulatory T cells (Tregs) in the liver. Altogether, these data provide the first clear evidence that GATA6+ peritoneal macrophages play critical roles in both the formation of hepatic immunopathology and the accumulation of Tregs cells.